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Nov.25.2022

Paroxetine

Indications/Dosage

Labeled

  • depression
  • generalized anxiety disorder (GAD)
  • hot flashes
  • menopause
  • obsessive-compulsive disorder (OCD)
  • panic disorder
  • posttraumatic stress disorder (PTSD)
  • premenstrual dysphoric disorder (PMDD)
  • social phobia (social anxiety disorder)

Off-Label

  • premature ejaculation
† Off-label indication

For the treatment of major depression

Oral dosage (immediate-release)

Adults

20 mg PO once daily, initially. Increase dose by 10 mg/day at intervals of at least 1 week if inadequate response and depending on tolerability. Max: 50 mg/day.[28260] [49961]

Older Adults

10 mg PO once daily, initially. Increase dose by 10 mg/day at intervals of at least 1 week if inadequate response and depending on tolerability. Max: 40 mg/day.[28260] [49961]

Oral dosage (controlled-release)

Adults

25 mg PO once daily, initially. Increase dose by 12.5 mg/day at intervals of at least 1 week if inadequate response and depending on tolerability. Max: 62.5 mg/day.[43999] [49961]

Older Adults

12.5 mg PO once daily, initially. Increase dose by 12.5 mg/day at intervals of at least 1 week if inadequate response and depending on tolerability. Max: 50 mg/day.[43999] [49961]

For the treatment of generalized anxiety disorder (GAD)

Oral dosage (immediate-release formulations e.g., Paxil, Pexeva)

Adults

20 mg PO once daily is the initial and usual effective dose, usually administered in the morning. May titrate the dose by 10 mg/day at weekly intervals if needed and tolerated. Max: 50 mg/day PO. Additional benefit does not appear to be gained with dosages higher than 20 mg/day. DEBILITATED or GERIATRIC ADULTS: 10 mg PO once daily initially, may titrate the dose by 10 mg/day at weekly intervals; Max: 40 mg/day. Anxiety disorders are chronic conditions; consider the continuation of the drug in a responding patient. Maintain the lowest effective dosage. Periodically reassess the need for continued treatment.[28260]

For the treatment of obsessive-compulsive disorder (OCD)

Oral dosage (immediate-release formulations; e.g., Paxil, Pexeva)

Adults

20 mg PO once daily initially, usually in the morning. Increase by 10 mg/day at weekly intervals, if tolerated, to the usual target dose of 40 mg PO once daily. Max: 60 mg/day PO. DEBILITATED or GERIATRIC ADULTS: 10 mg PO once daily initially; may titrate by 10 mg at weekly intervals; Max: 40 mg/day PO. Periodically reassess the need for continued treatment.[28260]

Children and Adolescents 7 years and older†

10 mg PO once daily for 1 week initially; may titrate at intervals of at least 7 days if needed based upon response and tolerability. Max: 50 mg/day PO. Periodically reassess the need for continued treatment. This regimen was studied in a large randomized, placebo-controlled trial (n = 207); the mean dose in children was 30.1 mg/day and the mean dose in adolescents was 36.5 mg/day. The change in the primary efficacy measure (the Children's Yale-Brown Obsessive-Compulsive Scale) and 3 of 6 secondary efficacy measures were statistically significant in favor of paroxetine. Global assessments showed no change between the groups. Evaluation of the long-term safety and efficacy of paroxetine in the treatment of childhood OCD is needed.[53505]

For the treatment of panic disorder, with or without agoraphobia

Oral dosage (immediate-release formulations; e.g., Paxil, Pexeva)

Adults

10 mg PO once daily initially, usually in the morning. Doses should be increased by 10 mg/day at weekly intervals as tolerated to the usual target dose of 40 mg/day. Usual Adult Max: 60 mg/day PO. DEBILITATED or GERIATRIC ADULTS Max: 40 mg/day PO. Anxiety disorders are chronic conditions; consider continuation of the drug in a responding patient. Use the lowest effective dosage. Periodically reassess the need for continued treatment.[28260]

Children and Adolescents 7 years and older†

Initially, 10 mg/day PO. 10 to 40 mg/day PO has been studied. To minimize the frequency and severity of adverse effects, slowly titrate at weekly intervals based on response and tolerability. Periodically reassess the need for continued treatment. Further study is needed to establish the safety and efficacy of SSRIs in the treatment of childhood panic disorder. Results from 1 naturalistic study (n = 18) used a mean initial dose of 8.9 mg/day PO followed by titration up to 40 mg/day PO depending on response and tolerability. Improvement began after a mean duration of 3 weeks treatment. The final mean dose was 24 mg/day (range: 10 to 40 mg/day). At study end, 83.3% of patients were considered responders, with 55.5% showing marked improvement on the CGI-Improvement scale score and 27.8% with moderate improvement.[53503]

Oral dosage (controlled-release tablets; e.g., Paxil CR)

Adults

12.5 mg PO once daily initially, usually in the morning. May increase as needed in increments of 12.5 mg, at a minimum of weekly intervals. The effective dosage range for younger adults was 12.5 to 75 mg/day in clinical trials. Usual Adult Max: 75 mg/day PO. DEBILITATED or GERIATRIC ADULTS Max: 50 mg/day PO. Anxiety disorders are chronic conditions; consider continuation of the drug in a responding patient. Use the lowest effective dosage. Periodically reassess the need for continued treatment.[43999]

For the treatment of social phobia (social anxiety disorder)

Oral dosage (immediate-release formulations; e.g., Paxil, Pexeva)

Adults

20 mg/day PO is the initial and usual effective dose, usually given in the morning. May titrate by 10 mg/day at weekly intervals if needed and tolerated. Effective dose range: 20 to 60 mg/day; however, doses above 20 mg/day do not appear to provide additional benefit. Max: 60 mg/day PO. DEBILITATED or GERIATRIC ADULTS: 10 mg PO once daily initially, may titrate by 10 mg/day at weekly intervals if needed and tolerated. Usual target dose is 20 mg/day; Max: 40 mg/day PO. Periodically reassess the need for continued treatment.[28260]

Children and Adolescents 8 years and older†

10 mg/day PO initially, then may titrate by 10 mg/day at intervals of at least 7 days based on response and tolerability. Max: 50 mg/day PO. Periodically reassess the need for continued treatment. Further study is needed to evaluate the safety and efficacy of SSRIs in the treatment of childhood anxiety disorders. The suggested regimen was used in a multicenter, placebo-controlled clinical trial (n = 322), at the study end (16 weeks) the mean dose for children was 26.5 mg/day and for adolescents was 35 mg/day. Overall, responders on the primary efficacy measure (CGI-I score) were statistically significant in favor of paroxetine vs. placebo (77.6% vs. 38.3%). The remission rate for paroxetine was also greater vs. placebo (47.8% vs. 14.9%).[53506]

Oral dosage (controlled-release formulations; e.g., Paxil CR)

Adults

12.5 mg PO once daily initially, usually given in the morning. If needed, titrate at intervals of at least 1 week, in increments of 12.5 mg/day. During clinical trials, effectiveness was demonstrated in a range of 12.5 to 37.5 mg PO once daily. Max: 37.5 mg/day PO. Periodically reassess the need for continued treatment.[43999]

For the treatment of posttraumatic stress disorder (PTSD)

Oral dosage (immediate-release formulations; e.g., Paxil, Pexeva)

Adults

20 mg PO once daily is the initial and usual effective dose, usually administered in the morning. May titrate by 10 mg/week if needed and tolerated. Effective dose range: 20 to 50 mg/day. Max: 50 mg/day PO. DEBILITATED or GERIATRIC ADULTS: 10 mg PO once daily initially, with titration by 10 mg/week if needed; Max: 40 mg/day PO. Paroxetine is effective in treating PTSD symptoms including re-experiencing/intrusion, avoidance/numbing, and hyperarousal. In one fixed-dose study, 40 mg/day PO did not show greater efficacy than 20 mg/day. Anxiety disorders are chronic conditions; consider continuation of the drug in a responding patient. Use the lowest effective dosage. Periodically reassess the need for continued treatment.[28260]

For the treatment of premenstrual dysphoric disorder (PMDD)

Oral dosage (controlled-release tablets e.g., Paxil CR)

Adult females

12.5 mg/day PO initially, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on provider assessment. In clinical trials, doses of 12.5 to 25 mg/day were effective. Dose changes should occur at intervals of at least 1 week. Effectiveness has not been evaluated beyond 3 menstrual cycles; however, symptoms generally continue and sometimes worsen. Therefore, it is reasonable to continue treatment in a responding patient.[43999]

Oral dosage (immediate-release formulations†, e.g., Paxil, Pexeva)

Adult females

Dosages have ranged from 5 to 30 mg/day PO, dependent on clinical response and tolerance. Continuous daily dosing or, alternatively, luteal phase administration during the 7 to 14 days prior to menses, has been effective.[25691]

For the treatment of moderate to severe hot flashes associated with menopause, including in women who have been treated for breast cancer

Oral dosage (formulations intended for this use; i.e., Brisdelle)

Adult females

7.5 mg PO once daily at bedtime with or without food.[55186] The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy indicate that paroxetine is an effective choice for treating vasomotor symptoms of menopause when hormonal therapy is not desired or is contraindicated.[62040]

Oral dosage (controlled-release tablets†, e.g., Paxil CR)

Adult females

Initially, 12.5 mg PO once daily. If 12.5 mg/day PO does not provide relief, the dose can be titrated to 25 mg PO once daily after 1 week if needed. Clinical trials indicate either dose is equally effective; individualize dosage. The North American Menopause Society (NAMS) Guidelines for non-hormonal therapy indicate that paroxetine is an effective choice for treating vasomotor symptoms of menopause when hormonal therapy is not desired or is contraindicated.[62040] In 165 menopausal women, after 6 weeks, the frequency of hot flashes was reduced by 62.2% in women taking 12.5 mg/day and 64.6% in women taking 25 mg/day versus 37.8% reductions for placebo.[32190]

For the treatment of premature ejaculation†

Oral dosage (immediate-release formulations e.g., Paxil, Pexeva)

Adult males

10 to 40 mg/day PO has been shown to increase ejaculatory latency; however, the benefit of increasing the dose to 40 mg/day is not well established. Based on the available evidence, treatment guidelines support a daily dose of 20 mg/day.[56274] In one study of men with lifelong rapid ejaculation [i.e., an intravaginal ejaculation latency time (IELT) of 1 minute or less], men treated with paroxetine had an increase in IELT to about 110 seconds. In another study, paroxetine 20 mg/day PO increased mean IELT by 480% (from a mean of 83 seconds to a mean of 602 seconds).[25412] Alternatively, 20 mg PO given 3 to 4 hours pre-intercourse has demonstrated efficacy and is suggested per treatment guidelines. It is unclear if daily or situational dosing is more effective in the management of premature ejaculation. Likewise, the optimal interval for situational dosing before intercourse is not well defined. The choice of regimen is individualized to each patient.[56274]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    60 mg/day PO for immediate-release formulation; 75 mg/day PO for controlled-release formulation.

  • Geriatric

    40 mg/day PO for immediate-release formulation; 50 mg/day PO for controlled-release formulation.

  • Adolescents

    Safety and efficacy have not been established; however, doses up to 50 mg/day PO have been used off-label for anxiety disorders.

  • Children

    7 to 12 years: Safety and efficacy have not been established; however, doses up to 50 mg/day PO have been used off-label for anxiety disorders.

    1 to 6 years: Safety and efficacy have not been established.

  • Infants

    Safety and efficacy have not been established.

  • Neonates

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Immediate-release dosage forms (i.e., Paxil, Pexeva): Initially, 10 mg/day PO in adults; final adult dosage should not exceed 40 mg/day PO. There are no guidelines available for pediatric patients.[28260]

 

Immediate-release 7.5 mg capsules (i.e., Brisdelle): No dose adjustment is considered necessary in patients with hepatic impairment.[55186]

 

Controlled-release tablets (Paxil CR): The initial dose is 12.5 mg/day PO in adults, with final adult dosage not to exceed 50 mg/day PO, regardless of indication. There are no guidelines available for pediatric patients.[43999]

Patients with Renal Impairment Dosing

Patients with renal impairment receiving immediate-release 7.5 mg capsules (i.e., Brisdelle): No dosage adjustment is considered necessary.[55186]

 

Patients with renal impairment receiving immediate-release dosage forms including Paxil or Pexeva:

CrCl 30—60 ml/min: Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available. Lower doses may be needed.

CrCl < 30 ml/min: Initially, 10 mg/day PO in adults; final adult dosage should not exceed 40 mg/day PO. There are no guidelines available for pediatric patients.[28260]

 

Patients with severe renal impairment receiving controlled-release dosage forms including Paxil CR:

The initial dose is 12.5 mg/day PO in adults, with final adult dosage not to exceed 50 mg/day PO, regardless of indication. There are no guidelines available for pediatric patients.[43999]

 

Intermittent hemodialysis

See dosage for patients with CrCl < 30 ml/min. Dosage adjustments are not necessary in patients receiving the Brisdelle brand.[55186] Paroxetine is unlikely to be significantly removed by hemodialysis given its large volume of distribution.

† Off-label indication
Revision Date: 11/25/2022, 09:03:53 PM

References

25412 - Waldinger MD, Hengeveld MW, Zwinderman AH, et al. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 1998;18:274-81.25691 - Sundblad C, Wikander I, Andersch B, et al. A naturalistic study of paroxetine in premenstrual syndrome: efficacy and side-effects during ten cycles of treatment. Eur Neuropsychopharmacol 1997;7:201-206.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.32190 - Stearns V, Beebe KL, Iyengar M, et al. Paroxetine controlled release in the treatment of menopausal hot flashes. JAMA 2003;289:2827-34.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.49961 - Practice Guideline for the treatment of patients with major depressive disorder, 3rd Edition. American Psychiatric Association Press. November 2010.53503 - Masi G, Toni C, Mucci M, et al. Paroxetine in child and adolescent outpatients with panic disorder. J Child Adolesc Psychopharm 2001;11:151-7.53505 - Geller DA, Wagner KD, Emslie G, et al. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 2004;43:1387-96.53506 - Wagner KD, Berard R, Stein MB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine in children and adolescents with social anxiety disorder. Arch Gen Psychiatry 2004;61:1153-62.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.56274 - Montague DK, Jarow J, Broderick GA, et al. AUA guideline on the pharmacologic management of premature ejaculation. J Urol 2004;172:290-4.62040 - North American Menopause Society. Non-hormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society. Menopause. 2015;22:1155-1172.

How Supplied

Paroxetine Hydrochloride Oral suspension

Paroxetine Hydrochloride 10mg/5mL Suspension (60505-0374) (Apotex Corp) (off market)Paroxetine Hydrochloride 10mg/5mL Suspension package photo

Paroxetine Hydrochloride Oral suspension

Paroxetine Hydrochloride 10mg/5mL Suspension (70954-0319) (Novitium Pharma, LLC ) null

Paroxetine Hydrochloride Oral suspension

Paxil 10mg/5mL Suspension (00029-3215) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral suspension

Paxil 10mg/5mL Suspension (60505-0402) (Apotex Corp) (off market)Paxil 10mg/5mL Suspension package photo

Paroxetine Hydrochloride Oral suspension

Paxil 10mg/5mL Suspension (60505-0402) (Apotex Corp) null

Paroxetine Hydrochloride Oral suspension

Paxil 10mg/5mL Suspension (00029-3215) (GlaxoSmithKline Group of Companies) (off market)Paxil 10mg/5mL Suspension package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (52343-0073) (Acetris Health, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (68084-0044) (American Health Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (60505-0097) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (65862-0154) (Aurobindo Pharma USA Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (13107-0154) (Aurolife Pharma, LLC an Aurobindo Company) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (50268-0640) (AvPAK; a Division of AvKARE Inc) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (71335-0544) (Bryant Ranch Prepack, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (60429-0734) (Golden State Medical Supply, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (59762-1808) (Greenstone Ltd) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (54458-0990) (International Laboratories LLC for Walmart) nullParoxetine Hydrochloride 10mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (59746-0457) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00904-6109) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00904-5676) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00904-5676) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00406-2097) (Mallinckrodt Pharmaceuticals) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (63739-0888) (McKesson Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (63739-0407) (McKesson Packaging Inc) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00378-7001) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (16714-0181) (NorthStar Rx LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (69584-0671) (Oxford Pharmaceuticals, LLC) nullParoxetine Hydrochloride 10mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (49884-0876) (Par Pharmaceuticals, an Endo Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (55289-0037) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (55289-0037) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00781-1967) (Sandoz Inc. a Novartis Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (43547-0347) (Solco Healthcare US LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (57664-0421) (Sun Pharmaceutical Industries, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (00093-7114) (Teva Pharmaceuticals USA) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (62037-0845) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (62037-0845) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (52817-0140) (TruPharma, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 10mg Tablet (68382-0097) (Zydus Pharmaceuticals (USA) Inc.) null

Paroxetine Hydrochloride Oral tablet

Paxil 10mg Tablet (60505-4517) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 10mg Tablet (00029-3210) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 10mg Tablet (60505-3663) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 10mg Tablet (00029-3210) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (52343-0074) (Acetris Health, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (68084-0045) (American Health Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (60505-0083) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (65862-0155) (Aurobindo Pharma USA Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (13107-0155) (Aurolife Pharma, LLC an Aurobindo Company) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (50268-0641) (AvPAK; a Division of AvKARE Inc) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (10544-0433) (Blenheim Pharmacal, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (60429-0735) (Golden State Medical Supply, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (59762-1810) (Greenstone Ltd) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (54458-0989) (International Laboratories LLC for Kroger ) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (54458-0989) (International Laboratories LLC for Walmart) nullParoxetine Hydrochloride 20mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (59746-0458) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00904-5677) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00904-5677) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00904-6110) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00406-2098) (Mallinckrodt Pharmaceuticals) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (63739-0963) (McKesson Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (51079-0774) (Mylan Institutional LLC ) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00378-7002) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (58517-0160) (New Horizon Rx Group, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (16714-0182) (NorthStar Rx LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (69584-0672) (Oxford Pharmaceuticals, LLC) nullParoxetine Hydrochloride 20mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (49884-0877) (Par Pharmaceuticals, an Endo Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (55289-0972) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (55289-0972) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (43063-0170) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00781-1991) (Sandoz Inc. a Novartis Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (43547-0348) (Solco Healthcare US LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (57664-0422) (Sun Pharmaceutical Industries, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (00093-7115) (Teva Pharmaceuticals USA) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (62037-0846) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (62037-0846) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (52817-0141) (TruPharma, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 20mg Tablet (68382-0098) (Zydus Pharmaceuticals (USA) Inc.) null

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (00029-3211) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (60505-4518) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (60505-3664) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (00029-3211) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (58864-0372) (PD-Rx Pharmaceuticals, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 20mg Tablet (55289-0216) (PD-Rx Pharmaceuticals, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (52343-0075) (Acetris Health, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (68084-0046) (American Health Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (60505-0084) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (65862-0156) (Aurobindo Pharma USA Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (13107-0156) (Aurolife Pharma, LLC an Aurobindo Company) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (50268-0642) (AvPAK; a Division of AvKARE Inc) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (60429-0736) (Golden State Medical Supply, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (59762-1812) (Greenstone Ltd) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (54458-0988) (International Laboratories LLC for Walmart) nullParoxetine Hydrochloride 30mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (59746-0459) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00904-6111) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00904-5678) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00904-5678) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00406-2099) (Mallinckrodt Pharmaceuticals) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00378-7003) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (16714-0183) (NorthStar Rx LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (69584-0673) (Oxford Pharmaceuticals, LLC) nullParoxetine Hydrochloride 30mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (49884-0878) (Par Pharmaceuticals, an Endo Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00781-1992) (Sandoz Inc. a Novartis Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (43547-0349) (Solco Healthcare US LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (57664-0424) (Sun Pharmaceutical Industries, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (00093-7116) (Teva Pharmaceuticals USA) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (62037-0847) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (62037-0847) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (52817-0142) (TruPharma, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 30mg Tablet (68382-0099) (Zydus Pharmaceuticals (USA) Inc.) null

Paroxetine Hydrochloride Oral tablet

Paxil 30mg Tablet (00029-3212) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 30mg Tablet (60505-4519) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 30mg Tablet (60505-3665) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 30mg Tablet (00029-3212) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (52343-0076) (Acetris Health, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (68084-0047) (American Health Packaging) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (60505-0101) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (65862-0157) (Aurobindo Pharma USA Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (13107-0157) (Aurobindo Pharma USA Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (50268-0643) (AvPAK; a Division of AvKARE Inc) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (10544-0809) (Blenheim Pharmacal, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (60429-0737) (Golden State Medical Supply, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (59762-1815) (Greenstone Ltd) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (59746-0460) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00904-5679) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00904-5679) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00904-6112) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00406-2001) (Mallinckrodt Pharmaceuticals) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (63739-0408) (McKesson Packaging Inc) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00378-7004) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (16714-0184) (NorthStar Rx LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (69584-0674) (Oxford Pharmaceuticals, LLC) nullParoxetine Hydrochloride 40mg Tablet package photo

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (49884-0879) (Par Pharmaceuticals, an Endo Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (55289-0053) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (55289-0053) (PD-Rx Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00781-1969) (Sandoz Inc. a Novartis Company) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (43547-0350) (Solco Healthcare US LLC) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (57664-0425) (Sun Pharmaceutical Industries, Inc.) null

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (00093-7121) (Teva Pharmaceuticals USA) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (62037-0848) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (62037-0848) (Teva/Actavis US) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (52817-0143) (TruPharma, LLC) (off market)

Paroxetine Hydrochloride Oral tablet

Paroxetine Hydrochloride 40mg Tablet (68382-0001) (Zydus Pharmaceuticals (USA) Inc.) null

Paroxetine Hydrochloride Oral tablet

Paxil 40mg Tablet (60505-3666) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 40mg Tablet (00029-3213) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 40mg Tablet (60505-4520) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet

Paxil 40mg Tablet (00029-3213) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet

Paxil 40mg Tablet (58864-0628) (PD-Rx Pharmaceuticals, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Controlled-Release Tablet (60505-1316) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Controlled-Release Tablet (60505-3673) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (42291-0579) (AvKARE, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (62135-0425) (Chartwell Pharmaceuticals) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (62175-0470) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (68180-0647) (Lupin Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (72241-0029) (Modavar Pharmaceuticals, LLC) nullParoxetine Hydrochloride 12.5mg Extended-Release Tablet package photo

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (51079-0824) (Mylan Institutional LLC ) nullParoxetine Hydrochloride 12.5mg Extended-Release Tablet package photo

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (00378-2003) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (42858-0703) (Rhodes Pharmaceuticals LP) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 12.5mg Extended-Release Tablet (69367-0335) (Westminster Pharmaceuticals, LLC) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 12.5mg Tablet (00029-3206) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 12.5mg Tablet (60505-3668) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 12.5mg Tablet (00029-4606) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 12.5mg Tablet (60505-4377) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 12.5mg Tablet (00029-3206) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Controlled-Release Tablet (60505-3674) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Controlled-Release Tablet (60505-1317) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (42291-0580) (AvKARE, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (62135-0426) (Chartwell Pharmaceuticals) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (62175-0471) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (68180-0646) (Lupin Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (72241-0030) (Modavar Pharmaceuticals, LLC) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (51079-0825) (Mylan Institutional LLC ) nullParoxetine Hydrochloride 25mg Extended-Release Tablet package photo

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (00378-2004) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (42858-0705) (Rhodes Pharmaceuticals LP) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 25mg Extended-Release Tablet (69367-0336) (Westminster Pharmaceuticals, LLC) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 25mg Tablet (00029-4607) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 25mg Tablet (00029-3207) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 25mg Tablet (60505-4378) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 25mg Tablet (60505-3669) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 25mg Tablet (00029-3207) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Controlled-Release Tablet (60505-3675) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Controlled-Release Tablet (60505-1318) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Controlled-Release Tablet (00378-2006) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (42291-0581) (AvKARE, Inc.) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (62135-0427) (Chartwell Pharmaceuticals) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (62175-0472) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (68180-0645) (Lupin Pharmaceuticals, Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (72241-0031) (Modavar Pharmaceuticals, LLC) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (00378-2005) (Mylan Pharmaceuticals Inc.) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (42858-0707) (Rhodes Pharmaceuticals LP) null

Paroxetine Hydrochloride Oral tablet, extended release

Paroxetine Hydrochloride 37.5mg Extended-Release Tablet (69367-0337) (Westminster Pharmaceuticals, LLC) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 37.5mg Tablet (60505-3670) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 37.5mg Tablet (60505-4379) (Apotex Corp) null

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 37.5mg Tablet (00029-3208) (Apotex Corp) (off market)

Paroxetine Hydrochloride Oral tablet, extended release

Paxil CR 37.5mg Tablet (00029-3208) (GlaxoSmithKline Group of Companies) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (63672-2010) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (68968-2010) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (68968-2010) (Noven Therapeutics, LLC ) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (68968-2010) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (54766-0201) (Sebela Pharmaceuticals Inc) null

Paroxetine Mesylate Oral tablet

Pexeva 10mg Tablet (63672-2010) (Synthon Pharmaceuticals Ltd) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (63672-2020) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (68968-2020) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (68968-2020) (Noven Therapeutics, LLC ) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (54766-0202) (Sebela Pharmaceuticals Inc) null

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (68968-2020) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 20mg Tablet (63672-2020) (Synthon Pharmaceuticals Ltd) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (68968-2030) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (63672-2030) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (68968-2030) (Noven Therapeutics, LLC ) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (68968-2030) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (54766-0203) (Sebela Pharmaceuticals Inc) null

Paroxetine Mesylate Oral tablet

Pexeva 30mg Tablet (63672-2030) (Synthon Pharmaceuticals Ltd) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (63672-2040) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (68968-2040) (JDS Pharmaceuticals) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (68968-2040) (Noven Therapeutics, LLC ) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (54766-0204) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (68968-2040) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Mesylate Oral tablet

Pexeva 40mg Tablet (63672-2040) (Synthon Pharmaceuticals Ltd) (off market)

Paroxetine Oral capsule

Brisdelle 7.5mg Capsule (68968-9075) (Noven Therapeutics, LLC ) (off market)Brisdelle 7.5mg Capsule package photo

Paroxetine Oral capsule

Brisdelle 7.5mg Capsule (68968-9075) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Oral capsule

Brisdelle 7.5mg Capsule (54766-0907) (Sebela Pharmaceuticals Inc) (off market)

Paroxetine Oral capsule

Paroxetine 7.5mg Capsule (00574-0279) (Paddock Laboratories Inc, a Perrigo Family) null

Paroxetine Oral capsule

Paroxetine 7.5mg Capsule (43547-0409) (Solco Healthcare US LLC) null

Description/Classification

Description

Paroxetine is an oral selective serotonin reuptake inhibitor (SSRI) that has no active metabolites. FDA-approved indications in adults include the treatment of major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and premenstrual dysphoric disorder (PMDD). Paroxetine was the first non-hormonal agent to be approved by the FDA for moderate to severe vasomotor symptoms associated with menopause. The drug is used off-label for treating premature ejaculation in men. Paroxetine is not FDA-approved for any indication in children or adolescents; however, the drug has been used off-label for certain childhood anxiety disorders. Paroxetine exhibits anticholinergic activity that may be problematic for some elderly adults. Clinically significant drug interactions may result from potent CYP2D6 inhibition by paroxetine. Paroxetine should be avoided during pregnancy due to data suggesting an increased risk for congenital malformations, particularly cardiac malformations, during first-trimester exposure. Product labels for all antidepressants contain a boxed warning related to an increased risk of suicidality in children, adolescents, and young adults during the initial stages of therapy when treating depression or other conditions; therefore, the necessity of pharmacologic therapy versus the potential risks should be carefully considered in these populations.[28260][43999][43998][55186][64280]

Classifications

  • Central Nervous System
    • Psychoanaleptics Excluding Anti-obesity Agents
      • Anti-depressants and Mood Stabilizers
        • Selective Serotonin Reuptake Inhibitor Antidepressants, SSRIs
Revision Date: 04/10/2020, 05:26:52 PM

References

28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.43998 - Pexeva (paroxetine mesylate) package insert. Roswell, GA: Sebela Pharmaceuticals, Inc. 2021 Sept.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.64280 - Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacol Bull. 2016;46:77-104. Review.

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Hazardous Drugs Classification

  • NIOSH 2016 List: Group 3 [63664]
  • NIOSH (Draft) 2020 List: Table 2
  • Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
  • Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.[63664][67506][67507]

Route-Specific Administration

Oral Administration

  • Administer as a single dose, usually in the morning. May be administered without regard to meals, however, food may minimize GI adverse effects.[28260]

Oral Solid Formulations

  • Controlled-release tablets: Patients should swallow tablets whole. Do not cut, chew, or crush. Do not administer concomitantly with antacids; the tablets are enteric-coated.[43999]

Oral Liquid Formulations

  • Oral suspension: Shake well before each use. To ensure accurate dosing, measure dosage with a calibrated measuring device.[28260]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 04/21/2022, 02:01:34 PM

    References

    28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.63664 - CDC National Institute for Occupational Safety and Health (NIOSH). NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2016. DHHS (NIOSH) Publication Number 2016-161, September 2016. Available on the World Wide Web at https://www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf?id=10.26616/NIOSHPUB201616167506 - American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2018; 75:1996-2031.67507 - NIOSH [2016]. NIOSH Alert: Preventing Occupational Exposures to Antineoplastics and Other Hazardous Drugs in Health Care Settings. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2016-161.

    Adverse Reactions

    Mild

    • abdominal pain
    • abnormal dreams
    • acne vulgaris
    • agitation
    • alopecia
    • amenorrhea
    • anorexia
    • anxiety
    • appetite stimulation
    • arthralgia
    • asthenia
    • back pain
    • breast discharge
    • breast enlargement
    • chills
    • cough
    • dental caries
    • dental pain
    • diarrhea
    • diplopia
    • dizziness
    • drowsiness
    • dysgeusia
    • dysmenorrhea
    • dyspepsia
    • ecchymosis
    • emotional lability
    • eructation
    • fatigue
    • fever
    • flatulence
    • gastroesophageal reflux
    • gingivitis
    • gynecomastia
    • headache
    • hiccups
    • hirsutism
    • hyperhidrosis
    • hyperkinesis
    • hyperventilation
    • hypoesthesia
    • hyporeflexia
    • hypothermia
    • increased urinary frequency
    • infection
    • insomnia
    • laryngitis
    • lethargy
    • leukocytosis
    • leukorrhea
    • libido decrease
    • libido increase
    • maculopapular rash
    • malaise
    • mastalgia
    • menorrhagia
    • muscle cramps
    • myalgia
    • mydriasis
    • nausea
    • nocturia
    • ocular pain
    • orgasm dysfunction
    • otalgia
    • pallor
    • paranoia
    • paresthesias
    • parosmia
    • pelvic pain
    • petechiae
    • pharyngitis
    • photosensitivity
    • polydipsia
    • polyuria
    • pruritus
    • ptosis
    • purpura
    • rash
    • restless legs syndrome (RLS)
    • rhinitis
    • seborrhea
    • sinusitis
    • skin discoloration
    • syncope
    • tinnitus
    • tongue discoloration
    • tremor
    • urinary urgency
    • urticaria
    • vertigo
    • vesicular rash
    • vomiting
    • weight gain
    • weight loss
    • xerosis
    • xerostomia
    • yawning

    Moderate

    • akathisia
    • amblyopia
    • amnesia
    • anemia
    • angina
    • aphasia
    • ataxia
    • atopic dermatitis
    • bleeding
    • blepharitis
    • blurred vision
    • bullous rash
    • bundle-branch block
    • candidiasis
    • cataracts
    • chest pain (unspecified)
    • cholelithiasis
    • choreoathetosis
    • colitis
    • confusion
    • conjunctivitis
    • constipation
    • contact dermatitis
    • cystitis
    • dehydration
    • delirium
    • depression
    • diabetes mellitus
    • dysarthria
    • dyskinesia
    • dysphagia
    • dysphonia
    • dyspnea
    • dystonic reaction
    • dysuria
    • edema
    • ejaculation dysfunction
    • elevated hepatic enzymes
    • eosinophilia
    • esophagitis
    • euphoria
    • exophthalmos
    • fecal incontinence
    • flank pain
    • furunculosis
    • galactorrhea
    • gastritis
    • gingival hyperplasia
    • glossitis
    • goiter
    • gout
    • growth inhibition
    • hallucinations
    • hematoma
    • hematuria
    • hemoptysis
    • hemorrhoids
    • hepatitis
    • hepatomegaly
    • hostility
    • hyperacusis
    • hyperalgesia
    • hyperbilirubinemia
    • hypercalcemia
    • hypercholesterolemia
    • hyperglycemia
    • hyperphosphatemia
    • hyperprolactinemia
    • hyperreflexia
    • hypertension
    • hyperthyroidism
    • hypertonia
    • hypocalcemia
    • hypoglycemia
    • hypokalemia
    • hyponatremia
    • hypotension
    • hypothyroidism
    • impotence (erectile dysfunction)
    • jaundice
    • leukopenia
    • lymphadenopathy
    • lymphocytosis
    • lymphopenia
    • mania
    • melena
    • memory impairment
    • meningitis
    • migraine
    • myasthenia
    • myoclonia
    • myopathy
    • nephrolithiasis
    • neuritis
    • neuropathic pain
    • nystagmus
    • oral ulceration
    • orthostatic hypotension
    • osteopenia
    • osteoporosis
    • palpitations
    • peripheral edema
    • peripheral vasodilation
    • phlebitis
    • photophobia
    • platelet dysfunction
    • pneumonitis
    • priapism
    • prolonged bleeding time
    • prostatitis
    • psychosis
    • pyuria
    • sialadenitis
    • sinus tachycardia
    • skin ulcer
    • stomatitis
    • supraventricular tachycardia (SVT)
    • teeth grinding (bruxism)
    • tetany
    • thrombocytopenia
    • trismus
    • urinary incontinence
    • urinary retention
    • vaginal bleeding
    • vaginitis
    • withdrawal

    Severe

    • agranulocytosis
    • akinesia
    • anaphylactoid reactions
    • angioedema
    • aplastic anemia
    • atrial fibrillation
    • bone fractures
    • bradycardia
    • bronchospasm
    • coma
    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
    • epididymitis
    • erythema multiforme
    • erythema nodosum
    • exfoliative dermatitis
    • GI bleeding
    • GI obstruction
    • Guillain-Barre syndrome
    • hearing loss
    • heart failure
    • hematemesis
    • hemolytic anemia
    • hepatic necrosis
    • hyperkalemia
    • ileus
    • keratoconjunctivitis
    • laryngospasm
    • muscle paralysis
    • myelitis
    • myocardial infarction
    • neonatal abstinence syndrome
    • ocular hemorrhage
    • ocular hypertension
    • oliguria
    • optic neuritis
    • pancreatitis
    • pancytopenia
    • peptic ulcer
    • persistent pulmonary hypertension of the newborn
    • porphyria
    • proteinuria
    • pulmonary edema
    • pulmonary embolism
    • pulmonary fibrosis
    • pulmonary hypertension
    • renal failure (unspecified)
    • retinal hemorrhage
    • seizures
    • serotonin syndrome
    • SIADH
    • Stevens-Johnson syndrome
    • stroke
    • suicidal ideation
    • teratogenesis
    • thrombosis
    • torsade de pointes
    • torticollis
    • toxic epidermal necrolysis
    • vasculitis
    • ventricular fibrillation
    • ventricular tachycardia
    • visual impairment

    Gastrointestinal side effects are some of the most commonly reported adverse events to SSRIs, including paroxetine. In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, nausea/vomiting occurred in 4.3% of paroxetine-treated patients and 2.3% of placebo-treated patients; abdominal pain lead to discontinuation of treatment in 0.3% of patients.[55186] In adult trials, nausea (17 to 26%), xerostomia (3 to 18%), constipation (5 to 16%), diarrhea (6 to 18%), abdominal pain (3 to 7%), anorexia (1 to 9%), appetite stimulation (2 to 4%), weight gain (1 to 3%), weight loss (1%), flatulence (4 to 6%), oropharynx disorder (2%), vomiting (2 to 3%), dyspepsia (2 to 5%), gingivitis (1%), and tooth disorder (1%) were reported. Thirst was reported infrequently (1% or less) and may be associated with dry mouth (xerostomia). In pediatric paroxetine trials, decreased appetite (anorexia) was reported in 2% or more of patients and at a rate at least twice that of placebo. With continued treatment over several weeks, adaptation to some GI adverse events (e.g., nausea) may occur, but other effects (e.g., dry mouth) may continue. Most GI effects appear to be dose-related and may respond well to dosage reduction. Other GI effects reported in 1% of adult patients during premarketing evaluation include teeth grinding (bruxism), colitis, dysphagia, eructation, gastritis, gastroenteritis, gastroesophageal reflux, glossitis, hypersalivation, hemorrhoids, melena, rectal hemorrhage, dental pain, and ulcerative stomatitis. Rare (less than 0.1%) were gingival hyperplasia, GI obstruction, peptic ulcer, stomach ulcer, and throat tightness. Also observed were aphthous stomatitis, bloody diarrhea, bulimia, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impaction, fecal incontinence, gum hemorrhage, hematemesis, ileitis, ileus, oral ulceration, salivary gland enlargement, sialadenitis, stomatitis, tongue discoloration, tongue edema, and dental caries. During postmarketing use, laryngospasm has been reported; however, the frequency is unknown and causality to the drug has not been established. Significant weight loss may be an undesirable result of treatment for some patients, but on average, patients in controlled trials had minimal (roughly 0.45 kg) weight loss vs. smaller changes on placebo or active control. However, because decreased appetite and weight loss have been observed during use of SSRIs, periodic monitoring of weight and height are recommended in pediatric patients or other patients at risk receiving paroxetine.[28260] [43998] [43999]

    In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, extrapyramidal effects were not reported.[55186] During adult clinical trial evaluation, hypertonia (2 to 3%), tremor (4 to 11%), and myoclonia (1 to 3%) occurred more frequently in patients receiving paroxetine than placebo. Extrapyramidal effects or movement disorders infrequently reported (0.1 to 1%) include ataxia, dystonia, dyskinesia, hypokinesia, and muscle paralysis. Extrapyramidal effects or movement disorders rarely reported (less than 0.1%) include akathisia, choreoathetosis, incoordination, fasciculations, abnormal gait, hyperkinesis, bradykinesia, akinesia, hyporeflexia, hyperreflexia, pseudoparkinsonism (cogwheel rigidity), dystonic reaction (e.g., torticollis, trismus), dysarthria, and nystagmus. Oculogyric crisis has occurred when paroxetine has been used in conjunction with pimozide. Tremor and hyperkinesis were reported in 2% or more of pediatric patients at a rate at least twice that of placebo during clinical trials..[28260] [43998] [43999]

    Neurologic side effects are common with paroxetine therapy. In clinical trials of paroxetine for the treatment of depression and other psychiatric or mood disorders, drowsiness (9 to 24%), headache (15 to 27%), migraine (1 to 2%), dizziness (6 to 14%), insomnia (8 to 24%), vertigo (2%), yawning (4 to 5%), paresthesias (1 to 4%), abnormal dreams (1 to 4%), impaired concentration (2 to 4%), memory impairment (2%), drugged feeling (2%), amnesia (1%), and confusion (1%) occurred in paroxetine-treated patients. Premarketing adverse effects reported in 0.1% to 1% of patients included abnormal thinking, hypoesthesia, neuralgia, neuropathy (neuropathic pain), and seizures. Rare events (less than 0.1%) included aphasia, circumoral paresthesias, coma, grand mal seizures, hyperalgesia, meningitis, myelitis, neuralgia, peripheral neuritis, and stupor. Guillain-Barre syndrome, restless legs syndrome (RLS), and status epilepticus have been reported postmarketing. Limited data suggest that paroxetine may increase seizure length in patients undergoing electroconvulsive therapy (ECT). In clinical trials for vasomotor symptoms associated with menopause, headache was reported in 6.3% of paroxetine-treated patients and attention disturbances lead to discontinuation of the drug in 0.3% of patients.[28260] [43998] [43999] [55186]

    In adult trials, psychiatric effects reported more frequently in patients receiving paroxetine than placebo included nervousness (2% to 9%), anxiety (2% to 5%), agitation (2% to 5%), lack of emotion (apathy, 2%), and emotional lability (1% or more). Other effects reported in 0.1% to 1% of patients included abnormal thinking, euphoria, hallucinations, hostility, neurosis, and paranoia. Rare events (less than 0.1%) included antisocial reaction, delirium, delusions, hysteria, psychosis, psychotic depression, and stupor. Mania can occur in predisposed patients during treatment with an antidepressant. Hypomania or mania occurred in approximately 1% of paroxetine-treated adult patients with major depressive disorder and mania was reported in 2.2% of a subset of patients classified as bipolar. Monitor all antidepressant-treated patients for any indication for worsening of depression or the condition being treated and the emergence of suicidal behaviors or suicidal ideation, especially during the initial few months of drug therapy and after dosage changes. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in the absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. No suicides occurred in any of the pediatric trials. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over 24 years of age; there was a reduction in risk with antidepressant use in patients aged 65 and older. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. During the clinical evaluation of paroxetine to treat vasomotor symptoms associated with menopause (7.5 mg/day dosing), suicidal ideation was reported in 3 paroxetine-treated patients, and 1 patient receiving the drug reported a suicide attempt.[28260] [43998] [43999] [55186]

    Hyponatremia was reported rarely (less than 0.1%) during premarketing evaluation of paroxetine in adult patients. Several cases of hyponatremia have been reported with the use of SSRIs. While the cases were complex, some instances may have been due to the syndrome of inappropriate antidiuretic hormone (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Like with all SSRIs, the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) presents as hyposmolarity of serum and urine, and hyponatremia. The hyponatremia appeared to be reversible when paroxetine was discontinued. The majority of cases have been seen in patients that are elderly, in patients taking diuretics, or in patients who are volume depleted. In a prospective cohort study, 9 of 75 (12%) elderly patients age 63 to 90 years taking paroxetine developed hyponatremia (plasma sodium less than 135 mEq/L). The median time to development of hyponatremia after initiation of paroxetine was 9 days (range 1 to 14 days). Predictors for development of hyponatremia included lower baseline plasma sodium (less than 138 mEq/L) and lower body mass index. Hyponatremia does not appear to be associated with plasma concentrations of paroxetine.[27868] Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness. More severe cases may cause hallucinations, fainting, seizures, coma, respiratory arrest, and death. Discontinuation of paroxetine may be necessary in those with symptomatic hyponatremia.[28260] [43998] [43999]

    Platelet dysfunction (i.e., impaired platelet aggregation) may occur during treatment with selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., GI bleeding, ecchymosis, epistaxis, hematoma, petechiae, hemorrhage). Hematologic and lymphatic effects reported in 0.1 to 1% of patients during premarketing evaluation of 1 or more paroxetine formulations included anemia, ecchymosis, eosinophilia, hematoma, hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, and purpura. Rare events (less than 0.1%) reported during use of one or more paroxetine formulations included abnormal erythrocytes, anisocytosis, basophilia, ecchymosis, prolonged bleeding time, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, lymphopenia, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia, and thrombocytopenia. During postmarketing use, thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis, and vasculitic syndromes such as Henoch-Schonlein purpura and vasculitis have been reported. An increased risk of bleeding complications is possible in patients receiving antiplatelet or anticoagulant medications concurrently with paroxetine.[28260] [43998] [43999]

    Cardiovascular events may occur during paroxetine treatment. In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause (Brisdelle), adverse cardiac effects were not reported.[55186] Clinical data from all other conditions studied indicate that the following cardiovascular effects occurred more frequently in those receiving immediate-release paroxetine mesylate or hydrochloride formulations than placebo: palpitations (2 to 3%), chest pain (unspecified) (3%), and unspecified peripheral vasodilation (3 to 4%). The following cardiac effects occurred more frequently in those receiving controlled-release paroxetine than placebo during all conditions studied: sinus tachycardia (1 to 2%), hypertension (2%), chest pain (unspecified) (1%), and vasodilation (2 to 3%). Hypertension and sinus tachycardia occurred in at least 1% of patients receiving immediate-release formulations. Other effects reported in 0.1 to 1% of patients during premarketing evaluation of one or more paroxetine formulations included angina, bradycardia, hypotension, orthostatic hypotension, supraventricular tachycardia (SVT), and syncope. Rare events (less than 0.1%) reported during use of 1 or more paroxetine formulations included angina pectoris, arrhythmia nodal, atrial fibrillation, bundle-branch block, cerebral ischemia, cerebrovascular accident (stroke), congestive heart failure, heart block (unspecified), low cardiac output, myocardial infarction, myocardial ischemia, pallor, phlebitis, pulmonary embolism, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headaches, and ventricular extrasystoles. No significant changes in ECG patterns were observed in patients treated with paroxetine versus placebo in controlled clinical trials. During postmarketing use, pulmonary hypertension, ventricular fibrillation, and ventricular tachycardia (including torsade de pointes) have been reported.[28260] [43998] [43999]

    Clinical data from clinical studies indicate that the following general effects occurred more frequently in those receiving immediate-release paroxetine mesylate or hydrochloride formulations than placebo: asthenia (12 to 22%), chills (2%), and unspecified trauma (3 to 6%). The following general effects occurred more frequently in those receiving controlled-release paroxetine than placebo during all conditions studied: asthenia (14 to 18%), unspecified trauma (3 to 5%), and generalized edema (1%). General effects reported in 0.1 to 1% of adult patients during premarketing evaluation for all conditions include chills, face edema, malaise, and neck pain. Rare events (less than 0.1%) reported include adrenergic syndrome, cellulitis, candidiasis, neck rigidity, peritonitis, ulcer, and sepsis.[28260] [43998] [43999] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, fatigue, malaise, or lethargy occurred in 4.9% of paroxetine-treated patients and 2.8% of placebo-treated patients.[55186]

    Hypersensitivity and allergic reactions (2% or less) have been reported with paroxetine use. The most common dermatologic reactions reported during adult clinical trials include hyperhidrosis (6 to 14%), rash (unspecified) (2 to 3%), flushing (1 to 4%), atopic dermatitis (1%), and pruritus (1% or more). During pediatric trials, hyperhidrosis occurred in 2% or more of patients at a rate at least twice that of placebo. The following allergic reactions occurred more frequently in those receiving immediate-release paroxetine than placebo in clinical trials: allergic reaction (unspecified, 2%). Serious reactions are not common; during clinical trials, anaphylaxis/anaphylactoid reactions (0.1 to 1%) were infrequent and angioedema, erythema multiforme, and exfoliative dermatitis were rare (less than 0.1%). Other infrequent (0.1 to 1%) dermatologic events reported include acne vulgaris, alopecia, contact dermatitis, xerosis, eczema, herpes simplex, photosensitivity, and urticaria. Rare events (less than 0.1%) included erythema nodosum, fungal dermatitis, furunculosis, herpes zoster, hirsutism, maculopapular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, decreased sweating, and vesiculobullous rash (vesicular rash or bullous rash). During postmarketing use, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), laryngospasm, and allergic alveolitis (also known as hypersensitivity pneumonitis) have been reported; however, the frequencies are unknown and causality to the drug has not been established.[28260] [43998] [43999] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported during postmarketing use of paroxetine according to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).[62974] Manifestations of DRESS typically include pyrexia, rash, facial swelling, and/or lymph node involvement in conjunction with other organ system abnormalities including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis. Eosinophilia is often present. Early manifestations of DRESS such as pyrexia and lymph node involvement may be present without evidence of a rash. Paroxetine should be promptly discontinued and appropriate medical treatment should be initiated in patients presenting with a rash or symptoms indicative of DRESS in whom an unrelated etiology cannot be identified.[62975] [62976] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, dermatologic effects were not reported.[55186]

    Rhinitis (3 to 4%), pharyngitis (4%), infection (unspecified) (5 to 8%), unspecified respiratory disorder (7%), increased cough (1 to 2%), bronchitis (1 to 2%), pharyngitis (more than 1%), and sinusitis (4 to 8%) have been reported during adult clinical trials of paroxetine. Respiratory/infectious effects reported in 0.1 to 1% of patients during premarketing evaluation include asthma (bronchospasm), bronchitis, dyspnea, flu syndrome, hyperventilation, fever, laryngitis, pneumonia, and sepsis. Rare events (less than 0.1%) reported include emphysema, hemoptysis, hiccups, pulmonary fibrosis, pulmonary edema, increased sputum, stridor, and voice alteration (dysphonia). Hypersensitivity reactions affecting the airway including laryngismus and allergic alveolitis/pneumonitis have been reported with postmarketing use.[28260] [43998] [43999] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause (Brisdelle), respiratory effects and infections were not reported.[55186]

    Infrequently, alterations in special senses such as blurred vision (2 to 4%), unspecified abnormal vision or visual impairment (1 to 5%), and dysgeusia (2%) were reported during adult clinical trials of paroxetine. Tinnitus occurred in at least 1% of patients. Other effects reported in 0.1 to 1% of adult patients include abnormal accommodation, conjunctivitis, ear pain (otalgia), ocular pain, keratoconjunctivitis, mydriasis, and otitis media. Rare events (less than 0.1%) included amblyopia, diplopia, anisocoria, blepharitis, cataracts, conjunctival edema, corneal edema, corneal ulcer, deafness (hearing loss), exophthalmos, ocular hemorrhage, glaucoma (ocular hypertension), hyperacusis, night blindness, otitis externa, parosmia, photophobia, ptosis, retinal hemorrhage, taste loss, and visual field defects occurred. During postmarketing use, optic neuritis has been reported although the frequency is unknown and causality to the drug has not been established. Due to reports of narrow-angle glaucoma with paroxetine and other SSRIs, use paroxetine with caution in patients with narrow angle glaucoma.[28260] [43998] [43999] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, adverse effects related to the special senses were not reported.[55186]

    Paroxetine is extensively metabolized in the liver. Adverse hepatobiliary effects reported infrequently (0.1 to 1%) in adult patients during premarketing evaluation of paroxetine included abnormal liver function tests (elevated hepatic enzymes). Rare events (less than 0.1%) included pancreatitis, hyperbilirubinemia, hepatomegaly and splenomegaly combined (hepatosplenomegaly), hepatitis, and jaundice. During postmarketing use, acute pancreatitis, porphyria, and elevated hepatic enzymes (in severe cases resulting in death due to hepatic necrosis, and grossly elevated transaminases associated with severe liver dysfunction) have been reported.[28260] [43998] [43999] Adverse hepatic effects were not reported in clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause.[55186]

    Genital and reproductive disorders have occurred in femal and male patients receiving paroxetine. Unspecified female (2 to 10%) and male (2 to 10%) genital and reproductive disordershave been reported. Most frequently, specific adverse events such as menstrual disorder (2% or less), dysmenorrhea (5% or less), menorrhagia (1% or less), vaginal moniliasis/candidiasis ( 1% or less), and vaginitis (1 to 2%) were reported in female patients. Infrequently (0.1 to 1%) amenorrhea and mastalgia occurred. Rare events (less than 0.1%) reported include breast enlargement, breast neoplasm, female lactation or breast discharge, metrorrhagia, salpingitis, pelvic pain, and enlarged uterine fibroids. Also observed were breast atrophy, endometrial disorder, epididymitis, fibrocystic breast, leukorrhea, mastitis, uterine spasm, and vaginal bleeding. Symptoms suggestive of galactorrhea, gynecomastia, and hyperprolactinemia have been reported during postmarketing use with SSRIs including paroxetine; hyperprolactinemia can induce some reproductive/genital symptoms. Sexual effects have also been reported in both males and females receiving paroxetine. Clinical data from all other conditions studied indicate that the following sexual effects occurred more frequently in those receiving immediate-release paroxetine than placebo: ejaculation dysfunction, reported primarily as delayed ejaculation (13 to 28%), male genital disorders (10%), impotence (erectile dysfunction) (4 to 9%), libido decrease (3 to 9%), and female genital disorders including orgasm dysfunction (reported as anorgasmia, 2 to 9%). The following effects occurred more frequently in those receiving controlled-release paroxetine than placebo during all conditions studied: abnormal ejaculation (15 to 27%), libido decrease (7 to 12%), and impotence (erectile dysfunction) (5 to 10%). Other effects reported in 0.1 to 1% of patients during premarketing evaluation included libido increase. Rare events (less than 0.1%) reported during use of 1 or more paroxetine formulations included spontaneous fetal abortion, ejaculatory disturbance, uterine fibroids enlarged, and vaginal candidiasis. Eclampsia has been reported during postmarketing use of the drug. Some studies have shown that SSRIs may affect sperm quality; fertility may be affected in some men. Although the initial frequency of sexual side effects was reported to be relatively low from clinical trial data, postmarketing experience has suggested that the frequency of sexual adverse events is actually much higher than previously recognized.[28260] [43999] [43998] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, sexual dysfunction was not reported.[55186] Priapism, a medical emergency in males, has been reported rarely with all SSRIs, including paroxetine, during postmarketing use. If priapism develops during treatment with an SSRI, the drug should be discontinued and appropriate medical interventions should be initiated.[28260] [43999] [43998]

    Clinical data from all other conditions studied indicate that the following urinary or renal effects occurred more frequently in those receiving immediate-release paroxetine mesylate or hydrochloride formulations than placebo: increased urinary frequency (2 to 3%), urination disorder/dysuria (3%), impaired urination (3%), and urinary tract infection (2%). The following effects occurred more frequently in those receiving controlled-release paroxetine than placebo during all conditions studied: urinary tract infection (3%), increased urinary frequency (2%), and impaired urination (2%). Other effects reported in 0.1 to 1% of patients during premarketing evaluation of 1 or more paroxetine formulations included albuminuria (proteinuria), cystitis, dysuria, hematuria, nocturia, polyuria, urinary incontinence, urinary retention, and urinary urgency. Rare events (less than 0.1%) reported during use of one or more paroxetine formulations included kidney calculus (nephrolithiasis), kidney flank pain, nephritis, prostatitis, epididymitis, oliguria, pyuria, urethritis, urinary casts, and urolithiasis. Acute renal failure (unspecified) has been reported during postmarketing use of the drug.[28260] [43999] [43998] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, urinary and renal effects were not reported.[55186]

    Clinical data from all other conditions studied indicate that the following musculoskeletal effects occurred more frequently in those receiving immediate-release paroxetine than placebo: myopathy (2%), myalgia (2 to 4%), myasthenia (1%), and back pain (3%). The following musculoskeletal effects occurred more frequently in those receiving controlled-release paroxetine than placebo during all conditions studied: back pain (4 to 5%), unspecified pain (3%), arthralgia (2%), and myalgia (5%). Arthralgia occurred in at least 1% of patients receiving immediate-release formulations. Other effects reported in 0.1 to 1% of patients during premarketing evaluation of one or more paroxetine formulations included arthritis, arthrosis, bursitis, neck pain, and tendonitis. Rare events (less than 0.1%) reported during use of 1 or more paroxetine formulations included bursitis, generalized muscle spasm (muscle cramps), myasthenia, myopathy, myositis, tenosynovitis, and tetany.[28260] [43998] [43999] In clinical trials of the 7.5 mg/day dose for vasomotor symptoms associated with menopause, musculoskeletal effects were not reported.[55186]

    Rare metabolic and nutritional events (less than 0.1%) reported during use of 1 or more paroxetine formulations included hyperglycemia and hypoglycemia. Endocrine effects reported rarely (less than 0.1%) included diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, and thyroiditis.[28260] [43998] [43999]

    Metabolic and nutritional effects reported in 0.1 to 1% of patients during premarketing evaluation of one or more paroxetine formulations included thirst (polydipsia) and peripheral edema. Rare events (less than 0.1%) reported during use of 1 or more paroxetine formulations included increased alkaline phosphatase, hyperbilirubinemia, increased BUN, increased creatinine phosphokinase, dehydration, increased gamma globulins, gout, hypercalcemia, hypercholesterolemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypokalemia, ketosis, increased lactic dehydrogenase, and increased non-protein nitrogen (NPN).[28260] [43998] [43999]

    Serotonin syndrome has been reported during use of SSRIs alone, during concurrent use of other medications known to increase CNS or peripheral serotonin levels, or during SSRI overdose. Serotonin syndrome has been noted in postmarketing reports with paroxetine. Signs and symptoms of serotonin syndrome with paroxetine include nausea, vomiting, excessive sedation, dizziness, diaphoresis (sweating), facial flush, mental status changes, myoclonus, restlessness, shivering, increased heart rate, and tremor. If serotonin syndrome becomes evident during treatment, the SSRI and any other serotonergic agents should be discontinued and appropriate medical treatment should be initiated.[28260] [43998] [43999]

    During pre-marketing evaluation of paroxetine, osteoporosis was reported rarely. Use selective serotonin reuptake inhibitors (SSRIs) with caution in patients with osteopenia or risk factors for osteopenia. Epidemiological studies suggest an association between the use of selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, and bone fractures.[28260] Some data suggest that chronic treatment with SSRIs may be associated with reduced bone density. Serotonin (5-HT) receptors and the serotonin reuptake transporter (5-HTT) have been found in osteoblasts and osteoclasts, and 5-HT functioning appears to be involved in bone architecture, bone mass, and bone density.[42688] Results of one observational retrospective study assessing the association between the degree of 5-HTT inhibition among antidepressants and the risk of osteoporotic and non-osteoporotic fractures indicated that use of antidepressants considered to have a high affinity for 5-HTT was associated with a higher risk of osteoporotic fractures than antidepressants with a moderate or low affinity for 5-HTT (OR 1.86, CI 1.63 to 2.13). There was no trend with increasing affinity for 5-HTT in non-osteoporotic fractures, although antidepressant use in general resulted in a 50% increase in this fracture type.[42688] In a separate prospective population-based cohort study, the risk of non-vertebral fractures was 2.35 in users of SSRIs compared to nonusers of antidepressants. A sub-analysis was conducted, which included current and prior antidepressant users only. The results showed that current users of SSRIs had a 2.07-fold increased risk of fracture compared to past users of tricyclic antidepressants or SSRIs, and this risk further increased with prolonged use.[42690]

    A withdrawal syndrome was reported rarely (less than 0.1%) during pre-marketing evaluation of paroxetine. The most commonly reported withdrawal symptoms from SSRI discontinuation include fatigue, abdominal pain or nausea, dizziness/light-headedness, tremor, chill, diaphoresis, and incoordination. Other reported symptoms include impaired memory, insomnia, shock sensations, ringing in the ears, dysphoric mood, irritability, anxiety, confusion, lethargy, emotional lability, hypomania, headaches, and agitation or aggression. Withdrawal symptoms usually begin 1 to 3 days after abrupt discontinuation of the SSRI and remit within 1 to 2 weeks. While these adverse events are usually transient, some may be severe. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of withdrawal symptoms. Even with gradual tapering, self-limited withdrawal events occurring in at least 2% of patients and greater than placebo have included: abnormal dreams, paresthesia, and dizziness. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the clinician may continue decreasing the dose but at a more gradual rate.[28260] [43998] [43999] Certain symptoms were seen more frequently in women at the time of discontinuation of low dose paroxetine compared to women discontinuing placebo; however, no specific tapering recommendations are available.[55186]

    Epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of teratogenesis (i.e., cardiovascular malformations, primarily ventricular and atrial septal defects). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously.[28260] [43998] [43999] In addition, non-teratogenic risks have been reported in the neonate. A neonatal abstinence syndrome has been reported in infants exposed to paroxetine in utero.[26455] After birth, symptoms consistent with withdrawal (i.e., poor feeding, hypoglycemia, hypothermia, lethargy or irritability, vomiting, etc.) were noted. Such complications can arise immediately upon delivery. Other symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, and constant crying. Serum concentrations of paroxetine were measurable in the infants affected. Several other symptoms (bloody stools, necrotizing enterocolitis) may have been attributable to rebound platelet activation on withdrawal of the exposure to the SSRI. Neonatal symptoms generally improved over several days. A cohort study of 55 women revealed that 22% (12/55) of neonates exposed to paroxetine in the third trimester had complications requiring treatment or extended hospitalization compared with 6% in comparison groups. Complications included respiratory distress (n = 9), hypoglycemia (n = 2) and jaundice (n = 1). The incidence of prematurity in the third trimester paroxetine group was significant at 20% vs. 3.7% of controls.[27398] These features are consistent with either a direct toxic effect of serotonergic agents, or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with the serotonin syndrome. A case-controlled epidemiologic report has been published that suggests a significant association between maternal use of SSRIs after 20 weeks of pregnancy and the development of persistent pulmonary hypertension of the newborn (PPHN) (odds ratio (OR) 5.1; 95% CI, 1.9 to 13.3). The study population consisted of 377 women whose infants had PPHN and 836 matched control women and their infants. There was no increased risk of PPHN when SSRI use was restricted to the first half of the pregnancy (OR = 0.3; 95% CI, 0.1 to 1.1). Additionally, the use of non-SSRI antidepressant drugs at any time during pregnancy was not associated with an increased risk of PPHN. The SSRIs that were used by women 20 weeks or more of gestation in the study included fluoxetine, paroxetine and sertraline. However, the numbers were too small to permit examination of the effects of dose size, specific SSRI used, or reduction of the length of exposure before delivery.[32025] More recent retrospective studies have not shown an increased risk of PPHN with SSRI exposure.[47179] [47180] [47181] In December 2011, the FDA issued a safety announcement stating that based on conflicting data, an increased risk of PPHN from SSRI exposure cannot be determined. The FDA advises that healthcare professionals should not alter their current practice of treating depression in pregnancy at this time.[47182] When treating a pregnant woman with an SSRI or other serotonergic agent, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the half-life into consideration, tapering of the serotonergic agent prior to delivery may be considered as an alternative.

    As with other SSRIs, decreased weight gain has been observed in children and adolescents receiving paroxetine. Data are inadequate to determine whether the chronic use of SSRIs causes long-term growth inhibition, but height and weight should be monitored periodically throughout therapy. In controlled clinical trials of paroxetine, patients had an average minimal weight loss of approximately 1 pound (2.2 kg) compared to smaller changes in those receiving placebo or active control. The mechanism of growth inhibition in children may be due to the suppression of growth hormone secretion, which is known to occur in adults taking SSRIs.[27238] [28260] [43998] [43999]

    Revision Date: 02/19/2020, 09:32:58 AM

    References

    26455 - Stiskal JA, Kulin N, Koren G, et al. Neonatal paroxetine withdrawal syndrome. Arch Dis Child Fetal Neonatal Ed 2001;84:F134-F135.27238 - Weintrob N, et al. Decreased growth during therapy with selective serotonin reuptake inhibitors. Arch Pediatric Adolesc Med 2002;156:696-701.27398 - Costei AM, Kozer E, Ho T, et al. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med. 2002;156:1129-32.27868 - Fabian TJ, Amico JA, Kroboth PD, et al. Paroxetine-induced hyponatremia in older adults: a 12-week prospective study. Arch Intern Med 2004;164:327-32.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.32025 - Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:579-87.42688 - Verdel BM, Souverein PC, Egberts TC, et al. Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone. 2010;47(5):604-9.42690 - Ziere G, Dieleman JP, van der Cammen TJ, et al. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28:411-7.43998 - Pexeva (paroxetine mesylate) package insert. Roswell, GA: Sebela Pharmaceuticals, Inc. 2021 Sept.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.47179 - Wichman CL, Morre KM, Lang TR, et al. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc 2009;84:23-7.47180 - Andrade SE, McPhillips H, Loren D, et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Safety 2009;18:246-52.47181 - Wilson KL, Zelig CM, Harvey JP, et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol 2011;28:19-24.47182 - Food and Drug Administration Drug Safety Communication. Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. Retrieved December 15, 2011. Available on the World Wide Web http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.62974 - Food and Drug Administration Adverse Event Reporting System. Potential signals of serious risks/new safety information identified from the FDA adverse event reporting system (FAERS): July - September 2017. Available on the worldwide web at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm592379.htm62975 - Descamps V, Ranger-Rogez S. DRESS syndrome. Joint Bone Spine 2014;81:15-21.62976 - Spriet S, Banks TA. Drug reaction with eosinophilia and systemic symptoms syndrome. Allergy Asthma Proc 2015;36:501-5.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • MAOI therapy
    • pregnancy
    • abrupt discontinuation
    • akathisia
    • anorexia nervosa
    • anticholinergic medications
    • anticoagulant therapy
    • bipolar disorder
    • bleeding
    • bone fractures
    • breast-feeding
    • cardiac disease
    • children
    • closed-angle glaucoma
    • congenital heart disease
    • dehydration
    • driving or operating machinery
    • electroconvulsive therapy (ECT)
    • ethanol ingestion
    • geriatric
    • growth inhibition
    • hepatic disease
    • hyponatremia
    • hypovolemia
    • increased intraocular pressure
    • mania
    • neonates
    • osteoporosis
    • renal failure
    • renal impairment
    • seizure disorder
    • seizures
    • sexual dysfunction
    • suicidal ideation
    • thrombolytic therapy

    Paroxetine is contraindicated in those patients with a hypersensitivity to paroxetine or any of the formulation components.

    Avoid abrupt discontinuation of any SSRI, like paroxetine, if possible. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of potential discontinuation symptoms. The product labeling offers some guidance to taper paroxetine prior to discontinuation to limit withdrawal-type effects. The taper phase regimen used in some clinical trials of paroxetine involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, this dose was continued for 1 week before treatment was stopped. In controlled trials of paroxetine CR, patients receiving 37.5 mg/day underwent an incremental decrease in the daily dose by 12.5 mg/day for 1 week before treatment was stopped. For patients receiving 12.5 or 25 mg/day, treatment was stopped without a taper. Adverse events were reported in some patients, even with this gradual taper regimen. Patients should be monitored when discontinuing treatment, regardless of the indication for which the SSRI is being prescribed. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, continue decreasing the dose but at a more gradual rate.[28260] [43999] [43998] When used for hot flashes at a dose of 7.5 mg/day, a taper during discontinuation has not been recommended.[55186]

    The use of antidepressants has been associated with the precipitation of mania or hypomania in susceptible individuals. If a patient develops manic symptoms, paroxetine should be withheld, and appropriate therapy initiated to treat the manic symptoms. Depression may also be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of agitation, irritability, unusual changes in behavior, or emergence of suicidality.[28260] [43999]

    Paroxetine is not FDA-approved for use in children and adolescents less than 18 years of age. Three well-controlled trials have shown that paroxetine is no more effective than placebo for the treatment of depression in pediatric patients. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. No suicides occurred in any of the pediatric trials. Data from a cohort of 36,842 children (age range of 6 to 18 years) suggested those who use multiple antidepressants have a higher risk of suicide behavior, most likely a result of increased severity of depression rather than drug effect. In a meta-analysis conducted by the manufacturer in adult patients with and without psychiatric disorders, a higher frequency of suicidal behavior occurred in young adults and adults treated with paroxetine compared with placebo. The need for an antidepressant in children or adolescents for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. The potential for growth inhibition in pediatric patients should be monitored during SSRI therapy; monitor height and weight periodically. Data are inadequate to determine whether the chronic use of SSRIs causes long-term growth inhibition; however, decreased weight gain has been observed in children and adolescents receiving SSRIs. The mechanism of growth inhibition in children may be due to the suppression of growth hormone secretion, which is known to occur in adults taking SSRIs.[27238] [28260] [43999]

    Concomitant use of MAOI therapy with paroxetine or within 14 days of stopping treatment with paroxetine is contraindicated because of an increased risk of serotonin syndrome. The use of paroxetine within 14 days of stopping MAOI therapy is also contraindicated. Starting paroxetine in a patient who is being treated with linezolid or intravenous methylene blue, both of which inhibit monoamine oxidase, is also contraindicated because of an increased risk of serotonin syndrome.[28260] [43999] [55186] Starting paroxetine in a patient being treated with an MAOI such as linezolid or methylene blue is also contraindicated; however, there may be circumstances when it is necessary to initiate treatment with a MAOI such as linezolid or methylene blue in a patient taking paroxetine. If acceptable alternatives are not available and benefits are judged to outweigh the risks of serotonin syndrome, paroxetine should be promptly discontinued before initiating treatment with the MAOI. Monitor the patient closely for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of MAOI, whichever comes first. Therapy with paroxetine may be resumed 24 hours after the last dose of MAOI.[28260] [43999] [55186] The development of a potentially life-threatening serotonin syndrome has been reported with the use of SSRIs such as paroxetine alone, but particularly with concomitant use of other serotonergic drugs. If concomitant use of paroxetine with certain other serotonergic drugs (i.e., triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamines, and St. John’s Wort) is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. Treatment with paroxetine and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.[28260] [43999] [55186]

    Paroxetine should be used with caution in patients with a history of seizure disorder. Seizures have been reported rarely in patients taking SSRIs; however, they have occurred primarily in cases of overdose. Paroxetine's effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date.

    Selective serotonin reuptake inhibitors (SSRIs), like paroxetine, may cause hyponatremia, which is frequently the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In some cases, serum sodium levels less than 110 mmol/L have been reported; however, the adverse effect appeared reversible upon discontinuation of the causative SSRI. Older patients (65 years of age or more), those receiving diuretics or prone to dehydration, and those who are otherwise volume depleted (e.g., hypovolemia) appear to be at greatest risk. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of the SSRI, as well as implementation of the appropriate medical interventions.

    Paroxetine should be used with caution in patients with severe renal impairment or renal failure because paroxetine clearance is reduced. Specific dosage adjustments are recommended in adult patients with severe renal impairment (creatinine clearance less than 30 mL/minute). A lower starting dose should be used in patients receiving most paroxetine formulations. The exception is those patients receiving the the 7.5 mg dose for menopause (e.g., Brisdelle) for which no dose adjustment is considered necessary. Quantitative guidelines are not available for pediatric patients.[28260] [43999] [55186]

    Paroxetine should be used cautiously in patients with hepatic disease. Adult patients with severe hepatic impairment have about a 2-fold increase in plasma concentrations of paroxetine compared to patients without hepatic impairment. Specific dosage adjustments are recommended in adult patients with severe hepatic impairment receiving all formulations except the 7.5 mg dose for menopause (e.g., Brisdelle) for which no dose adjustment is considered necessary. Quantitative guidelines are not available for pediatric patients.[28260] [43999] [55186]

    Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion. Paroxetine and other SSRIs may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulant therapy may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Patients and practitioners should be cautioned about the risk of bleeding associated with the concomitant use of paroxetine and NSAIDs, aspirin, anticoagulants, or other drugs that affect coagulation, such as thrombolytic therapy. Monitor patients for signs and symptoms of bleeding.[28260] [43999] [55186]

    Although clinical trial data indicate that paroxetine is not associated with the development of clinically significant ECG abnormalities in adults, the use of paroxetine has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable cardiac disease. Evaluation of electrocardiograms (ECGs) of 682 patients who received paroxetine in double-blind, placebo-controlled trials, however, did not indicate that paroxetine is associated with the development of significant ECG abnormalities. Paroxetine should be used with caution in patients with congenital heart disease or in those who are taking other medications concomitantly that might result in drug interactions. For example, QT prolongation, tachycardias, and other side effects have been reported in children taking clomipramine in combination with paroxetine for the treatment of obsessive-compulsive disorder (OCD), or in adult patients taking paroxetine (a CYP2D6 inhibitor) along with medications known to prolong the QT interval that are metabolized by CYP2D6. Additional monitoring may be necessary, especially when a patient receives combined treatments.[25690] [28260] [43999] [55186]

    Use selective serotonin reuptake inhibitors (SSRIs), including paroxetine, with caution in patients with osteoporosis. Epidemiological studies on bone fracture risk following exposure to SSRIs have reported an association between SSRI treatment and bone fractures. It is unknown to what extent fracture risk is directly attributable to SSRI treatment. If a paroxetine-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising, consider the possibility of a fragility fracture.[28260] [42688] [42690] [55186] Patients at risk for osteoporosis, such as postmenopausal females, may benefit from more frequent monitoring of bone density during long-term use of an SSRI. 

    Caution is recommended when prescribing paroxetine to patients with closed-angle glaucoma. The pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.[28260] [43999] [55186]

    The use of paroxetine or other SSRIs has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment.[28260]

    Decreased appetite and weight loss have been observed during administration of SSRIs.[28260] Therefore, caution is advisable when administering paroxetine to patients with anorexia nervosa or other conditions where weight loss is undesirable.

    Because any psychoactive drug may impair judgment, thinking, or motor skills, patients should use caution when driving or operating machinery, until they are reasonably certain that paroxetine does not affect them adversely. Although paroxetine has not been shown to increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid ethanol ingestion while taking paroxetine.[28260] [43999] [55186]

    Sexual dysfunction can occur in individuals taking paroxetine. For males, these effects may present as ejaculatory failure or delay, decreased libido, and/or erectile dysfunction. Females may experience decreased libido and delayed or absent orgasm. Prescribers should discuss sexual function prior to initiating treatment with paroxetine and throughout treatment and obtain a detailed history and timeline of any changes in sexual function to determine whether the changes are medication-related or may be attributed to the underlying psychiatric disorder. Clinicians should also discuss management strategies and treatment options with patients.[28260] [43998] [43999] [55186]

    All formulations of paroxetine may cause fetal harm during human pregnancy; the paroxetine capsule for treatment of menopause (e.g., Brisdelle) is contraindicated for use during pregnancy because menopausal vasomotor symptoms do not occur during pregnancy and paroxetine can cause fetal harm.[28260] [43998] [43999] [55186] Unless other treatment options are not available, do not initiate paroxetine during the first trimester of pregnancy or in women who plan to become pregnant in the near future. The FDA is evaluating data to better characterize the risk of congenital malformations resulting from infant exposure to paroxetine during pregnancy. Exposure in the first trimester may increase the risk for congenital malformations, particularly cardiac malformations. A retrospective, epidemiologic study derived from the Swedish National Registry, comprised of 6896 women prescribed antidepressants in early pregnancy (5,123 of these women exposed to SSRIs; 815 to paroxetine) suggests an increased risk of cardiovascular malformations, primarily ventricular (VSDs) and atrial (ASDs) septal defects in those with exposure to paroxetine. This increased risk was seen compared to the entire registry population (OR 1.8; 95% CI 1.1 to 2.8). The rate of cardiovascular malformations following paroxetine exposure was 2% vs. 1% in the entire registry population; however, there was no increase in the overall risk for congenital malformations in either group. In another retrospective, cohort study (a US health insurance claims database), evaluating infant outcomes in those whose mothers received antidepressants in the first trimester (n = 5,956 total ; 815 for paroxetine), a 1.5-fold elevated risk for cardiac malformations and a 1.8-fold elevated risk for overall congenital malformations was seen in the paroxetine group compared to the group that received other antidepressants in the first trimester (OR 1.5; 95% CI 0.8 to 2.9). The prevalence of cardiac malformations when drug was received in the first trimester was 1.5% for paroxetine and 1% for other antidepressants. Nine out of 12 newborns with cardiac malformations whose mothers received paroxetine in the first trimester had VSDs. Unlike the first study, there was an increased risk of overall major congenital malformations (inclusive of the cardiovascular defects) for paroxetine compared to other antidepressants (OR 1.8; 95% CI 1.2 to 2.8). The prevalence of all congenital malformations following first trimester exposure was 4% for paroxetine vs. 2% for other antidepressants. Results from 2 large case-control studies (each with more than 9,000 birth defect cases and more than 4,000 controls) showed a 2- to 3-fold increased risk of right ventricular outflow tract obstructions from infant exposures to paroxetine in utero during the first trimester of pregnancy, with 7 exposed in one study (OR 2.5; 95% CI, 1 to 6), and 6 exposed in the other study (OR 3.3; 95% CI 1.3 to 8.8). All of these studies were limited to first trimester exposure only, therefore the risk of fetal exposure to paroxetine in the second and third trimesters is not known.[28260] A prospective, cohort study was conducted to evaluate the outcome of newborns born to 267 women who took an SSRI during pregnancy (of whom 97 took paroxetine). Compared with a neonatal control group, SSRI-exposed neonates had similar rates of major malformation, spontaneous and elective abortion, and stillbirth.[25007] Mean birth weight and gestational age were similar among the two groups of neonates. In animal studies, SSRIs appear to downregulate serotonin receptors in the fetal cortex; the changes are present for a period of time after birth but the effect on neurological development is uncertain; the applicability of these findings to humans is also unknown. A neonatal abstinence syndrome has been reported at birth following in utero paroxetine exposure; exposed neonates may need to be monitored for associated symptoms. A cohort study of 55 women revealed that 22% (12 of 55) of neonates exposed to paroxetine in the third trimester had complications requiring treatment or extended hospitalization vs. 6% in comparison groups. Post-marketing reports indicate that premature births have occurred in pregnant women receiving paroxetine or other SSRIs. Additionally, epidemiologic reports suggest a possible association between maternal use of SSRIs after 20 weeks gestation and the development of persistent pulmonary hypertension (PPHN) of the newborn.[32025] More recent retrospective studies have not shown an increased risk of PPHN with SSRI exposure.[47179] [47180] [47181] In December 2011, the FDA issued a safety announcement stating that based on conflicting data, an increased risk of PPHN from SSRI exposure cannot be determined. The FDA advises that healthcare professionals should not alter their current practice of treating depression in pregnancy at this time.[47182] Increasing evidence suggests an association between antidepressant use during pregnancy and a subsequent diagnosis of autism spectrum disorder (ASD) in the offspring. In two separate population based case-control studies, an approximate 2-fold increased risk of autism spectrum disorder was observed. One study found the increased risk was associated only with SSRI use, while the other study found an increased risk associated with use of SSRIs and tricyclic antidepressants.[56001] [56002] Providers should inform women receiving paroxetine to the potential fetal risk if they should become pregnant or are currently in their first trimester. Discontinuing paroxetine and switching to another antidepressant should be considered when possible for these patients. Women who are pregnant, or are planning a pregnancy, and currently taking paroxetine should consult with their physician about whether to continue taking it. A prospective study of pregnant women receiving antidepressant treatment found that only 26% of those maintained on their antidepressant had relapsed versus 68% of those who had discontinued their medication.[32476] In individual cases, the benefits of continuing paroxetine may outweigh the potential risk to the fetus. The effect of SSRIs on labor and delivery in humans is unknown.[28260] [43998] [43999] [55186] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to paroxetine; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

    Paroxetine should be administered to a breast-feeding mother with caution.[28260] [43998] [43999] [55186] In one small trial, mothers ingested up to 50 mg/day PO of paroxetine for more than 10 days. Paroxetine was excreted into the breast milk, but at low concentrations (less than 2 ng/mL). None of the breast-fed infants had detectable serum concentrations and none experienced adverse effects from the medication.[26980] Other SSRIs (e.g., fluoxetine) are excreted in breast milk and have been reported to increase infant irritability. The long-term effects of paroxetine on a breast-feeding infant are unknown. A pooled analysis found that maternal use of paroxetine, along with nortriptyline and sertraline, usually produced undetectable or low drug concentrations in infant serum and, therefore, may be the preferred antidepressants in breast-feeding mothers.[45642] Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition.

    Paroxetine should be used with caution in geriatric patients. Pharmacokinetic data indicate that paroxetine clearance is reduced in the elderly. Although no difference in safety has been recorded, slow titration of dosage is recommended in the elderly. SSRIs may cause hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH); elderly patients appear to be at greater risk.[28260] [43998] [43999] [55186] Paroxetine also exhibits anticholinergic activity. These effects may be additive with other anticholinergic medications in any patient, but the geriatric adult may be more susceptible.[64280] According to the Beers Criteria, paroxetine is considered a potentially inappropriate medication (PIM) in geriatric patients; avoid use due to the potential for orthostatic hypotension, anticholinergic effects (e.g., constipation, urinary difficulties, blurred vision, dry mouth, delirium), or sedation. Avoid medications with anticholinergic properties in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (urinary retention or hesitancy). The Panel also recommends avoiding paroxetine in geriatric patients with a history of falls or fractures unless no other alternatives are available since SSRIs have the potential to cause ataxia, impaired psychomotor function, syncope, and additional falls; if paroxetine must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. SSRIs can cause or exacerbate hyponatremia and SIADH, and sodium levels should be closely monitored when starting or changing dosages in older adults.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities; the duration of therapy should be in accordance with pertinent literature and clinical practice guidelines. All residents being treated for depression with any antidepressant should be monitored closely for worsening of depression and suicidal behavior or thinking, especially during initiation of therapy and during dose changes. Antidepressants may cause side effects that can increase the risk of falls. Paroxetine has significant anticholinergic properties that may problematic in the elderly. Before discontinuation, SSRIs may need a taper to avoid a withdrawal syndrome. Review the continued need of an antidepressant at least quarterly, and document the rationale for continuation. When the drug is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated.[60742]

    Revision Date: 09/23/2021, 04:34:41 PM

    References

    25007 - Kulin NA, Pastuszak A, Sage SR, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors. JAMA 1998;279:609-10.25690 - Figueroa Y, Rosenberg DR, Birmaher B, et al. Combination treatment with clomipramine and selective serotonin inhibitors for obsessive-compulsive disorder in children and adolescents. J Child Adolesc Psychopharmacol 1998;8:61-67.26980 - Stowe ZN, Cohen LS, Hostetter A, et al. Paroxetine in human breast milk and nursing infants. Am J Psychiatry 2000 Feb;157(2):185-189.27238 - Weintrob N, et al. Decreased growth during therapy with selective serotonin reuptake inhibitors. Arch Pediatric Adolesc Med 2002;156:696-701.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.32025 - Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:579-87.32476 - Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006;295:499-507.42688 - Verdel BM, Souverein PC, Egberts TC, et al. Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone. 2010;47(5):604-9.42690 - Ziere G, Dieleman JP, van der Cammen TJ, et al. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28:411-7.43998 - Pexeva (paroxetine mesylate) package insert. Roswell, GA: Sebela Pharmaceuticals, Inc. 2021 Sept.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.45642 - Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161:1066-78.47179 - Wichman CL, Morre KM, Lang TR, et al. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc 2009;84:23-7.47180 - Andrade SE, McPhillips H, Loren D, et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Safety 2009;18:246-52.47181 - Wilson KL, Zelig CM, Harvey JP, et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol 2011;28:19-24.47182 - Food and Drug Administration Drug Safety Communication. Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. Retrieved December 15, 2011. Available on the World Wide Web http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.56001 - Rai D, Lee BK, Dalman C, et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013;346:f2059 doi: 10.1136/bmj.f2059.56002 - Croen LA, Grether JK, Yoshida CK, et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011:68:1104-12.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.64280 - Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacol Bull. 2016;46:77-104. Review.

    Mechanism of Action

    The precise antidepressant effect of the selective serotonin reuptake inhibitors (SSRIs) is not fully understood, but involves selective serotonin reuptake blockade at the neuronal membrane, which enhances the actions of serotonin (5-HT). Initially, SSRIs increase availability of serotonin in the somatodendritic area through serotonin reuptake blockade at the serotonin transport pump. During long-term administration of SSRIs, serotonin autoreceptors are down-regulated and desensitized, allowing the neuron to increase serotonin release in the axon terminal synapses and increase its neuronal impulses. Because of the delay in therapeutic response to SSRIs, it is theorized that the change in the balance of serotonin receptors over time is an important mechanism of effect. The therapeutic action of SSRIs in treating anxiety disorders is thought to occur from potent central serotonin reuptake blockade although the exact mechanism is unknown. SSRIs exhibit less sedative, anticholinergic, and cardiovascular effects than do tricyclic antidepressants due to decreased binding to histaminergic, muscarinic, and alpha-adrenergic receptors. However, paroxetine is noted to have the most anticholinergic activity of all the SSRIs. The mechanism of action of paroxetine in the treatment of vasomotor symptoms associated with menopause is unknown.[28260][53216][55186][64280]

    Revision Date: 06/06/2019, 02:58:33 PM

    References

    28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.53216 - Blier P, de Montigny C. Serotonin and drug-induced therapeutic responses in major depression, obsessive-compulsive and panic disorders. Neuropsychopharmacology 1999;21:91S-98S.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.64280 - Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacol Bull. 2016;46:77-104. Review.

    Pharmacokinetics

    Paroxetine formulations are administered orally. The drug is widely distributed, including into the CNS, with only 1% of paroxetine remaining in the plasma. Paroxetine is 93% to 95% bound to plasma protein; however, the drug does not displace other highly protein-bound drugs. Based on pharmacokinetic studies, the steady-state paroxetine exposure based on AUC is several-fold higher than with a single dose. The excess accumulation is a consequence of a saturable metabolic pathway. Paroxetine is extensively metabolized via oxidation, methylation and conjugation to several metabolites, none of which shows any appreciable pharmacological activity. Conjugates with glucuronic acid and sulfate predominate. Metabolism is achieved predominantly by CYP2D6. Due to saturation of CYP2D6 by paroxetine, the relationship between pharmacokinetics and dosage or duration of treatment is nonlinear. At steady-state, when the CYP2D6 is essentially saturated, paroxetine clearance becomes governed by CYP3A4, which, unlike CYP2D6, does not show evidence of saturation. The mean elimination half-life of the immediate-release paroxetine is approximately 21 hours while the elimination half-life for the controlled-release product is 15 to 20 hours. Excretion is mainly renal (about 62%), mostly as metabolites and about 2% as unchanged drug. Roughly 36% is excreted in the feces, mainly via the bile as metabolites.[28260][43999][55186]

     

    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6

    Paroxetine is a substrate and potent inhibitor of CYP2D6. In more than 90% of patients, CYP2D6 is saturated early in dosing with paroxetine (in roughly 10 to 14 days). Due to saturation of CYP2D6 by paroxetine, the relationship between pharmacokinetics and dosage or duration of treatment is nonlinear. At steady-state, when the CYP2D6 is essentially saturated, paroxetine clearance becomes governed by CYP3A4, which, unlike CYP2D6, does not show evidence of saturation. Paroxetine does not appear to inhibit other CYP isoenzymes, including CYP3A4, to any clinically significant degree.[28260]

    Route-Specific Pharmacokinetics

    Oral Route

    Paroxetine is absorbed completely after oral administration. Paroxetine immediate-release tablets and oral suspension are bioequivalent. Paxil CR controlled-release tablets are enteric coated to delay the start of drug release until the tablets have left the stomach; they are also designed via the Geomatrix polymeric matrix to allow for a 4 to 5 hour dissolution rate, with a Tmax occurring roughly 6 to 10 hours after dosing. The bioavailability of paroxetine, regardless of dosage form, is not affected by food. There appears to be individual patient variation in response, but steady-state concentrations are achieved in about 10 to 14 days with either the immediate-release or controlled-release formulations. The onset of action, however, typically requires 1 to 4 weeks of therapy.[28260][43999][65698]

    Special Populations

    Hepatic Impairment

    Paroxetine is extensively metabolized in the liver. Plasma concentrations of paroxetine are about 2-fold higher in adult patients with severe hepatic impairment. Lower initial and maximum daily doses are recommended in adult patients with severe hepatic impairment receiving all formulations except the 7.5 mg dose for menopause (e.g., Brisdelle) for which no dose adjustment is considered necessary in adults. Quantitative guidelines are not available for pediatric patients.[28260][43999][55186]

    Renal Impairment

    Increased plasma concentrations of paroxetine occur in patients with severe renal impairment (creatinine clearance less than 30 mL/minute). Mean plasma concentrations were about 4 times higher in adults with a creatinine clearance less than 30 mL/minute than in healthy volunteers. Patients with a creatinine clearance of 30 to 60 mL/minute had an approximate 2-fold increase in plasma concentrations. Lower initial and maximum daily doses are recommended in adult patients with severe renal impairment receiving all formulations except the 7.5 mg dose for menopause (e.g., Brisdelle) for which no dose adjustment is considered necessary for adults. Quantitative guidelines are not available for pediatric patients.[28260][43999][55186]

    Pediatrics

    More individual variability in pharmacokinetics occurs with lower doses than higher doses in children. In a 6-week multiple dose pharmacokinetic study in children (n = 27) and adolescents (n = 35), the Cmax and AUC were higher in children than adolescents at all doses studied (10 mg, 20 mg, 30 mg); however, the geometric mean values in children were about 100% higher than in adolescents at 10 mg/day, but less than 30% higher at 30 mg/day. These differences are primarily attributable to differences in weight between the groups. Oral clearance and volume of distribution were highly dependent on paroxetine dose, CYP2D6 genotype, and weight, but not age or gender. Side effects, such as gastrointestinal complaints and behavioral events, occurred more frequently in younger children than adolescents. Saturability of CYP2D6 suggests that modest increases in dose may be associated with disproportionate increases in plasma concentrations. Therefore, a more conservative approach to dosing in children, such as lower initial doses or slower titration, is advisable.[53499]

    Geriatric

    The elderly are predisposed to increased plasma concentrations of paroxetine, and thus usually require lower initial dosing.[28260][43999]

    Gender Differences

    In a meta-analysis of healthy volunteers receiving paroxetine 20 to 40 mg/day, males did not exhibit a significantly lower Cmax or AUC than females.[28260][43999][55186]

    Revision Date: 07/15/2020, 12:38:13 PM

    References

    28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.53499 - Findling RL, Nucci G, Piergies AA, et al. Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. Neuropsychopharmacology 2006;31:1274-85.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.65698 - Bourin M, Chue P, Guillon Y. Paroxetine: a review. CNS Drug Reviews 2001;7:25-47.

    Pregnancy/Breast-feeding

    neonates, pregnancy

    All formulations of paroxetine may cause fetal harm during human pregnancy; the paroxetine capsule for treatment of menopause (e.g., Brisdelle) is contraindicated for use during pregnancy because menopausal vasomotor symptoms do not occur during pregnancy and paroxetine can cause fetal harm.[28260] [43998] [43999] [55186] Unless other treatment options are not available, do not initiate paroxetine during the first trimester of pregnancy or in women who plan to become pregnant in the near future. The FDA is evaluating data to better characterize the risk of congenital malformations resulting from infant exposure to paroxetine during pregnancy. Exposure in the first trimester may increase the risk for congenital malformations, particularly cardiac malformations. A retrospective, epidemiologic study derived from the Swedish National Registry, comprised of 6896 women prescribed antidepressants in early pregnancy (5,123 of these women exposed to SSRIs; 815 to paroxetine) suggests an increased risk of cardiovascular malformations, primarily ventricular (VSDs) and atrial (ASDs) septal defects in those with exposure to paroxetine. This increased risk was seen compared to the entire registry population (OR 1.8; 95% CI 1.1 to 2.8). The rate of cardiovascular malformations following paroxetine exposure was 2% vs. 1% in the entire registry population; however, there was no increase in the overall risk for congenital malformations in either group. In another retrospective, cohort study (a US health insurance claims database), evaluating infant outcomes in those whose mothers received antidepressants in the first trimester (n = 5,956 total ; 815 for paroxetine), a 1.5-fold elevated risk for cardiac malformations and a 1.8-fold elevated risk for overall congenital malformations was seen in the paroxetine group compared to the group that received other antidepressants in the first trimester (OR 1.5; 95% CI 0.8 to 2.9). The prevalence of cardiac malformations when drug was received in the first trimester was 1.5% for paroxetine and 1% for other antidepressants. Nine out of 12 newborns with cardiac malformations whose mothers received paroxetine in the first trimester had VSDs. Unlike the first study, there was an increased risk of overall major congenital malformations (inclusive of the cardiovascular defects) for paroxetine compared to other antidepressants (OR 1.8; 95% CI 1.2 to 2.8). The prevalence of all congenital malformations following first trimester exposure was 4% for paroxetine vs. 2% for other antidepressants. Results from 2 large case-control studies (each with more than 9,000 birth defect cases and more than 4,000 controls) showed a 2- to 3-fold increased risk of right ventricular outflow tract obstructions from infant exposures to paroxetine in utero during the first trimester of pregnancy, with 7 exposed in one study (OR 2.5; 95% CI, 1 to 6), and 6 exposed in the other study (OR 3.3; 95% CI 1.3 to 8.8). All of these studies were limited to first trimester exposure only, therefore the risk of fetal exposure to paroxetine in the second and third trimesters is not known.[28260] A prospective, cohort study was conducted to evaluate the outcome of newborns born to 267 women who took an SSRI during pregnancy (of whom 97 took paroxetine). Compared with a neonatal control group, SSRI-exposed neonates had similar rates of major malformation, spontaneous and elective abortion, and stillbirth.[25007] Mean birth weight and gestational age were similar among the two groups of neonates. In animal studies, SSRIs appear to downregulate serotonin receptors in the fetal cortex; the changes are present for a period of time after birth but the effect on neurological development is uncertain; the applicability of these findings to humans is also unknown. A neonatal abstinence syndrome has been reported at birth following in utero paroxetine exposure; exposed neonates may need to be monitored for associated symptoms. A cohort study of 55 women revealed that 22% (12 of 55) of neonates exposed to paroxetine in the third trimester had complications requiring treatment or extended hospitalization vs. 6% in comparison groups. Post-marketing reports indicate that premature births have occurred in pregnant women receiving paroxetine or other SSRIs. Additionally, epidemiologic reports suggest a possible association between maternal use of SSRIs after 20 weeks gestation and the development of persistent pulmonary hypertension (PPHN) of the newborn.[32025] More recent retrospective studies have not shown an increased risk of PPHN with SSRI exposure.[47179] [47180] [47181] In December 2011, the FDA issued a safety announcement stating that based on conflicting data, an increased risk of PPHN from SSRI exposure cannot be determined. The FDA advises that healthcare professionals should not alter their current practice of treating depression in pregnancy at this time.[47182] Increasing evidence suggests an association between antidepressant use during pregnancy and a subsequent diagnosis of autism spectrum disorder (ASD) in the offspring. In two separate population based case-control studies, an approximate 2-fold increased risk of autism spectrum disorder was observed. One study found the increased risk was associated only with SSRI use, while the other study found an increased risk associated with use of SSRIs and tricyclic antidepressants.[56001] [56002] Providers should inform women receiving paroxetine to the potential fetal risk if they should become pregnant or are currently in their first trimester. Discontinuing paroxetine and switching to another antidepressant should be considered when possible for these patients. Women who are pregnant, or are planning a pregnancy, and currently taking paroxetine should consult with their physician about whether to continue taking it. A prospective study of pregnant women receiving antidepressant treatment found that only 26% of those maintained on their antidepressant had relapsed versus 68% of those who had discontinued their medication.[32476] In individual cases, the benefits of continuing paroxetine may outweigh the potential risk to the fetus. The effect of SSRIs on labor and delivery in humans is unknown.[28260] [43998] [43999] [55186] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to paroxetine; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

    breast-feeding

    Paroxetine should be administered to a breast-feeding mother with caution.[28260] [43998] [43999] [55186] In one small trial, mothers ingested up to 50 mg/day PO of paroxetine for more than 10 days. Paroxetine was excreted into the breast milk, but at low concentrations (less than 2 ng/mL). None of the breast-fed infants had detectable serum concentrations and none experienced adverse effects from the medication.[26980] Other SSRIs (e.g., fluoxetine) are excreted in breast milk and have been reported to increase infant irritability. The long-term effects of paroxetine on a breast-feeding infant are unknown. A pooled analysis found that maternal use of paroxetine, along with nortriptyline and sertraline, usually produced undetectable or low drug concentrations in infant serum and, therefore, may be the preferred antidepressants in breast-feeding mothers.[45642] Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition.

    Revision Date: 09/23/2021, 04:34:24 PM

    References

    25007 - Kulin NA, Pastuszak A, Sage SR, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors. JAMA 1998;279:609-10.26980 - Stowe ZN, Cohen LS, Hostetter A, et al. Paroxetine in human breast milk and nursing infants. Am J Psychiatry 2000 Feb;157(2):185-189.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.32025 - Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:579-87.32476 - Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006;295:499-507.43998 - Pexeva (paroxetine mesylate) package insert. Roswell, GA: Sebela Pharmaceuticals, Inc. 2021 Sept.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.45642 - Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161:1066-78.47179 - Wichman CL, Morre KM, Lang TR, et al. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc 2009;84:23-7.47180 - Andrade SE, McPhillips H, Loren D, et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Safety 2009;18:246-52.47181 - Wilson KL, Zelig CM, Harvey JP, et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol 2011;28:19-24.47182 - Food and Drug Administration Drug Safety Communication. Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. Retrieved December 15, 2011. Available on the World Wide Web http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.56001 - Rai D, Lee BK, Dalman C, et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013;346:f2059 doi: 10.1136/bmj.f2059.56002 - Croen LA, Grether JK, Yoshida CK, et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011:68:1104-12.

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    • Propranolol; Hydrochlorothiazide, HCTZ
    • Tedizolid
    Abciximab: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving abciximab. Monitor closely for signs and symptoms of bleeding. [28260] [28343] Abiraterone: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with abiraterone is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. [28260] [44156] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Acetaminophen; Aspirin: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of dihydrocodeine and paroxetine because of the potential risk of serotonin syndrome, reduced dihydrocodeine efficacy, and potential for opioid withdrawal symptoms. Discontinue dihydrocodeine if serotonin syndrome is suspected. It is recommended to avoid this combination when dihydrocodeine is being used for cough. Concomitant use may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30282] Acetaminophen; Caffeine; Pyrilamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Chlorpheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] Acetaminophen; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Acetaminophen; Diphenhydramine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Acetaminophen; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Acetaminophen; Oxycodone: (Moderate) If concomitant use of oxycodone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [39926] [43999] [60634] Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Acetaminophen; Pentazocine: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy. [28260] [28269] [28270] [28343] [32127] [50507] Adagrasib: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with adagrasib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and adagrasib is a moderate CYP2D6 inhibitor. [28260] [68325] Alfentanil: (Moderate) If concomitant use of alfentanil and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [30072] Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with paroxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue paroxetine and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28858] [31869] [32484] [41360] [43998] [43999] [55186] [57580] [58195] Alprazolam: (Minor) The manufacturer of alprazolam states that in vitro studies suggest paroxetine may inhibit the metabolism of alprazolam via inhibition of CYP3A4. However, paroxetine is typically considered a major inhibitor of CYP2D6, for which alprazolam is not a substrate. The potential for clinical interaction is uncertain. Be alert for any change in psychomotor performance or other benzodiazepine-related side effects when paroxetine is combined with alprazolam. [28040] Alteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI. [28260] [28343] Amiodarone: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with amiodarone is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and amiodarone is a moderate CYP2D6 inhibitor. [28224] [28260] [28896] Amitriptyline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Additionally, monitor for an increase in amitriptyline-related adverse reactions if coadministration with paroxetine is necessary; a dose reduction of amitriptyline may be necessary. Concurrent use may increase the plasma concentrations of amitriptyline. Amitriptyline is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Paroxetine and amitriptyline both exhibit significant anticholinergic effects that may be additive during concurrent use. [23615] [28260] [28557] [44116] [44117] [63923] Amoxapine: (Moderate) Paroxetine, a potent CYP2D6 inhibitor, may increase the plasma concentrations of the tetracyclic antidepressant amoxapine, which is partially metabolized by CYP2D6. In several cases, symptoms of toxicity, including seizures, have been reported when tricyclic antidepressants were coadministered with a selective serotonin reuptake inhibitor (SSRI). At least one case report exists of a death thought to be due to impaired clearance of the tricyclic antidepressant amitriptyline by fluoxetine. Additive anticholinergic effects are possible. This combination may represent duplicative therapy. Patients receiving amoxapine should be monitored closely for toxicity if paroxetine is added. [28558] [63923] Amphetamines: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant amphetamine and paroxetine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome. [28260] [29332] [33263] [33363] [43998] [55186] Anagrelide: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [4987] Anticholinergics: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Antithrombin III: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like antithrombin III. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] Apixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like apixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] [52739] Aripiprazole: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose during coadministration of paroxetine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor. Avoid concurrent use of Aristada Initio and paroxetine because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. Aripiprazole is a substrate for CYP2D6 and CYP3A4; paroxetine is a strong CYP2D6 inhibitor. Based on simulation studies, a 4.5-fold increase in aripiprazole exposure is expected when CYP2D6 extensive metabolizers are administered both a strong CYP2D6 and CYP3A4 inhibitor. [28260] [31327] [42845] [53394] [60196] [63328] Artemether; Lumefantrine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with lumefantrine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and lumefantrine is a moderate CYP2D6 inhibitor. [28260] [35401] Asenapine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with asenapine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and asenapine is a weak CYP2D6 inhibitor. [28260] [36343] Aspirin, ASA: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Butalbital; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like paroxetine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. [28260] [63923] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Carisoprodol: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. [28260] [28343] [48620] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Omeprazole: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Oxycodone: (Moderate) If concomitant use of oxycodone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [39926] [43999] [60634] (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Aspirin, ASA; Pravastatin: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Atazanavir; Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] Atomoxetine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving paroxetine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving paroxetine, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. In children and adolescents over 70 kg and adults receiving paroxetine, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. Paroxetine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6 increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure. [28260] [28405] Atropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with IV methylene blue, paroxetine should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome.[46610] One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. [37286] [37287] [37289] [37304] [37362] [45071] [46610] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. [5738] Atropine; Difenoxin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Atropine; Edrophonium: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Barbiturates: (Moderate) Barbiturates may induce various hepatic CYP450 isoenzymes, including those responsible for the metabolism of paroxetine. Clinicians should be aware of the potential for reduced SSRI efficacy with concurrent administration of a barbiturate, especially in chronic use. [4987] Belladonna; Opium: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Benzhydrocodone; Acetaminophen: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and paroxetine because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [43998] [62889] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with IV methylene blue, paroxetine should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome.[46610] One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. [37286] [37287] [37289] [37304] [37362] [45071] [46610] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. [5738] Benztropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Berotralstat: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with berotralstat is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and berotralstat is a moderate CYP2D6 inhibitor. [28260] [66159] Betrixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like betrixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [62037] Bismuth Subsalicylate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. [32127] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. [32127] Brexpiprazole: (Major) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving a strong CYP2D6 inhibitor and one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. It should be noted that no dosage adjustment is needed in patients taking a strong CYP2D6 inhibitor who are receiving brexpiprazole as adjunct treatment for major depressive disorder because CYP2D6 considerations are already factored into general dosing recommendations. [28260] [59949] Brimonidine; Timolol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of timolol with paroxetine is necessary. Concomitant use may enhance the beta-blocking properties of timolol resulting in further slowing of the heart rate or cardiac conduction. Timolol is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. [28260] [28540] Brompheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Phenylephrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as brompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Buprenorphine: (Moderate) If concomitant use of buprenorphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60270] Buprenorphine; Naloxone: (Moderate) If concomitant use of buprenorphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60270] Bupropion: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with bupropion is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. [28260] [41057] Bupropion; Naltrexone: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with bupropion is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. [28260] [41057] Buspirone: (Moderate) Coadministration of buspirone and paroxetine may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28501] [43998] [55186] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] Cangrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28343] [59845] Capsaicin; Metaxalone: (Moderate) Concomitant use of selective serotonin reuptake inhibitors (SSRIs) and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary. [30830] Carbetapentane; Chlorpheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbetapentane; Pyrilamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbinoxamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbinoxamine; Phenylephrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carbinoxamine; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as carbinoxamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, such as paroxetine, may inhibit the hepatic oxidative metabolism of carvedilol. [4718] [5267] Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with paroxetine is necessary. If paroxetine is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28314] [29935] [32475] [40634] [43998] [55186] Cevimeline: (Moderate) Monitor for an increase in cevimeline-related adverse effects if concomitant use of paroxetine is necessary. Concomitant use may increase cevimeline exposure. Cevimeline is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. [28260] [48617] Chlophedianol; Dexbrompheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlordiazepoxide; Amitriptyline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Additionally, monitor for an increase in amitriptyline-related adverse reactions if coadministration with paroxetine is necessary; a dose reduction of amitriptyline may be necessary. Concurrent use may increase the plasma concentrations of amitriptyline. Amitriptyline is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Paroxetine and amitriptyline both exhibit significant anticholinergic effects that may be additive during concurrent use. [23615] [28260] [28557] [44116] [44117] [63923] Chlordiazepoxide; Clidinium: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Chlorpheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of dihydrocodeine and paroxetine because of the potential risk of serotonin syndrome, reduced dihydrocodeine efficacy, and potential for opioid withdrawal symptoms. Discontinue dihydrocodeine if serotonin syndrome is suspected. It is recommended to avoid this combination when dihydrocodeine is being used for cough. Concomitant use may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30282] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Phenylephrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpheniramine; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as chlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Chlorpromazine: (Moderate) Monitor for an increase in chlorpromazine- and paroxetine-related adverse reactions, including QT prolongation, anticholinergic effects, orthostasis, somnolence, and serotonin syndrome, if coadministration is necessary. Concomitant use may increase the exposure of both drugs. Both chlorpromazine and paroxetine are CYP2D6 substrates; paroxetine is a strong CYP2D6 inhibitor and chlorpromazine is a moderate CYP2D6 inhibitor. [28260] [55214] [56203] [63923] Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for signs and symptoms of bleeding during concomitant magnesium salicylate and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [28343] [32127] (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate. [27414] [28343] [32127] Cilostazol: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. [4718] [4987] [5072] [5167] Cimetidine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with cimetidine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and cimetidine is a weak CYP2D6 inhibitor. [28260] [34364] [56579] [57012] Cinacalcet: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with cinacalcet is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and cinacalcet is a strong CYP2D6 inhibitor. [28126] [28260] Citalopram: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and citalopram, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and citalopram is a weak CYP2D6 inhibitor. [28260] [28269] Clemastine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as clemastine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Clobazam: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with clobazam is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and clobazam is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [46370] Clomipramine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of clomipramine, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and clomipramine may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Clopidogrel: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of paroxetine and clopidogrel. Selective serotonin reuptake inhibitors (SSRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding. [28260] [28435] Clozapine: (Moderate) Paroxetine is a potent inhibitor of CYP2D6, which may result in decreased clearance of CYP2D6 substrates such as clozapine. Minor to modest (less than 2-fold) elevations in concentrations of clozapine and its metabolites have been reported during concurrent use of paroxetine. Clozapine is associated with a risk for QT prolongation and torsade de pointe (TdP). Elevated plasma concentrations of clozapine occurring through CYP2D6 inhibition may increase the risk of life-threatening arrhythmias. sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP2D6 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary. Lastly, both paroxetine and clozapine may exhibit significant anticholinergic effects which may be additive during concurrent therapy. [28260] [28262] [59321] [63923] Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] Cocaine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. [28269] [5308] [5374] [6416] [6417] Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] Codeine; Guaifenesin: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] Codeine; Phenylephrine; Promethazine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Codeine; Promethazine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and paroxetine because of the potential risk of serotonin syndrome, reduced codeine efficacy, and potential for opioid withdrawal symptoms. Discontinue codeine if serotonin syndrome is suspected. It is recommended to avoid this combination when codeine is being used for cough. Concomitant use may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of paroxetine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If paroxetine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [33654] [34883] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Cyclobenzaprine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant cyclobenzaprine and paroxetine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome. [28260] [28425] Cyproheptadine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine. In addition, additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as cyproheptadine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [62228] [62229] [62230] [62231] Dabigatran: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [42121] [47184] Dacomitinib: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with dacomitinib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor. [28260] [63584] Dalteparin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant. [28260] [28269] [28270] [28343] [32127] [47184] Darifenacin: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with darifenacin is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and darifenacin is a moderate CYP2D6 inhibitor. [28260] [30711] Darunavir: (Moderate) Use caution when coadministering darunavir with paroxetine, as decreased SSRI concentrations may be seen. If paroxetine is coadministered with darunavir, carefully titrate the dose of paroxetine based on a clinical assessment of antidepressant response. [32432] Darunavir; Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] (Moderate) Use caution when coadministering darunavir with paroxetine, as decreased SSRI concentrations may be seen. If paroxetine is coadministered with darunavir, carefully titrate the dose of paroxetine based on a clinical assessment of antidepressant response. [32432] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] (Moderate) Use caution when coadministering darunavir with paroxetine, as decreased SSRI concentrations may be seen. If paroxetine is coadministered with darunavir, carefully titrate the dose of paroxetine based on a clinical assessment of antidepressant response. [32432] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ritonavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ritonavir is a weak CYP2D6 inhibitor. [28260] [60002] Delavirdine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with delavirdine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and delavirdine is a moderate CYP2D6 inhibitor. [28260] [28476] Desipramine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of desipramine, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and desipramine may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Desmopressin: (Minor) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake. [42295] [54986] [61806] [61810] [62924] [63256] [63305] Desvenlafaxine: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and desvenlafaxine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and desvenlafaxine is a weak CYP2D6 inhibitor at doses of 400 mg/day. [28260] [34940] Deutetrabenazine: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Paroxetine is a strong CYP2D6 inhibitor, and the metabolites of deutetrabenazine, alpha- and beta-HTBZ, are CYP2D6 substrates. The systemic exposure of alpha- and beta-HTBZ may be increased resulting in an increase in deutetrabenazine-related adverse reactions, like QT prolongation and drowsiness. After 8 days of paroxetine 20 mg PO daily, systemic exposure (AUC) of alpha- and beta-HTBZ increased 1.9-fold and 6.5-fold, respectively, following a single 22.5 mg dose of deutetrabenazine. The clearance of alpha- and beta-HTBZ was reduced, with corresponding increases in mean half-life of 1.5-fold and 2.7-fold, respectively. The Cmax of alpha- and beta-HTBZ increased 1.2-fold and 2.2-fold, respectively. [61845] Dexbrompheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Dexbrompheniramine; Pseudoephedrine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexbrompheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Dexchlorpheniramine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as dexchlorpheniramine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Bupropion: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with bupropion is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. [28260] [41057] (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Guaifenesin: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dextromethorphan; Quinidine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with quinidine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. [28260] [42280] [47357] (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] Dicyclomine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Digoxin: (Minor) Paroxetine may slightly decrease mean digoxin area under the curve values. Until more clinical data are known, patients should be monitored for loss of digoxin clinical effect if paroxetine is added. [4987] Dihydroergotamine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Diphenhydramine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Diphenhydramine; Ibuprofen: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Diphenhydramine; Naproxen: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Diphenhydramine; Phenylephrine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with diphenhydramine is necessary. Concomitant use may increase paroxetine exposure and risk for additive anticholinergic adverse effects. Paroxetine is a CYP2D6 substrate and diphenhydramine is a moderate CYP2D6 inhibitor. [28260] [63923] Diphenoxylate; Atropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. [28260] [28343] [48620] Disopyramide: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and paroxetine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. [28228] [63923] Diuretics: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. [28260] Dolasetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as paroxetine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. In addition, because dolasetron is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. [28260] [28308] [50275] [59321] Donepezil: (Moderate) Clinical monitoring for drug efficacy, GI or cholinergic effects (e.g., bradycardia or irregular heartbeat), or unusual changes in mood or behavior is recommended during coadministration of donepezil and paroxetine. The plasma concentrations of donepezil may be increased when administered concurrently with paroxetine. Paroxetine is a strong inhibitor of CYP2D6 inhibitor and donepezil undergoes some metabolism by CYP2D6. Paroxetine exhibits anticholinergic effects that may be problematic in the dementia population. [28260] [29640] [50121] [59322] [62457] [64280] [64386] Donepezil; Memantine: (Moderate) Clinical monitoring for drug efficacy, GI or cholinergic effects (e.g., bradycardia or irregular heartbeat), or unusual changes in mood or behavior is recommended during coadministration of donepezil and paroxetine. The plasma concentrations of donepezil may be increased when administered concurrently with paroxetine. Paroxetine is a strong inhibitor of CYP2D6 inhibitor and donepezil undergoes some metabolism by CYP2D6. Paroxetine exhibits anticholinergic effects that may be problematic in the dementia population. [28260] [29640] [50121] [59322] [62457] [64280] [64386] Dorzolamide; Timolol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of timolol with paroxetine is necessary. Concomitant use may enhance the beta-blocking properties of timolol resulting in further slowing of the heart rate or cardiac conduction. Timolol is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. [28260] [28540] Doxepin: (Moderate) Monitor patients for an increase in doxepin-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of doxepin and paroxetine, particularly during treatment initiation and dosage increases; a dose reduction of doxepin may be necessary. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concurrent use may also increase the exposure of doxepin. Doxepin is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. [28260] [39684] [63923] Doxercalciferol: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including selective serotonin reuptake inhibitors (SSRIs), may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if SSRIs are coadministered with doxercalciferol. [30802] [51248] Doxorubicin Liposomal: (Major) Avoid coadministration of paroxetine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Paroxetine is a strong CYP2D6 inhibitor and doxorubicin is a major substrate of CYP3D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interaction [28260] [56361] Doxorubicin: (Major) Avoid coadministration of paroxetine with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Paroxetine is a strong CYP2D6 inhibitor and doxorubicin is a major substrate of CYP3D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interaction [28260] [56361] Dronedarone: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with dronedarone is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and dronedarone is a moderate CYP2D6 inhibitor. [28260] [36101] Duloxetine: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and duloxetine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and duloxetine is a moderate CYP2D6 inhibitor. [28260] [29934] [43998] [55186] Dutasteride; Tamsulosin: (Moderate) Use caution if coadministration of paroxetine with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant treatment with paroxetine increased the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. [28260] [29677] Edoxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like edoxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] [58685] Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with paroxetine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue paroxetine and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28858] [29121] [32484] [41360] [43998] [43999] [55186] [57580] [58195] Eliglustat: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving paroxetine. Eliglustat is contraindicated in EMs and IMs who are receiving paroxetine plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving paroxetine plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving paroxetine plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Also, monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with eliglustat is necessary. Concomitant use may increase paroxetine exposure. Eliglustat is a substrate and moderate inhibitor of CYP2D6 and paroxetine is a substrate and strong inhibitor of CYP2D6. A strong CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 8.4-fold and 2.3-fold in extensive and intermediate metabolizers, respectively. Strong CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs). [28260] [57803] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4. [28269] [28270] [51664] [58000] Enoxaparin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant. [28260] [28269] [28270] [28343] [32127] [47184] Eptifibatide: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. [28260] [28343] [48620] Ergoloid Mesylates: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Ergonovine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Ergot alkaloids: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Ergotamine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Ergotamine; Caffeine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Escitalopram: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and escitalopram, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor. [28260] [28270] [43998] [55186] Everolimus: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with everolimus is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and everolimus is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [49823] Fedratinib: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with fedratinib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and fedratinib is a moderate CYP2D6 inhibitor. [28260] [64568] Fenfluramine: (Major) Concomitant use of fenfluramine and paroxetine may increase fenfluramine plasma concentrations and the risk of adverse reactions, including serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary. If concomitant use is unavoidable, do not exceed a maximum dose of fenfluramine 20 mg/day PO if coadministered with paroxetine and 17 mg/day PO if patient is also receiving stiripentol plus clobazam. Fenfluramine is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Coadministration with paroxetine increased fenfluramine overall exposure by 81% and decreased norfenfluramine overall exposure by 13%. [65634] Fentanyl: (Moderate) If concomitant use of fentanyl and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [29623] [40944] Flavoxate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Flecainide: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with paroxetine is necessary. Flecainide is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers. [28260] [42297] Fluoxetine: (Moderate) Monitor patients for an increase in adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and fluoxetine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine and/or fluoxetine exposure. Paroxetine is a substrate and strong inhibitor of CYP2D6 and fluoxetine is a substrate and strong inhibitor of CYP2D6. [28260] [32127] [43998] [44058] [44059] [55186] Fluphenazine: (Moderate) Monitor for an increase in paroxetine- and fluphenazine-related adverse reactions, including serotonin syndrome, extrapyramidal symptoms, and somnolence, if coadministration is necessary. Concomitant use may increase the exposure of both drugs. Both drugs are CYP2D6 substrates; paroxetine is a strong CYP2D6 inhibitor and fluphenazine is a weak CYP2D6 inhibitor. [28260] [65995] Fluvoxamine: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and fluvoxamine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and fluvoxamine is a weak CYP2D6 inhibitor. [28260] [43998] [50507] [55186] Fondaparinux: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like fondaparinux. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] Fosamprenavir: (Moderate) The combined use of fosamprenavir, boosted with ritonavir, and paroxetine significantly reduced plasma concentrations of paroxetine. Adjust paroxetine dosage based upon tolerability and efficacy of the combined regimen. [4987] Fosphenytoin: (Moderate) Monitor for loss of paroxetine efficacy during concomitant fosphenytoin use; a paroxetine dosage adjustment may be necessary. Fosphenytoin may impair paroxetine efficacy. [28535] Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and frovatriptan and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28269] [28270] [28343] [29266] [32127] [32484] [41360] [43998] [43999] [50507] [55186] [57580] [58195] Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with paroxetine is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and paroxetine is a strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism. [28260] [45935] Gilteritinib: (Major) Avoid coadministration of paroxetine with gilteritinib if possible due to the potential for decreased response to paroxetine. Gilteritinib inhibits human 5HT2B receptor or sigma nonspecific receptors, which may reduce the effects of drugs like paroxetine that target these receptors. [63787] Givosiran: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with givosiran is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and givosiran is a moderate CYP2D6 inhibitor. [28260] [64762] Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as paroxetine. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. [49815] Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during paroxetine treatment due to the risk of increased paroxetine exposure and adverse reactions. Paroxetine is a CYP2D6 substrate and grapefruit juice is a CYP2D6 inhibitor. [28260] [29087] [58104] Guaifenesin; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Guselkumab: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with guselkumab is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and guselkumab is a moderate CYP2D6 inhibitor. [28260] [62120] Haloperidol: (Major) Haloperidol is metabolized by CYP2D6 and CYP3A4 and concurrent use with inhibitors of these isoenzymes may result in elevated haloperidol plasma concentrations and adverse effects including extrapyramidal symptoms or QT prolongation. Paroxetine is a potent CYP2D6 inhibitor. Because symptoms consistent with elevated haloperidol levels have been observed during co-administration of SSRIs and haloperidol, patients receiving these combinations should be monitored for adverse effects such as dizziness, sedation, impaired psychomotor performance, extrapyramidal symptoms, and adverse cardiac effects. [28260] [59321] Heparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like heparin. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] Homatropine; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Hydrocodone; Ibuprofen: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Hydrocodone; Pseudoephedrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and paroxetine because of the potential risk of serotonin syndrome and prolonged opioid adverse reactions. Discontinue hydrocodone if serotonin syndrome is suspected. It is recommended to avoid this combination when hydrocodone is being used for cough. Concomitant use of hydrocodone with paroxetine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of paroxetine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If paroxetine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Paroxetine is a strong inhibitor of CYP2D6. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28260] [30379] [56303] Hydromorphone: (Moderate) If concomitant use of hydromorphone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [39635] Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with IV methylene blue, paroxetine should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome.[46610] One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. [37286] [37287] [37289] [37304] [37362] [45071] [46610] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. [5738] Ibuprofen; Oxycodone: (Moderate) If concomitant use of oxycodone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [39926] [43999] [60634] Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with paroxetine. If paroxetine is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Iloperidone is a CYP2D6 substrate. Paroxetine is a strong inhibitor of CYP2D6. Coadministration of paroxetine increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by about 1.6 fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. [36146] Imatinib: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with imatinib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and imatinib is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [58770] Imipramine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of imipramine, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and imipramine may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Indinavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with indinavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and indinavir is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [28731] Iobenguane I 123: (Major) Discontinue medications that decrease norepinephrine uptake, such as selective serotonin reuptake inhibitors (SSRIs), for at least 5 biological half-lives prior to iobenguane I 123 administration. Consider medication tapering or additional supportive therapy as appropriate to minimize the risk for precipitating SSRI withdrawal symptoms. Medications that decrease the uptake of norepinephrine can cause false negative imaging results. Increasing the dose of iobenguane I 123 will not overcome any potential uptake limiting effect of this medication. [35106] Isocarboxazid: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions. [27957] [29656] [30438] Isoniazid, INH: (Major) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs) should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with SSRIs. Concurrent use of SSRIs and MAOIs may lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therpay is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. [1271] [1425] [4987] [4996] [4997] [5072] [5635] [5738] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs) should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with SSRIs. Concurrent use of SSRIs and MAOIs may lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therpay is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. [1271] [1425] [4987] [4996] [4997] [5072] [5635] [5738] Isoniazid, INH; Rifampin: (Major) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs) should be avoided if possible. Isoniazid is chemically related to iproniazid, a drug that was known to possess MAO inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with SSRIs. Concurrent use of SSRIs and MAOIs may lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therpay is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. [1271] [1425] [4987] [4996] [4997] [5072] [5635] [5738] Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. [28260] [28269] [28270] [28343] [32127] [50507] [64685] Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of levomilnacipran with other drugs that have serotonergic properties, such as selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, levomilnacipran and concurrent serotonergic agents should be discontinued. [28269] [28270] [28343] [32127] [47184] [55469] Levorphanol: (Moderate) If concomitant use of levorphanol and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60958] Linezolid: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with linezolid, paroxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with paroxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid. [11159] [28260] [28599] [45066] Lithium: (Moderate) Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated. [28260] [43998] [47399] [55186] [59857] [59860] [59861] Lofexidine: (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and paroxetine. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. Coadministration with paroxetine increased the lofexidine AUC by 28%. [63161] Lopinavir; Ritonavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ritonavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ritonavir is a weak CYP2D6 inhibitor. [28260] [60002] Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms. [51065] Low Molecular Weight Heparins: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant. [28260] [28269] [28270] [28343] [32127] [47184] Loxapine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like paroxetine and loxapine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. [28260] [63923] Magnesium Salicylate: (Moderate) Monitor for signs and symptoms of bleeding during concomitant magnesium salicylate and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [28343] [32127] Maprotiline: (Major) Paroxetine is a potent inhibitor of CYP2D6, the primary isoenzyme responsible for the metabolism of maprotiline. In several cases, symptoms of toxicity, including seizures, have been reported when SSRIs and cyclic antidepressants have been used together. In addition, because maprotiline is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. Patients receiving maprotiline should be monitored closely for toxicity if paroxetine is added. [28260] [28759] [28810] [59321] Meclizine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with other medications having anticholinergic properties such as meclizine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Meperidine: (Moderate) If concomitant use of meperidine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [51182] Meperidine; Promethazine: (Moderate) If concomitant use of meperidine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [51182] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Metaxalone: (Moderate) Concomitant use of selective serotonin reuptake inhibitors (SSRIs) and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary. [30830] Methadone: (Moderate) Monitor patients for respiratory depression and sedation at frequent intervals if concomitant administration of methadone and paroxetine is necessary; consider reducing the methadone dose until stable effects are achieved. Concomitant use of methadone and paroxetine may increase the plasma concentration of methadone, resulting in increased or prolonged opioid effects. If paroxetine is discontinued, consider increasing the methadone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Methadone is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [33136] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with IV methylene blue, paroxetine should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome.[46610] One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. [37286] [37287] [37289] [37304] [37362] [45071] [46610] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Methscopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Methylene Blue: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with IV methylene blue, paroxetine should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome.[46610] One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. [37286] [37287] [37289] [37304] [37362] [45071] [46610] Methylergonovine: (Moderate) Use paroxetine and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment. [28886] [48628] [52524] Methylphenidate Derivatives: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented. [28260] [28343] [28518] [31287] [32127] [33387] [62067] [62068] [62069] [66501] Metoclopramide: (Major) When metoclopramide is used with a potent CYP2D6 inhibitor for the treatment of gastroesophageal reflux (GERD), dosage reductions of oral metoclopramide are required, with maximum oral dosage not to exceed 30 mg/day (e.g., 5 mg 4 times daily or 10 mg 3 times daily). There is a known increase in metoclopramide exposure and an increased risk for extrapyramidal adverse reactions. Metoclopramide is a substrate of CYP2D6 and paroxetine is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of paroxetine and consideration of alternative SSRI antidepressants when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a strong CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone. Additionally, concomitant use of metoclopramide and SSRIs such as paroxetine may increase the risk for serotonin syndrome. In rare cases postmarketing, NMS-like symptoms, which may overlap with serotonin syndrome symptoms, have been reported with metoclopramide when used with serotonergic agents. [28260] [40462] [43998] [43999] [55186] [57877] [65614] Metoprolol: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with paroxetine. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. [28260] [63198] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with paroxetine. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. [28260] [63198] Mexiletine: (Moderate) Paroxetine impairs metabolism of the cytochrome P-450 isoenzyme CYP2D6 pathway at therapeutic doses. Although no clinical data are available, paroxetine should be used cautiously in patients receiving mexiletine since this antiarrhythmic is metabolized by this isozyme. Inhibition of CYP2D6 can result in increased concentrations of drugs metabolized via the same pathway, including mexiletine, which may increase the risk of side effects or proarrhythmia. [4718] [4987] [5007] Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of milnacipran with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued. [23431] Mirabegron: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with mirabegron is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor. [28260] [51111] Mirtazapine: (Moderate) Coadministration of paroxetine and mirtazapine may increase the risk for serotonin syndrome. Cases of serotonin syndrome have been reported when mirtazapine has been administered with other selective serotonin reuptake inhibitors (SSRIs). Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical treatment should be implemented. [28636] [28637] [40942] [43998] [43999] [55186] Monoamine oxidase inhibitors: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions. [27957] [29656] [30438] Morphine: (Moderate) If concomitant use of morphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [40951] [43053] Morphine; Naltrexone: (Moderate) If concomitant use of morphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [40951] [43053] Nalbuphine: (Moderate) If concomitant use of nalbuphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [49631] Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering naratriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [29267] [32484] Nebivolol: (Major) Avoid the concomitant use of nebivolol and paroxetine. Concomitant use may increase the exposure of nebivolol and the risk of adverse effects. Nebivolol is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor caused an 8-fold increase in the AUC of d-nebivolol. [28260] [60860] [60986] Nebivolol; Valsartan: (Major) Avoid the concomitant use of nebivolol and paroxetine. Concomitant use may increase the exposure of nebivolol and the risk of adverse effects. Nebivolol is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor caused an 8-fold increase in the AUC of d-nebivolol. [28260] [60860] [60986] Nefazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as nefazodone and paroxetine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least one case report of serotonin syndrome from the concurrent use of nefazodone and a selective serotonin reuptake inhibitor (i.e., paroxetine) has been published. Additionally, when a 200 mg dose of nefazodone was administered to subjects who had been receiving fluoxetine for 1 week, there was an increased incidence of transient serotonin-related adverse events. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented. [28260] [28683] [29490] Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as paroxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. [49446] Nicardipine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with nicardipine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and nicardipine is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [50341] Nirmatrelvir; Ritonavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ritonavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ritonavir is a weak CYP2D6 inhibitor. [28260] [60002] Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants. [45206] Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Nortriptyline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of nortriptyline, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and nortriptyline may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Olanzapine: (Major) Concurrent use of paroxetine and olanzapine may result in additive anticholinergic effects, such as urinary retention, constipation, blurred vision, and xerostomia. In addition, paroxetine is a potent inhibitor of CYP2D6, which is a minor isoenzyme pathway for the metabolism of olanzapine. Adverse effects of olanzapine that may become evident include fatigue, dizziness, weight gain, prolactin elevation, orthostatic hypotension, sedation, or extrapyramidal symptoms. In addition, olanzapine is associated with a possible risk of QT prolongation and should be used cautiously with strong CYP2D6 inhibitors such as paroxetine. [28260] [28785] [59321] [63923] Olanzapine; Fluoxetine: (Major) Concurrent use of paroxetine and olanzapine may result in additive anticholinergic effects, such as urinary retention, constipation, blurred vision, and xerostomia. In addition, paroxetine is a potent inhibitor of CYP2D6, which is a minor isoenzyme pathway for the metabolism of olanzapine. Adverse effects of olanzapine that may become evident include fatigue, dizziness, weight gain, prolactin elevation, orthostatic hypotension, sedation, or extrapyramidal symptoms. In addition, olanzapine is associated with a possible risk of QT prolongation and should be used cautiously with strong CYP2D6 inhibitors such as paroxetine. [28260] [28785] [59321] [63923] (Moderate) Monitor patients for an increase in adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and fluoxetine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine and/or fluoxetine exposure. Paroxetine is a substrate and strong inhibitor of CYP2D6 and fluoxetine is a substrate and strong inhibitor of CYP2D6. [28260] [32127] [43998] [44058] [44059] [55186] Olanzapine; Samidorphan: (Major) Concurrent use of paroxetine and olanzapine may result in additive anticholinergic effects, such as urinary retention, constipation, blurred vision, and xerostomia. In addition, paroxetine is a potent inhibitor of CYP2D6, which is a minor isoenzyme pathway for the metabolism of olanzapine. Adverse effects of olanzapine that may become evident include fatigue, dizziness, weight gain, prolactin elevation, orthostatic hypotension, sedation, or extrapyramidal symptoms. In addition, olanzapine is associated with a possible risk of QT prolongation and should be used cautiously with strong CYP2D6 inhibitors such as paroxetine. [28260] [28785] [59321] [63923] Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and paroxetine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and paroxetine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If paroxetine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [65809] Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ritonavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ritonavir is a weak CYP2D6 inhibitor. [28260] [60002] Ondansetron: (Major) Concomitant use of ondansetron and paroxetine increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary. [28260] [31266] [59321] Oritavancin: (Moderate) Paroxetine is metabolized by CYP2D6; oritavancin is a weak CYP2D6 inducer. Plasma concentrations and efficacy of paroxetine may be reduced if these drugs are administered concurrently. [28260] [57741] Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like paroxetine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. [28260] [63923] Osilodrostat: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with osilodrostat is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and osilodrostat is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [65098] Oxybutynin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Oxycodone: (Moderate) If concomitant use of oxycodone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [39926] [43999] [60634] Oxymorphone: (Moderate) If concomitant use of oxymorphone and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [32438] Ozanimod: (Major) Coadministration of ozanimod with paroxetine is not recommended due to the potential for hypertensive crisis and serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Paroxetine may increase blood pressure or sertonergic side effects by increasing serotonin concentrations. [28260] [65169] Paliperidone: (Minor) Paroxetine is a potent inhibitor of CYP2D6, which may result in decreased clearance of partial CYP2D6 substrates such as paliperidone. Decreased metabolism of paliperidone may lead to clinically important adverse reactions such as extrapyramidal symptoms. In addition, paliperidone is associated with a risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with potent CYP2D6 inhibitors such as paroxetine. In one study of healthy subjects, paliperidone exposure was an average of 16% higher in extensive metabolizers of CYP2D6 who were receiving paroxetine 20 mg/day concurrently. The clinical significance of this interaction is unknown. [28260] [40936] [59321] Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as paroxetine. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. [49446] Panobinostat: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with panobinostat is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and panobinostat is a moderate CYP2D6 inhibitor. [28260] [58821] Pazopanib: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with pazopanib is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and pazopanib is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [49829] Peginterferon Alfa-2b: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with peginterferon alfa-2b is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and peginterferon alfa-2b is a weak CYP2D6 inhibitor. [28260] [29627] [43887] Pentamidine: (Moderate) Pentamidine is a substrate of CYP2D6 and paroxetine is a potent inhibitor of CYP2D6. Because pentamidine is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. [28260] [59321] Pentazocine: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy. [28260] [28269] [28270] [28343] [32127] [50507] Pentazocine; Naloxone: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy. [28260] [28269] [28270] [28343] [32127] [50507] Pentosan: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and pentosan, which has weak anticoagulant properties. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] Perphenazine: (Moderate) Monitor for an increase in paroxetine- and perphenazine-related adverse reactions, including serotonin syndrome, extrapyramidal symptoms, and somnolence, if coadministration is necessary. Concomitant use may increase the exposure of both drugs. Both drugs are CYP2D6 substrates; paroxetine is a strong CYP2D6 inhibitor and perphenazine is a weak CYP2D6 inhibitor. [28260] [63923] [65995] Perphenazine; Amitriptyline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Additionally, monitor for an increase in amitriptyline-related adverse reactions if coadministration with paroxetine is necessary; a dose reduction of amitriptyline may be necessary. Concurrent use may increase the plasma concentrations of amitriptyline. Amitriptyline is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Paroxetine and amitriptyline both exhibit significant anticholinergic effects that may be additive during concurrent use. [23615] [28260] [28557] [44116] [44117] [63923] (Moderate) Monitor for an increase in paroxetine- and perphenazine-related adverse reactions, including serotonin syndrome, extrapyramidal symptoms, and somnolence, if coadministration is necessary. Concomitant use may increase the exposure of both drugs. Both drugs are CYP2D6 substrates; paroxetine is a strong CYP2D6 inhibitor and perphenazine is a weak CYP2D6 inhibitor. [28260] [63923] [65995] Phenelzine: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions. [27957] [29656] [30438] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Phentermine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) together with caution due to a potential for serotonin syndrome. Monitor weight, cardiovascular status, and for potential serotonergic adverse effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome when combined with serotonergic agents. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses and some large controlled clinical studies have allowed patients to start phentermine-based therapy for obesity along with their SSRI as long as the antidepressant dose had been stable for at least 3 months prior. Such therapy was generally well-tolerated, especially at lower phentermine doses. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies. [46537] [46595] [51256] [57267] [57658] [57659] [57660] Phentermine; Topiramate: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) together with caution due to a potential for serotonin syndrome. Monitor weight, cardiovascular status, and for potential serotonergic adverse effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome when combined with serotonergic agents. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses and some large controlled clinical studies have allowed patients to start phentermine-based therapy for obesity along with their SSRI as long as the antidepressant dose had been stable for at least 3 months prior. Such therapy was generally well-tolerated, especially at lower phentermine doses. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies. [46537] [46595] [51256] [57267] [57658] [57659] [57660] Phenytoin: (Moderate) Monitor for loss of paroxetine efficacy during concomitant phenytoin use; a paroxetine dosage adjustment may be necessary. Phenytoin may impair paroxetine efficacy. [41239] Pimozide: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation. [28269] [43463] [4987] [4996] [4997] [5072] [5635] [5738] [6066] Pirfenidone: (Moderate) Pirfenidone is primarily metabolized by CYP1A2 with minor contributions from other CYP isoenzymes including CYP2D6. Paroxetine is a potent inhibitor of CYP2D6. Because pirfenidone is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events and should be approached with caution. [28260] [58189] [59321] Pitolisant: (Major) Initiate pitolisant at 8.9 mg once daily in patients taking paroxetine; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If paroxetine is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. Coadministration of paroxetine increased pitolisant exposure by 2.2-fold. [64562] Prasugrel: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving prasugrel. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Procarbazine: (Major) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should avoid the use of selective serotonin reuptake inhibitors (SSRIs) in patients receiving MAOIs. Fatalities have been reported when fluoxetine was administered to patients receiving MAOIs. Confusion, seizures, severe hypertension, and other, less severe symptoms have also been reported with this drug combination. Non-selective MAOIs inhibit both MAO types A and B. Since serotonin is metabolized by MAO type A, it is thought that this drug interaction may lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of therapy with an SSRI except fluoxetine. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and commencement of MAOI therapy. This 5-week period is needed because of the long half-lives of fluoxetine and its principle metabolite norfluoxetine. [4987] [4996] [4997] [5072] [5356] [5595] [5635] [5738] Prochlorperazine: (Moderate) Substantial increases in concentrations of phenothiazines may occur due to CYP2D6 inhibition by paroxetine. which may increase the risk of adverse effects, including extrapyramidal symptoms or QT prolongation. Phenothiazines with a possible risk of QT prolongation include prochlorperazine. Additive anticholinergic effects are also possible. [28260] [63923] Promethazine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Promethazine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of paroxetine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Additionally, monitor patients for signs and symptoms of serotonin syndrome. Concomitant use may increase dextromethorphan exposure and the risk for serotonin syndrome. Dextromethorphan is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use with paroxetine increased dextromethorphan overall exposure by 2.69-fold. [28260] [42280] [61317] [61721] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Promethazine; Phenylephrine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant paroxetine and promethazine use. Concomitant use may result in additive anticholinergic adverse effects. [28260] [43929] [63923] Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with paroxetine; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and paroxetine with a CYP3A4 inhibitor. Propafenone is a CYP3A4 and CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. [28260] [28287] Propantheline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Propranolol: (Minor) Paroxetine impairs metabolism of the hepatic CYP2D6 isoenzyme pathway at therapeutic doses, resulting in substantial increases in concentrations of other drugs metabolized via the same pathway, including propranolol. Clinicians should use paroxetine cautiously with propranolol; downward dose adjustments of the beta-blocker may be required if paroxetine is initiated; alternatively an upward dose adjustment of the beta blocker may be needed if paroxetine is discontinued. Patients should be advised to report increased effects of these medications, including hypotension or increased dizziness to their health care professional. [4718] Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Paroxetine impairs metabolism of the hepatic CYP2D6 isoenzyme pathway at therapeutic doses, resulting in substantial increases in concentrations of other drugs metabolized via the same pathway, including propranolol. Clinicians should use paroxetine cautiously with propranolol; downward dose adjustments of the beta-blocker may be required if paroxetine is initiated; alternatively an upward dose adjustment of the beta blocker may be needed if paroxetine is discontinued. Patients should be advised to report increased effects of these medications, including hypotension or increased dizziness to their health care professional. [4718] Protriptyline: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of protriptyline, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and protriptyline may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Pseudoephedrine; Triprolidine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Pyrilamine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as pyrilamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Quetiapine: (Moderate) Monitor patients for signs and symptoms of serotonin syndrome during concomitant use of paroxetine and quetiapine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. [28260] [63529] Quinidine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with quinidine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and quinidine is a strong CYP2D6 inhibitor. [28260] [42280] [47357] Quinine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with quinine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and quinine is a moderate CYP2D6 inhibitor. [28260] [31403] [34335] Ranolazine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ranolazine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ranolazine is a moderate CYP2D6 inhibitor. [28260] [31938] Rasagiline: (Major) It is recommended to avoid concurrent use of rasagiline and selective serotonin reuptake inhibitors (SSRIs). Severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. During postmarketing use of rasagiline, non-fatal cases of serotonin syndrome have been reported during concomitant antidepressant administration. At least 2 weeks should elapse between stopping rasagiline treatment and beginning therapy with any SSRI. Conversely, when discontinuing an SSRI, it is advisable to wait the length of 4 to 5 half-lives of the individual agent being discontinued prior to initiation with rasagiline. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and initiation of rasagiline. If coadministration of rasagiline and fluvoxamine is required, do not exceed a rasagiline dose of 0.5 mg once daily. Rasagiline is primarily metabolized by CYP1A2; fluvoxamine is a strong CYP1A2 inhibitor. When rasagiline was administered with another strong CYP1A2 inhibitor, the AUC of rasagiline increased by 83%. [28343] [32223] Remifentanil: (Moderate) If concomitant use of remifentanil and selective serotonin reuptake inhibitors (SSRIs) is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28897] Reteplase, r-PA: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI. [28260] [28343] Risperidone: (Major) Initiate risperidone at a reduced dose in patients receiving paroxetine as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when paroxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor. Daily dosing of paroxetine 20 mg PO in patients stabilized on risperidone (4 to 8 mg/day) increased mean plasma concentrations of risperidone roughly 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold. Other data suggest that daily administration of paroxetine increases plasma concentrations of risperidone 3- to 9-fold. [22256] [28260] [28414] [30990] [59321] [63411] Ritonavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with ritonavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and ritonavir is a weak CYP2D6 inhibitor. [28260] [60002] Rivaroxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like rivaroxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [44854] Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering rizatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after the initiation of the SSRI or dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [31864] [32484] Rolapitant: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with rolapitant is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor. The inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Exposure to another CYP2D6 substrate, following a single dose of rolapitant, increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured. [28260] [60142] Safinamide: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. [61825] Salsalate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate. [27414] [28343] [32127] Scopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Selegiline: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions. [32026] [32436] Sertraline: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and sertraline, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and sertraline is a weak CYP2D6 inhibitor. [28260] [28343] [43998] [55186] Sibutramine: (Major) Sibutramine is a serotonin reuptake inhibitor. Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering sibutramine with other drugs that have serotonergic properties such as selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. In addition, in vitro studies indicate that metabolism of sibutramine is mediated through CYP3A4. Theoretically, the metabolism of sibutramine may be decreased as a result of CYP3A4 inhibition by fluoxetine or fluvoxamine. Patients receiving sibutramine in combination with an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects. [5333] [5340] Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that are known to induce Antidiuretic Hormone Secretion (SIADH), such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), antipsychotics and carbamazepine, as these drugs may increase the risk of water retention and/or electrolyte imbalance. [51258] St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering paroxetine and St. John's Wort. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated. [28260] [43998] [45154] [55186] Sufentanil: (Moderate) If concomitant use of sufentanil and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [30966] Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28583] [29523] [31921] [32484] Sumatriptan; Naproxen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28583] [29523] [31921] [32484] Tamoxifen: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with paroxetine is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Paroxetine is a strong CYP2D6 inhibitor. In one study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors (e.g., paroxetine); plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. In another study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established. [28260] [63589] Tamsulosin: (Moderate) Use caution if coadministration of paroxetine with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant treatment with paroxetine increased the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. [28260] [29677] Tapentadol: (Moderate) If concomitant use of tapentadol and selective serotonin reuptake inhibitors (SSRIs) is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [36077] Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and selective serotonin reuptake inhibitors (SSRIs) due to the theoretical risk of serotonin syndrome. Animal studies did not predict serotonergic effects; however, patients on concurrent SSRIs were excluded from clinical trials. Addtionally, tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor and monoamine oxidase type A deaminates serotonin; therefore, coadministration theoretically could lead to serious reactions including serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid, which is structurally similar to tedizolid. [28260] [28599] [28642] [32127] [32308] [34303] [57468] Tenecteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI. [28260] [28343] Terbinafine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact. [43880] [43881] [44454] [47184] [4996] [4997] [54631] [6586] [8874] Tetrabenazine: (Major) The primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Coadministration of 50 mg of tetrabenazine following 10 days of 20 mg of paroxetine, a potent CYP2D6 inhibitor, resulted in an increase in Cmax of approximately 30% and a 3-fold increase in AUC for alpha-HTBZ. The Cmax and AUC for beta-HTBZ increased 2.4-fold and 9-fold, respectively. The elimination half-life of alpha-HTBZ and beta-HTBZ was approximately 14 hours when tetrabenazine was given with paroxetine. When tetrabenazine is given with a strong inhibitor of CYP2D6 such as paroxetine, the maximum single dose of tetrabenazine should not exceed 25 mg and the daily dose should not exceed 50 mg. In addition, because tetrabenazine is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. During use of this combination, monitor for adverse effects associated with tetrabenazine such as QT prolongation, excess sedation, and extrapyramidal symptoms. [28260] [34389] [59321] Theophylline, Aminophylline: (Major) Paroxetine has been reported to cause elevations of theophylline serum concentrations. Monitor aminophylline serum concentrations when paroxetine is given concurrently with aminophylline. Observe patients for signs or symptoms of aminophylline toxicity. [4987] (Major) Paroxetine has been reported to cause elevations of theophylline serum concentrations. The interaction has not been formally studied. It is recommended that theophylline serum concentrations be monitored when paroxetine is given concurrently with theophylline or aminophylline. Observe patients for signs or symptoms of theophylline toxicity. [4987] Thioridazine: (Contraindicated) Coadministration of thioridazine and paroxetine is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. [28260] [63923] Thiothixene: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with thiothixene is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and thiothixene is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [56203] [56844] Thrombin Inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28269] [28270] [28343] [32127] [47184] Thrombolytic Agents: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI. [28260] [28343] Ticagrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [28260] [28343] [28435] Ticlopidine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner. [4987] [5072] Timolol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of timolol with paroxetine is necessary. Concomitant use may enhance the beta-blocking properties of timolol resulting in further slowing of the heart rate or cardiac conduction. Timolol is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. [28260] [28540] Tipranavir: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with tipranavir is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and tipranavir is a strong CYP2D6 inhibitor. [28260] [31320] Tirofiban: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. [28260] [28343] [48620] Tolterodine: (Moderate) Paroxetine, a potent CYP2D6 inhibitor, may inhibit the metabolism of tolterodine, a CYP2D6 substrate. In a study assessing another potent CYP2D6 inhibitor (fluoxetine) and tolterodine, the metabolism of tolterodine immediate release was significantly decreased in CYP2D6 extensive metabolizers, resulting in a 4.8-fold increase in tolterodine AUC. There was a 52% decrease in Cmax and a 20% decrease in AUC of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine. The sums of unbound serum concentrations of tolterodine and 5-HMT were only 25% higher during the interaction. Although the manufacturer requires no dose adjustment during concurrent use of tolterodine and fluoxetine, the kinetic and clinical effects of paroxetine use are unknown. Both drugs exhibit anticholinergic effects that may be additive. In addition, because tolterodine is a primary substrate of CYP2D6 and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events. [28260] [31112] [59321] Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with paroxetine is necessary. If paroxetine is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28314] [29935] [32475] [40634] [43998] [55186] Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with paroxetine is necessary. If paroxetine is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and paroxetine is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [28314] [29935] [32475] [40634] [43998] [55186] Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions. [27957] [29656] [30438] Trazodone: (Moderate) Coadministration of trazodone and paroxetine may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28260] [43857] [43998] [55186] Trifluoperazine: (Moderate) Substantial increases in concentrations of phenothiazines may occur due to CYP2D6 inhibition by paroxetine, which may increase the risk of adverse effects, including extrapyramidal symptoms or QT prolongation. Phenothiazines with a possible risk of QT prolongation include trifluoperazine. Additive anticholinergic effects are also possible. [28260] [63923] Trihexyphenidyl: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant anticholinergic medication and paroxetine use. Concomitant use may result in additive anticholinergic adverse effects. [29597] [63923] [64280] Trimipramine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as tricyclic antidepressants. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In addition, paroxetine is a potent CYP2D6 inhibitor and may decrease the metabolism of trimipramine, a CYP2D6 substrate. Because there is a risk of QT prolongation and torsade de pointes (TdP) with tricyclics at elevated serum concentrations, coadministration should be approached with caution and close monitoring. Lastly, both paroxetine and trimipramine may exhibit significant anticholinergic effects that may be additive during concurrent use. [28260] [59321] [63923] Triprolidine: (Moderate) Of the selective serotonin reuptake inhibiting antidepressants (SSRIs), paroxetine is considered the most anticholinergic. Additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as triprolidine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28260] [63923] Tryptophan, 5-Hydroxytryptophan: (Major) Concurrent use of tryptophan and a selective serotonin reuptake inhibitor (SSRI) is not recommended. Since tryptophan is converted to serotonin, the use of tryptophan in patients receiving SSRIs could lead to serotonin excess and, potentially, serotonin syndrome. Discontinuation of tryptophan usually resolves symptoms. [28343] [32127] Valbenazine: (Major) Consider reducing the dose of valbenazine, based on tolerability, during co-administration with a strong CYP2D6 inhibitor, such as paroxetine. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, concentrations of the active metabolite of valbenazine may be higher in patients taking a strong CYP2D6 inhibitor and QT prolongation may become clinically significant. [61873] Valerian, Valeriana officinalis: (Moderate) Substances that act on the CNS, including psychoactive drugs, may theoretically interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. Persons taking medications such as SSRIs should discuss the use of herbal supplements with their health care professional prior to consuming these herbs. Patients should not abruptly stop taking their prescribed psychoactive medication. [28584] [28832] [28833] Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as selective serotonin reuptake inhibitors. Use together may increase the pressor and antidiuretic effects of vasopressin. [58023] Vemurafenib: (Moderate) Concomitant use of vemurafenib and paroxetine may result in increased paroxetine concentrations. Paroxetine is metabolized by CYP2D6 and vemurafenib is a weak CYP2D6 inhibitor. Monitor patients for toxicity. [45335] [4718] Venlafaxine: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and venlafaxine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and venlafaxine is a weak CYP2D6 inhibitor. [28260] [28275] Vilazodone: (Major) Due to possible additive effects on serotonin concentrations, it is advisable to avoid combining selective serotonin reuptake inhibitors (SSRIs) such as paroxetine with vilazodone. Interactions between vilazodone and serotonergic agents can lead to serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and paroxetine should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and paroxetine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. [43177] Viloxazine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with viloxazine is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and viloxazine is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%. [28260] [66575] Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as selective serotonin reuptake inhibitors (SSRIs). Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion. In addition, fluoxetine and fluvoxamine are CYP3A4 inhibitors and coadministration with vorapaxar, a CYP3A4 substrate, may result in increased serum concentrations of vorapaxar. Increased exposure to vorapaxar may increase the risk of bleeding complications. Patients should be instructed to monitor for signs and symptoms of bleeding while taking a SSRI with vorapaxar and to promptly report any bleeding events. [32127] [47184] [57151] Vortioxetine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, vortioxetine should generally not be co-administered with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Monitor for serotonin syndrome during a transition from vortioxetine to an SSRI. If coadministration is necessary, the manufacturer recommends a reduction in the vortioxetine dose by one-half when strong inhibitors of CYP2D6 such as paroxetine are used since CYP2D6 is the primary isoenzyme responsible for the metabolism of vortioxetine to its inactive metabolite. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. [56041] Warfarin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of paroxetine and warfarin. Carefully monitor patients receiving warfarin therapy if paroxetine is initiated or discontinued. Some data suggest there may be a pharmacodynamic interaction that causes increased bleeding without a change in prothrombin time. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding. [28260] [28549] Ziprasidone: (Major) Because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with drugs that are dopamine antagonists such as ziprasidone. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving ziprasidone and an SSRI should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects. [4987] [5072] [5738] Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28445] [32484] [49005] Zolpidem: (Moderate) Disorientation, delusions, or hallucinations have been reported rarely during co-administration of zolpidem and antidepressants. The duration of the visual hallucinations has ranged from 30 minutes to 7 hours. The interaction is thought to be pharmacodynamic in nature; therefore, a similar reaction is possible with paroxetine. Data from a clinical study in which SSRI-treated patients were given immediate-release zolpidem revealed that four of the seven discontinuations during double-blind treatment with zolpidem (n = 95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction. [28747] [57789]
    Revision Date: 12/31/2022, 02:31:00 AM

    References

    1271 - Evans ME, Kortas KJ. Potential interaction between isoniazid and selective serotonin-reuptake inhibitors. Am J Health-Syst Pharm 1995;52:2135-6.1425 - Robinson DS, Lovenberg W, Keiser H, et al. Effects of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem Pharmacol 1968;17:109-19.4718 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.4987 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.4996 - Celexa (citalopram) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2022 Feb.4997 - Lexapro (escitalopram) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.5007 - Mexiletine capsule package insert. Baudette, MN: ANI Pharmaceuticals, Inc; 2019 Dec.5072 - Zoloft (sertraline) package insert. Morgantown, WV: Viatris Specialty LLC; 2023 Jan.5167 - Pletal® (cilostazol) package insert. Tokushima, Japan: Otsuka Pharmaceutical Co., Ltd.; 2004 Feb.5267 - Coreg (carvedilol) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Sept.5308 - Prior FH, Isbister GK, Dawson AH, et al. Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine. Med J Aust 2002;176(5):240-241.5333 - Trakas K, Shear NH. Serotonin syndrome risk with antiobesity drug. Can J Clin Pharmacol. 2000;7(4):216.5340 - Meridia (sibutramine) package insert. North Chicago, IL: Abbott Laboratories; 2009 Apr.5356 - Matulane (procarbazine) package insert. Gaithersburg, MD: sigma-tau Pharmaceuticals, Inc.; 2002 July.5374 - Barrett J, Meehan O, Fahy T. SSRI and sympathomimetic interaction. Br J Psychiatry 1996;168:253.5595 - Bernstein JG. Chapter 12 - Drug Interactions. In: Drug Therapy in Psychiatry. 3rd ed. St. Louis MO: Mosby-Year Book, Inc.;1995:328-364.5635 - Fluvoxamine maleate package insert. Laurelton, NY: Eon Labs, Inc.; March 2005.5738 - OPEN REFERENCE6066 - Paxil CR™ (paroxetine HCL) controlled-release tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2005 Aug.6416 - Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998;46:245-9.6417 - Knudsen K, Beckman Suurkula M, Blomberg S, et al. Central nervous and cardiovascular effects of iv infusions of ropivacaine, bupivacaine, and placebo in volunteers. Br J Anesth 1997;78:507-14.6586 - Madani S, Barilla, D, Cramer J, et al. Effect of terbinafine on the pharmacokinetics and pharmacodynamics of desipramine in healthy volunteers identified as cytochrome P450 2D6 (CYP2D6) extensive metabolizers. J Clin Pharmacol 2002;42:1211-1218.8874 - Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab 2002;3:13-37.11159 - Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm 2007;64:59-62.22256 - Risperdal Consta (risperidone long-acting injection) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Feb.23431 - Savella (milnacipran hydrochloride) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2022 Dec.23615 - Preskorn SH, Baker B. Fatality associated with combined fluoxetine-amitriptyline therapy. JAMA 1997;277:1682.27414 - Dalton, SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin reuptake inhibitors and the risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003;163:59-64.27957 - Nardil (phenelzine) tablet package insert. New York, NY: Pfizer; 2009 Feb.28040 - Xanax (alprazolam tablet) package insert. New York, NY: Pharmacia & Upjohn Company; 2023 Jan.28126 - Sensipar (cinacalcet) package insert. Thousand Oaks, CA: Amgen Inc.; 2019 Dec.28224 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.28228 - Norpace and Norpace CR (disopyramide) package insert. Chicago, IL: G.D. Searle LLC division of Pfizer Inc; 2016 Aug.28260 - Paxil (paroxetine) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Seot.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc.; 2022 Dec.28269 - Celexa (citalopram) tablets package insert. Madison, NJ: Allergan USA, Inc.; 2022 Feb.28270 - Lexapro (escitalopram) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.28275 - Effexor (venlafaxine) package insert. Philadelphia, PA: Wyeth Pharmaceuticals, Inc.; 2021 Sept.28287 - Rythmol SR (propafenone hydrochloride) capsule extended release package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Nov.28308 - Anzemet (dolasetron mesylate) tablets package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2014 Sept.28314 - Ultram (tramadol immediate-release tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Sep.28343 - Zoloft (sertraline) package insert. Morgantown, WV: Viatris Specialty LLC; 2023 Jan.28405 - Strattera (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Jan.28414 - Risperdal (risperidone tablets, oral solution, and orally disintegrating tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Aug.28425 - Cyclobenzaprine tablet package insert. Fort Washington, PA: Rising Health, LLC; 2019 Dec.28435 - Plavix (clopidogrel) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2022 Sept28445 - Zomig (zolmitriptan) tablets package insert. Hayward, CA: Impax Specialty Pharma; 2018 Dec.28476 - Rescriptor (delavirdine) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Aug.28501 - Buspirone tablets package insert. North Wales, PA: Teva Pharmaceuticals USA Inc.; 2016 Dec.28518 - Ritalin and Ritalin SR (methylphenidate) package insert. East Hanover, NJ: Novartis Pharmaceutical Corp.; 2021 June.28535 - Cerebyx (fosphenytoin sodium) package insert. New York, NY: Pfizer Labs; 2022 Apr.28540 - Timolol tablets package insert. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2020 July.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28557 - Elavil (amitriptyline) tablet package insert. Birmingham, AL: Thompson Medical Solutions; 2016 Apr.28558 - Amoxapine package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2015 Feb.28583 - Imitrex (sumatriptan succinate) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Dec.28584 - Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.28599 - Zyvox (linezolid) package insert. New York, NY: Pharmacia and Upjohn Company; 2021 Oct.28636 - Benazzi F. Serotonin syndrome with mirtazapine-fluoxetine combination. Int J Geriatr Psychiatry 1998;13:495-6.28637 - Demers JC, Malone M. Serotonin syndrome induced by fluvoxamine and mirtazapine. Ann Pharmacother 2001;35:1217-20.28642 - Gillman PK. Linezolid and serotonin toxicity. Clin Infect Dis 2003;37:1274-5.28683 - Nefazodone tablet package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015 Sept.28731 - Crixivan (indinavir) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2016 Sept.28747 - Elko CJ, Burgess JL, Robertson WO. Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible interaction. J Toxicol Clin Toxicol 1998;36:195-203.28759 - Maprotiline HCl tablet package insert. Morgantown WV: Mylan Pharmaceuticals Inc; 2014 Dec.28785 - Zyprexa (olanzapine, all formulations) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Apr.28810 - Brachtendorf L, Jetter A, Beckurts KT, et al. Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol 2002;90:144-9.28832 - Leuschner J, Muller J, Rudmann M. Characterisation of the central nervous depressant activity of a commercially available valerian root extract. Arzneimittelforschung 1993;43:638-41.28833 - Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-16. Review.28858 - Eadie MJ. Clinically significant drug interactions with agents specific for migraine attacks. CNS Drugs 2001;15:105-18. Review.28886 - Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia 1996;16:323-7.28896 - Yamreudeewong W, DeBisschop M, Martin LG, et al. Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf 2003;26:421-38.28897 - Ultiva (remifentanil) package insert. Rockford, IL: Mylan Institutional LLC; 2019 Oct.29087 - Dahan A, Altman H. Food-drug interaction: grapefruit juice augments drug bioavailability-mechanism, extent, and relevance. Eur J Clin Nutr 2004;58:1-9.29121 - Relpax (eletriptan hydrobromide) package insert. New York, NY: Pfizer Inc.; 2020 Mar.29266 - Frova (frovatriptan) package insert. Malvern, PA: Endo Pharmaceuticals, Inc.; 2018 Aug.29267 - Amerge (naratriptan hydrochloride) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2016 Nov.29332 - Adderall XR (amphetamine; dextroamphetamine) package insert. Lexington, MA: Shire US Inc.; 2022 Feb.29490 - John L, Perreault MM, Tao T, et al. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med. 1997;29:287-9.29523 - Imitrex Nasal Spray (sumatriptan) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Dec.29597 - Hoffman BB, Lefkowitz RJ. Atropine, scopolamine, and related antimuscarinic drugs. Gilman AG, Rall TW, Nies AS, Taylor P, (eds.) In: Goodman and Gilman's Pharmacological Basis of Therapeutics. 8th ed., New York, Pergamon Press. 1990. 150-61.29623 - Duragesic (fentanyl transdermal system) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Mar.29627 - PegIntron (peginterferon alfa-2b) package insert. Whitehouse Station, NJ: Merck and Co., Inc.; 2019 Jan.29640 - Aricept (donepezil hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Co., Ltd.; 2017 March.29656 - Parnate (tranylcypromine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals; 2018 Jan.29677 - Flomax (tamsulosin) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014 Oct.29934 - Cymbalta (duloxetine hydrochloride) delayed-release capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2021 Sept.29935 - Egberts AC, ter Borgh J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol 1997;12:181-2.30072 - Alfentanil hydrochloride injection package insert. Lake Forest, IL: Akorn, Inc.; 2019 Oct.30282 - Synalgos-DC (aspirin; caffeine; dihydrocodeine) capsules package insert. Atlanta, GA: Mikart, Inc.; 2019 Oct.30379 - Hycodan (hydrocodone bitartrate; homatropine methylbromide) package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2018 Jun.30438 - Marplan (isocarboxazid) package insert. Parsippany, NJ: Validus Pharmaceuticals; 2018 Nov.30711 - Enablex (darifenacin extended-release tablets) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Jul.30802 - Hansten PD, Horn JR. Top 100 Drug Interactions Monographs. In: The Top 100 Drug Interactions - A guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:4-141.30830 - Skelaxin (metaxalone) tablet package insert. Bristol, TN: King Pharmaceuticals, Inc.; 2018 Mar.30966 - Sufenta (sufentanil citrate injection) package insert. Lake Forest, IL: Akorn Pharmaceuticals, Inc.; 2019 Oct30990 - de Leon J, Susce MT, Pan RM, et al. The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry. 2005;66:15-27.31112 - Detrol (tolterodine tartrate) package insert. New York, NY: Pharmacia and Upjohn Co., division of Pfizer; 2016 Nov.31266 - Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.31287 - Focalin XR (dexmethylphenidate extended-release) package insert. East Hanover, NJ: Novartis Pharmaceutical Corp; 2019 Nov.31320 - Aptivus (tipranavir) package insert. Ridgefield, CT: Boehringer Ingelheim; 2020 Jun.31327 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2020 Feb.31403 - Qualaquin (quinine sulfate) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Jun.31864 - Maxalt and Maxalt-MLT (rizatriptan) package insert. Whitehouse Station, NJ: Merck and Co Inc.; 2019 Oct.31869 - Axert (almotriptan) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2017 May.31921 - Imitrex Injection (sumatriptan injection) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Dec.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.32026 - Emsam (selegiline) transdermal system package insert. Morgantown, WV: Somerset Pharmaceuticals, Inc.; 2020 May.32127 - Prozac (fluoxetine) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2021 Oct.32223 - Azilect (rasagiline mesylate) tablets. Kansas City, MO: Teva Neurosciences, Inc.; 2020 Jun.32308 - Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: A review of postmarketing data. Clin Infect Dis 2006;42:1578-83.32432 - Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Oct.32436 - Zelapar (selegiline orally-disintegrating tablets) package insert. Bridgewater, NJ: Bausch Health U.S., LLC; 2021 Jun.32438 - Opana (oxymorphone hydrochloride) tablets package insert. Malvern, PA: Endo Pharmaceuticals, Inc.; 2019 Oct.32475 - Tramadol hydrochloride extended-release tablets package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2020 Jul.32484 - U.S. Food and Drug Administration (FDA). Combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. FDA Public Health Advisory. Accessed July 26, 2006. Available on the World Wide Web at: http://www.fda.gov/cder/drug/advisory/SSRI_SS200607.htm33136 - Dolophine (methadone) tablets package insert. Eatontown, NJ: West-Ward Pharmaceuticals Corp.; 2021 Jun.33263 - Vyvanse (lisdexamfetamine) capsules and chewable tablets package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2022 Jan.33363 - Desoxyn (methamphetamine hydrochloride) package insert. Deerfield, IL: Abbott Pharmaceuticals, Inc.; 2022 Feb.33387 - Concerta (methylphenidate hydrochloride) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 June.33654 - Codeine sulfate tablets package insert. Eatontown, NJ; West-Ward Pharmaceuticals Corp.: 2021 Mar.34303 - Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm 2007;64:59-62.34335 - Giao PT, de Vries PJ. Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet 2001;40:343-73.34364 - Humphries TJ, Merritt GJ. Review article: drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol Ther 1999;13:18-26.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.34883 - Promethazine and codeine oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2018 Jun.34940 - Pristiq (desvenlafaxine) extended-release tablets package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2021 Nov.35106 - AdreView (iobenguane I 123) package insert. Arlington Heights, IL: GE Healthcare, Medi-Physics, Inc; 2020 Mar.35401 - Coartem (artemether; lumefantrine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Aug.36077 - Nucynta (tapentadol immediate-release tablets) package insert. Stoughton, MA; Collegium Pharmaceutical, Inc.: 2021 Mar.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2020 Nov.36146 - Fanapt (iloperidone) package insert. Rockville, MD: Vanda Pharmaceuticals, Inc.; 2017 Mar.36343 - Saphris (asenapine) sublingual tablet package insert. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2017 Mar.37286 - Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol 2007;152:946-51.37287 - Ng BK, Cameron AJ, Liang R, et al. Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review. Can J Anaesth 2008;55:1-5.37289 - Khavandi A, Whitaker J, Gonna H. Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue. Med J Aust 2008;189:534-5.37304 - Kartha SS, Chacko CE, Bumpous JM, et al. Toxic metabolic encephalopathy after parathyroidectomy with methylene blue localization. Otolaryngol Head Neck Surg 2006;135:765-8.37362 - Stanford SC, Stanford BJ, Gillman PK. Risk of severe serotonin toxicity following co-administration of methylene blue and serotonin reuptake inhibitors: an update on a case report of post-operative delirium. J Psychopharmacol. 2010;24(10):1433-8. Epub 2009 May 7.39635 - Exalgo (hydromorphone hydrochloride) extended-release tablets package insert. Hazelwood, MO: Mallinckrodt Brand Pharmaceuticals Inc.; 2019 Oct.39684 - Silenor (doxepin) package insert. Morristown, NJ. Currax Pharmaceuticals, LLC.; 2020 Oct.39926 - OxyContin (oxycodone HCl extended-release) package insert. Stamford, CT: Purdue Pharma L.P.; 2021 Oct.40462 - Schillevoort I, van Puijenbroek EP, de Boer A, et al. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports. Int Clin Psychopharmacol 2002;17:75-79.40634 - Ultracet (acetaminophen; tramadol tablets) package insert. Titusville, NJ; Janssen Pharmaceuticals, Inc.; 2021 Sep.40936 - Invega Sustenna (paliperidone palmitate injectable suspension) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Jul.40942 - Remeron and Remeron SolTabs (mirtazapine tablets and ODT tablets) package insert. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021 Nov.40944 - Sublimaze (fentanyl citrate injection) package insert. Lake Forest, IL: Akorn, Inc.; 2019 Oct.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2021 Mar.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2022 Mar.41239 - Dilantin (extended phenytoin sodium capsules)package insert. New York, NY: Parke-Davis Division of Pfizer Inc; 2021 Mar.41360 - Gillman PK. Triptans, serotonin agonists, and serotonin syndrome (serotonin toxicity): a review. Headache 2010;50:264-72.42121 - Pradaxa (dabigatran) oral capsules package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021 Jun.42280 - Nuedexta (dextromethorphan hydrobromide; quinidine sulfate capsule) package insert. Aliso Viejo, CA: Avanir Pharmaceuticals, Inc.; 2019 Jun.42295 - DDAVP (desmopressin acetate) injection package insert. Parsippany NJ: Ferring Pharmaceuticals, Inc.; 2022 Jul.42297 - Flecainide package insert. Baudette, MN: Ani Pharmaceuticals, Inc.; 2015 Dec.42845 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2022 Nov.43053 - Morphine sulfate oral solution package insert. Berkley, NJ: Hikma Pharmaceuticals USA, Inc.; 2021 Jun.43177 - Viibryd (vilazodone) tablets package insert. Madison, NJ; Allergan USA, Inc.: 2021 July.43463 - Orap (pimozide) package insert. Sellersville, PA: Teva Pharmaceuticals USA; 2014 Mar.43857 - Trazodone HCl tablets package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2020 July43880 - Lamisil (terbinafine oral granules) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Mar.43881 - Terbinafine tablets package insert. Princeton, NJ: Bionpharma Inc.; 2021 Nov.43887 - Sylatron (peginterferon alfa-2b) package insert. Whitehouse Station, NJ: Merck & Co, Inc; 2018 Dec.43929 - Promethazine hydrochloride tablets package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2008 Aug.43998 - Pexeva (paroxetine mesylate) package insert. Roswell, GA: Sebela Pharmaceuticals, Inc. 2021 Sept.43999 - Paxil CR (paroxetine) tablets package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Sept.44058 - Prozac Weekly (fluoxetine hydrochloride delayed-release capsules) package insert. Indianapolis, IN: Lilly USA, LLC; 2017 Mar.44059 - Sarafem (fluoxetine hydrochloride) package insert. Madison, NJ: Allergan USA, Inc; 2021 Sept.44116 - amitriptyline hydrochloride package insert. Princeton, NJ: Sandoz, Inc.; 2011 Jan.44117 - Amitriptyline hydrochloride package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2016 Feb.44156 - Zytiga (abiraterone acetate) tablets package insert. Horsham, PA: Janssen Biotech, Inc.; 2021 Aug.44454 - Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 2005;33:262-70.44854 - Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2022 Jan.45066 - FDA Drug Safety Communication. Serious CNS reactions possible when linezolid (Zyvox) is given to patients taking certain psychiatric medications. Retrieved Oct. 21, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm276251.htm.45071 - Food and Drug Administration (US FDA) Drug Safety Communication. Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. Retrieved July 27, 2011. Available on the World Wide Web at http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm.45154 - Borrelli F, Izzo AA: Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J 2009;11(4):710-27.45206 - Nitro-Dur (nitroglycerin patch) package insert. Orlando, FL: Ingenus Pharmaceuticals, LLC.; 2017 Sept.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45935 - Gefitinib (Iressa) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021 May.46370 - Onfi (clobazam) package insert. Deerfield, IL: Lundbeck Inc.; 2023 Jan.46537 - Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2020 Sept.46595 - Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2018 Dec.46610 - Food and Drug Administration (US FDA) Drug Safety Communication. Updated information about the drug interaction between methylene blue (methylthioninium chloride) and serotonergic psychiatric medications. Retrieved November 2, 2011. Available on the World Wide Web at http://www.fda.gov/Drugs/DrugSafety/ucm276119.htm.47184 - Luvox (fluvoxamine) package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 July47357 - Quinidine gluconate extended-release tablet package insert. Princeton, NJ: Eywa Pharma Inc.; 2021 Dec.47399 - Lithobid extended-release tablets (lithium carbonate, USP) package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2022 Oct.48617 - Evoxac (cevimeline) package insert. Edison, NJ: Daiichi Sankyo Pharma Development; 2018 April.48620 - Pletal (cilostazol) package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2017 May.48628 - D.H.E. 45 (dihydroergotamine) injection package insert. Bridgewater, NJ: Bausch Health US, LLC; 2022 Apr.49005 - Zolmitriptan nasal spray package insert. Bridgewater, NJ: Amneal Pharmaceuticals; 2019 May.49446 - Aloxi (palonosetron hydrochloride) injection package insert. Woodcliff Lake, NJ: Eisai Inc.;2020 April.49631 - Nalbuphine hydrochloride injection package insert. Lake Forest, IL; Hospira, Inc.; 2020 Feb.49815 - Sancuso (granisetron) patch package insert. Bedminster, NJ: ProStrakan, Inc.; 2020 April.49823 - Afinitor (everolimus) tablets package insert. East Hanover, NJ:Novartis Pharmaceuticals Corporation; 2022 Feb.49829 - Votrient (pazopanib) tablet package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 Sept.50121 - Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition. Am J Psychiatry. 2007;164(12 Suppl):5-56.50275 - Anzemet (dolasetron mesylate) injection package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2014 Sept.50341 - Cardene SR (nicardipine) package insert. Bedminster, NJ: EKR Therapeutics, Inc.; 2016 Aug.50507 - Luvox CR (fluvoxamine maleate extended-release capsules) package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2017 Jan.51065 - Belviq and Belviq XR (lorcaserin hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Inc.; 2016 Nov.51111 - Myrbetriq (mirabegron extended-release tablets and oral suspension) package insert. Northbrook, Illinois: Astellas Pharma US, Inc.; 2021 March.51182 - Demerol (meperidine tablets and oral solution) package insert. Parsippany, NJ: Validus Pharmaceuticals, LLC; 2021 Mar.51248 - Hectorol (doxercalciferol) capsules and injection package insert. Cambridge, MA: Genzyme Corporation; 2018 Nov.51256 - Qsymia (phentermine and topiramate extended-release) package insert. Campbell, CA: Vivus, Inc.; 2022 June.51258 - Prepopik (Sodium picosulfate; magnesium oxide; anhydrous citric acid) package insert. Parsippany, NJ: Ferring Pharmaceuticals Inc.; 2018 Aug.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.52524 - Migranal (dihydroergotamine mesylate) nasal spray package insert. Bridgewater, NJ: Valeant Pharmaceuticals North America, LLC; 2019 Aug.52739 - Eliquis (apixaban) package insert. Bristol-Myers Squibb Company; Princeton, NJ. 2021 Apr.53394 - Abilify Maintena (aripiprazole) extended-release intramuscular injection package insert. Rockville, MD:Otsuka America Pharmaceutical, Inc.; 2020 June.54631 - Isoherranen N, Lutz JD, Chung SP, et al. Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data. Chem Res Toxicol 2012; 19:2285-2300.54986 - Stimate (desmopressin acetate) intranasal package insert. King of Prussia, PA: CSL Behring LLC; 2013 June.55186 - Brisdelle (paroxetine) capsules package insert. Roswell, GA: Sebela Pharmaceuticals, Inc.; 2021 Sept.55214 - Schillevoort I, de Boer A, van der Weide J, et al. Antipsychotic-induced extrapyramidal syndromes and cytochrome P450 2D6 genotype: a case-control study. Pharmacogenetics 2002;12:235-40.55469 - Fetzima (levomilnacipran) extended-release capsules package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.56041 - Trintellix (vortioxetine tablets) package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2021 Sept.56203 - Shin JG, Soukhova N, Flockhart DA. Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab Dispos 1999;27:1078-84.56303 - Zohydro ER (hydrocodone extended-release capsules) package insert. Morristown, NJ: Currax Pharmaceuticals LLC; 2021 Mar.56361 - Doxorubicin hydrochloride package insert. New York, NY: Pfizer Labs; 2013 Oct.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm56844 - Ereshefsky L, Saklad SR, Watanabe MD, et al. Thiothixene pharmacokinetic interactions; a study of hepatic enzyme inducers, clearance inhibitors, and demographic variable. J Clin Psychopharmacol 1991;11:296-301.57012 - Welage LS, Berardi RR. Drug interactions with anti-ulcer agents: considerations in the treatment of acid-peptic disease. J Pharm Pract. 1994;7:177-195.57151 - Zontivity (vorapaxar) package insert. Parsippany, NJ: Aralez Pharmaceuticals US Inc.; 2019 Nov.57267 - Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006;318:604-610.57468 - Sivextro (tedizolid) prescribing information. Whitehouse Station, NJ: Merck & Co. Inc.; 2021 Nov.57580 - Rolan PE. Drug interactions with triptans. Which are clinically significant? CNS Drugs 2012;26:949-57.57658 - Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341-1352. Epub 2011 Apr 8. Erratum in: Lancet. 2011;377:1494.57659 - O'Neill PM, Peterson, CA. Weight Loss and Depression in Overweight/Obese Subjects With a History of Depression Receiving Phentermine and Topiramate Extended-Release. Presented at the 166th Annual Meeting of the American Psychiatric Association (APA) San Francisco, CA; 2013 May 20. (unpublished).57660 - Allison DB, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330-342.57741 - Orbactiv (oritavancin) package insert. Lincolnshire, IL: Melinta Therapeutics, LLC; 2022 Jan.57789 - Ambien (zolpidem immediate-release tablets) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2022 Feb.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.57877 - Reglan (metoclopramide) oral tablet package insert. Baudette, MN: ANI Pharmaceuticals; 2020 Jun.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.58023 - Vasostrict (vasopressin injection) package insert. Chestnut Ridge, NY: Par Pharmaceutical Companies, Inc.; 2022 Dec.58104 - Girennavar B, Jayaprakasha GK, and Patil BS. Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. Journal of Food Science. 2007;72(8):C417-C421.58189 - Esbriet (pirfenidone) capsules and film-coated tablets package insert. South San Fransisco, CA: Genentech USA, Inc.; 2022 Feb.58195 - U.S. Food and Drug Administration 2006 July. FDA alert: Potentially life-threatening serotonin syndrome with combined use of SSRIs or SNRIs and triptan medications. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124915.htm. Accessed June 5, 2014.58685 - Savaysa (edoxaban) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2021 Apr.58770 - Gleevec (imatinib mesylate) tablet package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2022 Mar.58821 - Farydak (panobinostat) capsules package insert. Las Vegas, NV: Secura Bio, Inc.; 2021 Sept.59321 - CredibleMeds. QT drug lists. Available on the World Wide Web at http://www.crediblemeds.org.59322 - Howes LG. Cardiovascular effects of drugs used to treat alzheimer's disease. Drug Saf. 2014;37:391–395.59845 - Kengreal (cangrelor) injection. Cary, NC: Chiesi USA, Inc.; 2023 Jan.59857 - Fagiolini A, Buysse DJ, Frank E, et al. Tolerability of combined treatment with lithium and paroxetine in patients with bipolar disorder and depression. J Clin Psychopharmacol 2001;21:474-8.59860 - Sobanski T, Bagli M, Laux G, et al. Serotonin syndrome after lithium add-on medication to paroxetine. Pharmacopsychiatry 1997;30:106-7.59861 - Nelson JC, Baumann P, Delucchi K, et al. A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression. J Affect Disord 2014;168:269-75.59949 - Rexulti (brexpiprazole) tablets package insert. Rockville, MD: Otsuka America Pharmaceutical Inc; 2021 Dec.60002 - Technivie (ombitasvir; paritaprevir; ritonavir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.60142 - Varubi (rolapitant) package insert. Waltham, MA: Tesaro Inc; 2018 April.60196 - Aristada (aripiprazole lauroxil) extended-release intramuscular suspension package insert. Waltham, MA: Alkermes, Inc.; 2020 Feb.60270 - Belbuca (buprenorphine) buccal film package insert. BioDeliviery Sciences International, Inc.: Raleigh, NC; 2022 June.60634 - Oxaydo (oxycodone) immediate release tablets. Wayne, PA: Zyla Life Sciences US, Inc.; 2021 Mar.60860 - Byvalson (nebivolol and valsartan) tablets package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2016 Jun.60958 - Levorphanol tablet package insert. Solana Beach, CA: Sentynl Therapeutics, Inc.; 2021 Jan.60986 - Briciu C, Neag N, Muntean D, et al. A pharmacokinetic drug interaction study between nebivolol and paroxetine in healthy volunteers. J Clin Pharm Ther. 2014;29:535-540.61317 - Bem JL, Peck R: Dextromethorphan. An overview of safety issues. Drug Saf 1992;7(3):190-199.61721 - Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf 2008;7(5):587-596.61806 - Noctiva nasal spray (desmopressin acetate) package insert. Milford, PA: Serenity Pharmaceuticals LLC; 2017 Mar.61810 - DDAVP Rhinal Tube Nasal Solution (Desmopressin Acetate) package insert. Parsippany NJ: Ferring Pharmaceuticals, Inc.; 2014 Dec.61825 - Xadago (safinamide) package insert. Rockville, MD: MDD US Operations, LLC; 2021 Aug.61845 - Austedo (deutetrabenazine) tablets package insert. Parsippany, NJ: Teva Neuroscience, Inc.; 2022 May.61873 - Ingrezza (valbenazine) capsules package insert. San Diego, CA: Neurocrine Biosciences, Inc.; 2021 Apr.62037 - Bevyxxa (betrixaban) capsules package insert. South San Francisco, Ca: Portola Pharmaceuticals, Inc.; 2020 Aug.62067 - Ishii M, Tatsuzawa Y, Yoshino A, et al. Serotonin syndrome induced by augmentation of SSRI with methylphenidate. Psychiatry Clin Neurosci 2008;62:246.62068 - Park YM, Jung YK. Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:719-20.62069 - Turkoglu S. Serotonin syndrome with sertraline and methylphenidate in an adolescent. Clin Neuropharmacol 2015;38:65-6.62120 - Tremfya (guselkumab) injection package insert. Horsham, PA: Janssen Biotech, Inc.; 2020 Jul.62228 - Feder R. Reversal of Antidepressant Activity of Fluoxetine by Cyproheptadine in Three Patients. J Clin Psychiatry 1991; 52:163—4.62229 - Goldbloom DS, Kennedy SH. Adverse Interaction of Fluoxetine and Cyproheptadine in Two Patients With Bulimia Nervosa. J Clin Psychiatry 1991;52:261—2.62230 - Christensen RC. Adverse Interaction of Paroxetine and Cyproheptadine. J Clin Psychiatry 1995;56:433—4.62231 - McCormick S, Olin J, Brotman AW. Reversal of Fluoxetine-Induced Anorgasmia by Cyproheptadine in Two Patients. J Clin Psychiatry 1990;51:383—4.62457 - Caraci F, Sultana J, Drago F, et al. Clinically relevant drug interactions with anti-alzheimer's drugs. CNS Neurol Disord Drug Targets 2017;16:501-13.62889 - Apadaz (benzhydrocodone; acetaminophen) tablets package insert. Newton, PA: KVK-Tech, Inc.; 2021 Mar.62924 - Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: Expert Panel Recommendations. Am J Med 2013;126:S1-S42.63161 - Lucemyra (lofexidine) tablets package insert. Louisville, KY: US WorldMeds, LLC; 2018 May.63198 - Kapspargo sprinkle (metoprolol succinate) capsules extended-release package insert. Cranbury, NJ: Sun Pharmaceuticals Industries, Inc.; 2018 May.63256 - Desmopressin acetate nasal spray package insert. Mason, OH: Prasco Laboratories; 2018 May.63305 - Nocdurna (desmopressin acetate) sublingual tablets package insert. Parsippany, NJ: Ferring Pharmaceuticals Inc.; 2018 Jun.63328 - Aristada Initio (aripiprazole lauroxil extended-release injectable suspension) package insert. Altham, MA:Alkermes, Inc.; 2020 Feb.63411 - Perseris (risperidone extended-release subcutaneous injectable suspension) package insert. North Chesterfield, VA: Indivior, Inc.; 2022 Dec.63529 - Institute for Safe Medication Practices (ISMP). Acute Care ISMP Medication Safety Alert 2018;23:1-2.63584 - Vizimpro (dacomitinib) tablet package insert. New York, NY: Pfizer Labs; 2018 Sept.63589 - Soltamox (tamoxifen) oral solution package insert. Raleigh, NC: Midatech Pharma US Inc.; 2019 April.63787 - Xospata (gilteritinib) tablets package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2022 Jan.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.64280 - Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacol Bull. 2016;46:77-104. Review.64386 - Kalapatapu RK, Neugroschl JA. Update on neuropsychiatric symptoms of dementia: evaluation and management. Geriatrics 2009;64:20-26.64562 - Wakix (pitolisant) tablets package insert. Plymouth Meeting, PA: Harmony Biosciences, LLC; 2022 Dec.64568 - Inrebic (fedratinib) capsules package insert. Summit, NJ: Celgene Corporation; 2021 Dec.64685 - Reyvow (lasmiditan) tablets package insert. Indianapolis, IN: Eli Lilly and Company; 2022 Sep.64762 - Givlaari (givosiran) injection package insert. Cambridge, MA: Alnylam Pharmaceuticals, Inc.; 2021 Oct.65098 - Isturisa (osilodrostat) tablet package insert. Lebanon, NJ: Recordati Rare Disease, Inc.; 2020 Mar.65169 - Ozanimod (Zeposia) capsules package insert. Summit, NJ: Celgene Corporation; 2022 Sept.65614 - Gimoti (metoclopramide) nasal spray package insert. Solana Beach, CA: Evoke Pharma, Inc.; 2021 Jan.65634 - Fintepla (fenfluramine) oral solution package insert. Emeryville CA: Zogenix, Inc.; 2023 Jan.65809 - Olinvyk (oliceridine) injection package insert. Chesterbrook, PA: Trevana, Inc. 2021 Mar.65995 - Keepers GA, Fochtmann LJ, Anzia JM, et al; (Systematic Review). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Focus (Am Psychiatr Publ). 2020;18:493-497. Epub 2020 Nov 5.66159 - Orladeyo (berotralstat) package insert. Durham, NC;BioCryst Pharmaceuticals, Inc.: 2020 Dec.66501 - Azstarys (serdexmethylphenidate and dexmethylphenidate) package insert. Grand Rapids, MI: Corium; 2021 March.66575 - Qelbree (viloxazine) extended-release capsules package insert. Rockville, MD: Supernus Pharmaceuticals, Inc.; 2022 Apr.68325 - Krazati (adagrasib) tablets package insert. San Diego, CA: Mirati Therapeutics, Inc.; 2022 Dec.

    Monitoring Parameters

    • blood pressure
    • growth rate
    • heart rate
    • thyroid function tests (TFTs)
    • weight

    US Drug Names

    • Brisdelle
    • Paxil
    • Paxil CR
    • Pexeva
    ;