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Jan.22.2020

Bupropion

Indications/Dosage

Labeled

  • depression
  • seasonal affective disorder (SAD)
  • tobacco cessation

Off-Label

  • attention-deficit hyperactivity disorder (ADHD)
  • diabetic neuropathy
  • neuropathic pain
  • postherpetic neuralgia
† Off-label indication

For the treatment of major depression

Oral dosage (immediate-release bupropion hydrochloride tablets; e.g., Wellbutrin)

Adults

Initially, 100 mg PO twice daily; titrate after no less than 3 days to 100 mg PO 3 times per day if needed; no single dose should exceed 150 mg. The onset of antidepressant effects takes 1 to 3 weeks, maximal effect may not be noted for 4 weeks. Generally, acute episodes of depression require several months of sustained pharmacologic Reassess the patient periodically to determine the individual need for continued treatment. Use the lowest dosage that maintains remission.[41086]

Children† and Adolescents† 6 years and older

Dosage not established. Suggested dosage ranges from 1.4 to 6 mg/kg/day PO, titrated upward slowly and administered in divided doses. In trials, the average effective dose is roughly 3 mg/kg/day PO; the maximum dosage is generally 250 to 300 mg/day PO. Safety data are not extensive; most patients have also been diagnosed with ADHD.[25844]

Oral dosage (sustained-release bupropion hydrochloride tablets; e.g., Wellbutrin SR)

Adults

Initially, 150 mg PO once daily in the morning; titrate after no less than 4 days to 150 mg PO twice daily if needed. After several weeks, titrate to 200 mg PO twice daily if needed; administer doses at least 8 hours apart. The onset of antidepressant effects takes 1 to 3 weeks, maximal effect may not be noted for 4 weeks. Use the lowest dose that maintains remission.[40993]

Adolescents†

Limited data are available. Dosing may be weight based or may use a non-weight based titration similar to adults. One trial used initial doses up to 2 mg/kg (not to exceed 100 mg) PO once daily in the morning, followed by gradual titration to 3 mg/kg/dose every morning with 2 mg/kg/dose every evening at dinner. If needed, further titration to 3 mg/kg/dose PO twice daily occurred. Single doses of bupropion SR could not exceed 150 mg/dose. Max dose: 6 mg/kg/day PO, in divided doses.[62394] Other studies have used flat doses for titration. Initially, 150 mg PO once daily in the morning; titrate after no less than 4 days to 150 mg PO twice daily if needed. After several weeks, titrate to 200 mg PO twice daily if needed with doses at least 8 hours apart. In a small, 8-week open-label trial (n = 8), adolescents with major depression were given a mean dose of 362 mg/day PO of bupropion SR after titration; this regimen was effective as assessed by the expanded Hamilton Depression Rating Scale (SIGH-SAD). Insomnia and weight loss are common.[32355] Due to more rapid metabolism of bupropion SR in adolescents compared to adults, total daily doses in the adolescent age group should be given in 2 divided doses.

Oral dosage (extended-release bupropion hydrochloride tablets; e.g., Wellbutrin XL)

Adults

Initially, 150 mg PO once daily in the morning. After no less than 4 days, titrate to the usual target dose of 300 mg PO once daily in the morning based upon patient response and tolerance. Due to a dose-related risk of seizures, gradually titrate.Max: 450 mg PO once daily. When discontinuing treatment, doses of 300 mg/day or more should be tapered to 150 mg PO once daily prior to discontinuation.[41057]

Oral dosage (extended-release bupropion hydrobromide (HBr) tablets; e.g., Aplenzin)

Adults

174 mg PO once daily in the morning for initial dose. May be increased to the target dose of 348 mg PO once daily beginning on day 4 of treatment, if tolerated. If response is inadequate after several weeks at 348 mg/day, the dose may be increased to a maximum of 522 mg PO once daily in the morning. There should be a minimum interval of 24 hours between doses. As with many other antidepressants, the full therapeutic effect may not be evident for at least 4 weeks of treatment. For maintenance, use the lowest dosage that maintains remission. Periodically reassess to determine the need for continued treatment. When switching to Aplenzin from Wellbutrin, Wellbutrin SR, or Wellbutrin XL, use the equivalent total daily dose when possible (174 mg of bupropion HBr = 150 mg bupropion HCl; 348 mg of bupropion HBr = 300 mg bupropion HCl; 522 mg bupropion HBr = 450 mg bupropion HCl).

Oral dosage (extended-release bupropion tablets; i.e., Forfivo XL)

Adults

Not for initial treatment, due to fixed high dosage. Give 450 mg PO once per day, after titration with another product. Forfivo XL may be implemented in patients who are currently receiving 300 mg/day of another bupropion formulation for at least 2 weeks and who require an increased dosage. May also switch patients who are receiving other bupropion products at a dose of 450 mg/day to Forfivo XL. Geriatric patients may have decreased renal function which may affect tolerability to the fixed high dosage; monitoring of renal function in geriatric patients is suggested.[46944]

For the prevention of seasonal major depressive disorder episodes associated with seasonal affective disorder (SAD)

Oral dosage (extended-release bupropion hydrochloride tablets; e.g., Wellbutrin XL):

Adults

Initiate in the autumn prior to the onset of depressive symptoms with 150 mg PO once daily in the morning. After 7 days, the dose may be increased to the target dose of 300 mg PO once daily in the morning if tolerated. Continue through the winter season. Taper and discontinue in early spring. For patients receiving 300 mg/day, taper to 150 mg/day prior to discontinuation. Total daily doses above 300 mg/day PO were not evaluated in seasonal affective disorder (SAD) trials. The start and duration of treatment should be individualized based on the patient's historical pattern of seasonal major depressive episodes. Patients whose seasonal depressive episodes are infrequent or not associated with significant impairment should not generally be treated prophylactically.[41057]

Oral dosage (extended-release bupropion hydrobromide; i.e., Aplenzin)

Adults

Initially, 174 mg PO once daily in the morning. After 7 days, the dose may be increased to the target dose of 348 mg PO once daily. Total daily doses above 348 mg/day PO were not evaluated in clinical trials for seasonal affective disorder (SAD). Treatment should be individualized based upon the patient's pattern of seasonal major depressive disorder (MDD) episodes. For prevention of seasonal MDD episodes associated with SAD, initiate therapy in the autumn prior to the onset of depressive symptoms. Continue through winter, then taper and discontinue in early spring. For patients receiving 348 mg/day, the dose should be tapered to 174 mg/day before discontinuation.[44095]

For use as an adjunct to psychosocial interventions in the management of tobacco cessation (smoking cessation)

For the treatment of attention-deficit hyperactivity disorder (ADHD)†

For the symptomatic treatment of neuropathic pain† due to various causes, including pain associated with peripheral diabetic neuropathy† or postherpetic neuralgia†

Oral dosage (sustained-release bupropion HCl tablets; e.g., Wellbutrin SR)

Adults

In one trial, 150—300 mg/day PO was reported effective; 73% of patients receiving bupropion reported improvement in pain versus 10% with placebo. Patients began to experience pain relief at week 2 of treatment.[26722]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    Immediate-release tablets: 450 mg/day PO, no single dose should exceed 150 mg.

    Wellbutrin SR: 400 mg/day PO; no single dose should exceed 200 mg.

    Zyban: 300 mg/day PO for smoking cessation; no single dose should exceed 150 mg.

    Wellbutrin XL: 450 mg/day PO.

    Aplenzin: 522 mg/day PO; no single dose should exceed 522 mg.

    Forfivo XL: 450 mg/day PO.

  • Geriatric

    Immediate-release tablets: 450 mg/day PO, no single dose should exceed 150 mg.

    Wellbutrin SR: 400 mg/day PO; no single dose should exceed 200 mg.

    Zyban: 300 mg/day PO for smoking cessation; no single dose should exceed 150 mg.

    Wellbutrin XL: 450 mg/day PO.

    Aplenzin: 522 mg/day PO; no single dose should exceed 522 mg.

    Forfivo XL: 450 mg/day PO.

  • Adolescents

    Safety and efficacy have not been established; however, a total daily dosage up to 300 mg/day PO for immediate-release tablets has been suggested for the treatment of attention-deficit hyperactivity disorder (ADHD); doses up to 6 mg/kg/day (not to exceed 300 or 400 mg/day) PO of the bupropion SR products have been used in studies for treatment of depression.

  • Children

    6 to 12 years: Safety and efficacy have not been established; however, a total daily dosage up to 300 mg/day PO for immediate-release tablets has been suggested for the treatment of attention-deficit hyperactivity disorder (ADHD).

    5 years and younger: 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

In patients with moderate to severe hepatic impairment (Child-Pugh Score 7—15), initiate therapy at a lower dosage and do not exceed 75 mg/day PO of immediate-release Wellbutrin, 100 mg/day or 150 mg every other day of Wellbutrin SR, 150 mg every other day of Zyban or Wellbutrin XL, or 174 mg every other day of Aplenzin. Consider reduced dosage or dosage frequency in patients with mild hepatic impairment (Child-Pugh Score 5—6); however, no guidelines are available.[41057][41086][44095][44094] Use of Forfivo XL, a 450 mg extended-release tablet formulation, is not recommended in patients with hepatic impairment since there is no lower dose strength.[46944]

Patients with Renal Impairment Dosing

Consider reduced dosage and/or dosage frequency in patients with a CrCl < 90 mL/min; specific recommendations are not available. Bupropion and its metabolites are renally eliminated and may accumulate in patients with renal impairment.[41057][41086][44095][44094] Use of Forfivo XL, a 450 mg extended-release tablet formulation, is not recommended in patients with renal impairment because there is no lower dose strength.[46944]

† Off-label indication
Revision Date: 01/22/2020, 12:43:58 PM

References

24871 - Hurt RD, Sachs DPL, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997;337:1195-202.25844 - McConville BJ, Chaney RO, Browne KL, et al. Newer antidepressants-beyond selective serotonin reuptake inhibitor antidepressants. Pediatr Clin North Am 1998;45:1157-1171.25849 - Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-691.25850 - Conners CK, Casat CD, Gualtieri CT, et al. Bupropion versus methylphenidate for the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 1995;34:649-657.25851 - Barrickman LL, Perry PJ, Allen AJ, et al. Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry 1996;35:1314-1321.26722 - Semenchuk MR, Sherman S, Davis B. Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Neurology 2001;57:1583-1588.31600 - Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry 2005;57:793-801.31603 - Conners CK, Casat CD, Gualtieri CT, et al. Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry 1996;35:1314-21.32355 - Glod CA, Lynch A, Flynn E, et al. Open trial of bupropion SR in adolescent major depression. J Child Adolesc Psychiatr Nurs 2003;16:123-30.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.44094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2021 July.45900 - Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007;46(7):894-921.46924 - American Academy of Pediatrics subcommittee on attention-deficit/hyperactivity disorder, steering committee on quality improvement and management. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 2019;144(4):e20192528.46944 - Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.58374 - Kuperman S, Perry PJ, Gaffney GR, et al. Bupropion SR vs methylphenidate vs placebo for attention deficit hyperactivity disorder in adults. Ann Clin Psychiatry 2001;13(3):129-134.60873 - Maneeton N, Maneeton B, Intaprasert S, et al. A systematic review of randomized controlled trials of bupropion versus methylphenidate in the treatment of attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2014;10:1439-1449.60888 - Torgersen T, Gjervan B, Lensing MB, et al. Optimal management of ADHD in older adults. Neuropsychiatr Dis Treat. 2016;12:79-87.62394 - Daviss WB, Bentivoglio P, Racusin R, et al. Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivitydisorder and depression. J Am Acad Child Adolesc Psychiatry. 2001;40:307-314.62710 - Leischow SJ, Muramoto ML, et al. Adolescent Smoking Cessation With Bupropion: The Role of Adherence. Nicotine Tob Res. 2016;18:1202-1205.62711 - Gray KM, Carpenter MJ, Baker NL, et al. Bupropion SR and contingency management for adolescent smoking cessation. J Subst Abuse Treat. 2011;40:77-86.62712 - Fanshawe TR, Halliwell W, Lindson N, et al. Tobacco cessation interventions for young people. Cochrane Database Syst Rev. 2017 Nov 17;11:CD003289.64946 - Ng QX. A Systematic Review of the Use of Bupropion for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. J Child Adolesc Psychopharmacol. 2017;27:112-116. Epub 2016 Nov 4. Review.

How Supplied

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 174mg Extended-Release Tablet (00024-5810) (Bausch Health US, LLC) (off market)

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 174mg Extended-Release Tablet (00187-5810) (Bausch Health US, LLC) null

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 174mg Extended-Release Tablet (00024-5810) (Sanofi U.S. LLC) (off market)

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 348mg Extended-Release Tablet (00024-5811) (Bausch Health US, LLC) (off market)

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 348mg Extended-Release Tablet (00187-5811) (Bausch Health US, LLC) null

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 348mg Extended-Release Tablet (00024-5811) (Sanofi U.S. LLC) (off market)

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 522mg Extended-Release Tablet (00024-5812) (Bausch Health US, LLC) (off market)

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 522mg Extended-Release Tablet (00187-5812) (Bausch Health US, LLC) null

Bupropion Hydrobromide Oral tablet, extended release

Aplenzin 522mg Extended-Release Tablet (00024-5812) (Sanofi U.S. LLC) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (60687-0340) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (60505-0158) (Apotex Corp) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (23155-0191) (Avet Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (50268-0142) (AvPAK; a Division of AvKARE Inc) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (68001-0199) (BluePoint Laboratories) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (68001-0308) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (69097-0917) (Cipla USA, Inc) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (60429-0746) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00904-5914) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00904-6093) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00904-6635) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullBupropion Hydrochloride 75mg Tablet package photo

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (63739-0706) (McKesson Packaging) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (51079-0943) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00378-0433) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (43063-0284) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (43063-0880) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (64980-0201) (Rising Pharmaceuticals Inc) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00781-1053) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 75mg Tablet (00093-0280) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Wellbutrin 75mg Tablet (00173-0177) (GlaxoSmithKline Group of Companies) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (60687-0351) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (60505-0157) (Apotex Corp) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (23155-0192) (Avet Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (50268-0143) (AvPAK; a Division of AvKARE Inc) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (68001-0198) (BluePoint Laboratories) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (68001-0309) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (69097-0918) (Cipla USA, Inc) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (60429-0747) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00904-5913) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00904-6129) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00904-6636) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullBupropion Hydrochloride 100mg Tablet package photo

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (51079-0944) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00378-0435) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (66267-0614) (NuCare Pharmaceuticals Inc) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (55289-0733) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (43063-0994) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (72789-0070) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (64980-0202) (Rising Pharmaceuticals Inc) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00781-1064) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Tablet (00093-0290) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]

Wellbutrin 100mg Tablet (00173-0178) (GlaxoSmithKline Group of Companies) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Budeprion SR 100mg Extended-Release Tablet (00093-5501) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (68084-0470) (American Health Packaging) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (68084-0697) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (69097-0877) (Cipla USA, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (43598-0536) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (43598-0751) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (60429-0216) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (59746-0315) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (51079-0391) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (00378-3411) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (16714-0334) (Northstar Rx LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (10370-0159) (Par Pharmaceuticals, an Endo Company) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (72789-0158) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (77771-0174) (Radha Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (00185-0410) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (50228-0174) (ScieGen Pharmaceuticals, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (70436-0058) (Slate Run Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (43547-0288) (Solco Healthcare US LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (47335-0736) (Sun Pharmaceutical Industries, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (00591-0858) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (00591-3540) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (67767-0171) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (00591-3540) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (13668-0430) (Torrent Pharma, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 100mg Extended-Release (SR) Tablet (64679-0101) (Wockhardt USA, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Wellbutrin SR 100mg Extended-Release Tablet (00173-0947) (GlaxoSmithKline Group of Companies) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Budeprion SR 150mg Extended-Release Tablet (00093-5502) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (68084-0471) (American Health Packaging) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (68084-0708) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (69097-0878) (Cipla USA, Inc) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43598-0537) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43598-0752) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (60429-0217) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (59746-0316) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00904-6585) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (63739-0714) (McKesson Packaging) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (51079-0392) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00378-3412) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (16714-0335) (Northstar Rx LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (10370-0160) (Par Pharmaceuticals, an Endo Company) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43063-0243) (PD-Rx Pharmaceuticals, Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43063-0503) (PD-Rx Pharmaceuticals, Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43063-0744) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43063-0913) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (77771-0175) (Radha Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (33358-0364) (RxChange Co.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00185-0415) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (50228-0175) (ScieGen Pharmaceuticals, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (70436-0059) (Slate Run Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43547-0289) (Solco Healthcare US LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (47335-0737) (Sun Pharmaceutical Industries, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00591-0839) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00591-0839) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (67767-0133) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00591-3541) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (13668-0431) (Torrent Pharma, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (64679-0105) (Wockhardt USA, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Wellbutrin SR 150mg Extended-Release Tablet (00173-0135) (GlaxoSmithKline Group of Companies) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Wellbutrin SR 150mg Extended-Release Tablet (55289-0905) (PD-Rx Pharmaceuticals, Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (69097-0879) (Cipla USA, Inc) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (43598-0538) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (43598-0753) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (60429-0218) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (00115-5445) (Impax Generics, a division of Impax Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (59746-0317) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (00378-3413) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (16714-0336) (Northstar Rx LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (10370-0161) (Par Pharmaceuticals, an Endo Company) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (43063-0183) (PD-Rx Pharmaceuticals, Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (77771-0176) (Radha Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (00185-1111) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (50228-0176) (ScieGen Pharmaceuticals, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (70436-0060) (Slate Run Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (43547-0290) (Solco Healthcare US LLC) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (47335-0738) (Sun Pharmaceutical Industries, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (00591-3385) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (00591-3542) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (67767-0135) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (13668-0432) (Torrent Pharma, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 200mg Extended-Release (SR) Tablet (64679-0107) (Wockhardt USA, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Depression/Mood Disorders]

Wellbutrin SR 200mg Extended-Release Tablet (00173-0722) (GlaxoSmithKline Group of Companies) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Buproban 150mg Extended-Release Tablet (00093-5703) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (43598-0863) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00378-5521) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (65084-0414) (Rx Pak Div of Mckesson Corp) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00781-1529) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00781-5169) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00591-0867) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (67767-0117) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet (00591-3543) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Bupropion Hydrochloride 150mg Extended-Release (SR) Tablet Kit (00591-0867) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 12 hour [Smoking Cessation]

Zyban 150mg Sustained-Release Tablet (00173-0556) (GlaxoSmithKline Group of Companies) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Budeprion XL 150mg Extended-Release Tablet (00093-5350) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (16729-0443) (Accord Healthcare, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68084-0251) (American Health Packaging) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68084-0251) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (60687-0146) (American Health Packaging) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (60687-0312) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (42291-0182) (AvKARE, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (50268-0140) (AvPAK; a Division of AvKARE Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (70377-0034) (Biocon Pharma Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68001-0261) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68001-0287) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68001-0322) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (69097-0875) (Cipla USA, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (43598-0655) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (42806-0348) (Epic Pharma LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (60429-0357) (Golden State Medical Supply, Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (60429-0933) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (51407-0206) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (00115-6811) (Impax Generics, a division of Impax Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (59746-0758) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68180-0319) (Lupin Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (10135-0703) (Marlex Pharmaceuticals) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (63739-0449) (McKesson Packaging Inc) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (51079-0047) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (00378-2008) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (10370-0101) (Par Pharmaceuticals, an Endo Company) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (43063-0387) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (72789-0120) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (00781-5528) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (50228-0144) (ScieGen Pharmaceuticals, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (70436-0010) (Slate Run Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (63304-0723) (Sun Pharmaceutical Industries, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (67767-0141) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (00591-3331) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (67767-0141) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (45963-0141) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (24979-0101) (TWi Pharmaceuticals USA, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (69367-0288) (Westminster Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (64679-0102) (Wockhardt USA, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 150mg Extended-Release (XL) Tablet (68382-0353) (Zydus Pharmaceuticals (USA) Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 150mg Extended-Release Tablet (00173-0730) (Bausch Health US, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 150mg Extended-Release Tablet (64455-0730) (Bausch Health US, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 150mg Extended-Release Tablet (00187-0730) (Bausch Health US, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 150mg Extended-Release Tablet (00173-0730) (GlaxoSmithKline Group of Companies) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 150mg Extended-Release Tablet (55289-0922) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Budeprion XL 300mg Extended-Release Tablet (00093-5351) (Teva Pharmaceuticals USA) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (16729-0444) (Accord Healthcare, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (68084-0252) (American Health Packaging) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (42291-0183) (AvKARE, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (50268-0141) (AvPAK; a Division of AvKARE Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (70377-0035) (Biocon Pharma Inc.) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (68001-0264) (BluePoint Laboratories) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (68001-0321) (BluePoint Laboratories) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (69097-0876) (Cipla USA, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (43598-0656) (Dr. Reddy's Laboratories, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (42806-0349) (Epic Pharma LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (76282-0481) (Exelan Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (60429-0358) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (51407-0207) (Golden State Medical Supply, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (68180-0320) (Lupin Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (00904-6573) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (10135-0704) (Marlex Pharmaceuticals) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (63739-0450) (McKesson Packaging Inc) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (51079-0109) (Mylan Institutional LLC ) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (00378-2009) (Mylan Pharmaceuticals Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (10370-0102) (Par Pharmaceuticals, an Endo Company) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (43063-0388) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (72789-0112) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (00781-5529) (Sandoz Inc. a Novartis Company) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (50228-0145) (ScieGen Pharmaceuticals, Inc) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (70436-0011) (Slate Run Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (63304-0724) (Sun Pharmaceutical Industries, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (00591-3332) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (67767-0142) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (67767-0142) (Teva/Actavis US) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (45963-0142) (Teva/Actavis US) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (24979-0102) (TWi Pharmaceuticals USA, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (69367-0289) (Westminster Pharmaceuticals, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 300mg Extended-Release (XL) Tablet (68382-0354) (Zydus Pharmaceuticals (USA) Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 300mg Extended-Release Tablet (00173-0731) (Bausch Health US, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 300mg Extended-Release Tablet (64455-0731) (Bausch Health US, LLC) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 300mg Extended-Release Tablet (00187-0731) (Bausch Health US, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 300mg Extended-Release Tablet (00173-0731) (GlaxoSmithKline Group of Companies) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Wellbutrin XL 300mg Extended-Release Tablet (55289-0900) (PD-Rx Pharmaceuticals, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 450mg Extended-Release (XL) Tablet (47781-0637) (Alvogen, Inc.) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Bupropion Hydrochloride 450mg Extended-Release (XL) Tablet (64679-0830) (Wockhardt USA, LLC) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Forfivo XL 450mg Extended-Release Tablet (49909-0010) (Almatica Pharma, a subsidiary of Alvogen) (off market)

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Forfivo XL 450mg Extended-Release Tablet (52427-0575) (Almatica Pharma, a subsidiary of Alvogen) null

Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]

Forfivo XL 450mg Extended-Release Tablet (49909-0010) (Edgemont Pharmaceuticals, LLC.) (off market)

Description/Classification

Description

Bupropion is an oral antidepressant drug of the aminoketone class. It is not a tricyclic antidepressant and is unrelated to other known antidepressants. Bupropion has been well tolerated in patients experiencing orthostatic hypotension with tricyclic antidepressant drugs, however, it shows a greater potential for causing seizures than other antidepressants.[23945] Bupropion is also indicated for use as an aide to smoking cessation, and is used off-label for addiction to smokeless tobacco. The drug has been shown to help people with COPD quit smoking when combined with behavior modification. Bupropion is also used off-label for multiple neurological/psychological uses, including ADHD [31600] and neuropathic pain [26722]. Bupropion hydrochloride was originally approved by the FDA in December 1985 but was removed from marketing for several years due to concern over drug-induced seizures. It was reintroduced in July 1989 as an antidepressant (i.e., Wellbutrin), and later in a sustained-release formulation (i.e., Wellbutrin SR). Another sustained-release oral dosage form, Zyban, was approved for the management of smoking cessation in May 1997. Zyban received an additional indication for use in combination with nicotine transdermal systems (NTS) for treating the symptoms of smoking cessation in 1999. A controlled-release formulation (Wellbutrin XL) was approved in August 2003 as a once-daily formulation for major depression in adults.[31615][31616][31617] In June 2006, Wellbutrin XL was FDA-approved for prevention of major depressive episodes in patients with a history of seasonal affective disorder (SAD). Wellbutrin XL is the first prescription product approved for patients with a history of SAD.[32323] In April 2008, a once-daily formulation of bupropion hydrobromide (Aplenzin) was approved by the FDA for depression, and in August 2012 Aplenzin was approved for the prevention of seasonal major depressive episodes in patients with SAD. Aplenzin differs from all previously marketed formulations which are the hydrochloride salt of bupropion.

Classifications

  • Central Nervous System
    • Other CNS Agents
      • Antismoking Agents
    • Psychoanaleptics Excluding Anti-obesity Agents
      • Anti-depressants and Mood Stabilizers
        • Miscellaneous Antidepressants
Revision Date: 08/21/2012, 09:48:34 AM

References

23945 - Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacotherapy 1992;12:18-22.26722 - Semenchuk MR, Sherman S, Davis B. Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Neurology 2001;57:1583-1588.31600 - Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry 2005;57:793-801.31615 - Institute for Clinical Systems Improvement (ICSI). Major depression in adults for mental health care. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 May. Available on the World Wide Web at www.guideline.gov31616 - Care Management Institute, Kaiser Permanente. Adult primary care depression guidelines. Oakland (CA): Kaiser Permanente; 2004 Apr. Retrieved October 27, 2005. Available on the World Wide Web at www.guidelines.gov31617 - American Psychiatric Association. Practice guidelines for the treatment of patients with major depressive disorder. Am J Psychiatry 2000;157(4 Suppl):1-45.32323 - Modell JG, Rosenthal NE, Harriett AE, et al. Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biol Psychiatry 2005;58:658-67.

Administration Information

General Administration Information

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

  • A MedGuide is available which informs patients about the increased risk of suicidal thoughts and behaviors in children and young adults during early phase treatment with antidepressants.

Route-Specific Administration

Oral Administration

  • May administer with food, if needed to minimize gastric upset.
  • To avoid or limit the risk of insomnia, do not administer doses at bedtime.
  • Given that there are multiple dosing regimens and 2 salt forms of bupropion available, it is important to be familiar with each product's name and dosing schedule to avoid dosing errors.
  • It is advisable to follow the dosing instructions provided by each manufacturer to limit the risk of seizures or other adverse effects.

Oral Solid Formulations

  • Wellbutrin immediate-release bupropion hydrochloride tablets: It is advisable to separate doses by at least 6 hours. The total daily dose is usually administered in three divided doses.
  • Wellbutrin SR sustained-release bupropion hydrochloride tablets: It has been suggested that the tablets may be cut in half once, if needed, just prior to administration [25848]; however, the manufacturer states that the tablets should be swallowed whole and should not be cut, chewed, or crushed since this may lead to an increased risk of adverse effects including seizures.[40993] If multiple doses are administered daily, each dose should be given at least 8 hours apart.
  • Wellbutrin XL extended-release bupropion hydrochloride tablets: Do not chew, cut, or crush tablets since this may lead to an increased risk of adverse effects including seizures.[41057] Administer once daily, preferably in the morning.
  • Zyban sustained-release bupropion hydrochloride tablets: Do not crush, divide, or chew tablets. The total daily dose is usually administered in two divided doses. Each dose should be given at least 8 hours apart.
  • Aplenzin extended-release bupropion hydrobromide tablets: Do not chew, cut, or crush tablets. Administer once daily in the morning. It should be noted that the molecular weight of the hydrobromide salt is higher than the hydrochloride salt; therefore, a larger total mg dose of Aplenzin is needed to provide the same amount of active drug.
  • Forfivo XL, extended-release high dose bupropion hydrochloride tablets: Tablets should be swallowed whole. Do not crush, divide, or chew.[46944] Administer once daily, preferably in the morning.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
Revision Date: 11/30/2011, 06:25:22 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

References

25848 - Cochren BE. Splitting bupropion extended-release tablets. Am J Health-Syst Pharm 1999;56:575.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.46944 - Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.

Adverse Reactions

Mild

  • abdominal pain
  • abnormal dreams
  • acne vulgaris
  • agitation
  • alopecia
  • anorexia
  • anxiety
  • appetite stimulation
  • arthralgia
  • asthenia
  • back pain
  • chills
  • cough
  • dental pain
  • diarrhea
  • diplopia
  • dizziness
  • drowsiness
  • drug-induced body odor
  • dysgeusia
  • dysmenorrhea
  • dyspepsia
  • ecchymosis
  • emotional lability
  • epistaxis
  • fatigue
  • fever
  • flatulence
  • flushing
  • gastroesophageal reflux
  • gingivitis
  • gynecomastia
  • hair discoloration
  • headache
  • hirsutism
  • hyperhidrosis
  • hyperkinesis
  • hypersalivation
  • increased urinary frequency
  • infection
  • influenza
  • insomnia
  • irritability
  • lethargy
  • leukocytosis
  • libido decrease
  • libido increase
  • maculopapular rash
  • malaise
  • menstrual irregularity
  • muscle cramps
  • myalgia
  • mydriasis
  • nasal congestion
  • nausea
  • nocturia
  • pallor
  • paranoia
  • paresthesias
  • pharyngitis
  • photosensitivity
  • polydipsia
  • polyuria
  • pruritus
  • rash
  • restlessness
  • rhinitis
  • sinusitis
  • syncope
  • tinnitus
  • tremor
  • urinary urgency
  • urticaria
  • vaginal irritation
  • vertigo
  • vomiting
  • weight gain
  • weight loss
  • xerophthalmia
  • xerosis
  • xerostomia

Moderate

  • akathisia
  • amnesia
  • anemia
  • aphasia
  • ataxia
  • blurred vision
  • chest pain (unspecified)
  • colitis
  • confusion
  • constipation
  • cystitis
  • delirium
  • depression
  • dysarthria
  • dyskinesia
  • dyspareunia
  • dysphagia
  • dysphoria
  • dyspnea
  • dystonic reaction
  • dysuria
  • edema
  • EEG changes
  • ejaculation dysfunction
  • elevated hepatic enzymes
  • esophagitis
  • euphoria
  • glossitis
  • glycosuria
  • hallucinations
  • hepatitis
  • hostility
  • hot flashes
  • hyperglycemia
  • hypertension
  • hypertonia
  • hypoglycemia
  • hyponatremia
  • hypotension
  • impotence (erectile dysfunction)
  • jaundice
  • leukopenia
  • lymphadenopathy
  • mania
  • memory impairment
  • migraine
  • myasthenia
  • myoclonia
  • neuropathic pain
  • oral ulceration
  • orthostatic hypotension
  • palpitations
  • peripheral edema
  • peripheral vasodilation
  • phlebitis
  • pseudoparkinsonism
  • psychosis
  • sinus tachycardia
  • stomatitis
  • teeth grinding (bruxism)
  • testicular swelling
  • thrombocytopenia
  • urinary incontinence
  • urinary retention
  • vaginal bleeding

Severe

  • akinesia
  • anaphylactic shock
  • anaphylactoid reactions
  • angioedema
  • AV block
  • bronchospasm
  • coma
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  • erythema multiforme
  • exfoliative dermatitis
  • GI bleeding
  • GI perforation
  • hearing loss
  • myocardial infarction
  • neonatal abstinence syndrome
  • ocular hypertension
  • pancreatitis
  • pancytopenia
  • pulmonary embolism
  • rhabdomyolysis
  • seizures
  • serotonin syndrome
  • serum sickness
  • SIADH
  • Stevens-Johnson syndrome
  • stroke
  • suicidal ideation
  • tardive dyskinesia
  • Tourette's syndrome

Bupropion exhibits a greater potential for causing seizures than other antidepressants; the incidence of seizures with bupropion exceeds that of other commercially available antidepressants by up to 4-fold.[23945] [41086] The incidence of seizures occurring with bupropion is dose-dependent. Seizures occur in roughly 0.1% of patients receiving up to 300 mg/day (sustained-release) and 0.4% of patients receiving up to 450 mg/day (immediate-release) of bupropion. According to the manufacturer, the incidence of seizures in patients taking Wellbutrin XL as a single dose of 450 mg is 0.4%. Although seizure incidence has not been evaluated in clinical trials of the extended-release formulation of bupropion, its bioequivalence with the immediate-release and sustained-release formulations suggests that the risk may be similar to that encountered with use of these products. The incidence of seizures rises disproportionately at dosages > 450 mg/day (immediate-release).[23945] In patients receiving a 600-mg/day immediate-release regimen of bupropion, the risk of seizures was estimated to be 10-fold that of patients administered the 450-mg maximum daily recommended dose. The incidence of seizures during use of bupropion hydrobromide (Aplenzin) has not been formally evaluated by the manufacturer. To limit the risk of seizures, recommended single or maximum daily dosages of any dosage form of bupropion should not be exceeded. Some patients may be more at risk of experiencing seizures with bupropion therapy. The use or withdrawal of some medication regimens, including ethanol, may lower seizure threshold; these should be utilized cautiously with bupropion. When possible, concomitant use of these medications with bupropion should be avoided.[40993] [41057] [41086] [44094] [44095]

During clinical trials of immediate-release or extended-release bupropion formulations, the following centrally-mediated effects occurred more frequently with bupropion that placebo: insomnia (11—31% vs 6—21%), dizziness (6—11% vs 5—7%), tremor (2—21.1% vs < 1—7.6%), drowsiness (2—3% vs 1—2%), sedation or lethargy (19.8% vs 19.5%), cutaneous temperature disturbance (1.9% vs 1.6%), headache (25—34% vs 22.2—26%), migraine (1—25.7% vs 1—22.2%), impaired sleep quality (4% vs 1.6%), paresthesias (1—2% vs 1%), CNS stimulation or restlessness (1—2% vs 1%), and feeling jittery (3% vs 2%). In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following CNS effects and incidences were reported: insomnia (40%, 28%, 45%, 18%) and nervousness (1%, < 1%, 2%, 0%). The incidence of ataxia/incoordination ranged from < 0.1% to >= 1% of patients during pre-marketing or post-marketing use of bupropion. CNS effects reported in 0.1—1% of patients included vertigo, dysarthria, abnormal coordination, CNS stimulation, hypesthesia, and paresthesias. Rarely reported effects (< 0.1%) included EEG changes, abnormal neurological exam, impaired attention, and aphasia. Also observed were coma, neuralgia (neuropathic pain), neuropathy, and restlessness. Some symptoms may be dose-related and may respond to dosage reduction. To limit insomnia, do not give doses close to bedtime. In some cases these symptoms may require treatment with sedative/hypnotic therapy. In roughly 2% of patients treated, CNS symptoms will necessitate drug discontinuation.[40993] [41057] [41086] [44094] [44095]

All effective antidepressants can precipitate mania in predisposed individuals suffering from bipolar disorder. Mania and hypomania have been reported in 1% or more of bupropion recipients during clinical trials. Hypomania was reported rarely (less than 0.1%) during other pre-marketing evaluations. If mania occurs, bupropion should be held and appropriate therapy to treat the manic symptoms should be initiated.[40993] [41057] [41086] [44094] [44095]

Psychiatric effects reported more frequently with immediate-release or extended-release bupropion formulations than placebo during clinical trials included agitation (2% to 31.9%), anxiety (3.1% to 8%), memory impairment (less than 0.5 and up to 3% ), confusion (8.4%), delusions (1.2%), impaired concentration (3.1% to 9%), hostility (5.6%), irritability (2% to 3%), thinking abnormality (1%), and abnormal dreams (3% to 5%). These reactions may happen in patients treated for major depressive disorder (MDD) or in those who use bupropion for smoking cessation. In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following psychiatric effects and incidences were reported: dysphoria (less than 1%, 1%, 2%, 1%), anxiety (8%, 6%, 9%, 6%), impaired concentration (9%, 3%, 9%, 4%), and abnormal dreams (5%, 18%, 13%, 3%). During other pre-marketing or postmarketing use, hallucinations and agitation occurred in 1% or more of patients. Memory impairment, depersonalization, psychosis, confusion, dysphoria, emotional lability, hostility, paranoia, formal thought disorder (unspecified), and frigidity were reported in 0.1 to 1% of patients. Amnesia and derealization occurred rarely (less than 0.1%). Also observed were aggression, delirium, delusions. Aggression, paranoia, and abnormal dreams have been reported during postmarketing use.[40993] [41057] [41086] [44094] [44095]

Depressive symptoms have been reported in smoking cessation studies as well as psychiatric studies with bupropion. During clinical trials for major depressive disorder, akathisia (psychomotor restlessness) was reported in 1.5% of bupropion-treated patients. Suicide attempt and completed suicide have occurred in 0.1% to 1% of patients during clinical trial evaluation or postmarketing use of bupropion. Mania can occur in predisposed patients during treatment with an antidepressant. 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. A ten-year retrospective postmarketing safety review conducted by the FDA indicated that bupropion smoking cessation products were associated with 46 cases of suicidal ideation and 29 cases of suicidal behavior in patients with a prior psychiatric history (n = 18), without this history (n = 24), or an unknown psychiatric history (n = 33). In the cases of suicidal ideation for which demographics were available, 40% were male, 60% were female, and the median age was 46 years (range 26 to 70 years). In the cases reporting suicidal behavior, 59% were male, 41% were female, and the median age was 35 years (range 15 to 70 years). A significant change in thinking and/or behaviors was reported by 23% of the patients after treatment initiation. Seventy percent of the studied patients also had a diagnosis of depression. Of the cases considered serious (n = 59), outcomes were categorized as follows and were not mutually exclusive: death (17%), hospitalization (36%), life-threatening (27%), disability (8%), intervention required (3%), and other (31%). Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation.[44094] [40993] [41057] [41086] [44095]

Frequent neurological adverse events associated with bupropion include myoclonia. During clinical trials, the incidence of myoclonia in bupropion recipients was 1% or more. Patients with Gilles de la Tourette's syndrome or a family history of this syndrome may have motor or phonetic tics unmasked or exacerbated by the use of bupropion for ADHD symptoms. Exacerbation of tics may respond to dosage reduction; in some cases bupropion may need to be discontinued.[40993] [41057] [41086] [44094] [44095]

Bupropion may cause weight loss. A weight loss of more than 5 pounds occurred in 23.2% of patients taking immediate-release bupropion, approximately double that seen for patients on tricyclic antidepressants or placebo. Approximately 14% of patients on sustained-release formulations lose weight. Roughly 23% of patients receiving bupropion XL enrolled in seasonal affective disorder (SAD) trials had a weight loss of > 5 lbs. compared to 11% on placebo; alternatively 11% of bupropion XL patients had a weight gain > 5 lbs. compared to 21% on placebo. Weight gain may be associated with untreated depression. In general, weight gain is typically rare with bupropion treatment; across all formulations, weight gain occurred in 2—13.6% of bupropion recipients during clinical trials. It is not known if bupropion, like other ADHD therapies, causes growth inhibition in pediatric patients. The incidence of anorexia reported during trials was similar for patients taking bupropion and patients on placebo (roughly 1—18%) and may represent a symptom of the depressive illness rather than an adverse event. Although not as common, appetite stimulation (2—3.7%) was also reported following administration of bupropion during clinical trials.[40993] [41057] [41086] [44094] [44095]

Cardiac toxicity is relatively uncommon for bupropion when compared with tricyclic antidepressants. Hypertension occurred in 1—4.3% of patients taking bupropion during clinical trials, compared to 0—1.6% taking placebo. New onset or worsening of existing hypertension occurred in a higher percentage of patients (i.e., 6.1%) taking bupropion concurrently with nicotine transdermal systems (NTS) for smoking cessation; in some cases hypertension was severe. Other cardiovascular effects which occurred more frequently in those receiving immediate-release or extended-release bupropion formulations than placebo during clinical trials included: unspecified cardiac arrhythmias (5.3% vs 4.3%), dizziness (22.3% vs 16.2%), hypotension (2.5% vs 2.2%), palpitations (2—6% vs 0—2.2%), syncope (1.2% vs 0.5%), sinus tachycardia (10.8% vs 8.6%), chest pain (unspecified) (< 1% to 4% vs 1%), and flushing (1—4% vs < 0.5%). In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following cardiac effects and incidences were reported: hypertension (1%, < 1%, 2%, 0%), palpitations (2%, 0%, 1%, 0%), and chest pain (< 1%, 1%, 3%, 1%). Edema was reported in >= 1% of patients during pre-marketing evaluation of bupropion. Flushing was reported in <= 1% of patients. Cardiac effects reported in 0.1—1% of patients included unspecified chest pain, ECG abnormalities (premature beats and nonspecific ST-T changes), dyspnea, orthostatic hypotension, stroke, sinus tachycardia, and peripheral vasodilation. Pallor, phlebitis, syncope, and myocardial infarction occurred rarely (< 0.1%). Also observed were complete AV block, extrasystoles, and pulmonary embolism; however, the frequencies are unknown. Cardiac effects noted after overdose of bupropion as a single agent have included sinus tachycardia, ECG changes including QRS prolongation, and arrhythmias (unspecified). Hypotension has been reported after overdose of bupropion in conjunction with other medications.[40993] [41057] [41086] [44094] [44095]

Blurred vision affected 2—14.6% of bupropion-treated patients during clinical trials, compared to 2—10.3% taking placebo. Diplopia was reported in 2—3% of those receiving active drug versus 2% of those receiving placebo. During other pre-marketing or post-marketing use, blurred vision or diplopia was reported in > = 1% of patients. Other ocular effects that occurred in clinical trials or during post-marketing use included abnormal accommodation (0.1—1%), xerophthalmia (0.1—1%), ocular hypertension, and mydriasis.[40993] [41057] [41086] [44094] [44095]

During clinical trials of immediate-release or extended-release bupropion formulations, the following gastrointestinal effects and incidences compared to placebo included: dyspepsia (3.1% vs 2.2)), nausea (9—22.9% vs 8—18.9%), vomiting (2—22.9% vs 2—18.9%), diarrhea (4—7% vs 6—8.6%), constipation (5—26% vs 2—17.3%), xerostomia (10—27.6% vs 5—18.4%), hypersalivation (3.4% vs 3.8%), dysphagia (0—2% vs 0%), flatulence (6% vs 3%), abdominal pain (2—9% vs < 1—2%), and dysgeusia (2—4% vs < 0.5%). In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following GI effects and incidences were reported: nausea (9%, 7%, 11%, 4%), xerostomia (10%, 4%, 9%, 4%), constipation (8%, 4%, 9%, 3%), diarrhea (4%, 4%, 3%, 1%), oral ulceration (2%, 1%, 1%, 1%), abdominal pain (3%, 4%, 1%, 1%), dysgeusia (3%, 1%, 3%, 2%), and thirst (< 1%, < 1%, 2%, 0%). During other pre-marketing evaluations, stomatitis was reported in >= 1% of patients. Adverse digestive reactions occurring in roughly 0.1—1% of patients included teeth grinding (bruxism), elevated hepatic enzymes, jaundice, liver damage, excessive thirst (polydipsia), gastroesophageal reflux, gingivitis, glossitis, and hypersalivation. Rare events in < 0.1% of patients have included colitis, GI bleeding, GI perforation, and stomach ulcer. Digestive adverse reactions reported during post-marketing use of bupropion include esophagitis, gum bleeding, hepatitis, and pancreatitis. Due to the voluntary nature of post-market reports, neither incidence nor definitive association to bupropion can established.[40993] [41057] [41086] [44094] [44095]

Twice as many patients taking bupropion reported libido decrease (3.1%) compared to patients taking placebo (1.6%). Conversely, libido increase has been reported in >= 1% of patients receiving bupropion. Menstrual irregularity was reported as unspecified menstrual complaints by 4.7% of patients and as dysmenorrhea (2% vs < 1% for placebo) and/or vaginal bleeding in 0—2% of patients vs < 0.5% of placebo-treated patients. Impotence (erectile dysfunction) occurred in 3.4% and painful erections occurred in 0.1—1% of bupropion recipients during clinical trials. Cases of gynecomastia, prostate disorder, and testicular swelling have been reported in 0.1—1% of bupropion-treated patients. Other sexual or reproductive system reactions have also occurred and include ejaculation dysfunction (0.1—1%, reported as retarded ejaculation or painful ejaculation), painful erection, dyspareunia (< 0.1%), salpingitis, and vaginal irritation (0.1—1%). Causal effect may be uncertain as trials were not always conducted with adequate controls.[40993] [41057] [41086] [44094] [44095]

Depending on the dosage form of bupropion used, hot flashes have been reported in 1—3% of patients; menopause was reported in < 0.1% of bupropion recipients during clinical trials.[40993] [41057] [41086] [44094] [44095]

During clinical trials of immediate-release or extended-release bupropion formulations, hyperhidrosis occurred more frequently in the bupropion groups than the placebo groups (5—22.3% vs 2—14.6%). Rash (unspecified) (3—8%), pruritus (2—4%), urticaria (1—2%), alopecia (>= 1%), and xerosis (2%) were other dermatologic adverse reactions commonly reported by recipients of bupropion. Acne vulgaris (0.1—1%), maculopapular rash (< 0.1%), hirsutism (< 0.1%), photosensitivity (0.1—1%), and exfoliative dermatitis have also occurred infrequently or rarely with bupropion use. In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following dermatologic effects and incidences were reported: rash (4%, 3%, 3%, 2%), pruritus (3%, 1%, 5%, 1%), and urticaria (2%, 0%, 2%, 0%).[40993] [41057] [41086] [44094] [44095]

Some endocrine side effects have been reported during postmarketing use of bupropion. These rare endocrine-related side effects have included hyperglycemia, hypoglycemia, glycosuria, hyponatremia, and syndrome of inappropriate antidiuretic hormone (SIADH). Due to the voluntary nature of postmarketing reports, neither causality nor the incidence can be established.[40993] [41057] [41086] [44094] [44095]

Hematologic and lymphatic effects reported with bupropion include infrequent cases of ecchymosis (0.1—1%). Anemia, leukocytosis, leukopenia, lymphadenopathy, thrombocytopenia, pancytopenia, and changes in the INR and/or PT have been noted; the incidence has not been reported. Causality has not been established.[40993] [41057] [41086] [44094] [44095]

Musculoskeletal events reported during clinical trials by patients receiving bupropion therapy included arthralgia (1—5% vs 1—3%), asthenia (2—4% vs 2%), myalgia (2—6% vs 1—3%), and muscle spasms (1.9% vs 3.2%). Other musculoskeletal adverse reactions reported during bupropion use include muscle twitching (1—2% vs < 0.5%), arthritis (0—3.1% vs 0—2.7%), neck pain (2% vs 0—1%), sciatica (< 0.1%), pain in extremity (3% vs 2%), and pain (unspecified) (2—3% vs 2%). In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following musculoskeletal effects and incidences were reported: myalgia (4%, 3%, 5%, 3), arthralgia (5%, 3%, 3%, 2%), and neck pain (2%, 1%, < 1%, 0%). Musculoskeletal effects reported in 0.1—1% of patients receiving bupropion during pre-marketing or post-marketing use included leg muscle cramps, back pain, inguinal hernia, and muscle twitching. Musculoskeletal chest pain was reported in <= 1% of patients and sciatica occurred rarely (< 0.1%). Arthralgia, myalgia, muscle weakness (myasthenia), and muscle rigidity with increased temperature and rhabdomyolysis have been reported during post-marketing use.[40993] [41057] [41086] [44094] [44095]

Rarely, anaphylactoid reactions characterized by symptoms such as rash, pruritus, urticaria (1% to 2%), angioedema, edema, chest pain, and dyspnea (1%) requiring medical treatment have been reported in clinical trials with bupropion. Most of these events occur in 0.1% to 0.3% or less of patients treated. In addition, there have been rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome (SJS), and anaphylactic shock associated with bupropion. A case of a serum sickness reaction has also been reported in the literature. Serum-sickness-like reactions consist of delayed hypersensitivity reactions, arthralgia, myalgia, pyrexia, and rash.[40993] [41057] [41086] [44094] [44095] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported during postmarketing use of bupropion 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. Bupropion 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]

Infections (8—9% vs 6% for placebo) have been reported by bupropion recipients during clinical trials. The types of infection included upper respiratory tract infections (5—9%) (e.g., sinusitis (1—5%), pharyngitis (3—13%), bronchitis (2%), pneumonia (< 0.1%)), urinary tract infections (1%), pelvic infections (< 0.1%), and influenza (>= 2%). Symptoms reported during use of bupropion that may be associated with these infections included rhinitis (12%), epistaxis (2%), increased cough (1—4%), nasal congestion (>= 2%), sinus congestion (>= 2%), pharyngolaryngeal pain (>= 2%), malaise (< 0.1%), fever (1—2%), fever/chills (1.2%), and bronchospasm (< 0.1%). In a comparative trial of sustained-release bupropion (Zyban) monotherapy, nicotine transdermal system (NTS) monotherapy, Zyban/NTS combination, or placebo, the following effects and incidences were reported: rhinitis (12%, 11%, 9%, 8%), increased cough (3%, 5%, < 1%, 1%), pharyngitis (3%, 2%, 3%, 0%), sinusitis (2%, 2%, 2%, 1%), dyspnea (1%, 0%, 2%, 1%), and epistaxis (2%, 1%, 1%, 0%).[40993] [41057] [41086] [44094] [44095]

Adverse reactions reported by recipients of bupropion during pre-marketing or post-marketing use, and not discussed elsewhere in the monograph, include peripheral edema (0.1—1%), fatigue (5% vs 8.6% for placebo), dental pain (0.1—1%), drug-induced body odor (< 0.1%), facial edema (0.1—1%), and hair discoloration (< 0.1%). Facial edema was also reported in a comparative trial of sustained-release bupropion (Zyban) monotherapy (< 1%), nicotine transdermal system (NTS) monotherapy (0%), Zyban/NTS combination (1%), or placebo (0%).[40993] [41057] [41086] [44094] [44095]

Urinary tract reactions reported more frequently with immediate-release or extended-release bupropion formulations than placebo during clinical trials included increased urinary frequency (2—5% vs 2—2.2%), urinary urgency (< 0.5—2% vs 0%), urinary retention (1.9% vs 2.2%), and urinary tract infection (0—1% vs < 0.5%). Nocturia and urinary frequency occurred in >= 1% of patients during pre-marketing evaluation. Polyuria, urinary urgency, and prostate disorder were reported in 0.1—1% of patients. Cystitis and dysuria occurred rarely (< 0.1%). Also observed post-marketing were cystitis, dysuria, urinary incontinence, and urinary retention; however, the frequencies were not reported.[40993] [41057] [41086] [44094] [44095]

During clinical trials of immediate-release or extended-release bupropion formulations, the following extrapyramidal symptoms occurred in the bupropion groups at similar incidences to placebo: bradykinesia (8%), and pseudoparkinsonism (1.5%). Extrapyramidal syndrome (unspecified) has been reported during use of bupropion. Extrapyramidal symptoms that have occurred in 1% or more of patients during pre-marketing evaluation include dystonic reaction and dyskinesia. Hyperkinesis and hypertonia have been reported in 0.1% to 1% of patients. Akinesia, hypokinesia, dystonia, dyskinesia, pseudoparkinsonism, and unmasking of tardive dyskinesia have also occurred during postmarketing use; however, the incidences are unknown.[40993] [41057] [41086] [44094] [44095]

During clinical trials of immediate-release or extended-release bupropion formulation, tinnitus was reported more frequently in patients receiving bupropion than placebo (3—6% vs < 1% to 2%). Unspecified sensory disturbance (4% vs 3.2%), auditory or hearing disturbance (5.3% vs 3.2%), and gustatory disturbance (3.1% vs 1.1%) were also reported more frequently in active treatment groups than placebo groups. Tinnitus occurred during a comparative trial of sustained-release bupropion (Zyban) monotherapy (1%), nicotine transdermal system (NTS) monotherapy (0%), Zyban/NTS combination (< 1%), and placebo (0%). During pre-marketing or post-marketing use of bupropion, deafness (hearing loss) has been reported.[40993] [41057] [41086] [44094] [44095]

While not reported for bupropion, a neonatal abstinence syndrome has been reported in infants exposed to certain antidepressants in utero. 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. In some reports, serum concentrations of the agent were measurable in the infants affected, so the symptoms may have been due to a direct adverse effect of the antidepressant. The physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the drug half-life into consideration, appropriate tapering of the agent prior to delivery may be considered as an alternative.[40993] [41057] [41086] [44094] [44095]

Euphoria was reported more frequently with immediate-release or extended-release bupropion formulations than placebo during clinical trial evaluation (1.2% vs. 0.5%). During controlled trials in patients with a history of multiple substance abuse, normal volunteers, and depressed patients, there was an increase in motor activity and agitation/excitement. In a single dose study of bupropion 400 mg in a population of individuals experienced with drugs of abuse, a mild amphetamine-like activity was produced as compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug desirability. Although use of recommended daily dosages of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers, higher doses (that could not be tested because of seizure risk) could theoretically be modestly attractive to those who abuse CNS stimulant drugs.[41057] In addition, the inhalation of crushed tablets or injection of dissolved bupropion has been reported. Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection.[44094]

In an ISMP safety report, bupropion was noted as 1 of the 19 overall drugs and one of the 9 antidepressants having the strongest signals for serotonin syndrome with 18 cases reported over 1 year to the FDA Adverse Event Reporting System (FAERS). Serotonin syndrome rarely happens with single drug therapy, and more commonly is reported with interactions between multiple serotonergic drugs or accidental or intentional drug overdoses.[63529] How bupropion might promote serotonergic excess is unclear, as bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine, and does not inhibit the reuptake of serotonin. Bupropion does not inhibit monoamine oxidase. The manufacturers have not reported serotonin syndrome as a postmarketing event.

Revision Date: 02/12/2020, 02:41:01 PM

References

23945 - Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacotherapy 1992;12:18-22.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.44094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2021 July.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;36:501-5.63529 - Institute for Safe Medication Practices (ISMP). Acute Care ISMP Medication Safety Alert 2018;23:1-2.

Contraindications/Precautions

Absolute contraindications are italicized.

  • anorexia nervosa
  • brain tumor
  • bulimia nervosa
  • intracranial mass
  • MAOI therapy
  • seizure disorder
  • seizures
  • abrupt discontinuation
  • acute myocardial infarction
  • alcoholism
  • behavioral changes
  • benzodiazepine withdrawal
  • bipolar disorder
  • breast-feeding
  • cardiac disease
  • children
  • closed-angle glaucoma
  • depression
  • diabetes mellitus
  • driving or operating machinery
  • ethanol intoxication
  • geriatric
  • head trauma
  • heart failure
  • hepatic disease
  • hypertension
  • hypoglycemia
  • hyponatremia
  • hypoxemia
  • increased intraocular pressure
  • laboratory test interference
  • mania
  • obesity treatment
  • pregnancy
  • psychiatric event
  • renal disease
  • renal failure
  • renal impairment
  • schizophrenia
  • stroke
  • substance abuse
  • suicidal ideation
  • tics
  • tobacco smoking
  • Tourette's syndrome

IMPORTANT: Given that there are multiple dosage forms of bupropion available, it is important to be familiar with each product name, dosage form, and dosing schedule to avoid dosing errors. Bupropion products should not be used with other bupropion products, including the combination of bupropion-naltrexone. Duplication of bupropion can result in serious toxicity and convulsions.[28058][40993][41057][41086][44094][44095]

 

Bupropion is contraindicated in patients with a history of hypersensitivity to bupropion or any inactive ingredients in the formulations. Delayed hypersensitivity reactions, consisting of arthralgia, myalgia, fever and rash have been reported in association with bupropion and may resemble serum sickness. Anaphylactoid/anaphylactic reactions and serious rash including Stevens-Johnson syndrome have also been reported.[28058][40993][41057][41086][44094][44095]

Bupropion is contraindicated in patients with a pre-existing seizure disorder or conditions that increase the risk of seizures (e.g., severe head trauma, arteriovenous malformation, CNS tumor (e.g., brain tumor or intracranial mass), CNS infection, severe stroke, anorexia nervosa, bulimia nervosa, and in cases of abrupt benzodiazepine withdrawal as well as abrupt withdrawal from alcohol, barbiturates, or anti-epileptic drugs, because bupropion can cause seizures. Other predisposing factors that may increase the risk of seizures include alcoholism, substance abuse (e.g., cocaine or prescription abuse of stimulants such as amphetamines), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxemia), diabetes mellitus treated with oral hypoglycemic agents or insulin, excessive use of benzodiazepines, sedative/hypnotics, or opiates, use of anorectic drugs for obesity treatment, or use of concomitant medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, tramadol, systemic corticosteroids). Bupropion should be discontinued and not re-initiated in patients who experience a seizure during treatment. The incidence of seizures with bupropion is dose-dependent. In studies using bupropion hydrochloride sustained-release up to 300 mg/day, the incidence of seizures was about 0.1%. The incidence of seizures in patients taking bupropion hydrochloride immediate-release 300 mg/day to 450 mg/day was about 0.4%. At higher immediate-release dosages between 450 mg/day and 600 mg/day, the estimated risk of seizures increases 10-fold compared to the seizure risk at 450 mg/day. The incidence of seizures has not been formally evaluated for the use of Aplenzin, Forfivo XL, or Wellbutrin XL. Do not exceed maximum recommended single or total daily dosages of any bupropion product. Patients who are taking bupropion for smoking cessation (e.g., Zyban) should not also take bupropion for depressive disorders (e.g., Wellbutrin, Aplenzin), and vice-versa. Healthcare professionals should be aware that bupropion is available under several brand names for various indications in order to avoid duplicative administration. During controlled trial evaluation of immediate-release bupropion, an increase in motor activity and agitation/excitement was demonstrated in normal volunteers, subjects with a history of multiple drug abuse, and depressed patients. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, because clinical trial results may not reliably predict the abuse potential of drugs, the benefits of treatment should be weighed against the potential for abuse prior to administering bupropion to patients with a history of substance abuse. It should be noted that bupropion extended-release formulations are intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has resulted in seizures and/or cases of death.[40993] [41057] [41086] [44094] [44095]

The safety and efficacy of bupropion is not established in pediatric patients less than 18 years of age. Children 6 years and older with a major depressive episode or attention deficit hyperactivity disorder (ADHD) have been studied in clinical trials of bupropion, but data regarding pediatric safety are limited. Careful screening and monitoring is recommended by the American Heart Association if bupropion is used 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. Nevertheless, the need for an antidepressant in children, adolescents, or young adults 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. A change to the treatment regimen or discontinuation of bupropion may be necessary in patients with emerging suicidality or worsening depression.[34206] [44094] [41086] [46944]

Patients with Tourette's syndrome or tics should be closely monitored for emerging or worsening tics during treatment with bupropion. Like other stimulant medications, bupropion may precipitate motor or phonetic tics in those with Tourette's syndrome or a tic disorder.[60080] [60081]

The use of antidepressants, such as bupropion, has been associated with the development of mania or hypomania in susceptible individuals. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant, including a detailed personal and family history of bipolar disorder, depression, and suicidal thoughts or actions. 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 therapy and during dose adjustments. 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. If a patient develops manic symptoms, bupropion should be held, and appropriate therapy initiated to treat the manic symptoms.[41086] Patients should be observed for a potential psychiatric event or worsening of pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder) during treatment with bupropion, including smoking cessation products (e.g., Zyban), due to serious neuropsychiatric symptoms reported during postmarketing use of bupropion products for smoking cessation. If neuropsychiatric symptoms develop, evaluate the patient for symptom severity and the extent of benefit from treatment, and consider dose reduction or discontinuation, or continued treatment with closer monitoring. In many cases, resolution of symptoms has occurred after discontinuation, although the symptoms can persist; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. Postmarketing reports during use of bupropion smoking cessation products have included neuropsychiatric adverse events such as mood or behavioral changes (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide in patients with and without a psychiatric history. Some reported cases may have been complicated by symptoms of nicotine withdrawal, such as depressed mood, in patients who stopped smoking. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. Some reported neuropsychiatric events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol. Advise patients and caregivers that the patient should stop taking bupropion and contact a healthcare provider immediately if agitation, depressed mood, suicidal ideation, suicidal behavior, or other behavioral changes that are not typical for the patient are observed. The boxed warning in the bupropion smoking cessation product labeling regarding serious neuropsychiatric effects was removed in December 2016 following results from the Evaluating Adverse Events in a& Global Smoking Cessation Study (EAGLES), which was a large, randomized, double-blind, active- and placebo-controlled smoking cessation clinical trial assessing varenicline, bupropion, and nicotine replacement therapy in patients with (n = 4,003) and without (n = 3,912) a history of a psychiatric disorder. The results showed that the benefits of taking smoking cessation products outweigh the risks, which are less frequent and severe than previously suspected.[61618]

Bupropion is contraindicated with concurrent use of MAOI therapy intended to treat psychiatric disorders because of an increased risk of hypertensive reactions. At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and bupropion initiation. Conversely, allow at least 14 days after stopping bupropion before starting an MAOI intended to treat psychiatric disorders. Starting bupropion 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 urgent treatment with linezolid or intravenous methylene blue in a patient taking bupropion. If acceptable alternatives are not available and benefits are judged to outweigh the risks of hypertensive reactions, bupropion should be promptly discontinued before initiating treatment with linezolid or methylene blue. Monitor the patient closely for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion may be resumed 24 hours after the last dose of linezolid or methylene blue. The risk of administering methylene blue by non-intravenous routes (e.g., oral tablets, local injection) or intravenous doses much less than 1 mg/kg with bupropion is unclear; however, clinicians should be aware that the potential for an interaction exists.[41057] [41086]

Use bupropion with caution during pregnancy; use during pregnancy only if the potential benefit justifies the potential risk to the fetus. When treating a pregnant woman, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, tapering of the medication prior to labor and obstetric delivery may be considered. Pregnant smokers should be encouraged to attempt educational and behavioral interventions before pharmacologic approaches are used; nicotine has been used in pregnancy to help patients quit smoking. Smoking cessation programs in pregnancy reduce the proportion of women who continue to smoke, and reduce the risk for low birthweight and preterm birth. Data from epidemiological studies including pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations. In addition, no increased risk of cardiovascular malformations during first trimester exposure to bupropion has been observed. The rate of cardiovascular malformations following 675 exposures to bupropion in the first trimester was 1.3% versus a background rate of about 1%. Data collected from the United Healthcare database and the National Birth Defects Prevention Study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) did not show an overall increased risk from cardiovascular malformations after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO, and the Slone Epidemiology case control study did not find increased risk for LVOTO. Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure but did not find increased risk for any other cardiovascular malformations studied (including LVOTO). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits. However, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to or more than the maximum recommended human dose (MRHD) and decreased fetal weights were seen at doses twice the MRHD and greater. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to bupropion; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants by calling 1-866-961-2388 or 1-844-405-6185.[28058] [40993] [41057] [41086] [42078] [44094] [44095] [61843]

Bupropion and its metabolites are excreted into human breast milk, and caution should be exercised when bupropion is administered to a breast-feeding woman.[28058] [40993] [41057] [41086] [44094] [44095] Peak breast milk concentrations of bupropion and its metabolites are present within 2 to 4 hours after an oral dose. In one lactation study (n = 10), the average daily infant exposure to bupropion and its active metabolites (assuming 150 mL/kg daily consumption) was 2% of the maternal weight-adjusted dose.[47279] One case report describes a possible seizure in a breast-fed infant during maternal use of extended-release bupropion.[47277] In two other cases, no infant-related adverse events were noted during breast-feeding.[47278] Due to individual variability in response to antidepressants, it may be prudent to continue the existing regimen if ongoing treatment for depression is deemed necessary during breast-feeding. Alternatives may be considered in some cases. Because a pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum, these agents may be the preferred antidepressants when initiating antidepressant therapy in a breast-feeding mother.[45642] For smoking cessation treatment, nicotine replacement products may be considered as an alternate therapy to bupropion if non-pharmacologic interventions are inadequate. The decision of whether to use nicotine replacement therapy in a woman who is breast-feeding should be evaluated in comparison to the risks associated with exposure of the infant to nicotine and other tobacco contaminants in the breast milk as well as those of passive exposure to tobacco smoke. Breast-feeding and eliminating an infant's exposure to tobacco smoke are considered important protective factors for serious pediatric health risks.[37408]

Forfivo XL, a 450 mg extended-release tablet formulation of bupropion, is not recommended in patients with hepatic impairment because a lower dosage strength is not available for use in this patient population.[46944] For other bupropion formulations, the dosage or dosage frequency should be reduced in patients with moderate to severe hepatic impairment (Child-Pugh Score 7—15). For patients with mild hepatic dysfunction (Child-Pugh Score 5—6), reduced dosage or dosage frequency should be considered; however, no specific guidelines are available. Monitor patients with any degree of hepatic disease carefully. Bupropion undergoes extensive hepatic metabolism and excretion in the urine as metabolites; there is a risk for accumulation in hepatic impairment. In addition, caution is advisable when using bupropion in patients with severe hepatic impairment because this condition can increase the risk of seizures.[44095] [41086] [40993] [41057] [44094]

Forfivo XL, a 450 mg extended-release tablet formulation of bupropion, is not recommended in patients with renal impairment since a lower dosage strength is not available for use in this patient population.[46944] Other bupropion products should be used with extreme caution in patients with renal disease or renal failure because the parent compound or active metabolites could accumulate. Consider reduced dosages in these patient populations based on the degree of organ impairment, and closely monitor for adverse reactions that could indicate high drug or metabolite levels.

Of roughly 6,000 patients in bupropion sustained-release studies for both smoking cessation and depression, 275 were 65 and over and 47 were 75 and over. Several hundred geriatric patients 65 years and older have also been studied (in depression) with the immediate-release formulation. Both initial and maintenance bupropion doses should be reduced in geriatric patients if hepatic or renal impairment or debilitating disease is present; multiple-dose pharmacokinetic studies have indicated the elderly may be at risk for bupropion and metabolite accumulation. It may be useful to monitor renal function in the elderly. Bupropion may also cause weight loss which may be significant for elderly or otherwise debilitated patients.[44095] [41086] [40993] [41057] [44094] The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities. According to OBRA, follow the recommended duration of therapy per pertinent literature for the condition being treated, including 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 dizziness, nausea, diarrhea, anxiety, nervousness, insomnia, sedation, weight gain, anorexia, or increased appetite. Many of these effects can increase the risk of falls. Bupropion may increase seizure risk and activity in susceptible individuals. Before discontinuation, taper bupropion to avoid a withdrawal syndrome. Concurrent use of two or more antidepressants may increase the risk of side effects; in such cases, there should be documentation of expected benefits that outweigh the associated risks and monitoring for an increase in side effects. Monitoring should consist of a review for continued need at least quarterly, and documentation of 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]

Rarely, bupropion may cause a fast or irregular heart beat or increases in blood pressure in some patients. It should be used with caution in patients with a recent history of acute myocardial infarction or unstable cardiac disease, including heart failure. Pharmacokinetic studies suggest that left ventricular dysfunction results in lowered metabolism and excretion of bupropion and its metabolites. Because treatment with bupropion can result in elevated blood pressure and hypertension, patients should have their blood pressure checked prior to bupropion initiation and periodically throughout treatment. Bupropion may be used in combination with nicotine transdermal systems (NTS) as an aide to smoking cessation. In clinical trials, new onset treatment-induced hypertension or exacerbation of existing high blood pressure occurred more commonly in patients using the combination bupropion-NTS therapy. In some cases the exacerbation of hypertension required discontinuation of bupropion treatment. Patients should quit tobacco smoking prior to initiating the nicotine therapy in the bupropion-NTS combination regimen to reduce the risk of unwanted cardiac side effects. Close blood pressure monitoring is recommended.[41057] [41086] Patients who are taking bupropion should not self-treat with OTC nicotine products; the bupropion-NTS combination should only be used under the prescription and advice of a health-care prescriber. When used as monotherapy, patients should schedule to stop tobacco smoking during the second week of taking bupropion. When bupropion is used for smoking cessation, it should be noted that cessation of tobacco smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline and warfarin due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. Bupropion has been used in children and adolescents for the treatment of attention-deficit hyperactivity disorder (ADHD). Sudden unexplained death has occurred in adults and pediatric patients receiving stimulants at standard dosages for ADHD. Although bupropion is not a stimulant medication, the American Heart Association recommends conducting a detailed patient and family history and physical examination prior to initiating any ADHD pharmacologic treatment, and obtaining a baseline electrocardiogram (ECG) is a reasonable addition to the initial evaluation.[34206] Once the medication is started, a repeat ECG may be helpful if the original ECG was obtained before the child was 12 years old, if cardiac symptoms develop, or there is a change in family history. If a child or adolescent has any significant findings on physical examination, ECG, or family history, consult a pediatric cardiologist before initiating the medication.

Patients should be warned to use caution when driving or operating machinery or performing other tasks that require mental alertness until they know how bupropion will affect them. Some patients have reported lower alcohol tolerance during treatment with bupropion; advise patients that the consumption of alcohol should be minimized or avoided; avoid ethanol intoxication.

Caution is recommended when prescribing bupropion 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.[44095]

It is generally recommended to avoid abrupt discontinuation of antidepressants. If discontinuing bupropion, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. Because Forfivo XL is only available in a 450 mg tablet, the manufacturer recommends using another bupropion formulation for tapering the dose prior to discontinuation.[46944]

Laboratory test interference has been reported with bupropion use. False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. The false-positive result is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.[28058] [40993] [41057] [41086] [44094] [44095]

Revision Date: 05/11/2021, 04:32:00 PM

References

28058 - Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.34206 - Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Heart Defects Committee and the Council on Cardiovascular Nursing. Circulation 2008; 117: 2407-23.37408 - DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children’s health. Pediatrics. 2004;113:1007-1015.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.42078 - Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2009:CD00105544094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2021 July.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;161:1066-78.46944 - Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.47277 - Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: a case of a possible infant seizure. J Clin Psychiatry 2004;65:881-2.47278 - Baab SW, Peindl KS, Piontek CM, et al. Serum bupropion levels in 2 breastfeeding mother-infant pairs. J Clin Psychiatry 2002;63:910-11.47279 - Haas JS, Kaplan CP, Barenboim D, et al. Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use. Tob Control 2004;13:52-6.60080 - Wigal SB. Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults. CNS Drugs 2009;23:21-31.60081 - Spencer T, Biederman J, Steingard R, et al. Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome. J Am Acad Child Adolesc Psychiatry 1993;32:211-4.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.61618 - US Food and Drug Administration (FDA). FDA Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. Retrieved Dec 22, 2016. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery61843 - Massachusetts General Hospital Center for Women's Mental Health. National Pregnancy Registry for Psychiatric Medications. Available on the World Wide Web at: https://womensmentalhealth.org/research/pregnancyregistry/.

Mechanism of Action

The action of bupropion is not fully understood. Bupropion selectively inhibits the neuronal reuptake of dopamine and is significantly more potent than either imipramine or amitriptyline in this regard.[24817] Actions on dopaminergic systems, however, require doses higher than those needed for a clinical antidepressant effect.[24817] The blockade of norepinephrine reuptake at the neuronal membrane is weaker for bupropion than for tricyclic antidepressants. CNS-stimulant effects are dose-related. Bupropion does not inhibit monoamine oxidase or the reuptake of serotonin. Bupropion does exhibit moderate anticholinergic effects, and produces a sensation of mild local anesthesia on the oral mucosa. Antidepressant activity is usually noted within 1—3 weeks of initiation of bupropion treatment; full effects may not be seen until 4 weeks of therapy.

 

The mechanism by which bupropion enhances the ability to abstain from tobacco smoking is unknown, but is probably related to inhibition of noradrenergic or dopaminergic neuronal uptake. The resultant increase in norepinephrine may attenuate nicotine withdrawal symptoms. Increased dopamine at neuronal sites may reduce nicotine cravings and the urge to smoke. Because the onset of activity is usually after 1 week of treatment, patients should start bupropion 1—2 weeks prior to their chosen smoking 'quit-day'. In smoking cessation, the ability to abstain from smoking continuously through the seventh week of bupropion therapy is associated with maintenance of long-term abstinence. Patients who have not stopped smoking by the seventh week of treatment are generally considered non-responsive to bupropion treatment.

Revision Date: 07/09/2015, 03:51:42 PM

References

24817 - Bryant SG, Guernsey BG, Ingrim NB. Review of bupropion. Clin Pharm 1983;2:525-37.

Pharmacokinetics

Bupropion is administered orally as the hydrochloride salt (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban, Forfivo XL) or hydrobromide salt (Aplenzin). Bupropion is a racemic mixture; however, the pharmacologic actions and pharmacokinetics of the individual enantiomers have not been evaluated. The drug readily crosses the blood-brain barrier. Plasma protein binding is about 84%. Metabolism takes place in the liver, producing several metabolites; the 3 major active metabolites are hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. CYP2B6 is involved in forming hydroxybupropion, the major metabolite, previously known as morpholinol. All active metabolites are present in higher concentrations in the plasma than the parent compound. In mice, hydroxybupropion appears to have one-half the potency of bupropion; the other metabolites are one-tenth to one-half as potent. Bupropion appears to induce its own metabolism, but this does not appear to be clinically significant. The terminal elimination half-life of immediate-release bupropion is approximately 14 hours with a range of 8 to 24 hours. The terminal elimination half-life of the sustained-release hydrochloride product and the extended-release hydrobromide product is roughly 21 hours. Half-lives for hydroxybupropion, erythrohydroxybupropion, and threohydroxybupropion are 20 hours, 33 hours, and 37 hours, respectively. Less than 1% is excreted unchanged in the urine. Over 60% is excreted as metabolites in the urine within 24 hours; over 80% is eliminated in 96 hours. Less than 10% of metabolites are excreted in the feces. Steady-state concentrations of bupropion and its metabolites are achieved in 5 to 8 days; however, antidepressant effects have an onset of roughly 1 to 3 weeks.

 

Affected cytochrome P450 isoenzymes: CYP2D6, CYP2B6, OCT2

Because of the extensive metabolism of bupropion by CYP2B6, clinically significant drug interactions are possible with drugs that are metabolized by or are inhibitors or inducers of this isoenzyme.[41086]In vitro data indicate that bupropion and hydroxybupropion are inhibitors of CYP2D6. In vitro, bupropion and its 3 metabolites are inhibitors of the renal organic transporter OCT2 to a clinically significant extent; however, in vivo drug interaction studies have not found clinically significant drug-drug interactions with OCT-2 substrates.[41086][41057] [44095]

Route-Specific Pharmacokinetics

Oral Route

Based on animal data, the oral bioavailability is roughly 5—20%; oral bioavailability in humans has not been determined.

  • Wellbutrin, Wellbutrin SR, and Wellbutrin XL: Bupropion XL has been found to be bioequivalent to the immediate-release tablet, sustained-release tablet, and extended-release hydrobromide tablet. In studies of healthy volunteers, administration with food increased Cmax and AUC by 11—35% and 16—19%, respectively. These changes are not considered clinically significant; therefore, bupropion can be taken with or without food.[40993] Peak plasma concentrations are achieved within 1.5 hours after administration of immediate-release bupropion, and within 3 hours after administration of sustained-release hydrochloride formulations. Peak plasma concentrations of the active metabolite hydroxybupropion occur about 3 hours after administration of immediate-release bupropion.[41086] Peak plasma concentrations of hydroxybupropion are about 10 times those of bupropion at steady state.[41086] Plasma bupropion concentrations are dose-proportional following single doses of 100 to 250 mg; however, it is not known if the proportionality between dose and plasma levels are maintained in chronic use.
  • Aplenzin: Peak plasma concentrations are achieved within approximately 5 hours after administration of the hydrobromide tablet. Peak plasma concentrations of the active metabolite hydroxybupropion occur about 6 hours after administration. Peak plasma concentrations of hydroxybupropion are about 10 times those of bupropion at steady state.[44095]
  • Forfivo XL: Following a single dose of Forfivo XL, a 450 mg extended-release bupropion tablet formulation, the median time to peak plasma concentrations is about 5 hours under fasting conditions and 12 hours under fed conditions. The mean systemic exposure to bupropion is increased by 25% when taken with food. Peak plasma concentrations of hydroxybupropion occur about 10 hours after a dose of Forfivo XL under fasting conditions and 16 hours under fed conditions. The food effect is not considered clinically significant; therefore, Forfivo XL may be taken without regard to meals. In a single dose study under fasting conditions, one 450 mg dose of Forfivo XL was equivalent to a dose consisting of three 150 mg tablets of Wellbutrin XL.[46944]

Special Populations

Hepatic Impairment

Half-lives of bupropion and/or its major metabolites are prolonged in patients with alcoholic liver disease, cirrhosis, or left-ventricular dysfunction. In patients with hepatic disease, the mean AUC increased by roughly 1.5-fold for hydroxybupropion and roughly 2.5-fold for threo/erythrohydrobupropion. The median Tmax was observed 19 hours later for hydroxybupropion and 31 hours later for threo/erythrohydrobupropion. The mean half-lives for hydroxybupropion and threo/erythrohydrobupropion were increased 5- and 2-fold, respectively, in patients with severe hepatic cirrhosis compared to healthy volunteers. Dosage adjustment is required in patients with hepatic dysfunction.[41086][44095][44094] Use of Forfivo XL, a 450 mg extended-release tablet formulation, is not recommended in patients with hepatic impairment, as the dose is fixed and no lower strength is available.[46944]

Renal Impairment

An inter-study comparison of healthy subjects and those with end-stage renal failure showed that although the elimination of the parent compound was similar between groups, the Cmax and AUC of bupropion's active metabolites were increased in the renal failure group. In a separate study of patients with moderate to severe renal impairment, bupropion exposure after administration of the sustained-release product was about 2-fold higher in the renally impaired group than in normal subjects, while concentrations of the active metabolites of bupropion and placebo were similar.[41086] The clinical impact of these findings, if any, have not been described. Use of Forfivo XL, a 450 mg extended-release tablet formulation, is not recommended in patients with renal impairment as the dose is fixed and lower dosage strengths are not available.[46944]

Pediatrics

Adolescents have been shown to metabolize bupropion SR to its active metabolites more rapidly than adults.[32356] Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 h) and threohydrobupropion (26.3 h) were significantly shorter, and AUC ratios of metabolites to bupropion were 19 to 80% higher. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to adolescents.[32356]

Revision Date: 12/07/2018, 12:20:03 PM

References

32356 - Daviss WB, Perel JM, Rudolph GR, et al. Steady-state pharmacokinetics of bupropion SR in juvenile patients. J Am Acad Child Adolesc Psychiatry 2005;44:349-57.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.44094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2021 July.46944 - Forfivo XL (bupropion hydrochloride extended-release tablets) package insert. Buffalo, NY: IntelGenx Corp; 2019 Dec.

Pregnancy/Breast-feeding

pregnancy

Use bupropion with caution during pregnancy; use during pregnancy only if the potential benefit justifies the potential risk to the fetus. When treating a pregnant woman, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, tapering of the medication prior to labor and obstetric delivery may be considered. Pregnant smokers should be encouraged to attempt educational and behavioral interventions before pharmacologic approaches are used; nicotine has been used in pregnancy to help patients quit smoking. Smoking cessation programs in pregnancy reduce the proportion of women who continue to smoke, and reduce the risk for low birthweight and preterm birth. Data from epidemiological studies including pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations. In addition, no increased risk of cardiovascular malformations during first trimester exposure to bupropion has been observed. The rate of cardiovascular malformations following 675 exposures to bupropion in the first trimester was 1.3% versus a background rate of about 1%. Data collected from the United Healthcare database and the National Birth Defects Prevention Study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) did not show an overall increased risk from cardiovascular malformations after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO, and the Slone Epidemiology case control study did not find increased risk for LVOTO. Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure but did not find increased risk for any other cardiovascular malformations studied (including LVOTO). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits. However, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to or more than the maximum recommended human dose (MRHD) and decreased fetal weights were seen at doses twice the MRHD and greater. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to bupropion; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants by calling 1-866-961-2388 or 1-844-405-6185.[28058] [40993] [41057] [41086] [42078] [44094] [44095] [61843]

breast-feeding

Bupropion and its metabolites are excreted into human breast milk, and caution should be exercised when bupropion is administered to a breast-feeding woman.[28058] [40993] [41057] [41086] [44094] [44095] Peak breast milk concentrations of bupropion and its metabolites are present within 2 to 4 hours after an oral dose. In one lactation study (n = 10), the average daily infant exposure to bupropion and its active metabolites (assuming 150 mL/kg daily consumption) was 2% of the maternal weight-adjusted dose.[47279] One case report describes a possible seizure in a breast-fed infant during maternal use of extended-release bupropion.[47277] In two other cases, no infant-related adverse events were noted during breast-feeding.[47278] Due to individual variability in response to antidepressants, it may be prudent to continue the existing regimen if ongoing treatment for depression is deemed necessary during breast-feeding. Alternatives may be considered in some cases. Because a pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum, these agents may be the preferred antidepressants when initiating antidepressant therapy in a breast-feeding mother.[45642] For smoking cessation treatment, nicotine replacement products may be considered as an alternate therapy to bupropion if non-pharmacologic interventions are inadequate. The decision of whether to use nicotine replacement therapy in a woman who is breast-feeding should be evaluated in comparison to the risks associated with exposure of the infant to nicotine and other tobacco contaminants in the breast milk as well as those of passive exposure to tobacco smoke. Breast-feeding and eliminating an infant's exposure to tobacco smoke are considered important protective factors for serious pediatric health risks.[37408]

Revision Date: 05/11/2021, 04:32:00 PM

References

28058 - Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.37408 - DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children’s health. Pediatrics. 2004;113:1007-1015.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.42078 - Lumley J, Chamberlain C, Dowswell T, Oliver S, Oakley L, Watson L. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2009:CD00105544094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Mar.44095 - Aplenzin (bupropion extended-release tablet) package insert. Bridgewater, NJ: Sanofi-aventis, LLC.; 2021 July.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;161:1066-78.47277 - Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: a case of a possible infant seizure. J Clin Psychiatry 2004;65:881-2.47278 - Baab SW, Peindl KS, Piontek CM, et al. Serum bupropion levels in 2 breastfeeding mother-infant pairs. J Clin Psychiatry 2002;63:910-11.47279 - Haas JS, Kaplan CP, Barenboim D, et al. Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use. Tob Control 2004;13:52-6.61843 - Massachusetts General Hospital Center for Women's Mental Health. National Pregnancy Registry for Psychiatric Medications. Available on the World Wide Web at: https://womensmentalhealth.org/research/pregnancyregistry/.

Interactions

Level 1 (Severe)

  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Isocarboxazid
  • Linezolid
  • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
  • Methylene Blue
  • Monoamine oxidase inhibitors
  • Phenelzine
  • Pimozide
  • Rasagiline
  • Selegiline
  • Thioridazine
  • Tranylcypromine

Level 2 (Major)

  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Pseudoephedrine
  • Acetaminophen; Tramadol
  • Acrivastine; Pseudoephedrine
  • Amantadine
  • Amifampridine
  • Amitriptyline
  • Amitriptyline; Chlordiazepoxide
  • Amoxapine
  • Amphetamine
  • Amphetamine; Dextroamphetamine
  • Amphetamine; Dextroamphetamine Salts
  • Aripiprazole
  • Armodafinil
  • Asenapine
  • Atomoxetine
  • Benzphetamine
  • Brexpiprazole
  • Brompheniramine; Hydrocodone; Pseudoephedrine
  • Brompheniramine; Pseudoephedrine
  • Calcium, Magnesium, Potassium, Sodium Oxybates
  • Carbetapentane; Pseudoephedrine
  • Carbidopa; Levodopa
  • Carbidopa; Levodopa; Entacapone
  • Carbinoxamine; Dextromethorphan; Pseudoephedrine
  • Carbinoxamine; Hydrocodone; Pseudoephedrine
  • Carbinoxamine; Pseudoephedrine
  • Cariprazine
  • Cenobamate
  • Cetirizine; Pseudoephedrine
  • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
  • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
  • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Pseudoephedrine
  • Chlorpromazine
  • Clomipramine
  • Clozapine
  • Cocaine
  • Codeine; Phenylephrine; Promethazine
  • Codeine; Promethazine
  • Cyclobenzaprine
  • Dabrafenib
  • Desipramine
  • Desloratadine; Pseudoephedrine
  • Deutetrabenazine
  • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Dextroamphetamine
  • Dextromethorphan; Guaifenesin; Pseudoephedrine
  • Dextromethorphan; Promethazine
  • Diethylpropion
  • Dihydrocodeine; Guaifenesin; Pseudoephedrine
  • Doxepin
  • Doxorubicin
  • Efavirenz
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Encainide
  • Ethanol
  • Felbamate
  • Fexofenadine; Pseudoephedrine
  • Flecainide
  • Fluoxetine; Olanzapine
  • Fluphenazine
  • Guaifenesin; Hydrocodone; Pseudoephedrine
  • Guaifenesin; Pseudoephedrine
  • Haloperidol
  • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
  • Hydrocodone; Pseudoephedrine
  • Ibuprofen; Pseudoephedrine
  • Iloperidone
  • Imipramine
  • Iobenguane I 131
  • Levodopa
  • Lisdexamfetamine
  • Loratadine; Pseudoephedrine
  • Loxapine
  • Lurasidone
  • Maprotiline
  • Meperidine; Promethazine
  • Methamphetamine
  • Methylphenidate Derivatives
  • Metoclopramide
  • Mexiletine
  • Modafinil
  • Molindone
  • Naproxen; Pseudoephedrine
  • Non-Ionic Contrast Media
  • Nortriptyline
  • Olanzapine
  • Paliperidone
  • Pemoline
  • Perphenazine
  • Perphenazine; Amitriptyline
  • Phendimetrazine
  • Phentermine
  • Phentermine; Topiramate
  • Phenylephrine; Promethazine
  • Pitolisant
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Protriptyline
  • Pseudoephedrine
  • Pseudoephedrine; Triprolidine
  • Risperidone
  • Sodium Oxybate
  • Theophylline, Aminophylline
  • Thiethylperazine
  • Thiothixene
  • Tramadol
  • Tricyclic antidepressants
  • Trifluoperazine
  • Trimipramine
  • Vortioxetine
  • Ziprasidone

Level 3 (Moderate)

  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetaminophen; Caffeine
  • Acetaminophen; Caffeine; Dihydrocodeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Codeine
  • Acetaminophen; Hydrocodone
  • Acetaminophen; Oxycodone
  • Acetaminophen; Pentazocine
  • Acetaminophen; Propoxyphene
  • Acetazolamide
  • Alfentanil
  • Alosetron
  • Amobarbital
  • Anticonvulsants
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Oxycodone
  • Atazanavir; Cobicistat
  • Atropine
  • Atropine; Difenoxin
  • Atropine; Diphenoxylate
  • Atropine; Edrophonium
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • Azelastine; Fluticasone
  • Barbiturates
  • Beclomethasone
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Benztropine
  • Betamethasone
  • Bethanechol
  • Brompheniramine; Guaifenesin; Hydrocodone
  • Budesonide
  • Budesonide; Formoterol
  • Budesonide; Glycopyrrolate; Formoterol
  • Buprenorphine
  • Buprenorphine; Naloxone
  • Butabarbital
  • Butalbital; Acetaminophen
  • Butalbital; Acetaminophen; Caffeine
  • Caffeine
  • Caffeine; Ergotamine
  • Caffeine; Sodium Benzoate
  • Cannabidiol
  • Carbamazepine
  • Carbinoxamine; Hydrocodone; Phenylephrine
  • Cevimeline
  • Chlordiazepoxide; Clidinium
  • Chlorpheniramine; Codeine
  • Chlorpheniramine; Dihydrocodeine; Phenylephrine
  • Chlorpheniramine; Hydrocodone
  • Chlorpheniramine; Hydrocodone; Phenylephrine
  • Ciclesonide
  • Cimetidine
  • Citalopram
  • Clopidogrel
  • Cobicistat
  • Codeine
  • Codeine; Guaifenesin
  • Corticosteroids
  • Cortisone
  • Dalfampridine
  • Darifenacin
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Deflazacort
  • Dexamethasone
  • Dicyclomine
  • Digoxin
  • Diphenhydramine; Hydrocodone; Phenylephrine
  • Doxercalciferol
  • Duloxetine
  • Dutasteride; Tamsulosin
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Ethotoin
  • Fenfluramine
  • Fentanyl
  • Flavoxate
  • Fludrocortisone
  • Flunisolide
  • Fluoxetine
  • Fluticasone
  • Fluticasone; Salmeterol
  • Fluticasone; Umeclidinium; Vilanterol
  • Fluticasone; Vilanterol
  • Fluvoxamine
  • Formoterol; Mometasone
  • Fosphenytoin
  • Gabapentin
  • Gefitinib
  • Glycopyrrolate
  • Glycopyrrolate; Formoterol
  • Guaifenesin; Hydrocodone
  • Guanfacine
  • Homatropine; Hydrocodone
  • Hydantoins
  • Hydrochlorothiazide, HCTZ; Metoprolol
  • Hydrocodone
  • Hydrocodone; Ibuprofen
  • Hydrocodone; Phenylephrine
  • Hydrocodone; Potassium Guaiacolsulfonate
  • Hydrocortisone
  • Hydromorphone
  • Hyoscyamine
  • Ibuprofen; Oxycodone
  • Indacaterol; Glycopyrrolate
  • Isavuconazonium
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Ivosidenib
  • Lacosamide
  • Lamotrigine
  • Lasmiditan
  • Lemborexant
  • Levetiracetam
  • Lofexidine
  • Loperamide
  • Loperamide; Simethicone
  • Lopinavir; Ritonavir
  • Lorcaserin
  • Lumacaftor; Ivacaftor
  • Lumacaftor; Ivacaftor
  • Mepenzolate
  • Meperidine
  • Mephobarbital
  • Methadone
  • Methohexital
  • Methscopolamine
  • Methylprednisolone
  • Metoprolol
  • Midazolam
  • Mifepristone
  • Mometasone
  • Morphine
  • Morphine; Naltrexone
  • Nebivolol
  • Nebivolol; Valsartan
  • Nicotine
  • Oliceridine
  • Ombitasvir; Paritaprevir; Ritonavir
  • Oxcarbazepine
  • Oxybutynin
  • Oxycodone
  • Oxymorphone
  • Paroxetine
  • Pentazocine
  • Pentazocine; Naloxone
  • Pentobarbital
  • Phenobarbital
  • Phenytoin
  • Prednisolone
  • Prednisone
  • Primidone
  • Propantheline
  • Propoxyphene
  • Ranolazine
  • Rifampin
  • Ritonavir
  • Scopolamine
  • Secobarbital
  • Sertraline
  • Solriamfetol
  • Tamoxifen
  • Tamsulosin
  • Thiopental
  • Thiotepa
  • Tiagabine
  • Ticlopidine
  • tobacco
  • Tolterodine
  • Topiramate
  • Triamcinolone
  • Triazolam
  • Trihexyphenidyl
  • Trospium
  • Valproic Acid, Divalproex Sodium
  • Vigabatrin
  • Warfarin
  • Zolpidem
  • Zonisamide

Level 4 (Minor)

  • Brimonidine; Timolol
  • Carvedilol
  • Dorzolamide; Timolol
  • Hydrochlorothiazide, HCTZ; Propranolol
  • Nelfinavir
  • Nitroglycerin
  • Propranolol
  • Timolol
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Acetaminophen; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Acetaminophen; Oxycodone: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Acetaminophen; Pentazocine: (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Acetaminophen; Propoxyphene: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as propoxyphene may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Acetaminophen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Acetaminophen; Tramadol: (Major) Increased serum concentrations of tramadol and reduced serum concentrations of the O-desmethyltramadol metabolite (M1) would be expected from concurrent use of tramadol and a CYP2D6 inhibitor such as bupropion. As the analgesic activity of tramadol is due to both the parent drug and M1, inhibition of CYP2D6 by bupropion may affect the analgesic effect of tramadol; reduced analgesic effects are possible. Also, administration of tramadol may enhance the seizure risk in patients taking other medications that decrease the seizure threshold such as bupropion. [28001] [28314] Acetazolamide: (Moderate) It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorde; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions. Addiive CNS effects are possible, and the patient may feel dizzy, drowsy or more tired when taking these drugs together. [28058] [40993] [41086] [44094] Acrivastine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Alfentanil: (Moderate) If concomitant use of alfentanil and bupropion 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] Alosetron: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron. [28382] Amantadine: (Major) Use caution when concurrently administering bupropion and amantadine; if concurrent use is necessary, low initial dosing and slow dosage titration of bupropion should be considered. Both bupropion and amantadine have dopamine agonist effects, and coadministration may result in additive CNS dopaminergic effects. Reported adverse reactions have included neurologic side effects such as restlessness, agitation, gait disturbance, vertigo, and dizziness; some patients have required hospitalization. In reported cases, discontinuation of the drugs resulted in symptom resolution. [41057] Amifampridine: (Major) Carefully consider the need for concomitant treatment with bupropion and amifampridine, as coadministration may increase the risk of seizures. Consider alternatives to bupropion. If use together is medically necessary, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Bupropion is known to have a dose-dependent risk for seizures. [41057] [41086] [44094] [44095] [46944] [57922] [63790] Amitriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Amitriptyline; Chlordiazepoxide: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Amobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Amoxapine: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered. [28558] [4718] [4781] Amphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Amphetamine; Dextroamphetamine Salts: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Amphetamine; Dextroamphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Anticonvulsants: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Aripiprazole: (Major) Because aripiprazole is partially metabolized by CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP2D6 such as bupropion. Closely monitor for evidence of aripiprazole adverse events. Additionally, bupropion is associated with a dose-related risk of seizure; antipsychotics may increase this risk. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if a strong CYP2D6 inhibitor is used for more than 14 days. Adults receiving 662 mg or 882 mg of Aristada every 4 weeks should have their Aristada dose reduced to the next lower strength if a strong CYP2D6 inhibitor is used for more than 14 days. For patients receiving Aristada 882 mg every 6 weeks or 1,064 mg every 2 months, reduce the dose to 441 mg every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Avoid use of combination therapy with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days in patients receiving 662 mg, 882 mg, or 1,064 mg of Aristada; no dosage adjustment is necessary in patients taking 441 mg of Aristada, if tolerated. Avoid concurrent use of Aristada Initio and strong CYP2D6 inhibitors because the dose of Aristada Initio cannot be modified. [41057] [42845] [53394] [60196] [62642] [63328] Armodafinil: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [4781] Asenapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [36343] [41057] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Aspirin, ASA; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Aspirin, ASA; Oxycodone: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Atomoxetine: (Major) Dosage reduction of atomoxetine is recommended in patients receiving bupropion due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving bupropion, 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 bupropion, 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. Bupropion 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. [28405] Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Difenoxin: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Diphenoxylate: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Edrophonium: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30354] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28058] [28714] [30291] Azelastine; Fluticasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Barbiturates: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Beclomethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Benzphetamine: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants and anorectics that may induce seizures, including benzphetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together. [4781] [5043] Benztropine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [28001] [30312] Betamethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Bethanechol: (Moderate) Bupropion exhibits moderate anticholinergic properties. Avoid co-use when possible since the effects of bethanechol, a cholinergic agonist, may be diminished. If co-use is necessary, monitor for the intended clinical response. [24817] [29597] [29831] 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. Bupropion is a strong inhibitor of CYP2D6. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. 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. [41057] [59949] Brimonidine; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Brompheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Budesonide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Budesonide; Formoterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Buprenorphine: (Moderate) If concomitant use of buprenorphine and bupropion 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 bupropion 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] Butabarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Butalbital; Acetaminophen: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Butalbital; Acetaminophen; Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Caffeine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Caffeine; Ergotamine: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Caffeine; Sodium Benzoate: (Moderate) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including caffeine, is associated with an increased seizure risk and may increase this risk during the concurrent use of bupropion. Carefully consider a patient's caffeine intake from all sources, including medicines. Monitor for irritability, tremor, increased blood pressure, insomnia and seizures. Many non-prescription medicines and weight loss aids may contain caffeine and patients should read labels carefully. Examples of foods and beverages containing caffeine include coffee, teas, colas, energy drinks, chocolate, and some herbal or dietary supplements. Patients should be advised to limit excessive caffeine intake during bupropion therapy. [28058] Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually. [28528] [41057] Cannabidiol: (Moderate) Consider a dose adjustment of bupropion when coadministered with cannabidiol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a substrate of CYP2B6; cannabidiol may inhibit and/or induce CYP2B6 at clinically relevant concentrations. [41507] [63309] Carbamazepine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Carbamazepine induces hepatic enzymes and may lower bupropion exposure. Bupropion is a sensitive substrate of CYP2B6, and carbamazepine is a potent inducer for this enzyme. Monitor for signs of reduced bupropion efficacy during use together. Also monitor for any changes in seizure status if carbamazepine is used to treat seizures. [27843] [28058] [40993] [41086] [44094] Carbetapentane; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Carbidopa; Levodopa: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Carbidopa; Levodopa; Entacapone: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Carbinoxamine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Cariprazine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] [60164] Carvedilol: (Minor) Monitor for an increased incidence of carvedilol-related adverse effects if bupropion and carvedilol are used concomitantly. Coadministration of bupropion and carvedilol may result in increased plasma concentrations of carvedilol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Carvedilol is a CYP2D6 substrate. [28537] [41057] Cenobamate: (Major) Increase the dosage of bupropion as needed when coadministered with cenobamate due to the potential for reduced efficacy of bupropion. Multiple doses of cenobamate decreased bupropion exposure by 39%. Bupropion is a sensitive substrate of CYP2B6; cenobamate is a weak CYP2B6 inducer. [40993] [64768] Cetirizine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations. [28001] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Chlordiazepoxide; Clidinium: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should consider this when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [28058] Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Chlorpheniramine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Chlorpromazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of chlorpromazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of chlorpromazine may result in QT prolongation, somnolence, anticholinergic effects, or orthostasis. [28997] [41057] Ciclesonide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cimetidine: (Moderate) Cimetidine has resulted in increased plasma concentrations of the active metabolites, threohydrobupropion and erythrobupropion, but the clinical significance is not known. [4718] Citalopram: (Moderate) A pharmacokinetic interaction has been observed between bupropion and citalopram. In one study, bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively. Citalopram did not affect the kinetics of bupropion or its metabolites. The mechanism of this interaction has not been clearly established since citalopram is primarily metabolized by the isoenzymes CYP3A4 and CYP2C19 and bupropion and its metabolite hydroxybupropion are metabolized by CYP2B6 and are inhibitors of CYP2D6. [28058] [28269] Clomipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Clopidogrel: (Moderate) Dosage adjustment of bupropion may be necessary during coadministration with clopidogrel. Concomitant use may increase bupropion exposure but decrease hydroxybupropion exposure. Bupropion is primarily metabolized to hydroxybupropion via CYP2B6; clopidogrel is a weak CYP2B6 inhibitor. [34691] [41057] [56579] Clozapine: (Major) Monitor for evidence of clozapine-related adverse reactions and consider a clozapine dose reduction if necessary when coadministered with bupropion. If bupropion is discontinued after dose adjustments are made, monitor for lack of clozapine affect and consider increasing the clozapine dose if necessary. Concurrent use may result in increased clozapine exposure due to inhibition of CYP2D6 metabolism by bupropion. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. Furthermore, bupropion is associated with a dose-related risk of seizures; this risk may be increased by antipsychotics. [28262] [41057] Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Cocaine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as cocaine. This is of particular concern in those with excessive cocaine use (i.e., cocaine addition). Patients should be closely monitored if this combination is necessary. [4781] Codeine: (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Phenylephrine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Codeine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Moderate) Concomitant use of codeine with bupropion may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [33654] [34883] [41057] Corticosteroids: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Cyclobenzaprine: (Major) Concurrent use of cyclobenzaprine with bupropion increases the possibility of developing serotonin syndrome. If these drugs must be used together, closely monitor the patient for signs and symptoms of serotonin syndrome. If such a reaction develops, immediately discontinue both drugs. Additionally, cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, such as bupropion, anticholinergic side effects can be additive. Particular attention should be paid to GI problems because of the possible development of paralytic ileus. [28058] [28425] Dabrafenib: (Major) The concomitant use of dabrafenib and bupropion may lead to decreased bupropion concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents is unavoidable, monitor patients for loss of bupropion efficacy. In vitro, dabrafenib is an inducer of CYP2B6 via activation of the pregnane X receptor and constitutive androstane receptor nuclear receptors. Bupropion is a sensitive CYP2B6 substrate. [41057] [54802] Dalfampridine: (Moderate) Due to additive risks for seizure, extreme caution when coadministering bupropion with other drugs that lower seizure threshold (e.g., dalfampridine). Use low initial doses and increase the dose gradually. Monitor for seizure activity. Consider benefits against the risk of seizures. Consider alternatives to bupropion. Additionally, bupropion inhibits OCT2 in vitro, but the clinical relevance is not certain. Concurrent treatment with OCT2 inhibitors, such as bupropion, may cause increased exposure to dalfampridine. Elevated levels of dalfampridine increase the risk of seizures. The potential benefits of taking OCT2 inhibitors concurrently with dalfampridine should be considered against the risk of seizures in these patients. [41086] [41087] [43980] [44095] [57922] Darifenacin: (Moderate) Bupropion, an inhibitor of CYP2D6 may inhibit the metabolism of darifenacin. In addition, bupropion is associated with moderate anticholinergic effects which could be additive when coadministered with darifenacin. Patients should be monitored for increased anticholinergic effects or other adverse effects when these two drugs are coadministered. Dosage adjustments may be necessary. [28001] [28058] [30711] Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Deflazacort: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Desipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Desloratadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Deutetrabenazine: (Major) Do not exceed 18 mg/dose or 36 mg/day of deutetrabenazine if must use concurrently with a strong CYP2D6 inhibitor. Bupropion 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. [61845] Dexamethasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Dextroamphetamine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41086] [60070] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Dextromethorphan; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as bupropion. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur. [30090] Diethylpropion: (Major) Drugs which may lower the seizure threshold, such as diethylpropion, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [41057] Digoxin: (Moderate) Plasma digoxin concentrations and the patient's clinical response to digoxin therapy should be monitored during concurrent use with bupropion, due to the potential for decreased systemic exposure to digoxin. When a single oral dose of 0.5 mg of digoxin was administered 24 hours after a single 150 mg oral dose of extended-release bupropion in healthy volunteers, the digoxin exposure was decreased. [40993] [41086] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of dihydrocodeine with bupropion may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of bupropion 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 bupropion 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. Bupropion is a strong inhibitor of CYP2D6. [30282] [41057] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Dorzolamide; Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Doxepin: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like bupropion, 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 cytochrome P450 inhibitors are coadministered with doxercalciferol. [30802] [51248] Doxorubicin: (Major) In vitro, bupropion is a mild CYP2D6 inhibitor and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of bupropion and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity. [41057] [56361] Duloxetine: (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with bupropion. Concurrent use may result in increased duloxetine exposure resulting in excessive serotonin activity. Bupropion is a strong CYP2D6 inhibitor; duloxetine is a CYP2D6 substrate. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%. [28058] [29934] Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects. [28001] [28058] [29677] Efavirenz: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Efavirenz; Emtricitabine; Tenofovir: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of efavirenz 600 mg/day and bupropion in healthy volunteers resulted in a reduction of the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged and the Cmax of hydroxybupropion was increased by 50%. Healthcare providers are advised to increase the dose of bupropion based on clinical response during concurrent use with efavirenz; however, the maximum recommended dose of bupropion should not be exceeded. [28442] [32514] [40993] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with bupropion as there is a potential for elevated cobicistat concentrations. Bupropion is a CYP2D6 inhibitor in vitro, while cobicistat is a substrate of CYP2D6. [41057] [51664] [58000] Encainide: (Major) Encainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering encainide with CYP2D6 inhibitors, such as bupropion, since encainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions. [28001] [28058] Ethanol: (Major) Bupropion is associated with a dose-related risk of seizures. Both alcohol abuse and abrupt discontinuation of alcohol have been associated with seizures and fatalities, and may increase the risk of seizures and/or neuropsychiatric events with bupropion treatment. The use of alcohol or the abrupt discontinuation of ethanol should be avoided in patients taking bupropion. During post-marketing use of bupropion, some patients who were drinking alcohol reported reduced alcohol tolerance. [28058] [28449] Ethotoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Felbamate: (Major) Bupropion should not be used by patients taking anticonvulsants for seizures because it may decrease the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [4781] Fenfluramine: (Moderate) Use fenfluramine and bupropion with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [63529] [65634] Fentanyl: (Moderate) If concomitant use of fentanyl and bupropion 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. [40944] Fexofenadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Flavoxate: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [4781] Flecainide: (Major) Flecainide is significantly metabolized by CYP2D6 isoenzymes. Caution is recommended when administering flecainide with CYP2D6 inhibitors, such as bupropion; flecainide exhibits a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions. [4718] [4781] Fludrocortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Flunisolide: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluoxetine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluoxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. [28001] [28058] Fluoxetine; Olanzapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28785] [41057] (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluoxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. [28001] [28058] Fluphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of fluphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of fluphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43067] Fluticasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Salmeterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluticasone; Vilanterol: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fluvoxamine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including fluvoxamine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that fluvoxamine inhibits the hydroxylation of bupropion. [28058] Formoterol; Mometasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Fosphenytoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Gabapentin: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents. [28058] [40993] [41086] [44094] Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with bupropion 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 bupropion 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. [41057] [45935] Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Guaifenesin; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Guanfacine: (Moderate) There is one case report that describes a grand mal seizure that occurred in a child of 10 years of age receiving guanfacine and bupropion concurrently. It is not possible, based on this limited report, to determine if guanfacine was a contributor to the event. Causality has not been established. [28455] Haloperidol: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients. [41057] Homatropine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when homatropine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [26665] [28058] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydantoins: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration of bupropion. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled. [28539] [32916] [41057] Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Monitor for an increased incidence of propranolol-related adverse effects if bupropion and propranolol are used concomitantly. Coadministration of bupropion and propranolol may result in increased plasma concentrations of propranolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Propranolol is a CYP2D6 substrate. [41057] [53617] Hydrocodone: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocodone; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] (Moderate) Concomitant use of hydrocodone with bupropion may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of bupropion could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If bupropion is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Bupropion is a strong inhibitor of CYP2D6. [30379] [41057] [56303] Hydrocortisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Hydromorphone: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Ibuprofen; Oxycodone: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Ibuprofen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with bupropion. If bupropion is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Additionally, bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. Iloperidone is a CYP2D6 substrate. Bupropion is a strong inhibitor of CYP2D6. Coadministration of other strong CYP2D6 inhibitors increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by up to 3-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half. [36146] [41057] Imipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30355] Iobenguane I 131: (Major) Discontinue bupropion for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart bupropion until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as bupropion, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy. [63402] Isavuconazonium: (Moderate) Caution and close monitoring are advised when administering isavuconazonium concurrently with buproprion, as decreased buproprion serum concentrations may result. If decreased bupropion efficacy is noted, it may be necessary to increase the dose (not to exceed the maximum recommended dose). Isavuconazole, the active moiety of isavuconazonium, is an inducer of hepatic isoenzyme CYP2B6; bupropion is metabolized by this enzyme. [41086] [59042] Isocarboxazid: (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] Isoniazid, INH; Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] Ivosidenib: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of ivosidenib. A bupropion dose increase may be necessary; do not exceed the maximum recommended dose. Bupropion is a sensitive substrate of CYP2B6; ivosidenib may induce CYP2B6 leading to decreased bupropion concentrations. [41057] [63368] Lacosamide: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Lamotrigine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. 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. [63529] [64685] Lemborexant: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer. [40993] [41057] [41086] [44094] [44095] [56579] [64870] Levetiracetam: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Levodopa: (Major) Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa (e.g., carbidopa; levodopa and carbidopa; levodopa; entacapone). Both drugs are dopamine agonists; cumulative effects may result in central nervous system (CNS) toxicity. Adverse reactions reported with coadministration have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used concurrently, low initial dosing and slow dosage titration of bupropion may be warranted. [41057] Linezolid: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion 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 hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid. [41086] Lisdexamfetamine: (Major) The risk of seizures from the use of bupropion may be increased with concomitant use of CNS stimulants that may induce seizures, including the lisdexamfetamine. Concurrent use is not recommended. Extreme caution and close clinical monitoring is recommended if these agents must be used together. [41057] Lofexidine: (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and bupropion. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration with a strong CYP2D6 inhibitor increased the lofexidine AUC by 28%. [41057] [63161] Loperamide: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with bupropion, a weak in vitro CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). [30106] [41057] [60864] Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with bupropion, a weak in vitro CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest). [30106] [41057] [60864] Lopinavir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Loratadine; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Lorcaserin: (Moderate) 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, bupropion. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms. [51065] Loxapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme. [41057] [59891] Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of bupropion by decreasing its systemic exposure. If used together, monitor patients closely for loss of bupropion efficacy; a bupropion dosage adjustment may be required to obtain the desired therapeutic effect. Do not exceed the maximum recommended dose. Bupropion is a substrate of CYP2B6; in vitro data suggest that lumacaftor may induce this enzyme. [41057] [59891] Lurasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] [42227] Maprotiline: (Major) Concurrent administration of maprotiline with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of maprotiline leading to a potential for increased Cmax, AUC and half-life. Maprotiline appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving maprotiline, the need to reduce the maprotiline dosage should be considered. [4718] [4781] [5542] Mepenzolate: (Moderate) Additive anticholinergic effects may be seen when mepezolate is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30076] [42281] Meperidine: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Meperidine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Mephobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Methadone: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as methadone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28001] [28058] Methamphetamine: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as methamphetamine. If used together, use low initial doses of bupropion and increase the dose gradually. [33363] [41057] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30425] Methohexital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when methscopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [30076] [30424] Methylene Blue: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving intravenous methylene blue. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with intravenous methylene blue, bupropion should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits of methylene blue outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of methylene blue. It is not known if administration of methylene blue by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. [41086] Methylphenidate Derivatives: (Major) Medications which may lower the seizure threshold, such as methylphenidates, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [41057] Methylprednisolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] 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 bupropion is a strong CYP2D6 inhibitor. The manufacturer recommends avoidance of bupropion when oral metoclopramide is used in patients with diabetic gastroparesis. Healthy patients given 20 mg of metoclopramide and a potent CYP2D6 inhibitor for 8 days had a 40% and 90% increase in metoclopramide Cmax and AUC, respectively, compared to patients who received metoclopramide alone. [57877] Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration of bupropion. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled. [28539] [32916] [41057] Mexiletine: (Major) Coadministration of bupropion and mexiletine can increase the exposure of mexiletine. If used together, it may be necessary to decrease the dose of mexiletine and slowly titrate to effect. Mexiletine is primarily metabolized via CYP2D6 and bupropion and its metabolites are inhibitors of CYP2D6. [28001] [28280] [41057] Midazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of benzodiazepines is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. [28058] Mifepristone: (Moderate) Use mifepristone with caution with bupropion. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6, such as bupropion. The risk for bupropion-induced adverse reactions, including nausea, dry mouth, restlessness or difficulty with sleep, seizures, hypertension, or neuropsychiatric effects may be increased. Based on clinical response, dosage adjustment of bupropion may be necessary when coadministered with CYP2B6 inhibitors like mifepristone. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged. [28003] [48697] Modafinil: (Major) Bupropion is associated with a dose-related risk of seizures. It is unclear whether modafinil lowers the seizure threshold. Seizures have occurred during post-marketing use of modafinil, although the frequency is unknown. [28058] [40907] Molindone: (Major) Drugs which may lower the seizure threshold, such as molindone, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [28820] Mometasone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Monoamine oxidase inhibitors: (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Morphine: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Morphine; Naltrexone: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Naproxen; Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as bupropion, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. [41057] [60860] [60986] [60987] Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with bupropion. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as bupropion, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. [41057] [60860] [60986] [60987] Nelfinavir: (Minor) In vitro studies suggest that nelfinavir inhibits the hydroxylation of bupropion. The clinical significance of this finding is unknown. [40993] Nicotine: (Moderate) Combination of nicotine and bupropion may induce clinically significant blood pressure elevations in some patients. Close monitoring of blood pressure is recommended if this combination is prescribed. [28058] 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] Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure. [28963] [30355] [57419] Nortriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Olanzapine: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28785] [41057] 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 bupropion is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and bupropion may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If bupropion 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 bupropion 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. [41057] [65809] Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Oxcarbazepine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. [28058] [40993] [41086] [44094] Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when oxybutynin is used concomitantly with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that anticholinergic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Additive drowsiness may also occur. [28001] [29597] [29796] Oxycodone: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as oxycodone may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Oxymorphone: (Moderate) Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Paliperidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as paliperidone. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [32936] [41057] Paroxetine: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including paroxetine. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that paroxetine inhibit the hydroxylation of bupropion. [40993] [4718] [4781] Pemoline: (Major) Drugs which may lower the seizure threshold, such as pemoline, should be used with great caution or avoided in patients taking bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if this combination must be used concurrently; the patient should be closely monitored. [28058] Pentazocine: (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Pentazocine; Naloxone: (Moderate) Plasma concentrations of opiate agents metabolized by CYP2D6, such as pentazocine, may be increased if bupropion, an inhibitor of the CYP2D6 isoenzyme, is added. Dosage reductions of pentazocine may be needed. Conversely, if bupropion therapy is discontinued, dosages of pentazocine may need to be adjusted upward in some patients. [2173] Pentobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Perphenazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43070] Perphenazine; Amitriptyline: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of perphenazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of perphenazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43070] (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Phendimetrazine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of phendimetrazine is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Phenelzine: (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Phenobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Phentermine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] Phentermine; Topiramate: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Phenylephrine; Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Phenytoin: (Moderate) When anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), bupropion should not be used since bupropion lowers the seizure threshold. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as phenytoin (as well as other hydantoins like fosphenytoin or ethotoin). Monitor for reduced bupropion efficacy. [28058] [28535] [28823] [40993] [41086] [44094] Pimozide: (Contraindicated) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%. [28058] [43463] Pitolisant: (Major) Initiate pitolisant at 8.9 mg once daily in patients taking bupropion; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If bupropion is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate; bupropion is a strong CYP2D6 inhibitor. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. [41057] [64562] Prednisolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Prednisone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Primidone: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Prochlorperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of prochlorperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of prochlorperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [29498] [41057] Promethazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of promethazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of promethazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43930] Propafenone: (Major) Bupropion is an inhibitor of CYP2D6. Concentrations of medications metabolized by CYP2D6, such as propafenone, may be increased if bupropion is added. Dosage reductions of propafenone may be needed. [28058] [28287] Propantheline: (Moderate) Additive anticholinergic effects may be seen when propantheline is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [28714] [29597] [30425] Propoxyphene: (Moderate) Bupropion is an inhibitor of the CYP2D6 isoenzyme. Plasma concentrations of opiate agents metabolized by CYP2D6 such as propoxyphene may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. Excessive use of opioid agonists (e.g., opiate addiction) is associated with an increased seizure risk; seizures may be more likely to occur during concurrent use of bupropion in these patients since bupropion is associated with a dose-related risk of seizures. [28058] Propranolol: (Minor) Monitor for an increased incidence of propranolol-related adverse effects if bupropion and propranolol are used concomitantly. Coadministration of bupropion and propranolol may result in increased plasma concentrations of propranolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Propranolol is a CYP2D6 substrate. [41057] [53617] Protriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Pseudoephedrine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Pseudoephedrine; Triprolidine: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, including non-prescription stimulants and weight loss medications, is associated with an increased seizure risk; seizures may be more likely to occur in these patients during concurrent use of bupropion. Patients should be closely monitored if these combinations are necessary. [41057] Ranolazine: (Moderate) Bupropion inhibits CYP2D6. Coadministration of bupropion with medications that are metabolized by CYP2D6, like ranolazine, may result in increased ranolazine plasma concentrations if bupropion is added. [31938] [4718] Rasagiline: (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. The manufacturer of rasagiline advises against concurrent use with any antidepressant. [32223] [41086] Rifampin: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin. Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added. In healthy volunteers, coadministration of bupropion with rifampin reduced the mean AUC of bupropion by 3-fold and the mean half-life from 15.9 hours to 8.2 hours. [28001] [32802] Risperidone: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. 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 bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate. [41057] [56368] Ritonavir: (Moderate) Concurrent administration of bupropion with ritonavir results in decreased concentrations of bupropion and its active metabolite. According to the manufacturers of bupropion, increased doses of bupropion may be necessary during concurrent therapy; however, the maximum recommended dose of bupropion should not be exceeded. Closely monitor bupropion efficacy if these drugs are given together. Ritonavir induces CYP2B6, which is responsible for bupropion's metabolism. In one study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. In addition, exposure to the active metabolite of bupropion (hydroxybupropion) was decreased by 23%. When given with ritonavir 600 mg twice daily, the AUC and Cmax of bupropion decreased by 66% and 63% respectively and exposure to hydroxybupropion decreased by 78%. [28058] [28315] [34743] [34744] [34745] [34746] [44095] Scopolamine: (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30354] Secobarbital: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Selegiline: (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline. [28058] [40993] [41086] [44094] [57922] Sertraline: (Moderate) Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by CYP2D6 should be approached with caution. Many selective serotonin reuptake inhibitors (SSRIs) are CYP2D6 substrates including sertraline. Although clinical evidence of interactions is lacking, plasma concentrations of SSRIs metabolized by CYP2D6 may be increased if bupropion is added. In addition, in vitro studies suggest that sertraline inhibits the hydroxylation of bupropion. [28001] [40993] [41057] Sodium Oxybate: (Major) Use extreme caution when coadministering bupropion with other drugs that lower the seizure threshold, such as sodium oxybate. The risk of seizures with bupropion is dose related and is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment If used together, use low initial doses of bupropion and increase the dose gradually. [28528] [41057] Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as bupropion. Caution is recommended since this combination has not been evaluated. [64026] Tamoxifen: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with bupropion 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. Bupropion is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another 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; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no 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. [41057] [63589] Tamsulosin: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects. [28001] [28058] [29677] Theophylline, Aminophylline: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as aminophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. [41086] (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as theophylline. The manufacturer recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, when bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation. [28058] Thiethylperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of thiethylperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of thiethylperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [62314] Thiopental: (Moderate) Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function via CYP2B6 such as the barbiturates. While not systematically studied, these drugs may induce the metabolism of bupropion and may decrease bupropion exposure. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Advise patients that until they are reasonably certain that the combination does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery. [28058] [40993] [41086] [44095] Thioridazine: (Contraindicated) Bupropion is a strong inhibitor of CYP2D6 and the use of thioridazine with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias resulting from elevated serum concentrations of thioridazine. In addition, bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines, such as thioridazine, on lowering the seizure threshold. [41057] [43069] Thiotepa: (Moderate) The concomitant use of thiotepa and bupropion may increase the exposure of bupropion but decrease hydroxybupropion exposure; however, the clinical relevance of this interaction is unknown. Dosage adjustment of bupropion may be necessary based on clinical response. Thiotepa is a CYP2B6 inhibitor in vitro; bupropion is a sensitive substrate of CYP2B6 in vitro. [41057] [61718] Thiothixene: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [41057] Tiagabine: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Ticlopidine: (Moderate) Ticlopidine is a potent inhibitor of CYP2B6. By inhibiting this isoenzyme, ticlopidine theoretically could increase the plasma concentrations of drugs that are metabolized by CYP2B6, such as bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur. [28058] [34691] Timolol: (Minor) Monitor for an increased incidence of timolol-related adverse effects if bupropion and timolol are used concomitantly. Coadministration of bupropion and timolol may result in increased plasma concentrations of timolol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Timolol is a CYP2D6 substrate. [28540] [41057] Tobacco: (Moderate) Tobacco contains nicotine as one of its active components, but it is unclear if continuing to smoke concurrently with bupropion use increases the risk of blood pressure elevation. Bupropion has not been reported to interact pharmacokinetically with tobacco when used as monotherapy for smoking cessation; however, when bupropion is used as monotherapy, patients should schedule a date to stop tobacco smoking during the second week of taking bupropion. If the patient is prescribed a combination of bupropion with nicotine replacement therapy (like Nicotine patches) to stop smoking; then the patient should stop Tobacco smoking before starting to use the nicotine replacement therapy. Monitor blood pressure during smoking cessation treatment. [44094] Tolterodine: (Moderate) Bupropion exhibits moderate anticholinergic effects. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion. [4781] Topiramate: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Tramadol: (Major) Increased serum concentrations of tramadol and reduced serum concentrations of the O-desmethyltramadol metabolite (M1) would be expected from concurrent use of tramadol and a CYP2D6 inhibitor such as bupropion. As the analgesic activity of tramadol is due to both the parent drug and M1, inhibition of CYP2D6 by bupropion may affect the analgesic effect of tramadol; reduced analgesic effects are possible. Also, administration of tramadol may enhance the seizure risk in patients taking other medications that decrease the seizure threshold such as bupropion. [28001] [28314] Tranylcypromine: (Contraindicated) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs. [28058] [40993] [41086] [44094] [57922] Triamcinolone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Triazolam: (Moderate) Bupropion is contraindicated in patients undergoing abrupt withdrawal of benzodiazepines since the risk of seizures associated with bupropion may be increased. Excessive use of a benzodiazepine is associated with an increased seizure risk upon discontinuation of the drug; seizures may be more likely to occur in these patients during concurrent use of bupropion. [41086] [4781] Tricyclic antidepressants: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Trifluoperazine: (Major) Bupropion is associated with a dose-related risk of seizures and may have an additive effect with phenothiazines on lowering the seizure threshold. Low initial dosing and slow titration is recommended if this combination must be used. In addition, bupropion is a strong inhibitor of CYP2D6. Dosage reductions of trifluoperazine, a CYP2D6 substrate, may be needed during coadministration with bupropion. Increased serum concentrations of trifluoperazine may result in extrapyramidal symptoms, somnolence, or other adverse effects. [41057] [43071] Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when trihexyphenidyl is used concomitantly with bupropion. Additive drowsiness may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28058] [29597] [30336] Trimipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs). The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs. Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion. The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored. [28058] [29882] [41086] Trospium: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium and bupropion are used concomitantly. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients. [28058] [29236] Valproic Acid, Divalproex Sodium: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when valproic acid and its derivatives (valproate, divalproex) are used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Vigabatrin: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094] Vortioxetine: (Major) The primary isoenzyme involved in the metabolim of vortioxetine is CYP2D6; therefore, the manufacturer recommends a reduction in the vortioxetine dose by one-half during co-administration with strong inhibitors of CYP2D6 such as bupropion. The vortioxetine dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. [56041] Warfarin: (Moderate) When bupropion is used for smoking cessation, be aware that changes in the INR may occur in patients previously stabilized on warfarin as tobacco smoking is reduced or halted, as smoking affects CYP1A2, one of the enzymes involved in warfarin metabolism. Physiological changes resulting from smoking cessation, with or without treatment with bupropion, may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g.,warfarin) for which dosage adjustment may be necessary. A case report of potential interaction with warfarin and bupropion used for depression has been reported; when bupropion was abruptly halted in the patient prior to surgery, the patient's INR increased to 8.0. The authors could not discern a probable mechanism for the potential interaction, but the patient was also reducing his daily tobacco smoking status, Patients who are receiving warfarin with bupropion should be carefully monitored if the patient is also altering their smoking status. [44094] [62010] Ziprasidone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. [28233] [41057] Zolpidem: (Moderate) Rare cases of hallucinations have occurred when zolpidem was administered concurrently with bupropion. Dosage reductions in zolpidem may be needed if bupropion is used concurrently. [28747] Zonisamide: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with some anticonvulsant drugs that induce hepatic microsomal isoenzyme function. [28058] [40993] [41086] [44094]
Revision Date: 06/24/2021, 02:34:00 AM

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Monitoring Parameters

  • blood pressure
  • heart rate
  • weight

US Drug Names

  • Aplenzin
  • Budeprion SR
  • Budeprion XL
  • Buproban
  • Forfivo XL
  • Wellbutrin
  • Wellbutrin SR
  • Wellbutrin XL
  • Zyban
;