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    Naproxen

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    Apr.08.2024

    Naproxen

    Indications/Dosage

    Labeled

    • ankylosing spondylitis
    • arthralgia
    • bursitis
    • common cold
    • dental pain
    • dysmenorrhea
    • fever
    • gout
    • headache
    • juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA)
    • mild pain
    • moderate pain
    • musculoskeletal pain
    • osteoarthritis
    • rheumatoid arthritis
    • tendinitis

    Off-Label

    • heterotopic ossification
    • menstrual migraine prophylaxis
    • migraine
    • pericarditis
    † Off-label indication

    For the treatment of ankylosing spondylitis, osteoarthritis, or rheumatoid arthritis

    Oral dosage (naproxen tablets or suspension)

    Adults

    250 or 500 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.[32122] [66841]

    Oral dosage (naproxen sodium tablets)

    Adults

    275 or 550 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.[32122]

    Oral dosage (naproxen delayed-release tablets)

    Adults

    375 or 500 mg PO twice daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods of up to 6 months.[32122]

    Oral dosage (naproxen sodium controlled-release tablets)

    Adults

    750 or 1,000 mg PO once daily. May adjust the dose based on clinical response. Max: 1,500 mg/day for limited periods.[44091]

    For the treatment of juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA)

    Oral dosage (naproxen tablets)

    Children and Adolescents 2 to 17 years and weighing 50 kg or more

    5 mg/kg/dose (Max: 500 mg/dose) PO twice daily.[32122]

    Oral dosage (naproxen suspension)

    Children and Adolescents 2 to 17 years

    5 mg/kg/dose (Max: 500 mg/dose) PO twice daily.[66841]

    For the treatment of acute gout

    NOTE: Delayed-release naproxen is not recommended for the treatment of acute gout because of the absorption delay as compared to other naproxen formulations.[32122]

    Oral dosage (naproxen tablets or suspension)

    Adults

    750 mg PO once, then 250 mg PO every 8 hours as needed until the attack has subsided.[32122] [64373] [66841]

    Oral dosage (naproxen sodium tablets)

    Adults

    825 mg PO once, then 275 mg PO every 8 hours as needed until the attack has subsided.[32122]

    Oral dosage (naproxen controlled-release tablets)

    Adults

    1,000 to 1,500 mg PO once, then 1,000 mg PO once daily as needed until the attack has subsided.[44091]

    For the treatment of mild pain to moderate pain, including minor aches and pains associated with arthralgia, dental pain, headache, musculoskeletal pain (including backache), and/or the common cold

    NOTE: Delayed-release naproxen is not recommended for the initial treatment of pain because the absorption is delayed as compared to other naproxen formulations.[32122]

    NOTE: Naproxen sodium may be preferred to naproxen when fast-onset pain relief is needed.[32122]

    for the treatment of mild to moderate pain

    Oral dosage (naproxen tablets or suspension)

    Adults

    500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.[32122] [66841]

    Oral dosage (naproxen sodium tablets)

    Adults

    550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.[32122]

    Oral dosage (naproxen sodium controlled-release tablets)

    Adults

    1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.[44091]

    for the treatment of minor aches and pains associated with arthralgia, dental pain, headache, musculoskeletal pain (including backache), and/or the common cold

    Oral dosage (OTC naproxen sodium capsules or tablets)

    Adults

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day.[45292]

    Children and Adolescents 12 to 17 years

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day.[45292]

    For the treatment of dysmenorrhea

    Oral dosage (naproxen tablets or suspension)

    Adults

    500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.[32122] [66841]

    Oral dosage (naproxen sodium tablets)

    Adults

    550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.[32122]

    Oral dosage (naproxen sodium controlled-release tablets)

    Adults

    1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.[44091]

    Oral dosage (OTC naproxen sodium capsules or tablets)

    Adults

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if pain gets worse or lasts for more than 10 days.[45292]

    Children and Adolescents 12 to 17 years

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if pain gets worse or lasts for more than 10 days.[45292]

    For the treatment of fever

    Oral dosage (OTC naproxen sodium capsules or tablets)

    Adults

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if fever gets worse or lasts for more than 3 days.[45292]

    Children and Adolescents 12 to 17 years

    440 mg PO once, then 220 mg PO every 8 to 12 hours. Max: 660 mg/day. Discontinue use if fever gets worse or lasts for more than 3 days.[45292]

    For the treatment of bursitis and tendinitis

    Oral dosage (naproxen tablets or suspension)

    Adults

    500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.[32122] [66841]

    Oral dosage (naproxen sodium tablets)

    Adults

    550 mg PO once, then 550 mg PO every 12 hours or 275 mg PO every 6 to 8 hours as needed. Max: 1,375 mg on day 1, then 1,100 mg/day.[32122]

    Oral dosage (naproxen sodium controlled-release tablets)

    Adults

    1,000 or 1,500 mg PO once daily. Usual Max: 1,000 mg/day.[44091]

    For the acute treatment of migraine†

    Oral dosage (naproxen)

    Adults

    500 mg PO as a single dose. Guidelines classify naproxen as having established efficacy for the treatment of acute migraine.[64565] [69288]

    Oral dosage (naproxen sodium)

    Adults

    550 mg PO as a single dose. Guidelines classify naproxen as having established efficacy for the treatment of acute migraine.[64565] [69288]

    For menstrual migraine prophylaxis†

    Oral dosage (naproxen sodium tablets)

    Adults

    500 or 550 mg PO once or twice daily for 6 days starting 2 to 7 days before the expected onset of menses and repeated monthly with each menstrual cycle.[58995]

    For the prevention of heterotopic ossification†

    Oral dosage (naproxen tablets or oral suspension)

    Adults

    250 mg PO 3 times daily for 6 weeks or 500 mg PO twice daily for 7 days after total hip arthroplasty.[31930] [31966]

    For the treatment of acute or recurrent pericarditis†

    NOTE: Dosage expressed as naproxen base (200 mg naproxen base is equivalent to 220 mg naproxen sodium).[67419]

    for the treatment of acute pericarditis†

    Oral dosage (naproxen tablets or suspension)

    Adults

    250 to 500 mg PO every 12 hours, initially; may increase dose up to 1,500 mg/day if tolerated and needed and continue for 1 to 2 weeks, then decrease dose by 125 to 250 mg/day every 1 to 2 weeks in combination with colchicine.[67419]

    Children and Adolescents 2 to 17 years

    5 mg/kg/dose PO every 12 hours for 1 to 4 weeks; up to 15 mg/kg/day has been tolerated. Consider tapering dose gradually every 1 to 2 weeks.[67418] [67419]

    for the treatment of recurrent pericarditis†

    Oral dosage (naproxen tablets or suspension)

    Adults

    250 to 500 mg PO every 12 hours, initially; may increase dose up to 1,500 mg/day if tolerated and needed and continue for at least 2 to 4 weeks, then decrease dose by 125 to 250 mg/day every 1 to 2 weeks in combination with colchicine.[67419]

    Children and Adolescents 2 to 17 years

    5 mg/kg/dose PO every 12 hours for at least 2 to 4 weeks in combination with colchicine; up to 15 mg/kg/day has been tolerated. Consider tapering dose gradually every 1 to 2 weeks.[67418] [67419]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.

    • Geriatric

      Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.

    • Adolescents

      Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day PO.

    • Children

      >= 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; for non-prescription use, 660 mg/day PO.

      2 to < 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; non-prescription (self medication) use is not recommended.

      < 2 years: Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    Although specific guidelines are not available, dosage reduction may be necessary in patients with hepatic dysfunction.

    Patients with Renal Impairment Dosing

    CrCl >= 30 ml/min: No dosage adjustment needed.

    CrCl < 30 ml/min: Not recommended.

    † Off-label indication
    Revision Date: 04/08/2024, 02:15:00 AM

    References

    31930 - Vielpeau C, Joubert JM, Hulet C. Naproxen in the prevention of heterotopic ossification after total hip replacement. Clin Orthop 1999;369:279-88.31966 - Gebuhr PH, Wilbek H, Soelberg M. Eight days of naproxen therapy can prevent heterotopic ossification after total hip alloplasty. Ugeskr Laeger 1996;158:1076-8.32122 - EC Naprosyn (naproxen delayed-release tablets), Naprosyn (naproxen tablets), Anaprox DS (naproxen sodium tablets) package insert. Alpharetta, GA: Canton Laboratories, LLC; 2021 Apr.44091 - Naprelan (naproxen sodium extended-release tablets) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2021 Apr.45292 - Aleve (naproxen sodium 220mg) consumer package insert. Whippany, NJ: Bayer HealthCare LLC; 2022 Mar.58995 - Sances G, Martignoni E, Fioroni L, Blandini F, Facchinetti F, Nappi G. Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. Headache 1990; 30: 705-9.64373 - Qaseem A, Harris RP, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017;166:58-68.64565 - Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: The American Headache Society evidence assessment of migraine pharmacotherapies. Headache 2015;55:3-20.66841 - Naprosyn (naproxen) oral suspension package insert. Athens, GA: Athena Bioscience, LLC; 2021 Apr.67418 - Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines on the diagnosis and management of pericardial diseases. Eur Heart J. 2015;36:2921-2964.67419 - Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines on the diagnosis and management of pericardial diseases - Web Addenda. Eur Heart J. 2015; doi:10.1093/eurheart/ehv31869288 - Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 2021 ;61:1021-1039.

    How Supplied

    Naproxen Oral suspension

    Naprosyn 125mg/5mL Suspension (71511-0701) (Athena Bioscience, LLC.) nullNaprosyn 125mg/5mL Suspension package photo

    Naproxen Oral suspension

    Naprosyn 125mg/5mL Suspension (69437-0028) (Canton Laboratories) null

    Naproxen Oral suspension

    Naprosyn 125mg/5mL Suspension (00004-0028) (Genentech Inc) (off market)Naprosyn 125mg/5mL Suspension package photo

    Naproxen Oral suspension

    Naprosyn 125mg/5mL Suspension (70868-0700) (Key Therapeutics, LLC) (off market)

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (42192-0619) (Acella Pharmaceuticals, LLC) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (71297-0200) (Allegis Holdings, LLC.) (off market)

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (69238-1730) (Amneal Pharmaceuticals LLC) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (31722-0682) (Camber Pharmaceuticals Inc) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (00054-3630) (Hikma Pharmaceuticals USA Inc.) (off market)Naproxen 125mg/5mL Suspension package photo

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (00054-3630) (Hikma Pharmaceuticals USA Inc.) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (70868-0200) (Key Therapeutics, LLC) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (70954-0151) (Novitium Pharma, LLC ) null

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (68134-0363) (Palmetto Pharmaceuticals) (off market)Naproxen 125mg/5mL Suspension package photo

    Naproxen Oral suspension

    Naproxen 125mg/5mL Suspension (68134-0201) (Palmetto Pharmaceuticals) nullNaproxen 125mg/5mL Suspension package photo

    Naproxen Oral tablet

    Naprosyn 250mg Tablet (00004-6313) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naprosyn 250mg Tablet (00004-6312) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (33261-0128) (Aidarex Pharmaceuticals, LLC) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (65162-0076) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (53746-0188) (Amneal Pharmaceuticals LLC) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (65162-0188) (Amneal Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (65862-0520) (Aurobindo Pharma USA Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (50268-0594) (AvPAK; a Division of AvKARE Inc) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (71335-0217) (Bryant Ranch Prepack, Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (31722-0340) (Camber Pharmaceuticals Inc) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (69097-0853) (Cipla USA, Inc) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (55111-0366) (Dr. Reddy's Laboratories, Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (42806-0124) (Epic Pharma LLC) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (76282-0340) (Exelan Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (68462-0188) (Glenmark Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (68462-0188) (Glenmark Pharmaceuticals) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (70010-0137) (Granules Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00143-1346) (Hikma Pharmaceuticals USA Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (53746-0188) (Interpharm Inc) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00904-5535) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00904-6069) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00904-6295) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (52555-0712) (Martec Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (55370-0139) (Mova Pharmaceuticals Corp) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (55370-0521) (Mova Pharmaceuticals Corp) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (51079-0793) (Mylan Institutional LLC) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00378-0377) (Mylan Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (66267-0151) (NuCare Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (67253-0620) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (67253-0620) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (43063-0092) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (55289-0445) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (55289-0445) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (43063-0445) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (43063-0600) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (45802-0121) (Perrigo Pharmaceuticals Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (10768-7121) (Perrigo Rx) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (52605-0138) (Polygen Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (17236-0076) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (77771-0434) (Radha Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00781-1163) (Sandoz Inc. a Novartis Company) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00364-2562) (Schein Pharmaceutical Inc, an Actavis Company) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (50228-0434) (ScieGen Pharmaceuticals, Inc) null

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00182-8240) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00093-0147) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00182-1971) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00172-4107) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (50111-0555) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00591-0821) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (00591-5816) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (52544-0821) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 250mg Tablet (49483-0619) (Time Cap Laboratories Inc) null

    Naproxen Oral tablet

    Naprosyn 375mg Tablet (00004-6314) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naprosyn 375mg Tablet (00004-6311) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (65162-0077) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (53746-0189) (Amneal Pharmaceuticals LLC) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (65162-0189) (Amneal Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (50090-1583) (A-S Medication Solutions LLC) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (65862-0521) (Aurobindo Pharma USA Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (50268-0595) (AvPAK; a Division of AvKARE Inc) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (10544-0019) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (10544-0277) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (71335-0255) (Bryant Ranch Prepack, Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (31722-0341) (Camber Pharmaceuticals Inc) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (69097-0854) (Cipla USA, Inc) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (55111-0367) (Dr. Reddy's Laboratories, Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (42806-0125) (Epic Pharma LLC) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (76282-0341) (Exelan Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (68462-0189) (Glenmark Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (68462-0189) (Glenmark Pharmaceuticals) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (70010-0138) (Granules Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00143-1347) (Hikma Pharmaceuticals USA Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (52959-0191) (HJ Harkins Co Inc) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (53746-0189) (Interpharm Inc) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00005-3301) (Lederle Pharmaceutical Div American Cyanamid Co) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00904-5536) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00904-5590) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00904-5590) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00904-5590) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (55370-0140) (Mova Pharmaceuticals Corp) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (51079-0794) (Mylan Institutional LLC) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00378-0555) (Mylan Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (66267-0152) (NuCare Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (67253-0621) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (67253-0621) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (55289-0297) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (43063-0258) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (43063-0650) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (45802-0534) (Perrigo Pharmaceuticals Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (10768-7534) (Perrigo Rx) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (52605-0139) (Polygen Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (17236-0077) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (77771-0435) (Radha Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00781-1164) (Sandoz Inc. a Novartis Company) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00364-2563) (Schein Pharmaceutical Inc, an Actavis Company) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (50228-0435) (ScieGen Pharmaceuticals, Inc) null

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00093-0148) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00172-4108) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (50111-0556) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00591-0822) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (00591-5817) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 375mg Tablet (49483-0617) (Time Cap Laboratories Inc) null

    Naproxen Oral tablet

    Naprosyn 500mg Tablet (69437-0316) (Canton Laboratories) null

    Naproxen Oral tablet

    Naprosyn 500mg Tablet (00004-6316) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naprosyn 500mg Tablet (00004-6310) (Genentech Inc) (off market)

    Naproxen Oral tablet

    Naprosyn 500mg Tablet (55289-0420) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (65162-0078) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (69512-0190) (Alivio Medical Products) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (68084-0127) (American Health Packaging) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (60687-0268) (American Health Packaging) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (60687-0491) (American Health Packaging) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (53746-0190) (Amneal Pharmaceuticals LLC) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (65162-0190) (Amneal Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (50090-6666) (A-S Medication Solutions LLC) nullNaproxen 500mg Tablet package photo

    Naproxen Oral tablet

    Naproxen 500mg Tablet (50090-6667) (A-S Medication Solutions LLC) nullNaproxen 500mg Tablet package photo

    Naproxen Oral tablet

    Naproxen 500mg Tablet (65862-0522) (Aurobindo Pharma USA Inc.) nullNaproxen 500mg Tablet package photo

    Naproxen Oral tablet

    Naproxen 500mg Tablet (42291-0628) (AvKARE, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (50268-0596) (AvPAK; a Division of AvKARE Inc) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (69150-0140) (Biomes Pharmaceuticals, LLC) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10544-0010) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10544-0016) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10544-0044) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10544-0061) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10544-0278) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (71335-0345) (Bryant Ranch Prepack, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (31722-0342) (Camber Pharmaceuticals Inc) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (69097-0855) (Cipla USA, Inc) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (55111-0368) (Dr. Reddy's Laboratories, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (42806-0126) (Epic Pharma LLC) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (76282-0342) (Exelan Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (68462-0190) (Glenmark Pharmaceuticals) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (68462-0190) (Glenmark Pharmaceuticals) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (70010-0139) (Granules Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00143-1348) (Hikma Pharmaceuticals USA Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (52959-0193) (HJ Harkins Co Inc) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (53746-0190) (Interpharm Inc) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00005-3302) (Lederle Pharmaceutical Div American Cyanamid Co) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00440-1852) (Liberty Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00040-7852) (Liberty Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00904-5537) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00904-5591) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00904-5591) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00904-6297) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (63739-0403) (McKesson Packaging) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (55370-0141) (Mova Pharmaceuticals Corp) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (51079-0795) (Mylan Institutional LLC) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00378-0451) (Mylan Pharmaceuticals Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (66267-0153) (NuCare Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (67253-0622) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (67253-0622) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (67253-0003) (Par Pharmaceuticals, an Endo Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (55289-0298) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (55289-0298) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (43063-0344) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (43063-0920) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (43063-0937) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (55289-0298) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (72789-0321) (PD-Rx Pharmaceuticals, Inc.) nullNaproxen 500mg Tablet package photo

    Naproxen Oral tablet

    Naproxen 500mg Tablet (45802-0631) (Perrigo Pharmaceuticals Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (10768-7631) (Perrigo Rx) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (52605-0140) (Polygen Pharmaceuticals LLC) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (17236-0078) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (77771-0436) (Radha Pharmaceuticals, Inc.) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00781-1165) (Sandoz Inc. a Novartis Company) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00364-2564) (Schein Pharmaceutical Inc, an Actavis Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (50228-0436) (ScieGen Pharmaceuticals, Inc) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (60760-0190) (St. Mary's Medical Park Pharmacy) null

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00300-1547) (TAP Pharmaceuticals Inc, a Takeda Company) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00182-8241) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00093-0149) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00182-1973) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00172-4109) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (50111-0557) (Teva Pharmaceuticals USA) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00591-0791) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (00591-5818) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (52544-0791) (Teva/Actavis US) (off market)

    Naproxen Oral tablet

    Naproxen 500mg Tablet (49483-0618) (Time Cap Laboratories Inc) null

    Naproxen Oral tablet, biphasic release

    Naproxen 500mg Extended-Release Tablet (62037-0826) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (59630-0375) (Almatica Pharma, a subsidiary of Alvogen) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (52427-0272) (Almatica Pharma, a subsidiary of Alvogen) null

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (51674-0375) (Blansett Pharmacal Co Inc) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (00086-0090) (Elan Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (68453-0375) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (59630-0375) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (51674-0375) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 375 Controlled-Release Tablet (68453-0375) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naproxen 375mg Extended-Release Tablet (00480-0951) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, extended release

    Naproxen 375mg Extended-Release Tablet (62037-0825) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, extended release

    Naproxen Sodium 375mg Controlled-Release Tablet (47781-0153) (Alvogen, Inc.) null

    Naproxen Oral tablet, extended release

    Naproxen Sodium 375mg Controlled-Release Tablet (69420-1375) (SA3, LLC) null

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (59630-0850) (Almatica Pharma, a subsidiary of Alvogen) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (52427-0273) (Almatica Pharma, a subsidiary of Alvogen) null

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (00086-0091) (Elan Pharmaceuticals Inc) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (50383-0850) (Hi-Tech Pharmacal, a subsidiary of Akorn) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (68453-0850) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (59630-0850) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (50383-0850) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 500 Controlled-Release Tablet (68453-0850) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naproxen 500mg Extended-Release Tablet (00480-0952) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, extended release

    Naproxen 500mg Extended-Release Tablet (62037-0826) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, extended release

    Naproxen 500mg Extended-Release Tablet (62037-0826) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, extended release

    Naproxen Sodium 500mg Controlled-Release Tablet (47781-0154) (Alvogen, Inc.) null

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (59630-0777) (Almatica Pharma, a subsidiary of Alvogen) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (52427-0274) (Almatica Pharma, a subsidiary of Alvogen) null

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (43063-0242) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (68453-0777) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (59630-0777) (Shionogi USA, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naprelan 750 Controlled-Release Tablet (68453-0777) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, extended release

    Naproxen Sodium 750 Controlled-Release Tablet (47781-0155) (Alvogen, Inc.) null

    Naproxen Oral tablet, extended release

    Naproxen Sodium 750mg Controlled-Release Tablet (00480-0953) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, extended release, Naproxen Oral tablet, extended release

    Naprelan Dose Card Controlled-Release Tablet (68453-0900) (Victory Pharma, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 375mg Delayed-Release Tablet (69437-0415) (Canton Laboratories) null

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 375mg Delayed-Release Tablet (00004-6415) (Genentech Inc) (off market)

    Naproxen Oral tablet, gastro-resistant

    EC-Naproxen 375mg Delayed-Release Tablet (69784-0501) (Woodward Pharma Services LLC ) null

    Naproxen Oral tablet, gastro-resistant

    Enteric Coated Naproxen 375mg Tablet (58177-0302) (Ethex Corporation) (off market)

    Naproxen Oral tablet, gastro-resistant

    Enteric Coated Naproxen 375mg Tablet (55289-0921) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (42291-0629) (AvKARE, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (31722-0338) (Camber Pharmaceuticals Inc) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (69097-0851) (Cipla USA, Inc) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (71205-0060) (Proficient Rx LP) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (71205-0469) (Proficient Rx LP) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (00781-1646) (Sandoz Inc. a Novartis Company) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (62269-0289) (Sandoz, Inc. a Novartis Company) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (00093-1005) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (50111-0614) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (00228-2617) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (00228-2745) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 375mg Delayed-Release Tablet (69543-0425) (Virtus Pharmaceuticals) null

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 500mg Delayed-Release Tablet (72162-1935) (Bryant Ranch Prepack, Inc.) null

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 500mg Delayed-Release Tablet (69437-0416) (Canton Laboratories) null

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 500mg Delayed-Release Tablet (00004-6416) (Genentech Inc) (off market)

    Naproxen Oral tablet, gastro-resistant

    EC-Naprosyn 500mg Delayed-Release Tablet (55289-0693) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    EC-Naproxen 500mg Delayed-Release Tablet (63629-2484) (Bryant Ranch Prepack, Inc.) null

    Naproxen Oral tablet, gastro-resistant

    EC-Naproxen 500mg Delayed-Release Tablet (69784-0500) (Woodward Pharma Services LLC ) null

    Naproxen Oral tablet, gastro-resistant

    Enteric Coated Naproxen 500mg Tablet (58177-0303) (Ethex Corporation) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (50090-3025) (A-S Medication Solutions LLC) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (42291-0630) (AvKARE, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (31722-0339) (Camber Pharmaceuticals Inc) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (42494-0454) (Cameron Pharmaceuticals, LLC) nullNaproxen 500mg Delayed-Release Tablet package photo

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (69097-0852) (Cipla USA, Inc) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (52959-0516) (HJ Harkins Co Inc) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (52959-0516) (HJ Harkins Co Inc) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (55289-0307) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (55289-0307) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (72789-0003) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (00781-1653) (Sandoz Inc. a Novartis Company) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (62269-0290) (Sandoz, Inc. a Novartis Company) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (00093-1006) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (50111-0615) (Teva Pharmaceuticals USA) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (00228-2618) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (00228-2746) (Teva/Actavis US) (off market)

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (52817-0381) (TruPharma, LLC) null

    Naproxen Oral tablet, gastro-resistant

    Naproxen 500mg Delayed-Release Tablet (69543-0426) (Virtus Pharmaceuticals) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (25866-0528) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (25866-0528) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (25866-0528) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (25866-0558) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (25866-0561) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve 220mg Liquid Gel Capsule (00280-6080) (Bayer HealthCare LLC) null

    Naproxen Sodium Oral capsule, liquid filled

    Aleve Arthritis 220mg Liquid Gel Capsule (25866-0535) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (null) (CVS Health) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (null) (CVS Health) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (null) (CVS Health) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (59779-0742) (CVS Health) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (null) (CVS Health) null

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (null) (CVS Health) null

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (59779-0742) (CVS Health) null

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (59779-0742) (CVS Health) null

    Naproxen Sodium Oral capsule, liquid filled

    CVS Naproxen Sodium 220mg Liquid Gel Capsule (69842-0748) (CVS Health) null

    Naproxen Sodium Oral capsule, liquid filled

    Foster & Thrive Naproxen Sodium 220mg Liquid Gel Capsule (70677-1148) (McKesson Corporation) nullFoster & Thrive Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    GNP Naproxen Sodium 220mg Liquid Gel Capsule (46122-0038) (AmerisourceBergen Corporation) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    GNP Naproxen Sodium 220mg Liquid Gel Capsule (46122-0283) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral capsule, liquid filled

    GNP Naproxen Sodium 220mg Liquid Gel Capsule (46122-0283) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral capsule, liquid filled

    GNP Naproxen Sodium 220mg Liquid Gel Capsule (46122-0534) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral capsule, liquid filled

    Health Mart Naproxen Sodium 220mg Liquid Gel Capsule (62011-0007) (McKesson Corporation) null

    Naproxen Sodium Oral capsule, liquid filled

    Health Mart Naproxen Sodium 220mg Liquid Gel Capsule (62011-0249) (McKesson Corporation) null

    Naproxen Sodium Oral capsule, liquid filled

    Health Mart Naproxen Sodium 220mg Liquid Gel Capsule (62011-0369) (McKesson Corporation) (off market)

    Naproxen Sodium Oral capsule, liquid filled

    Leader Naproxen Sodium 220mg Liquid Gel Capsule (37205-0854) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral capsule, liquid filled

    Leader Naproxen Sodium 220mg Liquid Gel Capsule (37205-0854) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral capsule, liquid filled

    Naproxen Sodium 220mg Liquid Gel Capsule (69230-0305) (Camber Consumer Care, Inc.) null

    Naproxen Sodium Oral capsule, liquid filled

    Quality Choice Naproxen Sodium 220mg Liquid Filled Capsule (63868-0830) (Chain Drug Marketing Association) nullQuality Choice Naproxen Sodium 220mg Liquid Filled Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    RITE AID Naproxen Sodium 220mg Liquid Gel Capsule (null) (Rite Aid Corp) null

    Naproxen Sodium Oral capsule, liquid filled

    RITE AID Naproxen Sodium 220mg Liquid Gel Capsule (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    RITE AID Naproxen Sodium 220mg Liquid Gel Capsule (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Top Care Naproxen Sodium 220mg Liquid Gel Capsule (null) (Topco Associates LLC) null

    Naproxen Sodium Oral capsule, liquid filled

    Top Care Naproxen Sodium 220mg Liquid Gel Capsule (null) (Topco Associates LLC) null

    Naproxen Sodium Oral capsule, liquid filled

    Top Care Naproxen Sodium 220mg Liquid Gel Capsule (null) (Topco Associates LLC) null

    Naproxen Sodium Oral capsule, liquid filled

    Top Care Naproxen Sodium 220mg Liquid Gel Capsule (null) (Topco Associates LLC) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens All Day Pain Relief 12 Hour 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens All Day Pain Relief 12 Hour 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0742) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0742) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0174) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0748) (Walgreens Co) nullWalgreens Naproxen Sodium 220mg Liquid Gel Capsule package photo

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0177) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0177) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0177) (Walgreens Co) null

    Naproxen Sodium Oral capsule, liquid filled

    Walgreens Naproxen Sodium 220mg Liquid Gel Capsule (00363-0177) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0105) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0503) (Bayer Corp Consumer Care Div) (off market)

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0540) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0551) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0105) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0105) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0000) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (25866-0001) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Caplet (null) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Gelcap Tablet (25866-0054) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Gelcap Tablet (25866-0519) (Bayer Corp Consumer Care Div) (off market)

    Naproxen Sodium Oral tablet

    Aleve 220mg Tablet (25866-0105) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Tablet (25866-0513) (Bayer Corp Consumer Care Div) (off market)

    Naproxen Sodium Oral tablet

    Aleve 220mg Tablet (null) (Bayer Corp Consumer Care Div) (off market)

    Naproxen Sodium Oral tablet

    Aleve 220mg Tablet (25866-0558) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve 220mg Tablet (00280-6000) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Caplet (25866-0536) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Caplet (25866-0558) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Caplet (25866-0563) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Caplet (25866-0560) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Gelcap Tablet (null) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    Aleve Arthritis 220mg Tablet (null) (Bayer Corp Consumer Care Div) null

    Naproxen Sodium Oral tablet

    All Day Pain Relief 220mg Tablet (69230-0313) (Camber Consumer Care, Inc.) null

    Naproxen Sodium Oral tablet

    All Day Relief 220mg Caplet (00536-1022) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Naproxen Sodium Oral tablet

    All Day Relief 220mg Caplet (00536-1093) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

    Naproxen Sodium Oral tablet

    All Day Relief 220mg Tablet (50090-3356) (A-S Medication Solutions LLC) null

    Naproxen Sodium Oral tablet

    All Day Relief 220mg Tablet (00536-1023) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Naproxen Sodium Oral tablet

    All Day Relief 220mg Tablet (00536-1094) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

    Naproxen Sodium Oral tablet

    CAREALL Naproxen Sodium 220mg Tablet (51824-0072) (New World Imports Inc) null

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Caplet (59779-0368) (CVS Health) nullCVS All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Caplet (59779-0140) (CVS Health) nullCVS All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Caplet (65162-0197) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Caplet (59779-0061) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Caplet (59779-0368) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Tablet (59779-0490) (CVS Health) (off market)CVS All Day Pain Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Tablet (65162-0196) (CVS Health) (off market)

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Tablet (null) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS All Day Pain Relief 220mg Tablet (59779-0490) (CVS Health) (off market)

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Caplet (59779-0914) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Caplet (69842-0010) (CVS Health) nullCVS Naproxen Sodium 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (59779-0914) (CVS Health) (off market)

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (59779-0914) (CVS Health) (off market)

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (69842-0811) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (69842-0811) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (69842-0811) (CVS Health) null

    Naproxen Sodium Oral tablet

    CVS Naproxen Sodium 220mg Tablet (69842-0811) (CVS Health) null

    Naproxen Sodium Oral tablet

    Equaline All Day Relief 220mg Caplet (41163-0140) (Albertson's, Inc) (off market)

    Naproxen Sodium Oral tablet

    Equaline Naproxen Sodium 220mg Caplet (41163-0511) (Albertson's, Inc) null

    Naproxen Sodium Oral tablet

    Equaline Naproxen Sodium 220mg Tablet (41163-0707) (Albertson's, Inc) null

    Naproxen Sodium Oral tablet

    Equate 12 Hour All Day Pain Relief 220mg Caplet (79903-0005) (Wal-Mart Stores, Inc.) null

    Naproxen Sodium Oral tablet

    Equate All Day Pain Relief 220mg Caplet (49035-0767) (Wal-Mart Stores, Inc.) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (24385-0368) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0309) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0309) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0309) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0309) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0564) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0564) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Caplet (46122-0564) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Tablet (24385-0490) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Tablet (46122-0562) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GNP Naproxen Sodium 220mg Tablet (46122-0562) (AmerisourceBergen Corporation) null

    Naproxen Sodium Oral tablet

    GoodSense All Day Pain Relief 220mg Caplet (00113-0368) (Goodsense a Division of Perrigo) null

    Naproxen Sodium Oral tablet

    GoodSense All Day Pain Relief 220mg Caplet (00113-0368) (Goodsense a Division of Perrigo) null

    Naproxen Sodium Oral tablet

    GoodSense Naproxen Sodium 220mg Caplet (50090-3369) (A-S Medication Solutions LLC) null

    Naproxen Sodium Oral tablet

    GoodSense Naproxen Sodium 220mg Caplet (00113-4368) (Goodsense a Division of Perrigo) null

    Naproxen Sodium Oral tablet

    GoodSense Naproxen Sodium 220mg Tablet (00113-9490) (Goodsense a Division of Perrigo) null

    Naproxen Sodium Oral tablet

    GoodSense Naproxen Sodium 220mg Tablet (00113-0901) (Goodsense a Division of Perrigo) null

    Naproxen Sodium Oral tablet

    Health Mart Naproxen Sodium 220mg Caplet (62011-0017) (McKesson Corporation) (off market)

    Naproxen Sodium Oral tablet

    HEB RX Act All Day Pain Relief 220mg Tablet (37808-0490) (H-E-B) null

    Naproxen Sodium Oral tablet

    Kirkland Naproxen Sodium 220mg Caplet (63981-0368) (Costco Wholesale Corporation) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Caplet (37205-0261) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Caplet (37205-0744) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Caplet (37205-0744) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Caplet (70000-0201) (Cardinal Health, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Caplet (70000-0201) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Tablet (37205-0262) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Tablet (70000-0171) (Cardinal Health, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Leader All Day Pain Relief 220mg Tablet (70000-0171) (Cardinal Health, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Caplet (55289-0579) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Caplet (00536-4113) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Caplet (00182-1106) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (68084-0914) (American Health Packaging) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (52297-0847) (Cardinal Health, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (52297-0849) (Cardinal Health, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (57896-0951) (Geri-Care Pharmaceuticals) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (57896-0954) (Geri-Care Pharmaceuticals) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (00904-5229) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (00904-5230) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (66267-0343) (NuCare Pharmaceuticals Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (45802-0490) (Padagis US LLC) nullNaproxen Sodium 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (43063-0909) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (68788-8447) (Preferred Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (63187-0986) (Proficient Rx LP) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (71205-0595) (Proficient Rx LP) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (60814-0178) (Rexall Group) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (00182-1097) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 220mg Tablet (49483-0609) (Time Cap Laboratories Inc) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Caplet (68016-0462) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Caplet (68016-0660) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Caplet (68016-0660) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Tablet (68016-0464) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Tablet (68016-0661) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Premier Value Naproxen Sodium 220mg Tablet (68016-0661) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Naproxen Sodium Oral tablet

    Publix All Day Relief 220mg Caplet (56062-0368) (Publix Super Markets, Inc) null

    Naproxen Sodium Oral tablet

    Publix All Day Relief 220mg Tablet (56062-0490) (Publix Super Markets, Inc) null

    Naproxen Sodium Oral tablet

    Quality Choice Naproxen Sodium 220mg Caplet (63868-0466) (Chain Drug Marketing Association) null

    Naproxen Sodium Oral tablet

    Quality Choice Naproxen Sodium 220mg Tablet (63868-0465) (Chain Drug Marketing Association) null

    Naproxen Sodium Oral tablet

    RITE AID All Day Pain Relief 220mg Caplet (null) (Rite Aid Corp) nullRITE AID All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    RITE AID Naproxen Sodium 220mg Caplet (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    RITE AID Naproxen Sodium 220mg Caplet (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    RITE AID Naproxen Sodium 220mg Caplet (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    RITE AID Naproxen Sodium 220mg Tablet (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    RITE AID Naproxen Sodium 220mg Tablet (null) (Rite Aid Corp) nullRITE AID Naproxen Sodium 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Select Brand Naproxen Sodium 220mg Caplet (15127-0466) (Select Brand) null

    Naproxen Sodium Oral tablet

    Sunmark All Day Relief 220mg Caplet (49348-0819) (McKesson Corporation) null

    Naproxen Sodium Oral tablet

    Sunmark Naproxen Sodium 220mg Caplet (49348-0306) (McKesson Corporation) null

    Naproxen Sodium Oral tablet

    Sunmark Naproxen Sodium 220mg Caplet (49348-0306) (McKesson Corporation) (off market)

    Naproxen Sodium Oral tablet

    Sunmark Naproxen Sodium 220mg Tablet (49348-0260) (McKesson Corporation) null

    Naproxen Sodium Oral tablet

    Sunmark Naproxen Sodium 220mg Tablet (49348-0260) (McKesson Corporation) null

    Naproxen Sodium Oral tablet

    Today's Health Naproxen 220mg Tablet (null) (Today's Health, Inc.) null

    Naproxen Sodium Oral tablet

    Top Care All Day Pain Relief 220mg Caplet (36800-0140) (Topco Associates LLC) null

    Naproxen Sodium Oral tablet

    Top Care All Day Pain Relief 220mg Caplet (36800-0368) (Topco Associates LLC) null

    Naproxen Sodium Oral tablet

    Top Care All Day Pain Relief 220mg Tablet (36800-0490) (Topco Associates LLC) null

    Naproxen Sodium Oral tablet

    up & up Naproxen Sodium 220mg Caplet (11673-0368) (Target) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0140) (Walgreens Co) (off market)

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0140) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0168) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-0368) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-9608) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Caplet (00363-9608) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-0938) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-0490) (Walgreens Co) null

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-9608) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-9609) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-9609) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Pain Relief 220mg Tablet (00363-0490) (Walgreens Co) nullWalgreens All Day Pain Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Relief 220mg Caplet (00363-9608) (Walgreens Co) nullWalgreens All Day Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Relief 220mg Caplet (00363-9608) (Walgreens Co) nullWalgreens All Day Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Relief 220mg Caplet (00363-9608) (Walgreens Co) nullWalgreens All Day Relief 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Walgreens All Day Relief 220mg Tablet (null) (Walgreens Co) nullWalgreens All Day Relief 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Wal-Proxen 220mg Caplet (00363-0368) (Walgreens Co) (off market)Wal-Proxen 220mg Caplet package photo

    Naproxen Sodium Oral tablet

    Wal-Proxen 220mg Tablet (00363-0490) (Walgreens Co) nullWal-Proxen 220mg Tablet package photo

    Naproxen Sodium Oral tablet

    Anaprox 275mg Tablet (00004-6202) (Genentech Inc) (off market)

    Naproxen Sodium Oral tablet

    Anaprox 275mg Tablet (55289-0837) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (53265-0363) (Able Laboratories Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (53746-0193) (Amneal Pharmaceuticals LLC) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (65862-0515) (Aurobindo Pharma USA Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (42291-0531) (AvKARE, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (42291-0516) (AvKARE, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (50268-0592) (AvPAK; a Division of AvKARE Inc) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (10544-0275) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (55111-0107) (Dr. Reddy's Laboratories, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (43598-0494) (Dr. Reddy's Laboratories, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (68462-0178) (Glenmark Pharmaceuticals) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (59115-0002) (Hikma Pharmaceuticals) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00143-9916) (Hikma Pharmaceuticals USA Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (53746-0193) (Interpharm Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00904-6185) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00378-0537) (Mylan Pharmaceuticals Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (55289-0467) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (43063-0462) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00781-1187) (Sandoz Inc. a Novartis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (62269-0286) (Sandoz, Inc. a Novartis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00364-2553) (Schein Pharmaceutical Inc, an Actavis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (50228-0432) (ScieGen Pharmaceuticals, Inc) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00093-0536) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00172-4116) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (50111-0558) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (00591-0792) (Teva/Actavis US) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 275mg Tablet (52544-0792) (Teva/Actavis US) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 375mg Tablet (69150-0139) (Biomes Pharmaceuticals, LLC) null

    Naproxen Sodium Oral tablet

    Aflaxen 550mg Tablet (11584-0465) (International Ethical Laboratories Inc) (off market)

    Naproxen Sodium Oral tablet

    Anaprox DS 550mg Tablet (69437-0203) (Canton Laboratories) null

    Naproxen Sodium Oral tablet

    Anaprox DS 550mg Tablet (00004-6203) (Genentech Inc) (off market)

    Naproxen Sodium Oral tablet

    Anaprox DS 550mg Tablet (00004-6200) (Genentech Inc) (off market)

    Naproxen Sodium Oral tablet

    Anaprox DS 550mg Tablet (55289-0332) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (53265-0364) (Able Laboratories Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (53746-0194) (Amneal Pharmaceuticals LLC) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (65862-0516) (Aurobindo Pharma USA Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (42291-0532) (AvKARE, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (42291-0517) (AvKARE, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (50268-0593) (AvPAK; a Division of AvKARE Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (10544-0276) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (10544-0614) (Blenheim Pharmacal, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (55111-0108) (Dr. Reddy's Laboratories, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (43598-0495) (Dr. Reddy's Laboratories, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (68462-0179) (Glenmark Pharmaceuticals) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (59115-0001) (Hikma Pharmaceuticals) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00143-9908) (Hikma Pharmaceuticals USA Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (53746-0194) (Interpharm Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00904-6186) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (55370-0526) (Mova Pharmaceuticals Corp) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00378-0733) (Mylan Pharmaceuticals Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (58517-0300) (New Horizon Rx Group, LLC) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (55953-0533) (Novopharm USA Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (66267-0154) (NuCare Pharmaceuticals Inc) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (55289-0367) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (55289-0367) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (43063-0732) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (72789-0389) (PD-Rx Pharmaceuticals, Inc.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (33358-0259) (RxChange Co.) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00781-1188) (Sandoz Inc. a Novartis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (62269-0287) (Sandoz, Inc. a Novartis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00364-2554) (Schein Pharmaceutical Inc, an Actavis Company) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (50228-0433) (ScieGen Pharmaceuticals, Inc) nullNaproxen Sodium 550mg Tablet package photo

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00093-0537) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00182-1975) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00172-4275) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (50111-0559) (Teva Pharmaceuticals USA) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (00591-0793) (Teva/Actavis US) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (52544-0793) (Teva/Actavis US) (off market)

    Naproxen Sodium Oral tablet

    Naproxen Sodium 550mg Tablet (69784-0550) (Woodward Pharma Services LLC ) null

    Naproxen Sodium Oral tablet

    Naproxen Sodium DS 550mg Tablet (42494-0400) (Cameron Pharmaceuticals, LLC) null

    Naproxen Sodium Oral tablet, extended release

    Midol Extended Relief 220mg Tablet (12843-0517) (Bayer Corp Consumer Care Div) (off market)

    Naproxen Sodium Oral tablet, extended release

    Midol Extended Relief 220mg Tablet (12843-0543) (Bayer Corp Consumer Care Div) (off market)

    Description/Classification

    Description

    Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) of the propionic acid chemical class. This medicine possesses antipyretic and analgesic properties. Naproxen is a propionic acid derivative related to ibuprofen, ketoprofen, flurbiprofen, and fenoprofen. Many pharmacodynamic similarities exist among these agents, which are usually better tolerated than aspirin or indomethacin. All NSAIDs, including naproxen, carry an increased risk of serious gastrointestinal adverse effects including bleeding, ulceration, and perforation of the stomach or intestines, and may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke. The FDA approved labeling of both the OTC and prescription products stress dosing at the lowest effective dose for the shortest possible duration, as the risk for adverse effects may increase with increased use. A retrospective review by FDA Advisory Committees of short-term efficacy trials of non-prescription strength naproxen indicated that an increase in CV events was not apparent during the studies. However, it is important to note that CV risk was not the focus of the studies, and further information is needed to determine if a cause and effect relationship exists between non-prescription strength NSAID use and adverse cardiovascular outcomes. Naproxen is available as the anion and as the sodium salt; all formulations liberate naproxen as the active drug. Naproxen has been shown superior to ergotamine in the treatment of migraine.[23558] Naproxen was approved by the FDA in 1976. In January 1994, the FDA granted permission to market naproxen in a nonprescription form (e.g., Aleve).

    Classifications

    • Musculo-Skeletal System
      • Antiinflammatory Agents and Antirheumatic Agents
        • Antiinflammatory and Antirheumatic Agents
          • Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
    Revision Date: 04/08/2024, 02:15:00 AM

    References

    23558 - Welch KMA. Drug therapy of migraine. N Engl J Med 1993;329:1476-83.

    Administration Information

    General Administration Information

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

    Route-Specific Administration

    Oral Administration

    • Administer with milk, food, or antacids (preferably aluminum and magnesium hydroxide containing antacids) to minimize GI irritation. For self-medication, administer with a full glass of water or other liquid.

    Oral Solid Formulations

    • EC-Naprosyn delayed-release tablets: Do not break, crush, or chew.

    Oral Liquid Formulations

    • Oral suspension: Shake well before use. Administer using the measuring cup provided or other calibrated device appropriate for accurate administration of liquid medications.

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 04/08/2024, 02:15:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

    References

    Adverse Reactions

    Mild

    • abdominal pain
    • acne vulgaris
    • alopecia
    • anorexia
    • anxiety
    • arthralgia
    • asthenia
    • back pain
    • chills
    • cough
    • diaphoresis
    • diarrhea
    • diplopia
    • dizziness
    • drowsiness
    • dysmenorrhea
    • dyspepsia
    • ecchymosis
    • emotional lability
    • epistaxis
    • eructation
    • fever
    • flatulence
    • headache
    • increased urinary frequency
    • infection
    • influenza
    • insomnia
    • lacrimation
    • lichen planus-like eruption
    • malaise
    • menorrhagia
    • muscle cramps
    • myalgia
    • nausea
    • nocturia
    • ocular pain
    • paresthesias
    • pelvic pain
    • pharyngitis
    • photosensitivity
    • polyuria
    • pruritus
    • ptosis
    • purpura
    • pyrosis (heartburn)
    • rash
    • rhinitis
    • sinusitis
    • syncope
    • tinnitus
    • tremor
    • urticaria
    • vertigo
    • vomiting
    • weight loss
    • xerosis
    • xerostomia

    Moderate

    • amblyopia
    • amnesia
    • anemia
    • angina
    • bleeding
    • blurred vision
    • bone pain
    • bullous rash
    • bundle-branch block
    • chest pain (unspecified)
    • cholelithiasis
    • colitis
    • confusion
    • conjunctivitis
    • constipation
    • contact dermatitis
    • cystitis
    • dehydration
    • depression
    • dysphagia
    • dyspnea
    • dysuria
    • edema
    • elevated hepatic enzymes
    • eosinophilia
    • esophagitis
    • flank pain
    • gastritis
    • glossitis
    • glycosuria
    • hallucinations
    • hematuria
    • hepatitis
    • hepatomegaly
    • hypercholesterolemia
    • hyperglycemia
    • hypertension
    • hypertonia
    • hyperuricemia
    • hypoglycemia
    • hypokalemia
    • hyponatremia
    • hypotension
    • infertility
    • jaundice
    • leukopenia
    • lymphadenopathy
    • medication overuse headache
    • melena
    • metabolic alkalosis
    • migraine
    • myasthenia
    • neuritis
    • oral ulceration
    • palpitations
    • peripheral edema
    • peripheral vasodilation
    • phlebitis
    • photophobia
    • platelet dysfunction
    • pneumonitis
    • prolonged bleeding time
    • pyuria
    • respiratory depression
    • sinus tachycardia
    • skin ulcer
    • splenomegaly
    • stomatitis
    • subdural hematoma
    • thrombocytopenia
    • urinary incontinence
    • urinary retention
    • vaginitis
    • withdrawal

    Severe

    • agranulocytosis
    • anaphylactic shock
    • anaphylactoid reactions
    • angioedema
    • aplastic anemia
    • arrhythmia exacerbation
    • aseptic meningitis
    • azotemia
    • bone fractures
    • bronchospasm
    • cholecystitis
    • coma
    • corneal opacification
    • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
    • erythema multiforme
    • erythema nodosum
    • esophageal stricture
    • esophageal ulceration
    • exfoliative dermatitis
    • GI bleeding
    • GI perforation
    • glomerulonephritis
    • hearing loss
    • heart failure
    • hematemesis
    • hemolytic anemia
    • hepatic failure
    • hepatic necrosis
    • hyperkalemia
    • interstitial nephritis
    • keratoconjunctivitis
    • lupus-like symptoms
    • muscle paralysis
    • myocardial infarction
    • nephrotic syndrome
    • odynophagia
    • oliguria
    • optic neuritis
    • pancreatitis
    • pancytopenia
    • papilledema
    • peptic ulcer
    • proteinuria
    • pseudoporphyria
    • pulmonary edema
    • renal failure (unspecified)
    • renal papillary necrosis
    • seizures
    • skin necrosis
    • Stevens-Johnson syndrome
    • stroke
    • thromboembolism
    • toxic epidermal necrolysis
    • vasculitis
    • visual impairment

    The most frequently reported reactions to naproxen are gastrointestinal (GI) adverse events and may be more frequent with higher doses. NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, GI bleeding, ulceration (peptic ulcer), and GI perforation (gastric or intestinal). These events can be fatal and can occur at any time during therapy. Upper GI ulcers, bleeding, or perforation occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for a year, with trends continuing with longer duration of use. Constipation, pyrosis (heartburn), abdominal pain, and nausea occur in 3% to 9% of patients. Dyspepsia was reported in less than 3% to 14% of patients. Diarrhea has occurred in less than 3% to 9% of patients. Flatulence, gastritis, vomiting, dysphagia, and stomatitis are reported less frequently (less than 3%). Gastrointestinal adverse events noted in less than 1% of patients during naproxen trials include GI bleeding, anorexia, cholecystitis, cholelithiasis, eructation, GI hemorrhage, rectal hemorrhage, aphthous stomatitis, ulcerative stomatitis, oral ulceration, peptic ulcer, periodontal abscess, cardiospasm, colitis, gastroenteritis, GI disorder, rectal disorder, tooth disorder, melena, esophagus ulcer, necrosis, and non-peptic GI ulcer. In patients taking NSAIDs in general, flatulence, GI bleeding, GI perforation, GI ulcers (gastric, duodenal), and vomiting were reported in 1% to 10%, while xerostomia and glossitis were reported in less than 1%. GI events noted in postmarketing reports include GI perforation, hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease), non-peptic GI ulceration, ulcerative stomatitis, and peptic ulcer. Adverse effects reported by patients with rheumatoid arthritis appear to be more severe and frequent with higher dosages (1.5 g/day) than with lower dosages (750 mg/day). Gastrointestinal bleeding or erosive gastritis can be minor or life-threatening and may result from a combination of direct irritant action on the stomach mucosa and a prolonged bleeding time, due to changes in platelet aggregation. Weight loss has been reported in less than 1% of patients during naproxen clinical trials. Weight changes and appetite changes have occurred in less than 1% of patients taking NSAIDs. The incidence of gastrointestinal events in pediatric trials was similar to adult trials.[32122] [44091]

    Esophagitis (< 1%) and esophageal ulceration (< 1%) have been reported in patients receiving NSAIDs, such as naproxen.[32122] [44091] NSAID-induced esophagitis is characterized by sudden onset odynophagia, pyrosis (heartburn), retrosternal pain, and dysphagia. Severe complications such as esophageal ulceration, esophageal stricture, bleeding, and perforation have been reported rarely. Risk factors for NSAID-induced esophageal effects include taking the medication without water and at night. Symptoms usually resolve within days to weeks after stopping the medication.

    Naproxen has been shown to cause platelet dysfunction; this effect, however, is transient and reversible. As inhibition of platelet aggregation appears to correlate with effective plasma concentrations of the drug, the individual half-life of each NSAID determines the duration of this effect. Naproxen glucuronide, a metabolite of naproxen, may cause immune-mediated thrombocytopenia. Widespread petechial hemorrhages were noted 10 to 25 days after naproxen initiation in 3 individuals. All 3 adults had improvement in their platelet counts from 3 to 8 x109/L to within the normal concentration range 5 to 7 days after naproxen discontinuation and prednisone receipt. The sera from each patient had antibodies against platelets in the presence of naproxen glucuronide.[31419] Anemia has been noted in less than 3% of patients during naproxen trials. Other hematologic effects (less than 1%) due to naproxen include aplastic anemia, hemolytic anemia, thrombocytopenia, prolonged bleeding time, abnormal red and white blood cells, agranulocytosis, leukopenia, eosinophilia, and granulocytopenia. Aplastic anemia, hemolytic anemia, eosinophilia, leukopenia, and granulocytopenia have been noted in postmarketing reports. Rectal bleeding, lymphadenopathy, and pancytopenia were noted in less than 1% of patients taking NSAIDs. Blood loss from gastrointestinal damage caused by naproxen is usually not significant. However, blood loss over time can result in iron deficiency anemia. Patients on prolonged therapy should undergo regular blood monitoring. Interpretation of the hematocrit and hemoglobin should be considered in relation to the fluid status, as naproxen can cause fluid retention.[32122] [44091]

    The most common adverse CNS reactions with naproxen include headache (3% to 15%) and drowsiness (3% to 9%). Vertigo, lightheadedness, paresthesias, asthenia, and insomnia are reported in less than 3% of patients during naproxen trials. Dizziness has been reported in less than 3% to 9% of patients. Other CNS reactions occur less frequently (less than 1%), including depression, malaise, anxiety, hypertonia, nervousness, neuralgia, neuritis, amnesia, confusion, abnormal coordination, diplopia, emotional lability, subdural hematoma, muscle paralysis, dream abnormalities, cognitive dysfunction, muscle weakness (myasthenia), and an inability to concentrate (impaired concentration). Adverse events noted in postmarketing reports include depression, dream abnormalities, insomnia, myalgia, muscle weakness, cognitive dysfunction, and seizures. Somnolence, tremor, coma, and hallucinations were noted in less than 1% of patients taking NSAIDs.[32122] [44091] Overuse of drugs for treating acute headaches, including NSAIDs, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of naproxen for at least 15 days/month or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use.[66767] [66803]

    Visual impairment or disturbance, such as blurred vision, has been reported in < 3% of patients using naproxen. Other ocular adverse events reported in < 1% of patients included amblyopia, scleritis, cataracts, conjunctivitis, keratoconjunctivitis, lacrimation disorder, and ocular pain. Corneal opacification, papillitis, retrobulbar optic neuritis, and papilledema have been noted in post-marketing reports.[32122] [44091]

    Tinnitus (3—9%), hearing disturbances (< 3%),  hearing loss / deafness (< 1%), ear disorder (< 1%), and otitis media (< 1%) have occurred with naproxen during clinical trials. Additionally, hearing impairment, has been noted in post-marketing reports.[32122] [44091] Also, 6 cases of hearing loss have been reported in the literature. Two of the 6 patients had a post-treatment audiogram, which revealed a permanent severe bilateral sensorineural hearing loss. Of the other patients, 2 had recovery and 2 had no recovery of their hearing loss.[27729] Tinnitus and hearing loss have also occurred with the nonsteroidal anti-inflammatory drugs (NSAIDs) piroxicam and ketorolac. The hearing loss from NSAID usage is believed to be due to altered cochlear sensory cell function from tissue ischemia as a result of an imbalance between vasodilatory prostaglandins and vasoconstricting leukotrienes.[27726] Although no known morphologic changes are known to occur, hearing loss may be permanent. Coadministration of other ototoxic drugs, such as gentamicin or furosemide, may increase the risk of ototoxicity. Most ototoxic drugs have at least additive ototoxic interactions. Further, NSAIDs can be nephrotoxic, and impaired renal function can increase the ototoxic potential of NSAIDs. Patients taking long-term NSAIDs should be directly questioned about tinnitus and hearing loss.

    Rare cases of jaundice (< 1%), hepatic necrosis (< 1%), and fatal hepatitis or hepatic failure have been reported in patients receiving naproxen. Hepatosplenomegaly (hepatomegaly and splenomegaly) and pancreatitis have been reported in < 1% of patients. Elevated hepatic enzymes occur in up to 15% of patients receiving NSAIDs. Elevations that are greater than three times the upper limit of normal have occurred in fewer than 1% of patients who received naproxen. Hepatic enzyme abnormalities may progress, stabilize, or regress with continued naproxen use. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. Evaluate patients with signs or symptoms of liver dysfunction such as an abnormal liver test result for the development of a more severe hepatic reaction. Naproxen should be discontinued if clinical signs or symptoms consistent with liver disease develop or if systemic manifestations such as eosinophilia or rash occur.[32122] [44091]

    Naproxen has been associated with aseptic meningitis (incidence of < 1% in clinical trials) but a causal relationship has not been established.[32122] [44091] Ibuprofen has been the most common NSAID implicated in this adverse reaction; however, cases have been reported with sulindac, tolmetin, diclofenac, ketoprofen, rofecoxib, and piroxicam. Aseptic meningitis from one NSAID does not preclude use of another NSAID; most patients can be treated with another drug without incident. However, one patient with Sjogren's syndrome experienced aseptic meningitis after receipt of naproxen, ibuprofen, and rofecoxib at different times; aseptic meningitis developed about a week after each drug exposure, and the symptoms abated roughly 2 days following each drug cessation.[27710] The occurrence of aseptic meningitis is not related to NSAID chemical class or prostaglandin inhibition. A Type III or IV immunological hypersensitivity reaction is the proposed mechanism of action. Drug-induced aseptic meningitis usually occurs shortly after drug initiation but can occur after years of drug usage. Although NSAID-induced aseptic meningitis is primarily reported in patients with systemic lupus erythematosus (SLE), healthy patients and patients with other disease states such as ankylosing spondylitis, connective tissue disease, osteoarthritis, and rheumatoid arthritis have developed NSAID-induced aseptic meningitis. Symptoms of aseptic meningitis include confusion, drowsiness, general feeling of illness, severe headache, nausea, nuchal rigidity, and photophobia. As aseptic meningitis is a diagnosis of exclusion, the suspected drug should be discontinued and not restarted unless a rechallenge is desired.

    Renal disease including renal function abnormality, interstitial nephritis, nephrotic syndrome, hematuria, glomerulonephritis, hyperkalemia, renal failure (unspecified), and renal papillary necrosis have occurred in fewer than 1% of patients receiving naproxen. Overall abnormal renal function has been reported in < 1% of patients receiving NSAIDs. It is well known that vasodilatory renal prostaglandins and the potent vasoconstrictor angiotensin II work in concert to maintain renal blood flow. Inhibition of prostaglandin synthesis by NSAIDs potentiates water reabsorption. Renal toxicity has been reported in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. Other genitourinary adverse events reported in < 1% of patients include dysmenorrhea, dysuria, nocturia, prostate disorder, breast carcinoma or neoplasm, urinary incontinence, kidney calculus, menorrhagia, metrorrhagia, nephrosclerosis, kidney pain (flank pain), pyuria, abnormal urine, increased urinary frequency, urinary retention, uterine spasm, vaginitis, and menstrual disorders. Edema occurred in < 1 % to 9% and peripheral edema was reported in < 3% of patients receiving naproxen. Oliguria, polyuria, proteinuria, glycosuria, azotemia, and albuminuria have been reported in < 1% of patients receiving NSAIDs.[32122] [44091] Hyponatremia due to water intoxication has been reported with NSAID use.[33608] [33609] [33610] Monitoring of the patient's fluid status and renal function is recommended.

    NSAIDs, including naproxen, may cause an increased risk of serious cardiovascular thromboembolism, myocardial infarction (< 1%), and stroke, which can be fatal. Estimates of increased relative risk range from 10—50% or more, based on the drug and dose studied. The risk may increase with increased exposure, as measured in dose or duration. Significant cardiovascular risk has been observed within days to weeks of NSAID initiation. The relative increase in cardiovascular thrombotic events over baseline appears to be similar in patients with or without cardiovascular disease or risk factors for cardiovascular disease; however, patients with known cardiovascular disease or risk factors may be at greater risk because of a higher baseline risk of events.[59937] Hypertension was noted in < 3% of patients taking naproxen in clinical trials; in general, NSAIDs can lead to new onset or worsening hypertension, which may contribute to the increased incidence of cardiovascular events. Palpitations were noted in < 3% of patients taking naproxen in clinical trials. Adverse events noted in < 1% of patients included pulmonary edema, angina pectoris, coronary artery disease, deep thrombo-phlebitis, peripheral vasodilation, vascular anomaly, arrhythmia exacerbation, bundle-branch block, abnormal ECG, heart failure, hemorrhage (bleeding), migraine, aortic stenosis, syncope, vasculitis, and sinus tachycardia. Fluid retention caused by naproxen can elevate blood pressure, especially in patients with hypertension. Hypotension has been reported in < 1% of patients taking NSAIDs.[32122] [44091] In adults (76% White, 14% Black) with stable hypertension (systolic < 150 mmHg) and normal renal function, the mean change from baseline in average 24-hour systolic pressure was -0.8 +/- 1.1 mmHg and diastolic pressure was -1 +/- 0.6 mmHg after 6 weeks of naproxen 500 mg twice daily. Blood pressure was measured every 20 minutes during 24-hour ambulatory monitoring, and no antihypertensive drug changes were allowed (all patients took at least an angiotensin converting enzyme inhibitor or an angiotensin-2 receptor blocker). Similar findings were obtained when blood pressure was measured in a clinic between 7 and 11 in the morning. Of the 101 patients, an increase in the systolic blood pressure of 0—10 mmHg occurred in 37%, an increase in 10—20 mmHg occurred in 7%, and a > 20 mmHg increase occurred in 2%. Furthermore, of 57 patients who had a baseline ambulatory systolic blood pressure < 135 mmHg, 11 had a reading of >= 135 mmHg at week 6.[30756] Inform patients of the signs and symptoms of CV events, and advise them to seek medical help immediately if such signs or symptoms occur.

    The most frequent skin and soft tissue adverse events associated with naproxen include pruritus (less than 1% to 9%), skin eruptions (3% to 9%), rash (less than 1% to 9%), and ecchymosis (3% to 9%). Diaphoresis and purpura occur in less than 3% of patients. Other dermatologic reactions occur less frequently (less than 1%), including angiodermatitis, herpes simplex, xerosis, skin ulcer, acne vulgaris, alopecia, contact dermatitis, eczema, herpes zoster, nail disorder, skin necrosis, subcutaneous nodule, skin neoplasm, urticaria, photosensitivity reaction resembling porphyria cutanea tarda, epidermolysis bullosa (bullous rash), and photosensitive dermatitis. Erythema nodosum, fixed drug eruption, lichen planus-like eruption, pustular reaction, and systemic lupus erythematosus (lupus-like symptoms) were noted in postmarketing reports.[32122] [44091] Three patients developed pseudoporphyria during treatment with over-the-counter naproxen 400 mg/day 4 to 5 times weekly for osteoarthritis for an unspecified length of time. The patients had skin fragility, blistering, tense bullae and/or shallow erosions predominantly on sun-exposed areas. Histological analyses were consistent with porphyria, but urine and plasma porphyrins were within normal limits. Skin lesions resolved within 1 to 6 months of naproxen discontinuation. No recurrences were seen during 15 to 34 months of follow-up.[27624] Serious adverse events such as toxic epidermal necrolysis (less than 1%), erythema multiforme (less than 1%), exfoliative dermatitis (less than 1% of NSAID patients), and Stevens-Johnson syndrome (less than 1%) can occur with naproxen without warning. Advise patients to discontinue the medication and contact their health care provider if erythema, rash, blisters, or related skin reactions develop. Chills, eosinophilic pneumonitis, vasculitis, and anaphylactoid reactions including anaphylactic shock and angioedema occurred in less than 1% of patients in clinical trials of naproxen. Dyspnea occurred in 3% to 9% of patients.[32122] [44091]

    Musculoskeletal adverse events that occurred in 3—9% of patients taking naproxen in clinical trials included back pain and pain. Muscle cramps (leg), myalgia, arthralgia, joint disorder, and tendon disorder were reported in < 3% of patients. Adverse events noted in < 1% of patients include bone disorder, spontaneous bone fractures, fibro-tendinitis, bone pain, ptosis, general muscle spasm, and bursitis.[32122] [44091]

    Hyperglycemia and thirst have been reported in less than 3% of patients during naproxen clinical trials. Other metabolic and nutritional adverse events reported in less than 1% of patients include hypoglycemia, hypercholesterolemia, metabolic alkalosis, dehydration, decreased glucose tolerance, hyperuricemia, and hypokalemia.[32122] [44091]

    Infectious adverse events reported during naproxen trials include general infection (3% to 9%), urinary tract infection (3% to 9%), influenza-like syndrome (10%), cystitis (less than 3%), abscess (less than 1%), pneumonia (less than 1%), and pyelonephritis (less than 1%). Adverse events related to NSAID therapy and occurring in less than 1% include infection, sepsis, and pneumonia.[32122] [44091]

    Respiratory adverse events that have been noted in naproxen clinical trials include pharyngitis (3—9%), rhinitis (3—9%), sinusitis (3—9%), bronchitis (< 3%), increased cough (< 3%), asthma or bronchospasm (< 1%), pulmonary disorder (< 1%), epistaxis (< 1%), respiratory distress (< 1%), and respiratory disorder (< 1%). Asthma and respiratory depression have been reported in < 1% of patients taking NSAIDs.[32122] [44091]

    General adverse events reported during naproxen clinical trials include fever (less than 3%), injury or accident (less than 3%), chest pain (unspecified) (less than 3%), nuchal rigidity (less than 1%), neck pain (less than 1%), enlarged abdomen (less than 1%), carcinoma (less than 1%), cellulitis (less than 1%), LE syndrome (less than 1%), mucous membrane disorder (less than 1%), and pelvic pain (less than 1%). Death was reported in less than 1% of patients taking NSAIDs.[32122] [44091]

    NSAIDs, such as naproxen, may delay or prevent prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing infertility evaluation.[32122] Female infertility has been noted in post-marketing reports for naproxen.[32122] [44091]

    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a multi-organ hypersensitivity reaction, has occurred with NSAIDs. Some of these events have been life-threatening or fatal. DRESS typically presents as fever, rash, and/or lymphadenopathy in conjunction with other organ system involvement including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations such as fever and lymphadenopathy may be present without evidence of a rash. Discontinue the NSAID in patients presenting with such signs and symptoms in whom an alternative etiology cannot be identified.[32122]

    Revision Date: 04/08/2024, 02:15:00 AM

    References

    27624 - Nabumetone/naproxen/oxaprozin: Pseudoporphyria: 6 case reports. Reactions Weekly 2003;953:12.27710 - Ashwath ML, Katner HP. Recurrent aseptic meningitis due to different non-steroidal anti-inflammatory drugs including rofecoxib. Postgrad Med J 2003;79:295-6.27726 - Warltier DC, Sprung J, Bourke DL, et al. Perioperative hearing impairment. Anesthesiology 2003;98:241-57.27729 - Chapman P. Naproxen and sudden hearing loss. J Laryngol Otol 1982;96:163-6.30756 - Sowers JR, White WB, Pitt B, et al. The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med 2005;165:161-8.31419 - Bougie D, Aster R. Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Blood 2001;97:3846-50.32122 - EC Naprosyn (naproxen delayed-release tablets), Naprosyn (naproxen tablets), Anaprox DS (naproxen sodium tablets) package insert. Alpharetta, GA: Canton Laboratories, LLC; 2021 Apr.33608 - Rault RM. Case report: hyponatremia associated with nonsteroidal anti-inflammatory drugs. Am J Med Sci 1993;305:318-20.33609 - Petersson I, Nilsson G, Hansson BG, et al. Water intoxication associated with non-steroidal anti-inflammatory drug therapy. Acta Med Scand 1987;221:221-3.33610 - Blum M, Aviram A. Ibuprofen induced hyponatraemia. Rheumatol Rehabil 1980;19:258-9.44091 - Naprelan (naproxen sodium extended-release tablets) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2021 Apr.59937 - US Food and Drug Administration (FDA). Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDS): Drug Safety Communication - association with heart attacks or strokes. Retrieved July 9, 2015. Available on the World Wide Web at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM453941.pdf66767 - Diener HC, Antonaci F, Braschinsky M, et al. European Academy of Neurology guideline on the management of medication overuse headache. Eur J Neurol 2020;27:1102-1116.66803 - Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1-211.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • coronary artery bypass graft surgery (CABG)
    • NSAID hypersensitivity
    • salicylate hypersensitivity
    • acute bronchospasm
    • acute myocardial infarction
    • anemia
    • angina
    • anticoagulant therapy
    • asthma
    • breast-feeding
    • cardiac arrhythmias
    • cardiac disease
    • cardiomyopathy
    • cerebrovascular disease
    • coagulopathy
    • coronary artery disease
    • corticosteroid therapy
    • dehydration
    • ethanol ingestion
    • geriatric
    • GI bleeding
    • GI perforation
    • heart failure
    • hepatic disease
    • hypertension
    • hypoalbuminemia
    • hypovolemia
    • infertility
    • labor
    • laboratory test interference
    • myocardial infarction
    • myocardial infarction or stroke
    • nasal polyps
    • obstetric delivery
    • peptic ulcer disease
    • peripheral vascular disease
    • pregnancy
    • renal disease
    • renal failure
    • renal impairment
    • reproductive risk
    • serious rash
    • sodium restriction
    • stroke
    • tachycardia
    • thromboembolism
    • tobacco smoking
    • urticaria

    Naproxen is contraindicated in patients with known salicylate hypersensitivity or NSAID hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) and in patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. A subpopulation of patients with asthma may have aspirin-sensitive asthma, which may include chronic rhinosinusitis complicated by nasal polyps, severe and potentially fatal acute bronchospasm, and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported, naproxen is contraindicated in patients with aspirin-sensitive asthma. When naproxen is used in patients with preexisting asthma without known aspirin sensitivity, monitor patients for changes in the signs and symptoms of asthma. Naproxen is contraindicated in patients with previous serious rash or skin reactions to NSAIDs. The use of NSAIDs, including naproxen, may cause serious and potentially fatal skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Educate patients about the signs and symptoms of serious skin reactions and to discontinue the use of naproxen at the first appearance of skin rash or hypersensitivity.[32122]

    NSAIDs, including naproxen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and GI perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a more than 10-fold increased risk for developing a GI bleed compared to patients without risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy, concomitant oral corticosteroids, anticoagulant therapy, aspirin, or selective serotonin reuptake inhibitors (SSRIs), tobacco smoking, ethanol ingestion, older age, and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease or coagulopathy are at increased risk for GI bleeding. To minimize GI risks in NSAID-treated patients, use the lowest effective dosage for the shortest possible duration, and avoid administration of more than 1 NSAID at a time. In the setting of concomitant low-dose aspirin use for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Avoid NSAID use in higher risk populations unless the benefits are expected to outweigh the risks of bleeding; consider alternate therapy other than NSAIDs in higher risk patients as well as those with active GI bleeding. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.[32122]

    Naproxen is contraindicated in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of thromboembolism, including myocardial infarction or stroke, was found through analysis of data regarding the use of a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) for the treatment of pain in the first 10 to 14 days after CABG surgery. Naproxen, like all NSAIDs, may exacerbate heart failure and hypertension and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Avoid the use of naproxen in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If naproxen is used in patients with severe heart failure, monitor for signs of worsening heart failure. Trials demonstrated an approximately doubling of hospitalizations for heart failure in patients treated with selective and nonselective NSAIDs compared to placebo-treated patients. Additionally, fluid retention and edema have been observed with NSAID use. Consider the sodium content of naproxen sodium in patients requiring severe sodium restriction.[32122] Caution is recommended when administering naproxen to patients with cardiac disease, cardiomyopathy, cardiac arrhythmias (e.g., tachycardia), significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), hypertension, pre-existing renal disease, or fluid retention.[59937] Closely monitor blood pressure during naproxen receipt. Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or symptoms of a cardiovascular thrombotic event. Myocardial infarction or stroke can occur as early as the first weeks of using a NSAID, and risk may increase with higher doses and longer duration of use. NSAIDs may increase the risk of a cardiovascular thrombotic event in patients with or without underlying heart disease or risk factors for heart disease. Patients with known heart disease or risk factors appear to have a greater likelihood of an event after NSAID use, likely due to a higher baseline risk.[32122] While comprehensive data regarding relative cardiovascular safety of any particular NSAID compared to other NSAIDs is not available, celecoxib 100 mg twice daily was shown to be non-inferior to ibuprofen 600 to 800 mg 3 times daily or naproxen 375 to 500 mg twice daily for the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke in osteoarthritis or rheumatoid arthritis adult patients with or at high risk for cardiovascular disease. Celecoxib had negligible effect on average 24-hour systolic blood pressure, while average 24-hour systolic pressures increased by 3.7 mmHg and 1.6 mmHg in patients taking ibuprofen and naproxen, respectively.[56268] There is no consistent evidence that concomitant use of aspirin mitigates the increased risk for cardiovascular thrombotic events.[32122] Guidelines state NSAIDs should not be administered to patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.[55688] Observational data from a national registry demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning the first week of treatment. An increased relative risk of death in NSAID users continued during the follow-up period of 4 years. Data demonstrate that patients treated with NSAIDs were more likely to die in the first year following a myocardial infarction compared to those not treated with NSAIDs.[32122]

    Correct volume status in dehydrated or hypovolemic patients before starting naproxen. Monitor renal function in patients with renal impairment, heart failure, dehydration, or hypovolemia during naproxen use. Avoid naproxen use in patients with advanced renal disease or renal failure unless the benefits are expected to outweigh the risk of worsening renal function. If naproxen is used in patients with advanced renal disease, monitor patients for signs and symptoms of worsening renal function. Naproxen is not recommended for use in patients with moderate to severe and severe renal impairment (CrCl less than 30 mL/minute). Renal toxicity has been observed in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, NSAID use may cause a dose-dependent reduction in prostaglandin formation, and secondarily, renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.[32122]

    Use caution when high naproxen doses are required in patients with chronic alcoholic hepatic disease and other diseases with decreased or abnormal plasma proteins (i.e., hypoalbuminemia). Dosage adjustment may be required; use the lowest effective dose. In these patients, the total plasma concentration of naproxen may be reduced, but the plasma concentration of unbound naproxen is increased. Additionally, patients with advanced liver disease are at increased risk for gastrointestinal bleeding.[32122]

    Monitor hemoglobin values periodically in patients with initial hemoglobin values of 10 g/dL or less who are to receive long-term NSAID therapy. Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.[32122]

    Naproxen cannot be expected to substitute for corticosteroid therapy or treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Taper corticosteroid therapy slowly if a decision is made to discontinue corticosteroids for patients on prolonged corticosteroid therapy; observe the patient closely for any adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis. Additionally, concomitant use of oral corticosteroid therapy may increase the risk of GI bleeding in patients treated with NSAIDs.[32122]

    Geriatric adults are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal (GI), and renal adverse reactions. Most spontaneous reports of fatal GI events are in the geriatric population. If the anticipated benefit outweighs these potential risks, start naproxen therapy at the low end of the dosage range and monitor for adverse effects. Use caution when high doses are required; some dosage adjustment may be necessary for older adults. Use the lowest effective dose.[32122] According to the Beers Criteria, NSAIDs are considered potentially inappropriate medications (PIMs) in the older adult as NSAIDs may cause new or worsening gastric and duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk groups including those greater than 75 years of age, or those taking systemic corticosteroids, anticoagulants, or antiplatelet medications. The risk of GI ulcers, gross bleeding, or perforation is cumulative with continued use. Avoid the chronic use of NSAIDs in high-risk persons including those with a history of gastric or duodenal ulcers, unless other alternatives are not effective, and the person can take a gastroprotective agent. The use of a gastroprotective agent, like a proton pump inhibitor or misoprostol, reduces but does not eliminate GI risks. NSAIDs may also increase blood pressure and induce kidney injury. Avoid use of NSAIDs in geriatric adults with the following conditions due to the potential for symptom exacerbation or adverse effects: symptomatic heart failure (fluid retention, symptom exacerbation) or chronic kidney disease Stage 4 or higher (CrCl less than 30 mL/minute) (acute kidney injury, further decline of renal function). Use with caution in persons with asymptomatic heart failure.[63923]

    Naproxen may cause laboratory test interference. Naproxen may decrease platelet aggregation and prolong bleeding time. Consider this effect when bleeding times are determined. The administration of naproxen may also result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used. Additionally, naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA). Consider this effect when urinary 5-hydroxy indoleacetic acid is determined.[32122]

    Avoid naproxen use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate.[32122] If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.[66040] Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive. There are no adequate and well-controlled studies of naproxen in pregnant women.[32122] Naproxen is not recommended in labor and obstetric delivery because naproxen may adversely affect fetal circulation and inhibit uterine contractions, which may increase the risk of uterine hemorrhage.[33886]

    Naproxen is excreted into breast milk in concentrations approximately equivalent to 1% of the maximal maternal plasma concentrations. Consider the developmental and health benefits of breast-feeding along with the need for naproxen and any potential adverse effects on the breastfed infant from naproxen or the underlying condition.[32122] [44091] Naproxen use is usually considered compatible with breast-feeding; other alternative analgesic and antiinflammatory drugs considered to be usually compatible with breast-feeding include acetaminophen and ibuprofen.[27500]

    NSAIDs, such as naproxen, may pose a reproductive risk by delaying or preventing prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing infertility evaluation.[32122]

    Revision Date: 04/08/2024, 02:15:00 AM

    References

    27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.32122 - EC Naprosyn (naproxen delayed-release tablets), Naprosyn (naproxen tablets), Anaprox DS (naproxen sodium tablets) package insert. Alpharetta, GA: Canton Laboratories, LLC; 2021 Apr.33886 - Treximet (sumatriptan and naproxen sodium) tablets package insert. Morristown NJ: Currax Pharmaceuticals, LLC; 2021 Apr.44091 - Naprelan (naproxen sodium extended-release tablets) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2021 Apr.55688 - O'Gara P, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-e425.56268 - Celebrex (celecoxib) package insert. New York, NY: Pfizer, Inc.; 2021 Apr.59937 - US Food and Drug Administration (FDA). Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDS): Drug Safety Communication - association with heart attacks or strokes. Retrieved July 9, 2015. Available on the World Wide Web at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM453941.pdf63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.66040 - Food and Drug Administration MedWatch. Nonsteroidal anti-inflammatory drugs (NSAIDs): Drug safety communication - avoid use of NSAIDs in pregnancy at 20 weeks or later. Available at: https://www.fda.gov/safety/medical-product-safety-information/nonsteroidal-anti-inflammatory-drugs-nsaids-drug-safety-communication-avoid-use-nsaids-pregnancy-20. Accessed October 15, 2020.

    Mechanism of Action

    Mechanism of Action: Naproxen competitively inhibits both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, by blocking arachidonate binding resulting in analgesic, antipyretic, and anti-inflammatory pharmacologic effects. The enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step of the synthesis prostaglandins and thromboxanes that are involved in rapid physiological responses. COX isoenzymes are also responsible for a peroxidase reaction, which is not affected by NSAIDs. In addition, NSAIDs do not suppress leukotriene synthesis by lipoxygenase pathways. COX-1 is constitutively expressed in almost all tissues, while COX-2 appears to only be constitutively expressed in the brain, kidney, bones, reproductive organs, and some neoplasms (e.g., colon and prostate cancers). COX-1 is responsible for prostaglandin synthesis in response to stimulation by circulating hormones, as well as maintenance of normal renal function, gastric mucosal integrity, and hemostasis. However, COX-2 is inducible in many cells in response to certain mediators of inflammation (e.g., interleukin-1, tumor necrosis factor, lipopolysaccharide, mitogens, and reactive oxygen intermediates).

    •Anti-inflammatory Activity: The anti-inflammatory mechanism of naproxen is due to decreased prostaglandin synthesis via inhibition of COX-1 and COX-2. It appears that the anti-inflammatory effects may be primarily due to inhibition of the COX-2 isoenzyme. However, COX-1 is expressed at some sites of inflammation. COX-1 is expressed in the joints of rheumatoid arthritis or osteoarthritis patients, especially the synovial lining, and it is the primary enzyme of prostaglandin synthesis in human bursitis. Naproxen is slightly more selective for COX-1 than COX-2.

    •Analgesic Activity: Naproxen is effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, naproxen has an indirect analgesic effect by inhibiting the production of further prostaglandins and does not directly affect hyperalgesia or the pain threshold.

    •Antipyretic Activity: Naproxen promotes a return to a normal body temperature set point in the hypothalamus by suppressing the synthesis of prostaglandins, specifically PGE2, in circumventricular organs in and near the hypothalamus. Naproxen may mask fever in some patients, especially with high or chronic dosing.

    •GI Effects: Gastrointestinal side effects of naproxen are primarily contributed to COX-1 inhibition; however, potential role of COX-2 inhibition in the GI tract has not been fully elucidated.

    •Platelet Effects: The inhibition of platelet aggregation seen with naproxen is due to dose-dependent inhibition of COX-1 in platelets leading to decreased levels of platelet thromboxane A2 and an increase in bleeding time (see Adverse Reactions). The inhibition of platelet aggregation is reversible upon discontinuation of naproxen. This differs from aspirin, which irreversibly binds to COX-1 in platelets inhibiting this enzyme for the life of the cell. In an in vitro study, naproxen inhibited thromboxane production and platelet aggregation by 88% for up to 8 hours. Naproxen inhibited COX-1 (measured as thromboxane B2 generation in clotting whole blood) to a greater extent as compared to ibuprofen, diclofenac, or meloxicam (94.9%, 88.7%, 49.5%, and 53.3%, respectively).[27346] Clinically, naproxen may provide some cardioprotection benefits. However, naproxen produces less consistent inhibition of thromboxane A2 than low-dose aspirin, and in clinical trials, the cardioprotective effects of naproxen have been inconsistent.

    •Renal Effects: In the kidney, prostaglandins, produced by both COX-1 and COX-2, are important regulators of sodium and water reabsorption through PGE2 and of renal function and hemodynamics via PGI2 in response to vasoconstrictive factors (e.g., endothelin-1, a factor that increases peripheral vascular resistance) and through effects on the renin-angiotensin system. In conditions where renal blood flow is dependent upon prostaglandin synthesis, administration of NSAIDs can result in significant decreases in renal blood flow leading to acute renal failure. In addition, alterations in sodium and water reabsorption may worsen increased blood pressure, which can be significant in selected individuals.

    •Bone Effects: Nonsteroidal anti-inflammatory drugs appear to suppress bone formation via inhibition of COX-2. In vivo data from rabbits revealed a significant reduction of bone growth with both naproxen and rofecoxib as compared with placebo. Bone resorption does not appear to be a mechanism that leads to decreased net bone formation, as the number of CD51 positive osteoclast-like cells per section was decreased with either NSAID as compared with drinking water alone.[32351] As determined from in vitro data, NSAIDs appear to arrest the osteoblast cell cycle at the G(0)/G(1) phase and induce cytotoxicity and cell death of osteoblasts primarily by apoptosis rather than by necrosis.[32352]

    Revision Date: 04/08/2024, 02:15:00 AM

    References

    27346 - Van Hecken A, Schwartz JI, Depre M, et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy adults. J Clin Pharmacol 2000;40:1109-20.32351 - Goodman S, Ma T, Trindade M, et al. COX-2 selective NSAID decreases bone ingrowth in vivo. J Orthop Res 2002;2:1164-9.32352 - Chang JK, Wang GJ, Tsai ST, et al. Nonsteroidal anti-inflammatory drug effects on osteoblastic cell cycle, cytotoxicity, and cell death. Connect Tissue Res 2005;46:200-10.

    Pharmacokinetics

    Naproxen is administered orally. It is more than 99% bound to albumin. At doses more than 500 mg/day, a less than proportional increase in plasma concentrations occurs due to increased clearance because of saturation of plasma protein binding. It is extensively metabolized in the liver to 6-O-desmethyl naproxen. Both naproxen and 6-O-desmethyl naproxen are further metabolized to their respective acylglucoronide conjugated metabolites. Urinary excretion is the predominant elimination pathway. Approximately 95% of naproxen is excreted in the urine with less than 1% as unchanged drug, less than 1% as 6-O-desmethyl naproxen, and 66% to 92% as their conjugates. Small amounts, 3% or less of an administered dose, is excreted in the feces. The naproxen anion has a plasma half-life of 12 to 17 hours.[32122]

     

    Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2C8, CYP2C9

    Naproxen is a substrate of the hepatic cytochrome isoenzymes CYP1A2, CYP2C8, and CYP2C9; CYP2C9 appears to be the main substrate pathway.[34493][34495]

    Route-Specific Pharmacokinetics

    Oral Route

    The different dosage forms of naproxen are bioequivalent in terms of extent of absorption (AUC) and peak concentration; however, the products do differ in their pattern of absorption. Naproxen and naproxen sodium are rapidly and completely absorbed from the GI tract. Onset of pain relief can be within 1 hour in patients taking naproxen and 30 minutes in patients taking naproxen sodium. The analgesic effect has been found to last for up to 12 hours. Peak plasma concentrations of naproxen are achieved 2 to 4 hours and 1 to 2 hours after ingestion of naproxen and naproxen sodium, respectively. The difference in rates between the 2 products is due to the increased aqueous solubility of the sodium salt of naproxen. The enteric polymer coating for enteric-coated naproxen dissolves above pH 6. Enteric-coated naproxen dissolves primarily in the small intestine rather than in the stomach, so the absorption of the drug is delayed until the stomach is emptied. When enteric-coated naproxen was given to fasted subjects, peak plasma concentrations were achieved about 4 to 6 hours after the first dose (range: 2 to 12 hours). When enteric-coated naproxen was given with food, peak plasma concentrations were achieved in about 12 hours (range: 4 to 24 hours). The presence of food prolonged the time the tablets remained in the stomach, time to first detectable serum naproxen concentrations, and time to maximal naproxen concentrations, but did not affect peak naproxen concentrations. The elimination half-life of naproxen is unchanged across products ranging from 12 to 17 hours. Steady-state concentrations are reached in 4 to 5 days.[32122]

    Special Populations

    Hepatic Impairment

    Naproxen pharmacokinetics have not been determined in patients with hepatic insufficiency. In patients with chronic alcoholic hepatic disease and other diseases with decreased or abnormal plasma proteins (i.e., hypoalbuminemia), the total plasma concentration of naproxen may be reduced, but the plasma concentration of unbound naproxen is increased.[32122]

    Renal Impairment

    Naproxen pharmacokinetics have not been determined in patients with renal insufficiency. Naproxen metabolites may accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment.[32122]

    Pediatrics

    In pediatric patients aged 5 to 16 years with arthritis, plasma naproxen concentrations after a single naproxen suspension 5 mg/kg dose were found to be similar to those in normal adults after a 500 mg dose. The terminal half-life appears to be similar in pediatric and adult patients.[32122]

    Geriatric

    Although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly, although the unbound fraction is less than 1% of the total naproxen concentration. Unbound trough naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen concentration, compared with 0.05% to 0.075% in younger subjects. The clinical significance of this finding is unclear.[32122]

    Revision Date: 04/08/2024, 02:15:00 AM

    References

    32122 - EC Naprosyn (naproxen delayed-release tablets), Naprosyn (naproxen tablets), Anaprox DS (naproxen sodium tablets) package insert. Alpharetta, GA: Canton Laboratories, LLC; 2021 Apr.34493 - Miners JO, Coulter S, Tukey RH. Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochem Pharmacol 1996;51:1003-8.34495 - Tracy TS, Marra C, Wrighton SA, et al. Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol 1997;52:293-8.

    Pregnancy/Breast-feeding

    labor, obstetric delivery, pregnancy

    Avoid naproxen use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate.[32122] If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.[66040] Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive. There are no adequate and well-controlled studies of naproxen in pregnant women.[32122] Naproxen is not recommended in labor and obstetric delivery because naproxen may adversely affect fetal circulation and inhibit uterine contractions, which may increase the risk of uterine hemorrhage.[33886]

    breast-feeding

    Naproxen is excreted into breast milk in concentrations approximately equivalent to 1% of the maximal maternal plasma concentrations. Consider the developmental and health benefits of breast-feeding along with the need for naproxen and any potential adverse effects on the breastfed infant from naproxen or the underlying condition.[32122] [44091] Naproxen use is usually considered compatible with breast-feeding; other alternative analgesic and antiinflammatory drugs considered to be usually compatible with breast-feeding include acetaminophen and ibuprofen.[27500]

    Revision Date: 04/08/2024, 02:15:00 AM

    References

    27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.32122 - EC Naprosyn (naproxen delayed-release tablets), Naprosyn (naproxen tablets), Anaprox DS (naproxen sodium tablets) package insert. Alpharetta, GA: Canton Laboratories, LLC; 2021 Apr.33886 - Treximet (sumatriptan and naproxen sodium) tablets package insert. Morristown NJ: Currax Pharmaceuticals, LLC; 2021 Apr.44091 - Naprelan (naproxen sodium extended-release tablets) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2021 Apr.66040 - Food and Drug Administration MedWatch. Nonsteroidal anti-inflammatory drugs (NSAIDs): Drug safety communication - avoid use of NSAIDs in pregnancy at 20 weeks or later. Available at: https://www.fda.gov/safety/medical-product-safety-information/nonsteroidal-anti-inflammatory-drugs-nsaids-drug-safety-communication-avoid-use-nsaids-pregnancy-20. Accessed October 15, 2020.

    Interactions

    Level 1 (Severe)

    • Cidofovir
    • Ketorolac

    Level 2 (Major)

    • Acetaminophen; Aspirin
    • Acetaminophen; Aspirin, ASA; Caffeine
    • Acetaminophen; Aspirin; Diphenhydramine
    • Acetaminophen; Ibuprofen
    • Aldesleukin, IL-2
    • Aminosalicylate sodium, Aminosalicylic acid
    • Amlodipine; Celecoxib
    • Apixaban
    • Aspirin, ASA
    • Aspirin, ASA; Butalbital; Caffeine
    • Aspirin, ASA; Caffeine
    • Aspirin, ASA; Caffeine; Orphenadrine
    • Aspirin, ASA; Carisoprodol; Codeine
    • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
    • Aspirin, ASA; Dipyridamole
    • Aspirin, ASA; Omeprazole
    • Aspirin, ASA; Oxycodone
    • Bacitracin
    • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Betrixaban
    • Bismuth Subsalicylate
    • Bismuth Subsalicylate; Metronidazole; Tetracycline
    • Bupivacaine; Meloxicam
    • Busulfan
    • Butalbital; Aspirin; Caffeine; Codeine
    • Capreomycin
    • Carmustine, BCNU
    • Celecoxib
    • Celecoxib; Tramadol
    • Chlorambucil
    • Chlorpheniramine; Ibuprofen; Pseudoephedrine
    • Choline Salicylate; Magnesium Salicylate
    • Cladribine
    • Clofarabine
    • Colistimethate, Colistin, Polymyxin E
    • Colistin
    • Cytarabine, ARA-C
    • Dabigatran
    • Dacarbazine, DTIC
    • Dasatinib
    • Desmopressin
    • Diclofenac
    • Diclofenac; Misoprostol
    • Diflunisal
    • Diphenhydramine; Ibuprofen
    • Docetaxel
    • Edoxaban
    • Enoxaparin
    • Eplerenone
    • Ethanol
    • Etodolac
    • Fenoprofen
    • Floxuridine
    • Fluorouracil, 5-FU
    • Flurbiprofen
    • Hydrocodone; Ibuprofen
    • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
    • Ibritumomab Tiuxetan
    • Ibuprofen
    • Ibuprofen lysine
    • Ibuprofen; Famotidine
    • Ibuprofen; Oxycodone
    • Ibuprofen; Pseudoephedrine
    • Indomethacin
    • Ketoprofen
    • Lomustine, CCNU
    • Macimorelin
    • Magnesium Salicylate
    • Mannitol
    • Mechlorethamine, Nitrogen Mustard
    • Meclofenamate Sodium
    • Mefenamic Acid
    • Meloxicam
    • Methenamine; Sodium Salicylate
    • Methotrexate
    • Mitoxantrone
    • Nabumetone
    • Nelarabine
    • Omacetaxine
    • Oxaprozin
    • Paclitaxel
    • Pentamidine
    • Pentostatin
    • Piroxicam
    • Polymyxin B
    • Pralatrexate
    • Probenecid
    • Probenecid; Colchicine
    • Procarbazine
    • Rivaroxaban
    • Salsalate
    • Sulindac
    • Temozolomide
    • Thioguanine, 6-TG
    • tobacco
    • Tolmetin

    Level 3 (Moderate)

    • Abciximab
    • Acebutolol
    • Acyclovir
    • Adefovir
    • Albuterol; Budesonide
    • Aliskiren
    • Aliskiren; Hydrochlorothiazide, HCTZ
    • Alpha-blockers
    • Alteplase
    • Amikacin
    • Amiloride
    • Amiloride; Hydrochlorothiazide, HCTZ
    • Aminolevulinic Acid
    • Amlodipine
    • Amlodipine; Atorvastatin
    • Amlodipine; Benazepril
    • Amlodipine; Olmesartan
    • Amlodipine; Valsartan
    • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
    • Amphotericin B
    • Amphotericin B lipid complex (ABLC)
    • Amphotericin B liposomal (LAmB)
    • Anagrelide
    • Angiotensin II receptor antagonists
    • Angiotensin-converting enzyme inhibitors
    • Antithrombin III
    • Aprotinin
    • Argatroban
    • Atenolol
    • Atenolol; Chlorthalidone
    • Auranofin
    • Azathioprine
    • Azelastine; Fluticasone
    • Azilsartan
    • Azilsartan; Chlorthalidone
    • Beclomethasone
    • Benazepril
    • Benazepril; Hydrochlorothiazide, HCTZ
    • Beta-blockers
    • Betamethasone
    • Betaxolol
    • Bictegravir; Emtricitabine; Tenofovir Alafenamide
    • Bisoprolol
    • Bisoprolol; Hydrochlorothiazide, HCTZ
    • Bivalirudin
    • Brimonidine; Timolol
    • Budesonide
    • Budesonide; Formoterol
    • Budesonide; Glycopyrrolate; Formoterol
    • Bumetanide
    • Calcium Carbonate; Famotidine; Magnesium Hydroxide
    • Calcium Phosphate, Supersaturated
    • Calcium-channel blockers
    • Candesartan
    • Candesartan; Hydrochlorothiazide, HCTZ
    • Cannabidiol
    • Captopril
    • Captopril; Hydrochlorothiazide, HCTZ
    • Carteolol
    • Carvedilol
    • Chlorothiazide
    • Chlorthalidone
    • Cholinesterase inhibitors
    • Ciclesonide
    • Cilostazol
    • Cimetidine
    • Ciprofloxacin
    • Citalopram
    • Citric Acid; Potassium Citrate; Sodium Citrate
    • Clevidipine
    • Clopidogrel
    • Corticosteroids
    • Cortisone
    • Cyclosporine
    • Dabrafenib
    • Dalteparin
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Deferasirox
    • Deflazacort
    • Delafloxacin
    • Desvenlafaxine
    • Dexamethasone
    • Digoxin
    • Diltiazem
    • Dipyridamole
    • Donepezil
    • Donepezil; Memantine
    • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
    • Dorzolamide; Timolol
    • Doxazosin
    • Duloxetine
    • Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
    • Eltrombopag
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Emtricitabine
    • Emtricitabine; Rilpivirine; Tenofovir alafenamide
    • Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate
    • Emtricitabine; Tenofovir alafenamide
    • Emtricitabine; Tenofovir Disoproxil Fumarate
    • Enalapril, Enalaprilat
    • Enalapril; Hydrochlorothiazide, HCTZ
    • Entecavir
    • Epoprostenol
    • Eprosartan
    • Eprosartan; Hydrochlorothiazide, HCTZ
    • Eptifibatide
    • Erlotinib
    • Escitalopram
    • Esmolol
    • Ethacrynic Acid
    • Ethiodized Oil
    • Famotidine
    • Felodipine
    • Fludrocortisone
    • Flunisolide
    • Fluoxetine
    • Fluticasone
    • Fluticasone; Salmeterol
    • Fluticasone; Umeclidinium; Vilanterol
    • Fluticasone; Vilanterol
    • Fluvoxamine
    • Fondaparinux
    • Formoterol; Mometasone
    • Fosinopril
    • Fosinopril; Hydrochlorothiazide, HCTZ
    • Furosemide
    • Galantamine
    • Gemfibrozil
    • Gemifloxacin
    • Gentamicin
    • Ginkgo, Ginkgo biloba
    • Glimepiride
    • Glipizide
    • Glipizide; Metformin
    • Glyburide
    • Glyburide; Metformin
    • Gold
    • Guanfacine
    • H2-blockers
    • Heparin
    • Hyaluronidase, Recombinant; Immune Globulin
    • Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ; Moexipril
    • Hydrocortisone
    • Ibandronate
    • Iloprost
    • Immune Globulin IV, IVIG, IGIV
    • Indapamide
    • Inotersen
    • Iodine; Potassium Iodide, KI
    • Iodixanol
    • Iohexol
    • Iomeprol
    • Ionic Contrast Media
    • Iopamidol
    • Iopromide
    • Ioversol
    • Irbesartan
    • Irbesartan; Hydrochlorothiazide, HCTZ
    • Isosulfan Blue
    • Isradipine
    • Labetalol
    • Lamivudine; Tenofovir Disoproxil Fumarate
    • Leflunomide
    • Levamlodipine
    • Levobunolol
    • Levofloxacin
    • Levomilnacipran
    • Lisinopril
    • Lisinopril; Hydrochlorothiazide, HCTZ
    • Lithium
    • Losartan
    • Losartan; Hydrochlorothiazide, HCTZ
    • Lumacaftor; Ivacaftor
    • Lumacaftor; Ivacaftor
    • Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate
    • Mecamylamine
    • Methyldopa
    • Methylprednisolone
    • Methylsulfonylmethane, MSM
    • Metolazone
    • Metoprolol
    • Metoprolol; Hydrochlorothiazide, HCTZ
    • Mifepristone
    • Milnacipran
    • Moexipril
    • Mometasone
    • Moxifloxacin
    • Nadolol
    • Nebivolol
    • Nebivolol; Valsartan
    • Neostigmine
    • Neostigmine; Glycopyrrolate
    • Nicardipine
    • NIFEdipine
    • Nimodipine
    • Nisoldipine
    • Nizatidine
    • Non-Ionic Contrast Media
    • Ofloxacin
    • Olanzapine; Fluoxetine
    • Olmesartan
    • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
    • Olmesartan; Hydrochlorothiazide, HCTZ
    • Olopatadine; Mometasone
    • Oritavancin
    • Pamidronate
    • Paroxetine
    • Pentosan
    • Perindopril
    • Perindopril; Amlodipine
    • Phenoxybenzamine
    • Phentolamine
    • Photosensitizing agents (topical)
    • Physostigmine
    • Pindolol
    • Pioglitazone; Glimepiride
    • Platelet Inhibitors
    • Pneumococcal Vaccine, Polyvalent
    • Polyethylene Glycol; Electrolytes
    • Polyethylene Glycol; Electrolytes; Ascorbic Acid
    • Potassium
    • Potassium Acetate
    • Potassium Bicarbonate
    • Potassium Chloride
    • Potassium Citrate
    • Potassium Citrate; Citric Acid
    • Potassium Gluconate
    • Potassium Iodide, KI
    • Prasugrel
    • Prazosin
    • Prednisolone
    • Prednisone
    • Propranolol
    • Pyridostigmine
    • Quinapril
    • Quinapril; Hydrochlorothiazide, HCTZ
    • Quinolones
    • Ramipril
    • Ranitidine
    • Reteplase, r-PA
    • Rivastigmine
    • Sacubitril; Valsartan
    • Selective serotonin reuptake inhibitors
    • Sertraline
    • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
    • Sodium picosulfate; Magnesium oxide; Anhydrous citric acid
    • Sodium Sulfate; Magnesium Sulfate; Potassium Chloride
    • Sotalol
    • Sparsentan
    • Spironolactone
    • Spironolactone; Hydrochlorothiazide, HCTZ
    • Streptomycin
    • Sucralfate
    • Sulfonylureas
    • Tacrolimus
    • Telmisartan
    • Telmisartan; Amlodipine
    • Telmisartan; Hydrochlorothiazide, HCTZ
    • Tenecteplase
    • Tenofovir Alafenamide
    • Tenofovir Alafenamide
    • Tenofovir Disoproxil Fumarate
    • Terazosin
    • Teriflunomide
    • Thiazide diuretics
    • Thrombolytic Agents
    • Ticagrelor
    • Timolol
    • Tirofiban
    • Tobramycin
    • Torsemide
    • Trandolapril
    • Trandolapril; Verapamil
    • Trazodone
    • Treprostinil
    • Triamcinolone
    • Triamterene
    • Triamterene; Hydrochlorothiazide, HCTZ
    • Urea
    • Valacyclovir
    • Valsartan
    • Valsartan; Hydrochlorothiazide, HCTZ
    • Venlafaxine
    • Verapamil
    • Verteporfin
    • Vilazodone
    • Voclosporin
    • Vorapaxar
    • Voriconazole
    • Vortioxetine
    • Warfarin
    • Zoledronic Acid

    Level 4 (Minor)

    • Alendronate
    • Alendronate; Cholecalciferol
    • Aluminum Hydroxide
    • Aluminum Hydroxide; Magnesium Carbonate
    • Aluminum Hydroxide; Magnesium Hydroxide
    • Aluminum Hydroxide; Magnesium Hydroxide; Simethicone
    • Aluminum Hydroxide; Magnesium Trisilicate
    • Antacids
    • Aprepitant, Fosaprepitant
    • Atazanavir
    • Atazanavir; Cobicistat
    • Calcium Chloride
    • Cefotaxime
    • Cholestyramine
    • Drospirenone
    • Drospirenone; Estetrol
    • Drospirenone; Estradiol
    • Drospirenone; Ethinyl Estradiol
    • Drospirenone; Ethinyl Estradiol; Levomefolate
    • Elexacaftor; tezacaftor; ivacaftor
    • Ethotoin
    • Etidronate
    • Fenofibric Acid
    • Foscarnet
    • Fosphenytoin
    • Ganciclovir
    • Garlic, Allium sativum
    • Ginger, Zingiber officinale
    • Hydantoins
    • Ivacaftor
    • Levomefolate
    • Mafenide
    • Magnesium Hydroxide
    • Magnesium Salts
    • Mesalamine, 5-ASA
    • Methoxsalen
    • Neomycin
    • Omeprazole; Sodium Bicarbonate
    • Phenytoin
    • Risedronate
    • Sodium Bicarbonate
    • Sulfadiazine
    • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
    • Sulfasalazine
    • Sulfonamides
    • Telavancin
    • Tezacaftor; Ivacaftor
    • Valganciclovir
    • Vancomycin
    • Vemurafenib
    • Vigabatrin
    Abciximab: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Acebutolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Acetaminophen; Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Acetaminophen; Aspirin: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Acetaminophen; Aspirin; Diphenhydramine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Acyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of acyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. [34408] [56268] Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as nonsteroidal antiinflammatory drugs may increase the risk of developing nephrotoxicity even in patients who have normal renal function. The use of adefovir with NSAIDs may be done cautiously. As stated in the current adefovir prescribing information, 'Ibuprofen (800 mg PO three times daily), when given concomitantly with adefovir dipivoxil, increased the adefovir Cmax by 33% and AUC by 23%, as well as urinary recovery. The increase appears to be due to higher oral bioavailability, not a reduction in renal clearance of adefovir.' In an in vitro investigation, the antiviral effect of adefovir was unaltered and the renal proximal tubule accumulation of adefovir was inhibited by the presence of a NSAID. Adefovir is efficiently transported by the human renal organic anion transporter 1, and the presence of this transporter appears to mediate the accumulation of the drug in renal proximal tubules. The in vitro study suggests that the use of a NSAID with adefovir may potentially reduce the nephrotoxic potential of adefovir. Of course, NSAIDs are associated with nephrotoxicity of their own; therefore, further data on the interaction between NSAIDs and adefovir in humans are needed. [27615] Albuterol; Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Aldesleukin, IL-2: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. [41853] Alendronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. [28644] [52249] Alendronate; Cholecalciferol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. [28644] [52249] Aliskiren: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren. [30489] [33200] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren. [30489] [33200] Alpha-blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Alteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding. [28469] [30569] Aluminum Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Aluminum Hydroxide; Magnesium Carbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Aluminum Hydroxide; Magnesium Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Aluminum Hydroxide; Magnesium Trisilicate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Amikacin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin. [28370] [30110] [30268] Amiloride: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Aminolevulinic Acid: (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable. [42968] Aminosalicylate sodium, Aminosalicylic acid: (Major) Avoid concomitant use of naproxen with aminosalicylic acid due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Amlodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Amlodipine; Atorvastatin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Amlodipine; Benazepril: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Amlodipine; Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [28317] [32122] (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Amlodipine; Olmesartan: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Amlodipine; Valsartan: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Amphotericin B lipid complex (ABLC): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs. [28333] [30268] Amphotericin B liposomal (LAmB): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs. [28333] [30268] Amphotericin B: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs. [28333] [30268] Anagrelide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Antacids: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Antithrombin III: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Apixaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [52739] Aprepitant, Fosaprepitant: (Minor) Use caution if naproxen and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of naproxen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Naproxen is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant. [30676] [34493] [34495] [40027] Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as NSAIDs, as the risk of renal impairment may be increased. [5204] Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Aspirin, ASA: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Aspirin, ASA; Dipyridamole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Aspirin, ASA; Omeprazole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Aspirin, ASA; Oxycodone: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Atazanavir: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme. [11351] [28142] Atazanavir; Cobicistat: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme. [11351] [28142] Atenolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Auranofin: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy. [30110] [30268] Azathioprine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask fever, pain, swelling and other signs and symptoms of an infection. [6144] Azelastine; Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Azilsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Bacitracin: (Major) Avoid concurrent use of bacitracin with nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. [31047] [56268] Beclomethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of naproxen with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Beta-blockers: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Betamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Betaxolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and nonsteroidal antiinflammatory drugs (NSAIDs) are used concomitantly. Coadministration of betrixaban and NSAIDs may increase the risk of bleeding. [62037] Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Bismuth Subsalicylate: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Bisoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Bivalirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Brimonidine; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Budesonide; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Bumetanide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. [30489] [48492] Bupivacaine; Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [29611] [32122] Busulfan: (Major) Due to the thrombocytopenic effects of busulfan, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [4736] [5170] Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular protection. [32122] [61171] Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Calcium Chloride: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] Calcium-channel blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Candesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Cannabidiol: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. [34493] [34495] [63309] Capreomycin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [44155] Captopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Carmustine, BCNU: (Major) Due to the thrombocytopenic effects of carmustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the delayed myelosuppressive effects of carmustine. [5170] [5946] Carteolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Carvedilol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted. [28646] [29912] [57694] [57695] [58208] Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [28317] [32122] Celecoxib; Tramadol: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [28317] [32122] Chlorambucil: (Major) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [4757] [5170] Chlorothiazide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Cholestyramine: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered. [8934] Choline Salicylate; Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with choline salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] (Major) Avoid concomitant use of naproxen with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Cholinesterase inhibitors: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Ciclesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Cidofovir: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir. [28388] Cilostazol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Cimetidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Ciprofloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Citalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Cladribine: (Major) Due to the thrombocytopenic effects of cladribine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7226] Clevidipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Clofarabine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7557] Clopidogrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Colistimethate, Colistin, Polymyxin E: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug. [33636] Colistin: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug. [33636] Corticosteroids: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Cortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Cyclosporine: (Moderate) Serum creatinine ,potassium concentrations, and cyclosporine concentrations should be closely monitored when systemic cyclosporine is given with nonsteroidal antiinflammatory drugs (NSAIDs). Renal dysfunction associated with cyclosporine may be potentiated by concurrent usage of NSAIDs. The effects of NSAIDs on the production of renal prostaglandins may cause changes in the elimination of cyclosporine. Potentiation of renal dysfunction may especially occur in a dehydrated patient. Patients should be monitored for signs and symptoms of cyclosporine toxicity and infection, as NSAIDs may mask fever, pain, or swelling. Increased tear production was not seen in patients receiving ophthalmic NSAIDs or using punctual plugs concurrently with cyclosporine ophthalmic emulsion. [29198] Cytarabine, ARA-C: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore decreasing its antineoplastic activity. [5170] [7945] Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID therapy. [42121] Dabrafenib: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was decreased by 37%. [11351] [11353] [54802] Dacarbazine, DTIC: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7996] Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Dasatinib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib. [32387] [5170] Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly. [31807] Deflazacort: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Delafloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical symptoms of hyponatremia. [10457] [10458] [29202] Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by desvenlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be monitored for signs and symptoms of bleeding while taking desvenlafaxine with NSAIDs. [28275] [29934] Dexamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Diclofenac: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30115] [32122] Diclofenac; Misoprostol: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30115] [32122] Diflunisal: (Major) Avoid concomitant use of diflunisal with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. Additionally, concomitant administration of naproxen and diflunisal significantly decreased the urinary excretion of naproxen and its glucuronide metabolite; naproxen and diflunisal plasma concentrations were unaffected. [32122] [49143] Digoxin: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary. [28272] Diltiazem: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Diphenhydramine; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Dipyridamole: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Docetaxel: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [5235] Donepezil: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Donepezil; Memantine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] Dorzolamide; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Doxazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Drospirenone: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. [4716] Drospirenone; Estetrol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. [4716] Drospirenone; Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. [4716] Drospirenone; Ethinyl Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. [4716] Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. [4716] (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. [35581] Duloxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant duloxetine and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [29934] Edoxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] Elexacaftor; tezacaftor; ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. [34493] [48524] Eltrombopag: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID. [40392] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate. [34493] [34495] [51664] [58001] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate. [34493] [34495] [51664] [58001] Emtricitabine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. [35893] [51664] [64014] Enalapril, Enalaprilat: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring. [29732] Entecavir: (Moderate) The manufacturer of entecavir recommends monitoring for adverse effects when coadministered with NSAIDs. Entecavir is primarily eliminated by the kidneys; NSAIDs can affect renal function. Concurrent administration may increase the serum concentrations of entecavir and adverse events. [31230] Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating coadministration of eplerenone and nonsteroidal antiinflammatory drugs (NSAIDs), and monitor blood pressure. The concomitant use of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Patients who develop hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium concentrations. [27990] Epoprostenol: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways. [4087] Eprosartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Eptifibatide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with nonsteroidal antiinflammatory drugs (NSAIDs) is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases. Patients receiving concomitant NSAIDs may be at increased risk of perforation. [30555] Escitalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Esmolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Ethacrynic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. [30489] [48492] Ethanol: (Major) Advise patients to avoid alcohol and alcohol-containing products while taking NSAIDs. Concomitant ingestion of alcohol with NSAIDs increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol is a mucosal irritant and NSAIDs decrease platelet aggregation. Routine ingestion of alcohol and NSAIDs can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of NSAIDs and alcohol should be avoided. Chronic alcohol ingestion is often associated with hypoprothrombinemia and this condition increases the risk of bleeding. [30115] [30427] [30569] [31949] Ethiodized Oil: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Ethotoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. [6112] Etidronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. [28655] Etodolac: (Major) Avoid concomitant use of etodolac with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [45875] Famotidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Felodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid. [11351] [11353] [49952] Fenoprofen: (Major) Avoid concomitant use of fenoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30524] [32122] Floxuridine: (Major) Due to the thrombocytopenic effects of floxuridine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7446] Fludrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Flunisolide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Fluorouracil, 5-FU: (Major) Due to the thrombocytopenic effects of fluorouracil, 5-FU, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [5763] Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Flurbiprofen: (Major) Avoid concomitant use of flurbiprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30241] [32122] Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Fluticasone; Salmeterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Fluticasone; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Fluvoxamine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Formoterol; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Foscarnet: (Minor) The risk of renal toxicity may be increased if foscarnet is used in conjuction with other nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor renal function carefully during concurrent therapy. [28377] [30268] Fosinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Fosphenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. [6112] Furosemide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [32122] [48492] Galantamine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Ganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required. [32676] Garlic, Allium sativum: (Minor) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving drugs with a known potential risk for bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). [25588] [63043] Gemfibrozil: (Moderate) Use naproxen and gemfibrozil together with caution. Naproxen is a substrate of CYP2C8, and gemfibrozil is a strong CYP2C8 inhibitor. Coadministration may result in a significant increase in naproxen exposure. A dose reduction of naproxen may be required if used concomitantly with gemfibrozil. [34493] [34495] [48366] [56579] [57620] Gemifloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Gentamicin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as gentamicin. [28370] [30110] [30268] Ginger, Zingiber officinale: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes. However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity. [28470] [29960] Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and NSAIDs as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy. [25082] [25083] [25273] [28470] [41251] [41258] [41265] Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Glipizide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Glipizide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Glyburide: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Glyburide; Metformin: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Gold: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy. [30110] [30268] Guanfacine: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways. [805] H2-blockers: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [6859] [7020] [7823] Hydantoins: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. [6112] Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Hydrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of naproxen with phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Ibandronate: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or oral ibandronate, respectively, and nonsteroidal antiinflammatory drugs. Acute renal failure has been observed with intravenous ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. [29558] [31826] Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as nonsteroidal antiinflammatory drugs (NSAIDs); the risk of bleeding may be increased. If coadministration with NSAIDs is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia. [41826] (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Ibuprofen lysine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided. [30115] [30569] Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Ibuprofen; Famotidine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Ibuprofen; Oxycodone: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [35893] Iloprost: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [6859] [7020] [7823] Indapamide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [24233] [30489] [48492] Indomethacin: (Major) Avoid concomitant use of indomethacin with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [32122] [45886] Inotersen: (Moderate) Use caution with concomitant use of inotersen and nonsteroidal antiinflammatory drugs (NSAIDs) due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of NSAIDs in a patient taking inotersen with a platelet count of less than 50,000 per microliter. [63624] Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Iodixanol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Iohexol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Iomeprol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] Iopamidol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Iopromide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Ioversol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Irbesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Isosulfan Blue: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Isradipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. [34493] [48524] Ketoprofen: (Major) Avoid concomitant use of ketoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30548] [32122] Ketorolac: (Contraindicated) Concomitant use of ketorolac with another NSAID is contraindicated. Increased adverse gastrointestinal effects are possible if ketorolac is used with other systemic nonsteroidal antiinflammatory drugs (NSAIDs). [28331] [32122] Labetalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] Leflunomide: (Moderate) In vitro studies indicate that the M1 metabolite of leflunomide inhibits cytochrome P450 2C9, the enzyme responsible for the metabolism of many NSAIDs. Leflunomide altered protein binding and thus, increased the free fraction of ibuprofen by 13% to 50%. The clinical significance of the interactions with NSAIDs is unknown. There was extensive concomitant use of NSAIDs in phase III clinical studies of leflunomide in the treatment of rheumatoid arthritis, and no clinical differential effects were observed. However, because some NSAIDs have been reported to cause hepatotoxic effects, some caution may be warranted in their use with leflunomide. [49634] Levamlodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Levobunolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Levofloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Levomefolate: (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together. [35581] Levomilnacipran: (Moderate) Platelet aggregation may be impaired by SNRIs such as levomilnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking levomilnacipran and NSAIDs. [55469] Lisinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Lithium: (Moderate) Monitor serum lithium concentrations during concomitant nonsteroidal anti-inflammatory (NSAID) use; reduce the lithium dose based on serum lithium concentrations and clinical response. NSAIDs decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations. [54241] Lomustine, CCNU: (Major) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7668] Losartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. [34993] [34995] [59891] (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. [34493] [48524] Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. [34993] [34995] [59891] Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as nonsteroidal antiinflammatory drugs (NSAIDs). Healthcare providers are advised to discontinue NSAID therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test. [62723] Mafenide: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. [6112] Magnesium Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Magnesium Salts: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). [41573] Mannitol: (Major) Avoid use of mannitol and nonsteroidal anti-inflammatory drugs (NSAIDs), if possible. If use together is necessary, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Concomitant administration of nephrotoxic drugs, such as NSAIDs, increases the risk of renal failure after administration of mannitol. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. [30489] [33007] [48492] Mecamylamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Mechlorethamine, Nitrogen Mustard: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7997] Meclofenamate Sodium: (Major) Avoid concomitant use of meclofenamate sodium with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30574] [32122] Mefenamic Acid: (Major) Avoid concomitant use of mefenamic acid with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30570] [32122] Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [29611] [32122] Mesalamine, 5-ASA: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity. [11423] Methenamine; Sodium Salicylate: (Major) Avoid concomitant use of naproxen with sodium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Methotrexate: (Major) Do not administer nonsteroidal anti-inflammatory drugs (NSAIDs) before or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths from severe hematologic and gastrointestinal toxicity. Use caution when NSAIDs are administered concomitantly with lower doses of methotrexate as they have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Despite potential interactions, patients with rheumatoid arthritis (RA) are often receiving concurrent treatment with NSAIDs without apparent problems. However, these doses are lower than those used in psoriasis or malignancy; higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. NSAIDs may be continued in patients with RA receiving treatment with methotrexate, although the possibility of increased toxicity has not been fully explored. [56263] [57771] [60517] [61900] [66594] Methoxsalen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic therapy may be advisable. [6625] Methyldopa: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Methylprednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Methylsulfonylmethane, MSM: (Moderate) Patients taking methylsulfonylmethane, MSM have reported increased bruising or blood in the stool. These effects have not been confirmed in published medical literature or during clinical studies. Use methylsulfonylmethane, MSM with caution in patients who are taking drugs with the potential for additive bleeding, including nonsteroidal antiinflammatory drugs (NSAIDs). During an available, published clinical trials in patients with osteoarthritis, patients with bleeding disorders or using anticoagulants or platelet inhibiting drugs were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving NSAIDs should be observed for potential bleeding. [32984] [32986] Metolazone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Metoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Mifepristone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions. [48697] Milnacipran: (Moderate) Platelet aggregation may be impaired by milnacipran due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding in patients taking milnacipran and NSAIDs. [28275] [29934] Mitoxantrone: (Major) Due to the thrombocytopenic effects of mitoxantrone, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [41139] Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Moxifloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Nabumetone: (Major) Avoid concomitant use of nabumetone with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [31941] [32122] Nadolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Nebivolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Nebivolol; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Nelarabine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [8493] Neomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, such as aminoglycosides. [5046] [5062] Neostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Neostigmine; Glycopyrrolate: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Nicardipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] NIFEdipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Nimodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Nisoldipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Nizatidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Non-Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. [28692] [28702] Ofloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Olopatadine; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and nonsteroidal antiinflammatory drugs (NSAIDs) when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding. [52213] Omeprazole; Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Oritavancin: (Moderate) Naproxen is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated naproxen plasma concentrations. If these drugs are administered concurrently, monitor patients for NSAID-induced toxicity, such as nausea, GI bleeding, or renal dysfunction. [11351] [11353] [57741] Oxaprozin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30565] [32122] Paclitaxel: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5938] Pamidronate: (Moderate) Monitor renal function during concomitant pamidronate and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity. [31027] [32122] Paroxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Pentamidine: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable. [28879] Pentosan: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Pentostatin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [5512] Perindopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Perindopril; Amlodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Phenoxybenzamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Phentolamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Phenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. [6112] Photosensitizing agents (topical): (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and during photodynamic therapy may be advisable. [42968] Physostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Pindolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Pioglitazone; Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Piroxicam: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [29613] [32122] Platelet Inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as nonsteroidal antiinflammatory drugs (NSAIDS), may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic acetaminophen. [39165] Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). [41573] Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). [41573] Polymyxin B: (Major) The chronic coadministration of systemic polymyxins may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since Polymyxin B is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug. [28447] Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Pralatrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant administration of drugs that undergo substantial renal clearance, such as nonsteroidal antiinflammatory drugs (NSAIDs), may result in delayed clearance of pralatrexate. [36890] Prasugrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Prazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Prednisolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Prednisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Probenecid: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance. [23583] [29374] Probenecid; Colchicine: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance. [23583] [29374] Procarbazine: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [5356] Propranolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Pyridostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Quinapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Quinolones: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones have been shown to provoke convulsions in preclinical studies and postmarketing. [28423] [28424] [28764] [29947] [43411] [65562] Ramipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Ranitidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. [32122] Reteplase, r-PA: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding. [28469] [30569] Risedronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients. [42080] Rivaroxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory response closely during concurrent use. [29732] [40621] [49946] Rivastigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. [27344] Sacubitril; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Salsalate: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. [32122] [61171] Selective serotonin reuptake inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Sertraline: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. [27414] [32127] Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. [6112] [8934] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. [32159] [32160] Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). [51258] Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. [30272] [53793] Sotalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Sparsentan: (Moderate) Monitor for worsening renal function during concomitant use of sparsentan and nonsteroidal antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX-2) inhibitors. Concomitant use increases the risk for nephrotoxicity, especially in patients with additional risk factors such as hypovolemia and chronic renal impairment. [68641] Spironolactone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [32018] [48492] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [32018] [48492] Streptomycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as streptomycin. [28370] [30110] [30268] Sucralfate: (Moderate) Separate sucralfate and naproxen administration by at least 2 hours. Concomitant administration of sucralfate and enteric-coated or delayed-release naproxen tablets can delay the absorption of naproxen. [29374] [32122] Sulfadiazine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. [6112] Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. [6112] Sulfasalazine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. [6112] Sulfonamides: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. [6112] Sulfonylureas: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. [24711] [29374] [51000] Sulindac: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [28340] [32122] Tacrolimus: (Moderate) Monitor patients for signs of worsening renal function during coadministration of tacrolimus and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. [28611] Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as nonsteroidal antiinflammatory drugs (NSAIDS) may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance. [36615] [7020] Telmisartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Telmisartan; Amlodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Temozolomide: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [7578] Tenecteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding. [28469] [30569] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. [30268] [60269] [60688] Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. [28193] [30268] Terazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Teriflunomide: (Moderate) Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8 substrates, such as naproxen. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for increased adverse effects, including additive hepatotoxicity. [51794] Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. [34493] [48524] Thiazide diuretics: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Thioguanine, 6-TG: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [5170] [5853] Thrombolytic Agents: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding. [28469] [30569] Ticagrelor: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. [32122] Tirofiban: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Tobacco: (Major) Advise patients to avoid smoking tobacco while taking nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of NSAIDs with tobacco smoking may enhance the risk of gastrointestinal side effects, including peptic ulcer and GI bleeding. Patients using tobacco and NSAIDs concurrently should be monitored closely for GI adverse reactions. [28327] [30496] [32018] [56268] Tobramycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as tobramycin. [28370] [30110] [30268] Tolmetin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. [30242] [32122] Torsemide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. [30489] [48492] Trandolapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Trandolapril; Verapamil: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [32122] [61325] Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with medications that impair platelet function and to promptly report any bleeding events to the practitioner. [38831] Treprostinil: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal and peripheral vasoactive pathways. [4087] Triamcinolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. [24574] [29611] [35893] Triamterene: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [32122] [48492] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [32122] [48492] Urea: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. [30489] [48492] Valacyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of valacyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. [29970] [56268] Valganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with valganciclovir should be done cautiously to avoid additive nephrotoxicity. [5193] Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. [27388] [27991] [28608] [29130] [32122] [60860] (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. [35893] [48492] Vancomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin. [28370] [28468] [30110] [30268] Vemurafenib: (Minor) Concomitant use of vemurafenib and naproxen may result in increased naproxen concentrations. Vemurafenib is a CYP2C9 and CYP1A2 inhibitor and naproxen is a CYP2C9 and CYP1A2 substrate. Patients should be monitored for toxicity. [11351] [11353] [45335] Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor patients for signs and symptoms of bleeding when coadministering venlafaxine with NSAIDs. [28275] Verapamil: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. [24233] [26486] [27388] [30489] Verteporfin: (Moderate) Use caution if coadministration of verteporfin with nonsteroidal anti-inflammatory drugs is necessary due to the risk of decreased verteporfin efficacy. Oxaprozin may additionally worsen photosensitivity. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation like nonsteroidal anti-inflammatory drugs could decrease the efficacy of verteporfin therapy. [30003] Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin. [36250] Vilazodone: (Moderate) Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with NSAIDs and to promptly report any bleeding events to the practitioner. [43177] Voclosporin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. [66336] [66357] Vorapaxar: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. [28435] [36055] Voriconazole: (Moderate) The hepatic isoenzyme CYP2C9 is responsible for the metabolism of many NSAIDs. Voriconazole is known to be an inhibitor of CYP2C9 and may lead to increased plasma levels of some NSAIDs, such as naproxen. The clinical significance of this potential interaction is unknown. Monitor for NSAID-related side-effects, such as fluid retention or GI irritation, and adjust the dose of the NSAID if needed. [4882] Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with medications which impair platelet function and to promptly report any bleeding events to the practitioner. [56041] Warfarin: (Moderate) Monitor patients for signs or symptoms of bleeding during concurrent use of warfarin and nonsteroidal antiinflammatory drugs (NSAIDs). To minimize the potential for GI bleeding, use the lowest effective NSAID dose for the shortest possible duration. If signs or symptoms of bleeding occur, promptly evaluate and treat. Systemic hematological effects may also occur with the use of topical NSAIDs. NSAIDs inhibit platelet aggregation and may prolong bleeding time in some patients. [28549] [33554] [56268] [61088] Zoledronic Acid: (Moderate) Monitor renal function during concomitant zoledronic acid and nonsteroidal antiinflammatory drug use due to risk for additive nephrotoxicity. [32122] [58724]
    Revision Date: 04/08/2024, 02:15:00 AM

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    Monitoring Parameters

    • CBC
    • LFTs
    • serum creatinine/BUN

    US Drug Names

    • Aflaxen
    • Aleve
    • Aleve Arthritis
    • All Day Pain Relief
    • All Day Relief
    • Anaprox
    • Anaprox DS
    • EC-Naprosyn
    • Midol Extended Relief
    • Naprelan
    • Naprelan Dose Card
    • Naprosyn
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