AHFS Class:

• Reversible COX-1/COX-2 Inhibitors 28:08.04.04

Generic Name(s):

• Oxaprozin

Oxaprozin is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).1,2,3,4,5,6,7,8

Oxaprozin is used for anti-inflammatory and analgesic effects in the symptomatic treatment of osteoarthritis and rheumatoid arthritis in adults.1,2,3 For additional information on the management of osteoarthritis, see Uses: Osteoarthritis, in Celecoxib 28:08.04.08. For additional information on the management of rheumatoid arthritis, see Uses: Rheumatoid Arthritis, in Methotrexate 10:00.

Oxaprozin also is used for the symptomatic management of juvenile rheumatoid arthritis in pediatric patients 6-16 years of age.1

The potential benefits and risks of oxaprozin therapy as well as alternative therapies should be considered prior to initiating oxaprozin therapy.1 The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.1

Patients should be advised that oxaprozin, like other nonsteroidal anti-inflammatory agents (NSAIAs), is not free of potential adverse effects, including some that can cause discomfort, and that more serious effects (e.g., myocardial infarction, stroke, GI bleeding), which may require hospitalization and may even be fatal, also can occur.1,500,508 NSAIAs, including selective cyclooxygenase-2 (COX-2) inhibitors and prototypical NSAIAs, increase the risk of serious adverse cardiovascular thrombotic events, including myocardial infarction and stroke, in patients with or without cardiovascular disease or risk factors for cardiovascular disease.11,12,13,500,502,508 Available data suggest that the increase in risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500,502,505,506,508 Use of NSAIAs also is associated with an increased risk of heart failure.500,508 (See Cautions: Cardiovascular Effects, in Celecoxib 28:08.04.08.) The risk of potentially serious adverse GI effects also should be considered in patients receiving oxaprozin, particularly in patients receiving chronic therapy with the drug.1 (See Cautions: GI Effects, in Naproxen 28:08.04.92.) NSAIAs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.508 Patients should be advised to read the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.1

Administration

The potential benefits and risks of oxaprozin therapy as well as alternative therapies should be considered prior to initiating oxaprozin therapy.1

Oxaprozin is administered orally.1,2,3,6 The rate but not the extent of GI absorption of the drug may be reduced by concomitant administration with food.1,2,3,4,6 The rate and extent of absorption do not appear to be affected when the drug is administered with antacids.1 Oxaprozin usually is administered once daily.1,2,3,6,7 However, administration of the drug in divided doses daily may improve tolerance in some patients.1

Dosage

The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed.1 Dosage of oxaprozin must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage.1

The manufacturer states that safety and efficacy of oxaprozin in children younger than 6 years of age have not been established.1

For the symptomatic treatment of rheumatoid arthritis or osteoarthritis, the usual dosage of oxaprozin for normal-weight adults is 1.2 g once daily.1,2,3 The usual dosage for low-weight adults is 600 mg once daily; if an adequate response is not achieved, the dosage may be increased to 1.2 g daily.1 If rapid onset of action is required in adults, a one-time loading dose of 1.2-1.8 g (not to exceed 26 mg/kg) may be given.1

Dosages of oxaprozin exceeding 1.2 g daily may be given, if needed, to adults who weigh more than 50 kg, have normal renal and hepatic functions, are at low risk of peptic ulcer, and have not experienced adverse GI, hepatic, renal, or dermatologic effects while receiving lower dosages.1 The manufacturer states that the maximum dosage of oxaprozin in adults should not exceed 1.8 g or 26 mg/kg daily, whichever is lower, given in divided doses.1

The manufacturer states that clinically important differences in the pharmacokinetic profile of oxaprozin were not observed in studies in healthy geriatric adults.1 Therefore, dosage adjustment solely on the basis of age generally is not required for healthy, normal-weight geriatric patients.1 However, the possible need for dosage adjustment in geriatric patients should be considered for those with low body weight, decreased renal function, or other disorders of age.1 In addition, the possibility that geriatric patients may tolerate oxaprozin less well than younger adults should be considered.1

For the symptomatic management of juvenile rheumatoid arthritis in children 6-16 years of age, oxaprozin dosages of 600 mg, 900 mg, or 1.2 g daily for children weighing 22-31, 32-54, or 55 kg or more, respectively, may be used.1 The manufacturer states that these dosages were based on comparisons of the pharmacokinetics of oxaprozin in adults and pediatric patients and are estimated to result in oxaprozin exposure similar to that reported in 70-kg adults with rheumatoid arthritis receiving an oxaprozin dosage of 1.2 g daily.1 In an uncontrolled trial in children with juvenile rheumatoid arthritis, oxaprozin was administered at a dosage of 10-20 mg/kg daily; controlled trials of oxaprozin in children with juvenile rheumatoid arthritis have not been conducted.1 The manufacturer states that dosages exceeding 1.2 g daily have not been studied in children.1

Dosage in Renal and Hepatic Impairment

Since pharmacokinetics of oxaprozin are altered in patients with renal impairment1,2,3,8 and in those undergoing hemodialysis,1 the manufacturer states that oxaprozin should be initiated at 600 mg daily in adults with severe renal impairment and in those undergoing hemodialysis.1,3,8 If an adequate response is not achieved, dosage may be increased to 1.2 g daily with caution.1,8 Supplemental doses for patients undergoing hemodialysis are not necessary because the drug is highly protein bound.1

Modification of oxaprozin dosage is not necessary in patients with well-compensated cirrhosis;1,2,3 however, since the drug is metabolized extensively in the liver,1,3 the manufacturer states that oxaprozin should be used with caution in patients with severe hepatic impairment.1

Description

Oxaprozin, a propionic acid derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA).1,2,3,4,5,6,7,8

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Searle. Daypro^® (oxaprozin) caplets prescribing information. New York, NY; 2006 Mar.

2. Miller LG. Oxaprozin: a once-daily nonsteroidal anti- inflammatory drug. Clin Pharm . 1992; 11:591-603. [PubMed 1617910]

3. Todd PA, Brogden RN. Oxaprozin: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs . 1986; 32:291-312. [PubMed 3536423]

4. Chiang ST, Knowles JA, Hubsher JA et al. Effects of food on oxaprozin bioavailability. J Clin Pharmacol . 1984; 24:381-5. [PubMed 6480879]

5. Lewis AJ, Carlson RP, Chang J et al. The pharmacological profile of oxaprozin, an antiinflammatory and analgesic agent with low gastrointestinal toxicity. Curr Ther Res . 1983; 34:777-94.

6. Janssen FW, Chiang ST, Walker BR et al. Disposition of oxaprozin in healthy subjects and certain disease states. Curr Ther Res . 1984; 35:363-76.

7. Greenblatt DJ, Matlis R, Scavone JM et al. Oxaprozin pharmacokinetics in the elderly. Br J Clin Pharmacol . 1985; 19:373-8. [PubMed 3986088][PubMedCentral]

8. Chiang ST, Morrison G, Knowles JA et al. Oxaprozin disposition in renal disease. Clin Pharmacol Ther . 1982; 31:509-15. [PubMed 7060332]

9. Searle. Skokie, IL: Personal communication.

10. Searle. Daypro Alta^® (oxaprozin potassium) tablets prescribing information. New York, NY; 2006 Mar.

11. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA . 2006; 296: 1633-44. [PubMed 16968831]

12. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ . 2006; 332: 1302-5. [PubMed 16740558][PubMedCentral]

13. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA . 2006; 296:1653-6. [PubMed 16968830]

500. Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD; 2015 Jul 9. From the FDA web site. Accessed 2016 Mar 22. [Web]

501. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet . 2013; 382:769-79. [PubMed 23726390][PubMedCentral]

502. Food and Drug Administration. FDA briefing document: Joint meeting of the arthritis advisory committee and the drug safety and risk management advisory committee, February 10-11, 2014. From FDA web site [Web]

503. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ . 2011; 342:c7086. [PubMed 21224324][PubMedCentral]

504. Gislason GH, Rasmussen JN, Abildstrom SZ et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med . 2009; 169:141-9. [PubMed 19171810]

505. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation . 2011; 123:2226-35. [PubMed 21555710]

506. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med . 2011; 8:e1001098. [PubMed 21980265][PubMedCentral]

507. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2013; 62:e147-239. [PubMed 23747642]

508. Pfizer. Daypro^® (oxaprozin) caplets prescribing information. New York, NY; 2016 May.

511. Olsen AM, Fosbøl EL, Lindhardsen J et al. Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study. Circulation . 2012; 126:1955-63. [PubMed 22965337]

512. Olsen AM, Fosbøl EL, Lindhardsen J et al. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study. PLoS One . 2013; 8:e54309.

516. Bavry AA, Khaliq A, Gong Y et al. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med . 2011; 124:614-20. [PubMed 21596367][PubMedCentral]

1200. US Food and Drug Administration. FDA drug safety communication: FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. 2020 Oct 15. From the FDA website. [Web]

1201. Pfizer. Daypro^® (oxaprozin) caplets prescribing information. New York, NY; 2020 Dec.

1202. Actavis Pharma. Sulindac tablets prescribing information. Parsippany, NJ; 2020 Oct.