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Oxaprozin Potassium

Pronunciation

Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: 4,5-Diphenyl-2-oxazolepropionic acid
Molecular Formula: C18H15NO3
CAS Number: 21256-18-8
Brands: Daypro, Daypro Alta

Warning(s)

  • Cardiovascular Risk
  • Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 10 Risk may increase with duration of use.1 10 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 10 (See Cardiovascular Effects under Cautions.)

  • Contraindicated for the treatment of pain in the setting of CABG surgery.1 10

  • GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 10 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 10 Geriatric individuals are at greater risk for serious GI events.1 10 (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA;1 2 3 4 5 6 7 8 10 propionic acid derivative.1 2 3 4 5 6 7 8

Uses for Oxaprozin Potassium

Consider potential benefits and risks of oxaprozin therapy as well as alternative therapies before initiating therapy with the drug.1 10 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 10

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Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.1 2 3 10

Management of juvenile rheumatoid arthritis in children 6-16 years of age.1

Oxaprozin Potassium Dosage and Administration

General

  • Consider potential benefits and risks of oxaprozin therapy as well as alternative therapies before initiating therapy with the drug.1 10

Administration

Oral Administration

Administer orally once daily;1 2 3 6 7 10 divided doses may improve tolerance in some patients.1 10

Dosage

Available as oxaprozin and oxaprozin potassium; dosage expressed in terms of oxaprozin.1 10

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 10 Adjust dosage based on individual requirements and response; attempt to titrate to lowest effective dosage.1 10

Pediatric Patients

Inflammatory Disease
Juvenile Rheumatoid Arthritis
Oral
Children 6–16 years of age: Dosage Based on Child’s Body Weight1

Weight (kg)

Dosage

22–31

600 mg once daily

32–54

900 mg once daily

≥55

1.2 g once daily

Adults

Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis
Oral

Initially, 1.2 g once daily.1 2 3 10 Reserve long-term use of dosages >1.2 g daily for adults with severe disease who weigh >50 kg, have normal renal and hepatic function, and low risk for GI toxicity.1

If rapid onset of action needed, administer one-time loading dose of 1.2–1.8 g (up to 26 mg/kg).1

Patients with low body weight: Initially, 600 mg once daily.1 10 May increase to 1.2 g daily if needed.1

Prescribing Limits

Pediatric Patients

Juvenile Rheumatoid Arthritis
Oral

Doses >1.2 g daily not studied.1

Adults

Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis
Oral

Oxaprozin: Maximum 1.8 g or 26 mg/kg daily (whichever is lower).1 Maximum loading dose is 26 mg/kg.1

When administered as oxaprozin potassium: 1.2 g daily.10

Special Populations

Renal Impairment

Severe renal impairment and in those undergoing hemodialysis: Initially, 600 mg once daily.1 3 8 May increase to 1.2 g daily if needed.1 8 Supplemental doses after hemodialysis not needed.1

Hepatic Impairment

Dosage adjustment not needed in patients with well-compensated cirrhosis.1 2 3 10

Geriatric Patients

Dosage adjustment may be necessary in patients with low body weight, decreased renal function, or age-related concomitant disease.1 10

Cautions for Oxaprozin Potassium

Contraindications

  • Known hypersensitivity to oxaprozin or any ingredient in the formulation.1 10

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1 10

  • Treatment of perioperative pain in the setting of CABG surgery.1 10

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.1 10 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.11 12 13 Current data insufficient to assess risk associated with oxaprozin.11 12 13

Use NSAIAs with caution, careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.1 10

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).a

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events.1 10 (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 10 Use with caution in patients with hypertension; monitor BP.1 10 Impaired response to certain diuretics may occur.1 10 (See Specific Drugs under Interactions.)

Fluid retention and edema reported.1 10 Caution in patients with fluid retention or heart failure.1 10

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 10

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol; alternatively, consider concomitant use of proton pump inhibitor (e.g., omeprazole) or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1 10

Potential for overt renal decompensation.1 10 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 10 b

Sensitivity Reactions

Hypersensitivity

Anaphylactoid reactions (e.g., anaphylaxis, angioedema) reported.1 10

Immediate medical intervention and discontinuance for anaphylaxis.1 10

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1 10

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 10 Discontinue at first appearance of rash or any other signs of hypersensitivity (e.g., blisters, fever, pruritus).1 10

Photosensitivity

Rash on sun-exposed areas of the body reported.1 10

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1 10

Elevations of serum ALT or AST reported.1 10

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 10 Discontinue if signs or symptoms of liver disease or systemic manifestation (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1 10

Hematologic Effects

Anemia reported rarely.1 10 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.1 10

May inhibit platelet aggregation and prolong bleeding time.1 10

Other Precautions

Do not use multiple oxaprozin-containing preparations concomitantly.10

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1 10

May mask certain signs of infection.1 10

Obtain CBC and chemistry profile periodically during long-term use.1 10

Specific Populations

Pregnancy

Category C.1 10 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1 10

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 10 Discontinue nursing or the drug.1 10

Pediatric Use

Oxaprozin: Safety and efficacy not established in children <6 years of age.1

Oxaprozin: Safety and efficacy in pediatric patients 6–16 years of age with juvenile rheumatoid arthritis supported by studies in adults with rheumatoid arthritis and by safety and pharmacokinetic data from trials in children with juvenile rheumatoid arthritis.1

Oxaprozin potassium: Safety and efficacy not established in children.10

Geriatric Use

No overall differences in efficacy or safety were observed between geriatric and younger adults.1 10 Possibility exists of greater sensitivity in some geriatric individuals.1

Caution advised.1 10 Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.1 10

Select dosage with caution because of age-related decreases in renal function.1 10 May be useful to monitor renal function.1 10

Hepatic Impairment

Use with caution in patients with severe hepatic impairment.1 10

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1 10 Dosage adjustment needed.1 10 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Abdominal pain, anorexia, constipation, diarrhea, flatulence, GI ulcers, GI bleeding/perforation, dyspepsia, heartburn, nausea, vomiting, renal function abnormalities, anemia, confusion, depression, sleep disturbance, dizziness, dysuria or increased frequency, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, sedation, somnolence, tinnitus.1 10

Interactions for Oxaprozin Potassium

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor 1 10

Monitor BP1 10

Acetaminophen

Pharmacokinetic interaction unlikely1

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonistb

Monitor BPb

Antacids

Change in oxaprozin bioavailability unlikely1 10

Aspirin

Increased risk of GI ulceration and other complications1 10

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs 1 10 a

Possible pharmacokinetic interaction (altered plasma protein binding)1 10

Manufacturer states that concomitant use not recommended1 10

β-Adrenergic blocking agents

Reduced BP response to metoprolol reported1 10

Monitor BP1 10

Diuretics (furosemide, thiazides)

Reduced natriuretic effects possible1 10

Monitor for diuretic efficacy and renal failure1 10

Estrogens, conjugated

Pharmacokinetic interaction unlikely1

Glyburide

Pharmacokinetic interaction; no effect on hypoglycemic effects1 10

Monitor blood glucose if concomitant therapy initiated1 10

Histamine H2-receptor antagonists (cimetidine, ranitidine)

Decreased clearance of oxaprozin1 10

Lithium

Increased plasma lithium concentrations 1 10

Monitor for lithium toxicity1 10

Methotrexate

Possible toxicity associated with increased plasma methotrexate concentration1 10

Caution advised1 10

Warfarin

Possibility of bleeding complications1 10

Caution advised1 10

Oxaprozin Potassium Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.1 10

Food

Food may reduce the rate of absorption, but does not affect extent of absorption.1 2 3 4 6 10

Distribution

Extent

Distributed into synovial tissues in patients with rheumatoid arthritis.1

Plasma Protein Binding

99% (mainly albumin).1 10

Elimination

Metabolism

Metabolized, principally in the liver, to inactive metabolites.1 10

Elimination Route

Excreted in urine (65%) and in feces (35%) as metabolites; approximately 5% is excreted in urine as unchanged drug.1 10

Half-life

Approximately 38–44 hours.1 10

Special Populations

Renal clearance decreased in patients with renal impairment; renal clearance contributes minimally to excretion of oxaprozin.1 10 Not removed by hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).1 10

Stability

Storage

Oral

Tablets

Tight, light resistant containers at 25°C (may be exposed to 15–30°C).1 10

Actions

  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.1 10

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.1 10

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1 10

  • Risk of serious cardiovascular events with long-term use.1 10

  • Risk of GI toxicity and ulceration.1 10

  • Risk of serious skin reactions.1 10 Risk of anaphylactoid and other sensitivity reactions.1 10

  • Risk of hepatotoxicity.1 10

  • Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1 10

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1 10

  • Importance of discontinuing therapy and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 10 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1 10

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1 10

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 10 Importance of avoiding oxaprozin in late pregnancy (third trimester).1 10

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.1 10

  • Importance of informing patients of other important precautionary information.1 10 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Oxaprozin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

600 mg*

Daypro Caplets (scored)

Searle

Oxaprozin Potassium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

600 mg (of oxaprozin)

Daypro Alta

Searle

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Daypro 600MG Tablets (PFIZER U.S.): 60/$207.00 or 180/$599.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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. [IDIS 298181] [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. [IDIS 222514] [PubMed 3536423]

4. Chiang ST, Knowles JA, Hubsher JA et al. Effects of food on oxaprozin bioavailability. J Clin Pharmacol. 1984; 24:381-5. [IDIS 190514] [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. [IDIS 199385] [PubMed 3986088]

8. Chiang ST, Morrison G, Knowles JA et al. Oxaprozin disposition in renal disease. Clin Pharmacol Ther. 1982; 31:509-15. [IDIS 149003] [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]

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

a. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

b. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

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