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Oxaprozin

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

Medically reviewed by Drugs.com. Last updated on Nov 9, 2020.

Warning

Special Alerts:

[Posted 10/15/2020]

AUDIENCE: Consumer, Patient, Health Professional, Pharmacy

ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.

For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.

For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: [Web]. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.

BACKGROUND:

NSAIDs

  • are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.

  • are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.

  • work by blocking the production of certain chemicals in the body that cause inflammation.

  • are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.

Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

RECOMMENDATION:

Consumers/Patients

  • If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.

  • Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: [Web], to find out if the medicines contain NSAIDs.

  • Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.

  • Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.

Health Care Professionals

  • FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that 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.

  • If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.

  • The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.

  • 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.

For more information visit the FDA website at: [Web] and [Web].

Warning

    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke). Risk may occur early in treatment and may increase with duration of use. (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.

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

Introduction

Prototypical NSAIA; propionic acid derivative.

Uses for Oxaprozin

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.

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

Oxaprozin Dosage and Administration

General

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

Administration

Oral Administration

Administer orally once daily; divided doses may improve tolerance in some patients.

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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. Adjust dosage based on individual requirements and response; attempt to titrate to lowest effective dosage.

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. 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.

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

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

Prescribing Limits

Pediatric Patients

Juvenile Rheumatoid Arthritis
Oral

Doses >1.2 g daily not studied.

Adults

Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis
Oral

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

Special Populations

Renal Impairment

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

Hepatic Impairment

Dosage adjustment not needed in patients with well-compensated cirrhosis.

Geriatric Patients

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

Cautions for Oxaprozin

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

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

  • In the setting of CABG surgery.

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs. FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease. Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia. Contraindicated in the setting of CABG surgery.

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

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.

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).

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events. Use with caution in patients with hypertension; monitor BP.

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur. (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema. (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.

Renal Effects

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

Potential for overt renal decompensation. 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.

Sensitivity Reactions

Hypersensitivity

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

Immediate medical intervention and discontinuance for anaphylaxis.

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

Dermatologic Reactions

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

Photosensitivity

Rash on sun-exposed areas of the body reported.

General Precautions

Hepatic Effects

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

Elevations of serum ALT or AST reported.

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results. 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.

Hematologic Effects

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

May inhibit platelet aggregation and prolong bleeding time.

Other Precautions

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

May mask certain signs of infection.

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

Specific Populations

Pregnancy

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

Lactation

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

Pediatric Use

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

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.

Geriatric Use

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

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

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

Hepatic Impairment

Use with caution in patients with severe hepatic impairment.

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used. Dosage adjustment needed. (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.

Interactions for Oxaprozin

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor

Monitor BP

Acetaminophen

Pharmacokinetic interaction unlikely

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist

Monitor BP

Antacids

Change in oxaprozin bioavailability unlikely

Aspirin

Increased risk of GI ulceration and other complications

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

Possible pharmacokinetic interaction (altered plasma protein binding)

Manufacturer states that concomitant use not recommended

β-Adrenergic blocking agents

Reduced BP response to metoprolol reported

Monitor BP

Diuretics (furosemide, thiazides)

Reduced natriuretic effects possible

Monitor for diuretic efficacy and renal failure

Estrogens, conjugated

Pharmacokinetic interaction unlikely

Glyburide

Pharmacokinetic interaction; no effect on hypoglycemic effects

Monitor blood glucose if concomitant therapy initiated

Histamine H2-receptor antagonists (cimetidine, ranitidine)

Decreased clearance of oxaprozin

Lithium

Increased plasma lithium concentrations

Monitor for lithium toxicity

Methotrexate

Possible toxicity associated with increased plasma methotrexate concentration

Caution advised

Warfarin

Possibility of bleeding complications

Caution advised

Oxaprozin Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.

Food

Food may reduce the rate of absorption, but does not affect extent of absorption.

Distribution

Extent

Distributed into synovial tissues in patients with rheumatoid arthritis.

Plasma Protein Binding

99% (mainly albumin).

Elimination

Metabolism

Metabolized, principally in the liver, to inactive metabolites.

Elimination Route

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

Half-life

Approximately 38–44 hours.

Special Populations

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

Stability

Storage

Oral

Tablets

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

Actions

  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.

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

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

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

  • Risk of serious cardiovascular events (e.g., MI, stroke).

  • Risk of GI toxicity and ulceration.

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

  • Risk of hepatotoxicity.

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.

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

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

  • 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.

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* 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 (scored)

Searle

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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