Oxaprozin

Pronunciation

(oks a PROE zin)

U.S. Brand Names

Daypro®

Generic Available

Yes

Canadian Brand Names

Apo-Oxaprozin®; Daypro®; Rhoxal-oxaprozin

Use

Acute and long-term use in the management of signs and symptoms of osteoarthritis and rheumatoid arthritis; juvenile rheumatoid arthritis

Pregnancy Risk Factor

C/D (3rd trimester)

Pregnancy Implications

Safety and efficacy in pregnant women have not been established. Exposure late in pregnancy may lead to premature closure of the ductus arteriosus and may inhibit uterine contractions.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to oxaprozin, aspirin, other NSAIDs, or any component of the formulation; advanced kidney disease; pregnancy (3rd trimester)

Warnings/Precautions

Fatal asthmatic and anaphylactoid reactions have occurred in patients with "aspirin triad." Use with caution in patients with CHF, hypertension, dehydration, decreased renal or hepatic function, history of GI disease (bleeding, ulcers, or previous GI symptoms with NSAID use), or those receiving anticoagulants and/or corticosteroids. Use lowest effective dose for shortest period possible; bleeding risk has been correlated to dose and duration of therapy. Gastrointestinal bleeding may occur without prior symptoms of gastrointestinal irritation. Elderly are at a high risk for adverse effects from NSAIDs. As many as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically.

Use of NSAIDs can compromise existing renal function especially when Clcr<30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations; however, elderly may demonstrate these adverse effects at lower doses than younger adults. Do not exceed 3200 mg/day. Withhold for at least 4-6 half-lives prior to surgical or dental procedures.

Rare cases of severe hepatic reactions (including necrosis, jaundice, fulminant hepatitis) have been reported. May cause mild photosensitivity reactions. Safety and efficacy have not been established in children <6 years of age.

Adverse Reactions

1% to 10%:

Cardiovascular: Edema

Central nervous system: Confusion, depression, dizziness, headache, sedation, sleep disturbance, somnolence

Dermatologic: Pruritus, rash

Gastrointestinal: Abdominal distress, abdominal pain, anorexia, constipation, diarrhea, flatulence, gastrointestinal ulcer, gross bleeding with perforation, heartburn, nausea, vomiting

Hematologic: Anemia, bleeding time increased

Hepatic: Liver enzyme elevation

Otic: Tinnitus

Renal: Dysuria, renal function abnormal, urinary frequency

<1% (effects reported with oxaprozin or other NSAIDs): Acute interstitial nephritis, acute renal failure, agranulocytosis, alopecia, anaphylaxis, angioedema, anxiety, asthma, blurred vision, bruising, CHF, conjunctivitis, cystitis, dream abnormalities, drowsiness, dyspnea, eosinophilia, erythema multiforme, esophagitis, exfoliative dermatitis, fever, gastritis, GI bleeding, glossitis, hearing decreased, hematemesis, hematuria, hemorrhoidal bleeding, hepatitis, hypersensitivity reaction, hypertension, infection, insomnia, jaundice, leukopenia, liver function abnormalities, malaise, melena, menstrual flow increased/decreased, nephrotic syndrome, nervousness, oliguria, palpitation, pancreatitis, pancytopenia, paresthesia, peptic ulcer, photosensitivity, pneumonia, polyuria, proteinuria, pseudoporphyria, pulmonary infection, purpura, rectal bleeding, renal insufficiency, respiratory depression, sepsis, serum sickness, sinusitis, Stevens-Johnson syndrome, stomatitis, syncope, tachycardia,taste alteration, thrombocytopenia, toxic epidermal necrolysis, tremor, upper respiratory tract infection, vertigo, weakness, weight changes, xerostomia

Overdosage/Toxicology

Symptoms of overdose include acute renal failure, vomiting, drowsiness, and leukocytes. Management of NSAID intoxication is supportive and symptomatic. Since many NSAIDs undergo enterohepatic cycling, multiple doses of charcoal may be needed to reduce the potential for delayed toxicities.

Drug Interactions

ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure. Oxaprozin may decrease serum concentration of enalapril.

Angiotensin II antagonists: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Anticoagulants (warfarin, heparin, LMWHs) in combination with NSAIDs can cause increased risk of bleeding.

Other antiplatelet drugs (ticlopidine, clopidogrel, aspirin, abciximab, dipyridamole, eptifibatide, tirofiban) can cause an increased risk of bleeding.

Corticosteroids may increase the risk of GI ulceration; avoid concurrent use.

Cyclosporine: NSAIDs may increase serum creatinine, potassium, blood pressure, and cyclosporine levels; monitor cyclosporine levels and renal function carefully.

Hydralazine's antihypertensive effect is decreased; avoid concurrent use.

Lithium levels can be increased; avoid concurrent use if possible or monitor lithium levels and adjust dose. Sulindac may have the least effect. When NSAID is stopped, lithium will need adjustment again.

Loop diuretics efficacy (diuretic and antihypertensive effect) may be reduced.

Methotrexate: Severe bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant NSAID therapy. Avoid use during moderate or high-dose methotrexate (increased and prolonged methotrexate levels). NSAID use during low-dose treatment of rheumatoid arthritis has not been fully evaluated; extreme caution is warranted.

Thiazides antihypertensive effects are decreased; avoid concurrent use.

Warfarin's INRs may be increased by piroxicam. Other NSAIDs may have the same effect depending on dose and duration. Monitor INR closely. Use the lowest dose of NSAIDs possible and for the briefest duration.

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Stability

Store at 25°C (77°F); protect from light; keep bottle tightly closed

Mechanism of Action

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors

Pharmacodynamics/Kinetics

Absorption: Almost complete

Protein binding: >99%

Metabolism: Hepatic via oxidation and glucuronidation; no active metabolites

Half-life elimination: 40-50 hours

Time to peak: 2-4 hours

Excretion: Urine (5% unchanged, 65% as metabolites); feces (35% as metabolites)

Dosage

Oral (individualize dosage to lowest effective dose to minimize adverse effects):

Children 6-16 years: Juvenile rheumatoid arthritis:

22-31 kg: 600 mg once daily

32-54 kg: 900 mg once daily

55 kg: 1200 mg once daily

Adults:

Osteoarthritis: 600-1200 mg once daily; patients should be titrated to lowest dose possible; patients with low body weight should start with 600 mg daily

Rheumatoid arthritis: 1200 mg once daily; a one-time loading dose of up to 1800 mg/day or 26 mg/kg (whichever is lower) may be given

Maximum daily dose: 1800 mg or 26 mg/kg (whichever is lower) in divided doses

Dosing adjustment in renal impairment: 600 mg once daily; dose may be increased to 1200 mg with close monitoring

Dosing adjustment in hepatic impairment: Use caution in patients with severe dysfunction

Monitoring Parameters

Monitor CBC; hepatic, renal, and ocular function

Test Interactions

False-positive urine immunoassay screening tests for benzodiazepines have been reported and may occur several days after discontinuing oxaprozin.

Patient Education

Take this medication exactly as directed; do not increase dose without consulting prescriber. Do not crush tablets. Take with food or milk to reduce GI distress. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Do not use alcohol, aspirin or aspirin-containing medication, or any other anti-inflammatory medications without consulting prescriber. You may experience drowsiness, dizziness, or nervousness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, or heartburn (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain. Discontinue medication and contact prescriber if persistent abdominal pain, cramping, or blood in stool occurs. Report vaginal bleeding; breathlessness, respiratory difficulty, or unusual cough; chest pain, rapid heartbeat, palpitations; unusual bruising or bleeding (blood in urine, mouth, or vomitus); swollen extremities; skin rash or itching; acute fatigue; or swelling of face, lips, tongue, or throat. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Breast-feeding is not recommended.

Anesthesia and Critical Care Concerns/Other Considerations

The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) suggest that NSAIDs may be used in combination with opioids in select patients for pain management. Concern about adverse events (increased risk of renal dysfunction, altered platelet function and gastrointestinal irritation) limits its use in patients who have other underlying risks for these events.

In short-term use, NSAIDs vary considerably in their effect on blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema; may precipitate renal failure in dehydrated patients.

Cardiovascular Considerations

In short-term use, NSAIDs vary considerably in their effect on blood pressure. A recent meta-analysis (see References) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with congestive heart failure, particularly in the elderly population.

Dental Health: Effects on Dental Treatment

NSAID formulations are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness is common; may cause nervousness; may rarely cause drowsiness, confusion, insomnia, or depression

Mental Health: Effects on Psychiatric Treatment

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

Dosage Forms

Tablet: 600 mg

References

Brooks PM and Day RO, "Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities," N Engl J Med , 1991, 324(24):1716-25.

Clinch D, Banerjee AK, and Ostick G, "Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer," Age Ageing , 1984, 13(2):120-3.

Clive DM and Stoff JS, "Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1984, 310(9):563-72.

Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5.

Graham DY, "Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Anti-inflammatory Drug Therapy," Gastroenterology , 1989, 96(2 Pt 2 Suppl):675-81.

Gurwitz JH, Avorn J, Ross-Degnan D, et al, "Nonsteroidal Anti-Inflammatory Drug-Associated Azotemia in the Very Old," JAMA , 1990, 264(4):471-5.

Hawkey CJ, Karrasch JA, Szczepañski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1998, 338(11):727-34.

Heerdink ER, Leufkens HG, Herings RM, et al, "NSAIDs Associated With Increased Risk of Congestive Heart Failure in Elderly Patients Taking Diuretics," Arch Intern Med , 1998, 158(10):1108-12.

Jacobi J, Fraser GL, Coursin DB, et al, "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult," Crit Care Med , 2002, 30(1):119-41. Available at: http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.

Knodel LC, "Preventing NSAID-Induced Ulcers: The Role of Misoprostol," Consult Pharm , 1989, 4:37-41.

Morgan TO, Anderson A, and Bertram D, "Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril," Am J Hypertens , 2000, 13(11):1161-7.

Page J and Henry D, "Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients: An Underrecognized Public Health Problem," Arch Intern Med , 2000, 160(6):777-84.

Pope JE, Anderson JJ, and Felson DT, "A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure," Arch Intern Med , 1993, 153(4):477-84.

Pounder R, "Silent Peptic Ulceration: Deadly Silence or Golden Silence?" Gastroenterology , 1989, 96(2 Pt 2 Suppl):626-31.

Yeomans ND, Tulassay Z, Juhasz L, et al, "A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med , 1998, 338(11):719-26.

International Brand Names

Apo-Oxaprozin® (CA); Asirial® (AR); Danoprox® (DE); Daypro® (CA); Dayrun® (DE); Deflam® (ZA); Rhoxal-oxaprozin (CA); Walix® (IT)

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