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Oxaprozin

Pronunciation

Pronunciation: OX-a-PROE-zin
Class: NSAID

Trade Names

Daypro
- Tablets, oral oxaprozin (as base) 600 mg

Daypro Alta
- Tablets, oral oxaprozin potassium 600 mg

Apo-Oxaprozin (Canada)

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

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Pharmacokinetics

Absorption

Bioavailability is 95%. T max ranged from 1.6 to 3 h. Food may delay the rate of absorption, but does not affect the extent of absorption.

Distribution

99% is protein bound (albumin). Vd is 10 to 16 L ( Daypro Alta ) and 11 to 17 L ( Daypro ).

Metabolism

Metabolized in the liver by microsomal oxidation (65%) and glucuronic acid conjugation (35%). Less than 5% of active phenolic metabolites are produced

Elimination

Glucuronide metabolites are eliminated in the urine (65%) and in the feces (35%). The mean elimination half-lives of total drug and protein unbound after multiple doses were 38 h and 16.4 h ( Daypro Alta ) and 41.4 h and 19.5 h ( Daypro ), respectively.

Special Populations

Renal Function Impairment

Renal Cl decreases proportionally with CrCl and becomes clinically important in those patients with highly decreased CrCl. Plasma protein binding may decrease in patients with severe renal deficiency. Dosage reduction is recommended.

Hepatic Function Impairment

Patients with well-compensated cirrhosis do not require reduced doses as compared with patients with healthy hepatic function. Use with caution in patients severe hepatic dysfunction.

Children

No clinically important age-dependent changes in Cl of unbound oxaprozin ( Daypro ) between adults and children were observed when adjustments were made for differences in body weight. Daypro Alta has not been investigated in children younger than 16 y.

Gender

No differences in pharmacokinetic parameters have been observed between male and female subjects.

Race

Pharmacokinetic differences because of race have not been identified.

Cardiac failure

Well-compensated cardiac failure does not affect the plasma protein binding or pharmacokinetics of oxaprozin.

Elderly

Pharmacokinetics did not show any statistically significant differences between age groups.

Indications and Usage

Relief of signs and symptoms of rheumatoid arthritis, osteoarthritis; relief of signs and symptoms of juvenile rheumatoid arthritis ( Daypro only).

Contraindications

Known hypersensitivity to oxaprozin; treatment of perioperative pain in the setting of coronary artery bypass graft surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.

Dosage and Administration

Osteoarthritis/Rheumatoid Arthritis
Adults Daypro

PO 1,200 mg once a day (max, 1,800 mg/day or 26 mg/kg, whichever is lower). For patients of low body weight, an initial dosage of 600 mg once daily may be appropriate. 1,200 to 1,800 mg may be used as a one-time loading dose when a quick onset of action is important.

Daypro Alta

PO 1,200 mg once daily (max, 1,200 mg/day). For osteoarthritis patients of low body weight with milder disease, an initial dosage of 600 mg once daily may be appropriate.

Juvenile Rheumatoid Arthritis
Children 6 to 16 years Daypro

PO For patients weighing 22 to 31 kg, administer 600 mg once daily; for patients weighing 32 to 54 kg, administer 900 mg once daily; for patients weighing 55 kg or more, administer 1,200 mg once daily.

Renal Function Impairment
Daypro

PO Initiate therapy with 600 mg once daily in patients with severe renal impairment and/or patients on dialysis; may cautiously increase dose to 1,200 mg, but only with close monitoring.

General Dosing Information
  • Divided doses may be tried in patients unable to tolerate single doses.

Storage/Stability

Store between 59° and 86°F in a tight, light-resistant container. Protect from moisture.

Drug Interactions

ACE inhibitors (eg, enalapril)

The antihypertensive effects of ACE inhibitors may be diminished. Also, the risk of nephrotoxicity associated with ACE inhibitors or oxaprozin may be increased. Closely monitor BP. If BP control deteriorates, consider stopping oxaprozin. Periodic measurement of renal function is warranted.

Alcohol, smoking

The risk of GI bleeding may be increased.

Aminoglycosides (eg, tobramycin)

The risk of acute renal failure may be increased. Avoid coadministration.

Azole antifungal agents (eg, fluconazole, voriconazole)

Oxaprozin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the clinical response and adjust the oxaprozin dose as needed.

Beta-blockers (eg, metoprolol)

Antihypertensive effects may be decreased. Monitor BP when starting oxaprozin therapy in patients taking beta-blockers.

Bisphosphonates (eg, alendronate)

The risk of GI adverse reactions (eg, gastric ulceration) may be increased. Use with caution. Closely monitor for GI adverse reactions. Instruct patients to report signs of GI irritation (eg, nausea/vomiting) to their health care provider.

Clopidogrel, dabigatran, desirudin, oral corticosteroids (eg, prednisone), prasugrel

The risk of bleeding may be increased. Use with caution. Closely monitor patients and instruct them to report any signs or symptoms of bleeding.

Cyclosporine, tacrolimus

The nephrotoxicity of each agent may be increased. Closely monitor renal function and cyclosporine and tacrolimus concentrations. If an interaction is suspected, decrease the cyclosporine and tacrolimus dose or discontinue oxaprozin.

Glyburide

Oxaprozin may alter the pharmacokinetics of glyburide; however, the AUC or the magnitude or duration of control was not affected in type 2 diabetic patients. Monitor patients' blood glucose closely in the beginning phase of coadministration.

Heparin

The risk of heparin-induced bleeding may be increased. If coadministration cannot be avoided, close clinical and laboratory monitoring is warranted.

Histamine H 2 antagonists (eg, cimetidine, ranitidine)

Coadministration of oxaprozin and cimetidine or ranitidine may reduce the total body Cl of oxaprozin; no other pharmacokinetic parameter was affected. The change of Cl lies within the range of normal variation and is unlikely to be clinically relevant.

Lithium

May increase lithium levels, increasing the pharmacologic effects and risk of adverse reactions. Monitor lithium plasma concentrations and the clinical response. Monitor for signs of lithium toxicity. Adjust the lithium dose as needed.

Loop diuretics (eg, furosemide), thiazide diuretics (eg, hydrochlorothiazide)

Diuretic effects may be decreased. In addition, renal toxicity has been reported. Closely observe the patient for diuretic efficacy and signs of renal failure.

Methotrexate

May increase methotrexate levels, increasing the risk of toxicity. Use with caution. Consider lower methotrexate doses. Consider longer leucovorin rescue when giving NSAIDs and methotrexate at antineoplastic doses. Monitor methotrexate concentrations and for renal impairment.

Probenecid

Pharmacologic and toxic effects of oxaprozin may be increased. Closely monitor for signs of oxaprozin toxicity. Adjust the oxaprozin dose as needed.

Rivaroxaban

Because of additive effects on the inhibition of normal clotting mechanisms, the risk of bleeding may be increased. Coadminister with caution. Careful clinical monitoring is warranted.

Salicylates (eg, aspirin)

The risk of serious GI events may be increased. Coadministration is not recommended because oxaprozin displaces salicylates from plasma protein binding sites. Coadministration would be expected to increase the risk of salicylate toxicity.

Serotonin reuptake inhibitors (eg, fluoxetine, venlafaxine)

The risk of upper GI bleeding may be increased. If coadministration cannot be avoided, close clinical monitoring for signs of GI bleeding is warranted. Use of acid suppression therapy may be considered. Instruct patients to report any signs or symptoms of bleeding.

Triamterene

The risk of acute renal failure may be increased. If coadministration cannot be avoided, closely monitor renal function. If renal function decreases, consider stopping one or both drugs.

Warfarin

May increase risk of gastric erosion and bleeding. Monitor coagulation status and adjust the anticoagulant dosage as needed. Monitor for signs of GI bleeding.

Laboratory Test Interactions

False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking oxaprozin.

Adverse Reactions

CNS

CNS inhibition, confusion, depression, disturbance of sleep, dizziness, headache, sedation, somnolence (more than 1%).

Dermatologic

Rash, pruritus (more than 1%); erythema multiforme, exfoliative dermatitis, pseudoporphyria, Stevens- Johnson syndrome, TEN (Lyell syndrome) (postmarketing).

EENT

Tinnitus (more than 1%).

GI

Abdominal pain/distress, anorexia, constipation, diarrhea, dyspepsia, flatulence, GI ulcers (gastric/duodenal), gross GI bleeding/perforation, heartburn, nausea, vomiting (more than 1%); pancreatitis (postmarketing).

Genitourinary

Abnormal renal function, dysuria or frequency (more than 1%); acute interstitial nephritis, acute renal failure, nephrotic syndrome (postmarketing).

Hematologic

Anemia, increased bleeding time (more than 1%); agranulocytosis (postmarketing).

Hepatic

Liver enzyme elevation (more than 1%); hepatitis (postmarketing).

Miscellaneous

Edema (more than 1%); serum sickness (postmarketing).

Precautions

Warnings

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with duration of use. Patients with CV disease or risk factors for CV disease may be at greater risk. NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, inflammation, perforation of the stomach or intestines, and ulceration, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.


Monitor

Monitor for signs/symptoms of GI tract ulcerations and bleeding. In patients on long-term treatment, periodically check CBC and chemistry profile. Closely monitor patients receiving therapy that affects hemostasis and BP during the initiation of NSAID treatment and throughout the course of therapy. Check hemoglobin or hematocrit in patients on long-term treatment if they exhibit signs or symptoms of anemia


Pregnancy

Category C . Avoid late in pregnancy

Lactation

Undetermined.

Children

Safety and efficacy not established in pediatric patients younger than 6 y for the treatment of juvenile rheumatoid arthritis ( Daypro ). Safety and effectiveness of Daypro Alta have not been established in pediatric patients.

Elderly

Increased risk of adverse reactions. May need to reduce dose because of low body weight or disorders associated with aging.

Renal Function

May need to reduce dose. Not recommended in patients with advanced renal disease.

Hepatic Function

Exercise caution when administering to patients with severe hepatic dysfunction.

Special Risk Patients

Use with caution in patients with fluid retention, heart failure, or hypertension.

Photosensitivity

Associated with rash and/or mild photosensitivity in dermatologic testing.

Anaphylactoid reactions

Anaphylactoid reactions may occur. Do not give oxaprozin to patients with the aspirin triad, which typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or those who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.

Asthma

Patients with asthma may have aspirin-sensitive asthma, which may be associated with severe and sometimes fatal bronchospasm when these patients use aspirin. Do not administer oxaprozin to patients with this type of aspirin sensitivity because of possible cross-reactivity.

Dermatologic effects

Serious and sometimes fatal skin adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, may occur.

Hematologic effects

Anemia has been reported and may be the result of fluid retention, occult or gross GI bleeding, or an incompletely described effect on erythropoiesis.

Hepatic effects

Elevations of 1 or more LFTs may occur in patients taking oxaprozin. Cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis, and liver failure, have been reported.

Hypertension

New hypertension or worsening of preexisting hypertension, either of which may contribute to increased risk of CV events, may occur.

Inflammation and fever

The activity of oxaprozin in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Platelet aggregation

May inhibit platelet aggregation; use with caution in patients with coagulation disorders or those on anticoagulant therapy.

Renal effects

Renal papillary necrosis and other renal injury may occur with long-term use. Patients at greatest risk for renal toxicity are those with impaired renal function, heart failure, or liver dysfunction, those taking diuretics or ACE inhibitors, and elderly patients.

Overdosage

Symptoms

Acute renal failure, anaphylactoid reaction, coma, drowsiness, epigastric pain, GI bleeding, hypertension, lethargy, nausea, respiratory depression, vomiting

Patient Information

  • Instruct patients to take medication as prescribed and not to make up missed doses.
  • Inform patients that analgesic effects are usually achieved after a single dose, but that it requires several days of dosing to reach the max effect.
  • Instruct patients to inform their health care provider of symptom relief so that the dosage is individualized to the lowest effective dose to minimize adverse reactions.
  • Caution patients to avoid taking other NSAIDs, aspirin, alcohol, or other OTC medications unless advised to do so by the health care provider.
  • Advise patients to discontinue drug and notify health care provider if any of the following occur: persistent GI upset or headache, skin rash, itching, visual disturbances, black stools, weight gain or edema, changes in urine pattern, joint pain, fever, or blood in urine.
  • Inform patients that NSAIDs can cause serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, which may result in hospitalization and even death. Advise patients to be alert for skin rash, skin blisters, fever, and itching, and to seek medical advice if any of these occur. Advise patients to stop oxaprozin immediately and contact their health care provider if any type of skin rash develops.
  • Inform patients of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms). If these occur, instruct patients to stop therapy and seek immediate medical attention.
  • Inform patients that oxaprozin, like other NSAIDs, may cause CV side effects, such as MI or stroke. Alert patients to the signs and symptoms of chest pain, shortness of breath, weakness, and slurring of speech. They should seek medical advice immediately if any of these symptoms are observed.
  • Advise patients on long-term therapy that lab tests may be required and to keep appointments.
  • Advise elderly or debilitated patients regarding their increased risk of adverse reactions.
  • Caution patients regarding the possibility of photosensitivity and to use protective measures until tolerance is determined.
  • Advise patients that medication may cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness.
  • Advise women of childbearing potential that use of oxaprozin in late pregnancy should be avoided because of the risk of premature closure of the ductus arteriosus.

Copyright © 2009 Wolters Kluwer Health.

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