2.1 General Dosing Instructions

Carefully consider the potential benefits and risks of oxaprozin and other treatment options before deciding to use oxaprozin. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].

2.2 Osteoarthritis

For OA, the dosage is 1200 mg (two 600 mg tablets) given orally once a day [see Dosage and Administration (2.5)].

2.3 Rheumatoid Arthritis

For RA, the dosage is 1200 mg (two 600 mg tablets) given orally once a day [see Dosage and Administration (2.5)].

2.4 Juvenile Rheumatoid Arthritis

For JRA, in patients 6 to 16 years of age, the recommended dosage given orally once per day should be based on body weight of the patient as given in Table 1 [see Dosage and Administration (2.5)].

2.5 Individualization of Dosage

After observing the response to initial therapy with oxaprozin, the dose and frequency should be adjusted to suit an individual patient's needs. In osteoarthritis and rheumatoid arthritis and juvenile rheumatoid arthritis, the dosage should be individualized to the lowest effective dose of oxaprozin to minimize adverse effects. The maximum recommended total daily dose of oxaprozin in adults is 1800 mg (26 mg/kg, whichever is lower) in divided doses. In children, doses greater than 1200 mg have not been studied.

Patients with low body weight should initiate therapy with 600 mg once daily. Patients with severe renal impairment or on dialysis should also initiate therapy with 600 mg once daily. If there is insufficient relief of symptoms in such patients, the dose may be cautiously increased to 1200 mg, but only with close monitoring [see Clinical Pharmacology (12.3)].

In adults, in cases where a quick onset of action is important, the pharmacokinetics of oxaprozin allows therapy to be started with a one-time loading dose of 1200 mg to 1800 mg (not to exceed 26 mg/kg). Doses larger than 1200 mg/day on a chronic basis should be reserved for patients who weigh more than 50 kg, have normal renal and hepatic function, are at low risk of peptic ulcer, and whose severity of disease justifies maximal therapy. Physicians should ensure that patients are tolerating doses in the 600 mg to 1200 mg/day range without gastroenterologic, renal, hepatic, or dermatologic adverse effects before advancing to the larger doses. Most patients will tolerate once-a-day dosing with oxaprozin, although divided doses may be tried in patients unable to tolerate single doses.

5.1 Cardiovascular Thrombotic Events

Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as oxaprozin, increases the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)].

5.2 Gastrointestinal Bleeding, Ulceration, and Perforation

NSAIDs, including oxaprozin, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.

5.3 Hepatotoxicity

Elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.

Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including oxaprozin.

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash), discontinue oxaprozin immediately, and perform a clinical evaluation of the patient.

5.4 Hypertension

NSAIDs, including oxaprozin, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs [see Drug Interactions (7)].

Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

5.5 Heart Failure and Edema

The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of oxaprozin may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see Drug Interactions (7)].

Avoid the use of oxaprozin in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If oxaprozin is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

5.6 Renal Toxicity and Hyperkalemia

5.7 Anaphylactic Reactions

Oxaprozin has been associated with anaphylactic reactions in patients with and without known hypersensitivity to oxaprozin and in patients with aspirin-sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.8)].

Seek emergency help if an anaphylactic reaction occurs.

5.8 Exacerbation of Asthma Related to Aspirin Sensitivity

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, oxaprozin is contraindicated in patients with this form of aspirin sensitivity [see Contraindications (4)]. When oxaprozin is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

5.9 Serious Skin Reactions

NSAIDs, including oxaprozin, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of oxaprozin at the first appearance of skin rash or any other sign of hypersensitivity. Oxaprozin is contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4)].

5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as oxaprozin. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue oxaprozin and evaluate the patient immediately.

5.11 Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus

Avoid use of NSAIDs, including oxaprozin, in pregnant women at about 30 weeks gestation and later. NSAIDs, including oxaprozin, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs, including oxaprozin, at about 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, for example, 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 necessary between about 20 weeks and 30 weeks gestation, limit oxaprozin use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if oxaprozin treatment extends beyond 48 hours. Discontinue oxaprozin if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].

5.12 Hematologic Toxicity

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with oxaprozin has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including oxaprozin, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet drugs (e.g., aspirin), SSRIs, and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions (7)].

5.13 Masking of Inflammation and Fever

The pharmacological activity of oxaprozin in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.14 Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a complete blood count (CBC) and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].

5.15 Photosensitivity

Oxaprozin has been associated with rash and/or mild photosensitivity in dermatologic testing. An increased incidence of rash on sun-exposed skin was seen in some patients in the clinical trials.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reaction data were derived from patients who received oxaprozin in multidose, controlled, and open-label clinical trials. Rates for events from clinical trial experience are based on 2253 patients who took 1200 mg to 1800 mg oxaprozin per day in clinical trials. Of these, 1721 patients were treated for at least 1 month, 971 patients for at least 3 months, and 366 patients for more than 1 year.

Incidence Greater Than 1%

In clinical trials of oxaprozin or in patients taking other NSAIDs, the following adverse reactions occurred at an incidence greater than 1%.

Cardiovascular system

Edema.

Digestive system

Abdominal pain/distress, anorexia, constipation, diarrhea, dyspepsia, flatulence, gastrointestinal ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, liver enzyme elevations, nausea, vomiting.

Hematologic system

Anemia, increased bleeding time.

Nervous system

CNS inhibition (depression, sedation, somnolence, or confusion), disturbance of sleep, dizziness, headache.

Skin and appendages

Pruritus, rash.

Special senses

Tinnitus.

Urogenital system

Abnormal renal function, dysuria or frequency.

Incidence Greater Than 1%

The following adverse reactions were reported in clinical trials or in patients taking other NSAIDs.

Body as a whole

Appetite changes, death, drug hypersensitivity reactions including anaphylaxis, fever, infection, sepsis.

Cardiovascular system

Arrhythmia, blood pressure changes, congestive heart failure, hypertension, hypotension, myocardial infarction, palpitations, tachycardia, syncope, vasculitis.

Digestive system

Alteration in taste, dry mouth, eructation, esophagitis, gastritis, glossitis, hematemesis, jaundice, liver function abnormalities including liver failure, stomatitis, hemorrhoidal or rectal bleeding.

Hematologic system

Aplastic anemia, ecchymoses, eosinophilia, hemolytic anemia, lymphadenopathy, melena, purpura, thrombocytopenia, leukopenia.

Metabolic system

Hyperglycemia, weight changes.

Nervous system

Anxiety, asthenia, coma, convulsions, dream abnormalities, drowsiness, hallucinations, insomnia, malaise, meningitis, nervousness, paresthesia, tremors, vertigo, weakness.

Respiratory system

Asthma, dyspnea, pulmonary infections, pneumonia, sinusitis, symptoms of upper respiratory tract infection, respiratory depression.

Skin

Alopecia, angioedema, urticaria, photosensitivity, sweat.

Special senses

Blurred vision, conjunctivitis, hearing decrease.

Urogenital

Cystitis, hematuria, increase in menstrual flow, oliguria/ polyuria, proteinuria, renal insufficiency, decreased menstrual flow.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of oxaprozin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a whole

Serum sickness.

Digestive system

Hepatitis, pancreatitis.

Hematologic system

Agranulocytosis, pancytopenia.

Skin

Pseudoporphyria, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Urogenital

Acute interstitial nephritis, nephrotic syndrome, acute renal failure.

8.1 Pregnancy

Risk Summary

Use of NSAIDs, including oxaprozin, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of oxaprozin use between about 20 and 30 weeks of gestation, and avoid oxaprozin use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data).

Premature Closure of Fetal Ductus Arteriosus

Use of NSAIDs, including oxaprozin, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, oral administration of oxaprozin to pregnant rabbits at doses 0.1-times the maximum daily human dose (based on body surface area) resulted in evidence of teratogenicity; however, oral administration of oxaprozin to pregnant mice and rats during organogenesis at doses equivalent to the maximum recommended human dose revealed no evidence of teratogenicity or embryotoxicity. In rat reproduction studies in which oxaprozin was administered through late gestation failure to deliver and a reduction in live birth index was observed at doses equivalent to the maximum recommended human dose. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as oxaprozin, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including oxaprozin, can cause premature closure of the fetal ductus arteriosus (see Data).

Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If oxaprozin treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue oxaprozin and follow up according to clinical practice (see Data).

Labor or Delivery

There are no studies on the effects of oxaprozin during labor or delivery. In animal studies, NSAIDS, including oxaprozin, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.

Data

Human Data

Premature Closure of Fetal Ductus Arteriosus

Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with 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. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.

Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.

Animal data

Teratology studies with oxaprozin were performed in mice, rats, and rabbits in pregnant animals administered oral doses up to 200 mg/kg/day, 200 mg/kg/day, and 30 mg/kg/day, respectively, during the period of organogenesis. In rabbits, malformations were observed at doses greater than or equal to 7.5 mg/kg/day of oxaprozin (0.1 times the maximum recommended human daily dose [MRHD] of 1800 mg based on body surface area). However, in mice and rats, no drug-related developmental abnormalities or embryo-fetal toxicity were observed at doses up to 50 and 200 mg/kg/day of oxaprozin, respectively (0.1 times and 1.1 times the maximum recommended human daily dose of 1800 mg based on a body surface area comparison, respectively).

In fertility/reproductive studies in rats, 200 mg/kg/day oxaprozin was orally administered to female rats for 14 days prior to mating through lactation day (LD) 2, or from gestation day (GD) 15 through LD 2 and the females were mated with males treated with 200 mg/kg/day oxaprozin for 60 days prior to mating. Oxaprozin administration resulted in failure to deliver and a reduction in live birth index at 200 mg/kg/day (1.1-times the maximum recommended human daily dose of 1800 mg based on a body surface area comparison).

8.2 Lactation

Risk Summary

Lactation studies have not been conducted with oxaprozin. It is not known whether oxaprozin is excreted in human milk. Oxaprozin should be administered to lactating women only if clearly indicated. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for oxaprozin and any potential adverse effects on the breastfed infant from the oxaprozin or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

Infertility

Females

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including oxaprozin, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including oxaprozin, in women who have difficulties conceiving or who are undergoing investigation of infertility.

Males

Testicular degeneration was observed in beagle dogs treated with 37.5 mg/kg/day (0.7-times the maximum recommended human daily dose based on body surface area) of oxaprozin for 42 days or 6 months [see Nonclinical Toxicology (13.1)].

8.4 Pediatric Use

Safety and effectiveness of oxaprozin in pediatric patients below the age of 6 years of age have not been established. The effectiveness of oxaprozin for the treatment of the signs and symptoms of juvenile rheumatoid arthritis (JRA) in pediatric patients aged 6 to 16 years is supported by evidence from adequate and well controlled studies in adult rheumatoid arthritis patients, and is based on an extrapolation of the demonstrated efficacy of oxaprozin in adults with rheumatoid arthritis and the similarity in the course of the disease and the drug’s mechanism of effect between these two patient populations. Use of oxaprozin in JRA patients 6 to 16 years of age is also supported by the following pediatric studies.

The pharmacokinetic profile and tolerability of oxaprozin were assessed in JRA patients relative to adult rheumatoid arthritis patients in a 14 day multiple dose pharmacokinetic study. Apparent clearance of unbound oxaprozin in JRA patients was reduced compared to adult rheumatoid arthritis patients, but this reduction could be accounted for by differences in body weight [see Clinical Pharmacology (12.3)]. No pharmacokinetic data are available for pediatric patients under 6 years. Adverse events were reported by approximately 45% of JRA patients versus an approximate 30% incidence of adverse events in the adult rheumatoid arthritis patient cohort. Most of the adverse events were related to the gastrointestinal tract and were mild to moderate.

In a 3 month open label study, 10 to 20 mg/kg/day of oxaprozin were administered to 59 JRA patients. Adverse events were reported by 58% of JRA patients. Most of those reported were generally mild to moderate, tolerated by the patients, and did not interfere with continuing treatment. Gastrointestinal symptoms were the most frequently reported adverse effects and occurred at a higher incidence than those historically seen in controlled studies in adults. Fifty-two patients completed 3 months of treatment with a mean daily dose of 20 mg/kg. Of 30 patients who continued treatment (19 to 48 week range total treatment duration), nine (30%) experienced rash on sun-exposed areas of the skin and 5 of those discontinued treatment. Controlled clinical trials with oxaprozin in pediatric patients have not been conducted.

8.5 Geriatric Use

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see Warnings and Precautions (5.1, 5.2, 5.3, 5.6, 5.14)].

No adjustment of the dose of oxaprozin is necessary in the elderly, although many elderly may need to receive a reduced dose because of low body weight or disorders associated with aging [see Clinical Pharmacology (12.3)].

Of the total number of subjects evaluated in four placebo controlled clinical studies of oxaprozin, 39% were 65 and over, and 11% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Although selected elderly patients in controlled clinical trials tolerated oxaprozin as well as younger patients, caution should be exercised in treating the elderly.

Oxaprozin is substantially excreted by the kidney, and the risk of toxic reactions to oxaprozin may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Warnings and Precautions (5.6)].

12.1 Mechanism of Action

Oxaprozin has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of oxaprozin, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Oxaprozin is a potent inhibitor of prostaglandin synthesis in vitro. Oxaprozin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because oxaprozin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14.1 Osteoarthritis

Oxaprozin was evaluated for the management of the signs and symptoms of osteoarthritis in a total of 616 patients in active controlled clinical trials against aspirin (N=464), piroxicam (N=102), and other NSAIDs. Oxaprozin was given both in variable (600 to 1200 mg/day) and in fixed (1200 mg/day) dosing schedules in either single or divided doses. In these trials, oxaprozin was found to be comparable to 2600 to 3200 mg/day doses of aspirin or 20 mg/day doses of piroxicam. Oxaprozin was effective both in once daily and in divided dosing schedules. In controlled clinical trials several days of oxaprozin therapy were needed for the drug to reach its full effects [see Dosage and Administration (2.5)].

14.2 Rheumatoid Arthritis

Oxaprozin was evaluated for managing the signs and symptoms of rheumatoid arthritis in placebo and active controlled clinical trials in a total of 646 patients. Oxaprozin was given in single or divided daily doses of 600 to 1800 mg/day and was found to be comparable to 2600 to 3900 mg/day of aspirin. At these doses there was a trend (over all trials) for oxaprozin to be more effective and cause fewer gastrointestinal side effects than aspirin.

Oxaprozin was given as a once-a-day dose of 1200 mg in most of the clinical trials, but larger doses (up to 26 mg/kg or 1800 mg/day) were used in selected patients. In some patients, oxaprozin may be better tolerated in divided doses. Due to its long half-life, several days of oxaprozin therapy were needed for the drug to reach its full effect [see Dosage and Administration (2.5)].

Storage

Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.

KEEP TIGHTLY CLOSED.

KEEP OUT OF THE REACH OF CHILDREN.