Oxaprozin tablets are indicated: For relief of the signs and symptoms of osteoarthritis For relief of the signs and symptoms of rheumatoid arthritis For relief of the signs and symptoms of juvenile rheumatoid arthritis
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 General Pharmacokinetic Characteristics In dose proportionality studies utilizing 600 mg, 1,200 mg and 1,800 mg doses, the pharmacokinetics of oxaprozin in healthy subjects demonstrated nonlinear kinetics of both the total and unbound drug in opposite directions, i.e., dose exposure related increase in the clearance of total drug and decrease in the clearance of the unbound drug. Decreased clearance of the unbound drug was related predominantly to a decrease in the volume of distribution of the unbound drug and not an increase in the elimination half-life. This phenomenon is considered to have minimal impact on drug accumulation upon multiple dosing. The pharmacokinetic parameters of oxaprozin in healthy subjects receiving a single dose or multiple once-daily doses of 1200 mg are presented in Table 3. Table 3. Oxaprozin Pharmacokinetic Parameters [Mean (%CV)] (1200 mg) Healthy Adults (19 to 78 years) Total Drug Unbound Drug Single N=35 Multiple N=12 Single N=35 Multiple N=12 Tmax (hr) 3.09 (39) 2.44 (40) 3.03 (48) 2.33 (35) Oral Clearance (L/hr/70 kg) 0.150 (24) 0.301 (29) 136 (24) 102 (45) Apparent Volume of Distribution at Steady State (Vd/F; L/70 kg) 11.7 (13) 16.7 (14) 6230 (28) 2420 (38) Elimination Half-life (hr) 54.9 (49) 41.4 (27) 27.8 (34)…
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2.1 General Dosing Instructions Carefully consider the potential benefits and risks of oxaprozin tablets and other treatment options before deciding to use oxaprozin tablets. 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 1,200 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 1,200 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)]. Table 1. Recommended Daily Dose of Oxaprozin by Body Weight in Pediatric Patients Body Weight Range (kg) Dose (mg) 22 to 31 600 32 to 54 900 ≥55 1200 2.5 Individualization of Dosage After observing the response to initial therapy with oxaprozin tablets, 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 tablets to minimize adverse effects. The maximum recommended total daily dose of oxaprozin tablets in adults is 1,800 mg (26 mg/kg, whichever is lower) in divided doses. In children, doses greater than 1,200 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 1,200 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…
The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions (5.1)] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.2)] Hepatotoxicity [see Warnings and Precautions (5.3)] Hypertension [see Warnings and Precautions (5.4)] Heart Failure and Edema [see Warnings and Precautions (5.5)] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)] Anaphylactic Reactions [see Warnings and Precautions (5.7)] Serious Skin Reactions [see Warnings and Precautions (5.9)] Hematologic Toxicity [see Warnings and Precautions (5.12) ] 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 2,253 patients who took 1,200 mg to 1,800 mg oxaprozin per day in clinical trials. Of these, 1,721 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,…
Oxaprozin tablets are contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to oxaprozin or any components of the drug product [see Warnings and Precautions (5.7, 5.9)] History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.8)] In the setting of CABG surgery [see Warnings and Precautions (5.1)]
See Table 2 for clinically significant drug interactions with oxaprozin [see Clinical Pharmacology (12.3)]. Table 2: Clinically Significant Drug Interactions with Oxaprozin Drugs That Interfere with Hemostasis Clinical Impact: Oxaprozin and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of oxaprozin and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of oxaprozin with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see Warnings and Precautions (5.11)]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions (5.12)]. Intervention: Concomitant use of oxaprozin and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [seeWarnings and Precautions (5.12)]. Oxaprozin is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may…
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)]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are…