Oxaprozin Information
Oxaprozin () Description
Oxaprozin () is a non-steroidal anti-inflammatory drug (NSAID), chemically designated as 4,5-diphenyl-2-oxazole-propionic acid, and has the following chemical structure:
CHNOM.W. 293
Oxaprozin () is a white to off-white powder with a slight odor and a melting point of 162°C to 163°C. It is slightly soluble in alcohol and insoluble in water, with an octanol/water partition coefficient of 4.8 at physiologic pH (7.4). The pK in water is 4.3.
Oxaprozin () oral tablets contain 600 mg of Oxaprozin () .
Inactive ingredients in Oxaprozin () oral tablets are carnauba wax, hypromellose, magnesium stearate, methylcellulose, microcrystalline cellulose, polacrilin potassium, polyethylene glycol, polysorbate 80, pregelatinized starch, and titanium dioxide.
Oxaprozin () Clinical Studies
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 ,).
Oxaprozin () Indications And Usage
Carefully consider the potential benefits and risks of Oxaprozin () tablets and other treatment options before deciding to use Oxaprozin () tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
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
Oxaprozin () Contraindications
Oxaprozin () tablets are contraindicated in patients with known hypersensitivity to Oxaprozin () .
Oxaprozin () tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see , and ,).
Oxaprozin () tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Oxaprozin () Warnings
NSAIDs, including Oxaprozin () tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the 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 occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a who use NSAIDs have a greater than 10 fold increased risk for developing a GI bleed compared to patients treated with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Oxaprozin () Precautions
Oxaprozin () tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of Oxaprozin () tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Oxaprozin () tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Oxaprozin () tablets. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Oxaprozin () tablets should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including Oxaprozin () tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with Oxaprozin () tablets should have their hemoglobin or hematocrit values determined if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Oxaprozin () tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
In oncogenicity studies, Oxaprozin () administration for 2 years was associated with the exacerbation of liver neoplasms (hepatic adenomas and carcinomas) in male CD mice, but not in female CD mice or rats. The significance of this species-specific finding to man is unknown.
Oxaprozin () did not display mutagenic potential. Results from the Ames test, forward mutation in yeast and Chinese hamster ovary (CHO) cells, DNA repair testing in CHO cells, micronucleus testing in mouse bone marrow, chromosomal aberration testing in human lymphocytes, and cell transformation testing in mouse fibroblast all showed no evidence of genetic toxicity or cell-transforming ability.
Oxaprozin () administration was not associated with impairment of fertility in male and female rats at oral doses up to 200 mg/kg/day (1180 mg/m); the usual human dose is 17 mg/kg/day (629 mg/m). However, testicular degeneration was observed in beagle dogs treated with 37.5 to 150 mg/kg/day (750 to 3000 mg/m) of Oxaprozin () for 6 months, or 37.5 mg/kg/day for 42 days, a finding not confirmed in other species. The clinical relevance of this finding is not known.
Safety and effectiveness in pediatric patients below the age of 6 years 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 , ). 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.
No adjustment of the dose of Oxaprozin () is necessary in the elderly for reasons, although many elderly may need to receive a reduced dose because of low body weight or disorders associated with aging. No significant differences in the pharmacokinetic profile for Oxaprozin () were seen in studies in the healthy elderly (see ,).
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 as well as younger patients, caution should be exercised in treating the elderly, and extra care should be taken when choosing a dose. As with any NSAID, the elderly are likely to tolerate adverse reactions less well than younger patients.
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 , ).
Oxaprozin () Adverse Reactions
Adverse reaction data were derived from patients who received Oxaprozin () in multidose, controlled, and open-label clinical trials, and from worldwide marketing experience. Rates for events occurring in more than 1% of patients, and for most of the less common events, are based on 2253 patients who took 1200 to 1800 mg Oxaprozin () per day in clinical trials. Of these, 1721 were treated for at least 1 month, 971 for at least 3 months, and 366 for more than 1 year. Rates for the rarer events and for events reported from worldwide marketing experience are difficult to estimate accurately and are only listed as less 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:
Digestive system:
Hematologic system:
Nervous system:
Skin and appendages:
Special senses:
Urogenital system:
The following adverse reactions were reported in clinical trials, from worldwide marketing experience () or in patients taking other NSAIDs.
Cardiovascular system
Metabolic system
Nervous system
Respiratory system
Special senses
Oxaprozin () Drug Abuse And Dependence
Oxaprozin () is a non-narcotic drug. Usually reliable animal studies have indicated that Oxaprozin () has no known addiction potential in humans.
Oxaprozin () Overdosage
No patient experienced either an accidental or intentional overdosage of Oxaprozin () in the clinical trials of the drug. Symptoms following acute overdose with other NSAIDs are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain and are generally reversible with supportive care. Gastrointestinal bleeding and coma have occurred following NSAID overdose. Hypertension, acute renal failure, and respiratory depression are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Gut decontamination may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). This should be accomplished via emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) with an osmotic cathartic. Forced diuresis, alkalization of the urine, or hemoperfusion would probably not be useful due to the high degree of protein binding of Oxaprozin () .
Oxaprozin () Dosage And Administration
Carefully consider the potential benefits and risks of Oxaprozin () tablets and other treatment options before deciding to use Oxaprozin () tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Oxaprozin () tablets, the dose and frequency should be adjusted to suit an individual patient's needs.
Oxaprozin () Safety And Handling
Oxaprozin () is supplied as a solid dosage form in closed containers, is not known to produce contact dermatitis, and poses no known risk to healthcare workers. It may be disposed of in accordance with applicable local regulations governing the disposal of pharmaceuticals.
Oxaprozin () How Supplied
Oxaprozin () tablets USP, 600 mg are white to off-white, capsule-shaped, film-coated tablets. On one side scored and debossed with the numbers “9” and “3” on each side of the score. On the other side debossed “0924”.
Supplied in bottles of 100 and 500.
Keep bottles tightly closed. Store at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure (as required).
Manufactured In Israel By:
Jerusalem, 91010, Israel
Manufactured For:
Sellersville, PA 18960
Rev. F 6/2008
Oxaprozin ()
Oxaprozin () Principal Display Panel
Oxaprozin ()
Tablets USP
600 mg
Each tablet contains:
Oxaprozin () 600mg
ATTENTION PHARMACIST:
is required to receive a Medication Guide.
Rx only
100 TABLETS
TEVA
