Daypro Side Effects, and Drug Interactions - Oxaprozin

Daypro Side Effects, and Drug Interactions - Oxaprozin

SIDE EFFECTS

Adverse reaction data were derived from patients who received Daypro 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 Daypro 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%.

INCIDENCE GREATER THAN 1%: In clinical trials of Daypro 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 LESS THAN 1%: The following adverse reactions were reported in clinical trials, from worldwide marketing experience (in italics) or in patients taking other NSAIDs.
Body as a whole: appetite changes, death, drug hypersensitivity reactions including anaphylaxis, fever, infection, sepsis, serum sickness.
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 hepatitis, liver failure, stomatitis, hemorrhoidal or rectal bleeding, pancreatitis.
Hematologic system: agranulocytosis, aplastic anemia, ecchy moses, eosinophilia, hemolytic anemia, lymphadenopathy, melena, pancytopenia, 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, pseudo-porphyria, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, sweat, toxic epidermal necrolysis (Lyell’s syndrome).
Special senses: blurred vision, conjunctivitis, hearing decrease.
Urogenital: acute interstitial nephritis, cystitis, hematuria, increase in menstrual flow, nephrotic syndrome, oliguria/ polyuria, proteinuria, renal insufficiency, acute renal failure, decreased menstrual flow.

DRUG ABUSE AND DEPENDENCE
Daypro is a non-narcotic drug. Usually reliable animal studies have indicated that Daypro has no known addiction potential in humans.

DRUG INTERACTIONS

Aspirin: Concomitant administration of Daypro and aspirin is not recommended because oxaprozin displaces salicylates from plasma protein binding sites. Coadministration would be expected to increase the risk of salicylate toxicity.

Methotrexate: Coadministration of oxaprozin with methotrexate results in approximately a 36% reduction in apparent oral clearance of methotrexate. A reduction in methotrexate dosage may be considered due to the potential for increased methotrexate toxicity associated with the increased exposure.

ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. Oxaprozin has been shown to alter the pharmacokinetics of enalapril (significant decrease in dose-adjusted AUC0-24 and Cmax) and its active metabolite enalaprilat (significant increase in dose-adjusted AUC_0-24). This interactionshould be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.

Furosemide: Clinical studies, as well as post marketing observations, have shown that Daypro can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see PRECAUTIONS: Renal effects), as well as to assure diuretic efficacy.

Lithium: Coadministration of oxaprozin with lithium carbonate can cause an increase in serum lithium levels. Whenever oxaprozin is added to or removed from patients on lithium therapy, therapeutic drug monitoring of lithium levels should be performed.

Glyburide: While oxaprozin does alter the pharmacokinetics of glyburide, coadministration of oxaprozin to type II non-insulin dependent diabetic patients did not affect the area under the glucose concentration curve nor the magnitude or duration of control. However, it is advisable to monitor patients’ blood glucose in the beginning phase of glyburide and oxaprozin cotherapy.

Warfarin: The effects of warfarin and NSAIDs on gastrointestinal (GI) bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that of users of either drug alone.

H2-receptor antagonists: The total body clearance of oxaprozin was reduced by 20% in subjects who concurrently received therapeutic doses of cimetidine or ranitidine; no other pharmacokinetic parameter was affected. A change of clearance of this magnitude lies within the range of normal variation and is unlikely to produce a clinically detectable difference in the outcome of therapy.

Beta-blockers: Subjects receiving 1200 mg Daypro QD with 100 mg metoprolol bid exhibited statistically significant but transient increases in sitting and standing blood pressures after 14 days. Therefore, as with all NSAIDs, routine blood pressure monitoring should be considered in these patients when starting Daypro therapy.

Other drugs: The coadministration of oxaprozin and antacids, acetaminophen, or conjugated estrogens resulted in no statistically significant changes in pharmacokinetic parameters in single- and/or multiple-dose studies. The interaction of oxaprozin with cardiac glycosides has not been studied.

Laboratory test interactions: False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking Daypro. This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of Daypro therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish Daypro from benzodiazepines.