Motrin (Ibuprofen) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Coumarin-type anticoagulants:   Several short-term controlled studies failed to show that iburprofen significantly affected prothrombin times or a variety of other clotting factors administered to individuals on coumarin-type anticoagulants. Because bleeding has been reported when ibuprofen and other nonsteroidal anti-inflammatory agents have been administered to patients on coumarin-type anticoagulants, the physician should be cautious when administering MOTRIN to patients on anticoagulants.

Aspirin:   Animal studies show that aspirin given with NSAIDs, including ibuprofen, yields a net decrease in anti-inflammatory activity with lowered blood levels of the non-aspirin drug. Single-dose bioavailability studies in normal volunteers have failed to show an effect of aspirin on ibuprofen blood levels. Correlative clinical studies have not been done.

Methotrexate:   Ibuprofen, as well as other NSAIDs, has been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that ibuprofen could enhance the toxicity of methotrexate. Caution should be used, therefore, if MOTRIN is administered concomitantly with methotrexate.

H-2 Antagonists:   In studies with human volunteers, coadministration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

ACE-inhibitors:   Reports suggest that NSAIDs, including ibuprofen, may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking MOTRIN concomitantly with ACE-inhibitors.

Furosemide:   Clinical studies, as well as random observations, have shown that ibuprofen 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 MOTRIN, the patient should be observed closely for signs of renal failure (see PRECAUTIONS, Renal Effects), as well as to assure diuretic efficacy.

Lithium:   Ibuprofen produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers. The mean minimum lithium concentration increased 15% and the renal clearance of lithium was decreased by 19% during this period of concomitant drug administration. This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when MOTRIN and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy.)

Teratogenic Effects--Pregnancy Category B: Reproductive studies conducted in rats and rabbits at doses somewhat less than the maximal clinical dose did not demonstrate evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. As there are no adequate and well-controlled studies in pregnant women, this drug should be used during pregnancy only if clearly needed. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during late pregnancy should be avoided. Administration of MOTRIN is not recommended during pregnancy.

Labor and Delivery: As with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia and delayed parturition occurred in rats. Administration of MOTRIN is not recommended during labor and delivery.

Nursing Mothers: In limited studies, an assay capable of detecting 1 µg/mL did not demonstrate ibuprofen in the milk of lactating mothers. Because of the limited nature of these studies, however, and the possible adverse effects of prostaglandin inhibiting drugs on neonates, MOTRIN is not recommended for use in nursing mothers.

Pediatric Use: Safety and efficacy of MOTRIN in children below the age of 6 months has not been established (see CLINICAL PHARMACOLOGY -Clinical Studies). There is no evidence of age-dependent kinetics in patients 2 to 11 years old (see CLINICAL PHARMACOLOGY -Pharmacokinetics). Dosing of MOTRIN in children 6 months or older should be guided by their body weight (see DOSAGE AND ADMINISTRATION).

OVERDOSAGE

The toxicity of ibuprofen overdose is dependent upon the amount of drug ingested and the time elapsed since ingestion, though individual response may vary, which makes it necessary to evaluate each case individually. Although uncommon, serious toxicity and death have been reported in the medical literature with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy and drowsiness. Other central nervous system symptoms include headache, tinnitus, CNS depression and seizures. Metabolic acidosis, coma, acute renal failure and apnea (primarily in very young children) may rarely occur. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia and atrial fibrillation, also have been reported.

The treatment of acute ibuprofen overdose is primarily supportive. Management of hypotension, acidosis and gastrointestinal bleeding may be necessary. In cases of acute overdose, the stomach should be emptied through ipecac-induced emesis or lavage. Emesis is most effective if initiated within 30 mintues of ingestion. Orally administered activated charcoal may help in reducing the absorption and reabsorption of ibuprofen.

In children, the estimated amount of ibuprofen ingested per body weight may be helpful to predict the potential for development of toxicity although each case must be evaluated. Ingestion of less than 100 mg/kg is unlikely to produce toxicity. Children ingesting 100 to 200 mg/kg may be managed with induced emesis and a minimal observation time of four hours. Children ingesting 200 to 400 mg/kg of ibuprofen should have immediate gastric emptying and at least four hours observation in a health care facility. Children ingesting greater than 400 mg/kg require immediate medical referral, careful observation and appropriate supportive therapy. Ipecac-induced emesis is not recommended in overdoses greater than 400 mg/kg because of the risk for convulsions and the potential for aspiration of gastric contents.

In adult patients the history of the dose reportedly ingested does not appear to be predictive of toxicity. The need for referral and follow-up must be judged by the circumstances at the time of the overdose ingestion. Symptomatic adults should be admitted to a health care facility for observation.

CONTRAINDICATIONS

MOTRIN should not be used in patients with previously demonstrated hypersensitivity to ibuprofen, or in individuals with a history of allergic manifestations to aspirin or other NSAIDs. Severe anaphylactic-like reactions to ibuprofen have been reported in such patients, some with fatal outcome.