Ketoprofen (ketoprofen)

The lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient should be employed. Dosage of ketoprofen must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage.

Since ketoprofen and its metabolites are excreted mainly by the kidneys, the manufacturers recommend that the maximum daily dosage of the drug be reduced in patients with renal impairment. The maximum dosage of ketoprofen given as conventional or extended-release capsules in patients with mild renal impairment is 150 mg daily, while the maximum dosage in patients with more severe renal impairment (i.e., those with creatinine clearances less than 25 mL/minute per 1.73 m2 or end-stage renal disease) is 100 mg daily (given as conventional or extended-release capsules). Use of ketoprofen in patients with severe renal impairment is not recommended; however, if ketoprofen is used in these patients, close monitoring is recommended. Patients with impaired hepatic function and serum albumin concentrations less than 3.5 g/dL should receive an initial ketoprofen dosage of 100 mg daily as conventional or extended-release capsules. The manufacturers also recommend that ketoprofen therapy be initiated at low dosages in patients with both hypoalbuminemia and renal impairment, since these patients may be at greater risk of developing adverse effects secondary to increased plasma concentrations of free ketoprofen. If the drug is used in patients with both hypoalbuminemia and impaired renal or hepatic function, the patients should be closely monitored.

When ketoprofen is used for relief of mild to moderate pain or dysmenorrhea, the manufacturers recommend that therapy be initiated with relatively small dosages in patients with renal or hepatic disease.

The potential benefits and risks of ketoprofen therapy as well as alternative therapies should be considered prior to initiating ketoprofen therapy.

Ketoprofen is administered orally. Adverse GI effects may be minimized by administering the drug with meals, milk, or an antacid. Extended-release capsules of ketoprofen are not recommended for the management of acute pain. In addition, concomitant use of ketoprofen conventional and extended-release capsules is not recommended.

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There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Use of NSAIAs during pregnancy at about 30 weeks of gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks of gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks of gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks of gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice. Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks of gestation.

Known effects of NSAIAs on the human fetus during the third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible (generally within 3-6 days) following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Deaths associated with neonatal renal failure have been reported. Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as ketoprofen, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development. In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses.

In animal reproduction studies in mice and rats, no teratogenic or embryotoxic effects were observed at ketoprofen dosages up to approximately 0.2 times the maximum recommended human dosage of 185 mg/m2 daily. In rabbits, maternally toxic dosages were associated with embryotoxicity but not with teratogenicity.

The effects of ketoprofen on labor and delivery in humans currently are not known, but the drug has delayed parturition in rats when administered in doses of 6 mg/kg (about 0.2 times the maximum daily recommended human dosage based on body surface area) before the onset of labor.

It is not known whether ketoprofen is distributed into human milk; 4-5% of circulating plasma concentrations of the drug are distributed into the milk of lactating dogs. In rats, perinatal development was not adversely affected in nursing offspring whose mothers received ketoprofen doses of 9 mg/kg (approximately 0.3 times the maximum daily recommended human dosage based on body surface area). The manufacturers recommend that ketoprofen not be used in nursing women.

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