Phenylpropanolamine and stroke: the study, the FDA ruling, the implications.

Following a recent case-control study that linked the use of phenylpropanolamine (PPA) in diet aids to the risk of hemorrhagic stroke, the Food and Drug Administration requested that drug companies stop marketing products that contain PPA. Dozens of over-the-counter and prescription diet aids and cough and cold remedies will need to be reformulated or discontinued. This paper reviews the study and its implications for physicians.

Entacapone.

OBJECTIVE: To introduce entacapone, a new catechol-O-methyltransferase inhibitor, and discuss its pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, drug interactions, adverse events, dosage guidelines, and therapeutic and formulary considerations. DATA SOURCE: A MEDLINE database search (1966-December 1999) was performed to identify relevant English-language articles including recent studies, abstracts, and reviews. Search terms included entacapone, OR-611, catechol-O-methyltransferase inhibitor, and Parkinson's disease. STUDY SELECTION: Relevant published human studies were chosen to summarize the pharmacokinetics, clinical efficacy, adverse effects, and drug interactions. DATA EXTRACTION: All available human clinical trials were reviewed. DATA SYNTHESIS: Entacapone is the second medication of a new class of drugs, the catechol-O-methyltransferase inhibitors, indicated for clinical use as an adjunct to levodopa/carbidopa to treat patients with idiopathic Parkinson's disease who experience the signs and symptoms of end-of-dose wearing-off. Entacapone in combination with levodopa/dopa decarboxylase inhibitor has been shown to increase the AUC of levodopa, which leads to less fluctuation of levodopa plasma concentrations. Clinically, the duration of motor response to levodopa was prolonged as reflected by an increase in the mean on time. The addition of entacapone resulted in a decrease in the mean daily dosage of levodopa. The recommended dosage of entacapone is 200 mg administered orally with each dose of levodopa/carbidopa, up to a maximum of eight doses per day. Common adverse effects include dyskinesia, nausea, diarrhea, and urine discoloration. CONCLUSIONS: Entacapone should be considered as add-on treatment to levodopa/carbidopa in Parkinson's disease patients with end-of-dose wearing-off effect.

Warfarin and celecoxib interaction.

OBJECTIVE: To report a case of increased international normalized ratio (INR) in a patient receiving warfarin and celecoxib. CASE SUMMARY: A 73-year-old white woman with hypothyroidism and heart failure was admitted to the hospital with increased orthopnea, dyspnea on exertion, and hemoptysis. On laboratory evaluation, she was noted to have an increased INR. The only reported change in her medications was the addition of celecoxib approximately five weeks before admission. Her INR had previously been stable. After discontinuation of warfarin and celecoxib, fresh frozen plasma and vitamin K were administered to normalize INR. The patient was not rechallenged. DISCUSSION: Warfarin is an oral anticoagulant with numerous reports of drug interactions. It is possible that other drug therapies or disease states may have contributed to the elevation in INR; however, the observed increase in INR occurred five weeks after beginning celecoxib therapy. The Food and Drug Administration has issued a notice about the possibility of interactions between these two medications. CONCLUSIONS: Celecoxib may potentiate the anticoagulant effects of warfarin. Patients receiving warfarin should be carefully monitored when adding, changing, or removing celecoxib from their medication regimen.