Entacapone

Entacapone tablets USP are indicated as an adjunct to levodopa and carbidopa to treat end-of-dose "wearing-off" in patients with Parkinson's disease (see CLINICAL PHARMACOLOGY, Clinical Studies ). Entacapone's effectiveness has not been systematically evaluated in patients with Parkinson's disease who do not experience end-of-dose "wearing-off".

• The recommended dose of entacapone is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg × 8 = 1,600 mg per day)
• Clinical experience with daily doses above 1,600 mg is limited
• Entacapone should always be administered in association with levodopa and carbidopa
• Entacapone has no antiparkinsonian effect of its own
• In clinical studies, the majority of patients required a decrease in daily levodopa dose if their daily dose of levodopa had been greater than or equal to 800 mg or if patients had moderate or severe dyskinesia before beginning treatment
• To optimize an individual patient's response, reductions in daily levodopa dose or extending the interval between doses may be necessary
• In clinical studies, the average reduction in daily levodopa dose was about 25% in those patients requiring a levodopa dose reduction. (More than 58% of patients with levodopa doses above 800 mg daily required such a reduction.) Entacapone can be combined with both the immediate and sustained-release formulations of levodopa and carbidopa
• Entacapone may be taken with or without food (see CLINICAL PHARMACOLOGY )
• Patients With Impaired Hepatic Function Patients with hepatic impairment should be treated with caution
• The AUC and C max of entacapone approximately doubled in patients with documented liver disease, compared to controls. …

• Safety and effectiveness
• In pediatric patients have not been established

• Instruct patients to take entacapone only as prescribed
• Inform patients that hallucinations and/or other psychotic-like behavior can occur
• Advise patients that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating
• Hypotension may occur more frequently during initial therapy
• Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with entacapone. …

Entacapone is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

See PRECAUTIONS, Drug Interactions . Drug Interactions In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 microM to over 1,000 microM; an oral 200 mg dose achieves a highest level of approximately 5 microM in people); these enzymes would therefore not be expected to be inhibited in clinical use. In an interaction study in healthy volunteers, entacapone did not significantly change the plasma levels of S-warfarin while the AUC for R-warfarin increased on average by 18% [Cl90 11% to 26%], and the INR values increased on average by 13% [Cl90 6% to 19%]. …

Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of entacapone and a non-selective MAO inhibitor (e.g., phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. For this reason, patients should ordinarily not be treated concomitantly with entacapone and a non-selective MAO inhibitor. Entacapone can be taken concomitantly with a selective MAO-B inhibitor (e.g., selegiline). …

Because clinical studies are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment per total number of patients treated) observed in the clinical studies of a drug cannot be directly compared to the incidence of adverse reactions in the clinical studies of another drug and may not reflect the incidence of adverse reactions observed in practice. A total of 1,450 patients with Parkinson's disease were treated with entacapone in premarketing clinical studies. Included were patients with fluctuating symptoms, as well as those with stable responses to levodopa therapy. …

Pregnancy Pregnancy Category C In embryofetal development studies, entacapone was administered to pregnant animals throughout organogenesis at doses of up to 1,000 mg/kg/day in rats and 300 mg/kg/day in rabbits. Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. …

The postmarketing data include several cases of overdose. The highest reported dose of entacapone was at least 40,000 mg. The acute symptoms and signs commonly seen in these cases included somnolence and decreased activity, states related to depressed level of consciousness (e.g., coma, confusion and disorientation) and discolorations of skin, tongue, and urine, as well as restlessness, agitation, and aggression. COMT inhibition by entacapone treatment is dose-dependent. …

Entacapone is not a controlled substance. Animal studies to evaluate the drug abuse and potential dependence have not been conducted. Although clinical studies have not revealed any evidence of the potential for abuse, tolerance or physical dependence, systematic studies in humans designed to evaluate these effects have not been performed.

Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]

Tome assim que lembrar, a menos que esteja quase na hora da próxima dose. Nesse caso, pule a dose esquecida. Nunca tome duas doses de uma vez para compensar. Confira a bula, pois alguns medicamentos são diferentes.