Entacapone (Page 5 of 5)

DRUG ABUSE AND DEPENDENCE

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.

OVERDOSAGE

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. A massive overdose of entacapone may theoretically produce a 100% inhibition of the COMT enzyme in humans, thereby preventing the metabolism of endogenous and exogenous catechols.
The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with levodopa and carbidopa for 14 days in 15 Parkinson’s disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2 mcg per mL (at 45 minutes, compared to 1 mcg per mL and 1.2 mcg per mL with 200 mg entacapone at 45 minutes). Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2,000 mg entacapone have been administered as 200 mg 10 times daily with levodopa and carbidopa or levodopa and benserazide for at least 1 year in 10 patients, for at least 2 years in 8 patients and for at least 3 years in 7 patients. Overall, however, clinical experience with daily doses above 1,600 mg is limited.
The range of lethal plasma concentrations of entacapone based on animal data was 80 mcg per mL to 130 mcg per mL in mice. Respiratory difficulties, ataxia, hypoactivity, and convulsions were observed in mice after high oral (gavage) doses.
Management of Overdose
Management of entacapone overdose is symptomatic; there is no known antidote to entacapone. Hospitalization is advised, and general supportive care is indicated. There is no experience with hemodialysis or hemoperfusion, but these procedures are unlikely to be of benefit, because entacapone is highly bound to plasma proteins. An immediate gastric lavage and repeated doses of charcoal over time may hasten the elimination of entacapone by decreasing its absorption and reabsorption from the gastrointestinal (GI) tract. The adequacy of the respiratory and circulatory systems should be carefully monitored and appropriate supportive measures employed. The possibility of drug interactions, especially with catechol-structured drugs, should be borne in mind.

DOSAGE AND ADMINISTRATION

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 x 8 = 1,600 mg per day). Clinical experience with daily doses above 1,600 mg is limited.
Entacapone tablets 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 tablets can be combined with both the immediate and sustained-release formulations of levodopa and carbidopa.
Entacapone tablets 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 Cmax of entacapone approximately doubled in patients with documented liver disease, compared to controls. However, these studies were conducted with single-dose entacapone without levodopa and dopa decarboxylase inhibitor coadministration, and therefore the effects of liver disease on the kinetics of chronically administered entacapone have not been evaluated (see CLINICAL PHARMACOLOGY, Pharmacokinetics of Entacapone).
Withdrawing Patients from Entacapone Tablets
Rapid withdrawal or abrupt reduction in the entacapone tablets dose could lead to emergence of signs and symptoms of Parkinson’s disease (see CLINICAL PHARMACOLOGY, Clinical Studies), and may lead to hyperpyrexia and confusion, a symptom complex resembling NMS (see PRECAUTIONS, Other Events Reported With Dopaminergic Therapy). This syndrome should be considered in the differential diagnosis for any patient who develops a high fever or severe rigidity. If a decision is made to discontinue treatment with entacapone tablets, patients should be monitored closely and other dopaminergic treatments should be adjusted as needed. Although tapering entacapone tablets has not been systematically evaluated, it seems prudent to withdraw patients slowly if the decision to discontinue treatment is made.

HOW SUPPLIED

Entacapone Tablets USP, 200 mg are light brownish-orange colored, film-coated, oval shaped tablets debossed “Y 16” on one side and plain on other side.
Cartons of 30 tablets (10 blister cards x 3) NDC 0904-6822-04
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 032, India

Packaged and Distributed By:

MAJOR® PHARMACEUTICALS

Indianapolis, IN 46268 USA

Refer to package label for Distributor’s NDC Number
Revised: 05/2023

PACKAGE LABEL-PRINCIPAL DISPLAY — 200 mg

Entacapone Tablets, USP

200 mg

30 Tablets

Entacapone Label
(click image for full-size original)
ENTACAPONE entacapone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0904-6822(NDC:65862-654)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ENTACAPONE (ENTACAPONE) ENTACAPONE 200 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM
GLYCERIN
HYDROGENATED COTTONSEED OIL
HYPROMELLOSE 2910 (6 MPA.S)
FERRIC OXIDE RED
FERRIC OXIDE YELLOW
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MANNITOL
MICROCRYSTALLINE CELLULOSE
POLYSORBATE 80
SODIUM STARCH GLYCOLATE TYPE A POTATO
SUCROSE
TITANIUM DIOXIDE
Product Characteristics
Color BROWN (Light brownish orange) Score no score
Shape OVAL Size 17mm
Flavor Imprint Code Y;16
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0904-6822-04 30 BLISTER PACK in 1 CARTON contains a BLISTER PACK
1 1 TABLET, FILM COATED in 1 BLISTER PACK This package is contained within the CARTON (0904-6822-04)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA203437 06/19/2015
Labeler — Major Pharmaceuticals (191427277)

Revised: 02/2024 Major Pharmaceuticals

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