Entacapone (9 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- CARBIDOPA, LEVODOPA AND ENTACAPONE
- COMTAN
- ENTACAPONE
- STALEVO 100
- STALEVO 125
- STALEVO 150
- STALEVO 200
- STALEVO 50
- STALEVO 75
Indications and Usage
Carbidopa, levodopa and entacapone tablets are indicated for the treatment of Parkinson’s disease. Carbidopa, levodopa and entacapone tablets can be used: • To substitute (with equivalent strengths of each of the three components) carbidopa/levodopa and entacapone previously administered as individual products. • To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearing-off” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias.
Dosage and Administration
Carbidopa, levodopa and entacapone tablets should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. However, some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with carbidopa, levodopa and entacapone tablets if a decision has been made to add entacapone (see below). Therapy should be individualized and adjusted according to the desired therapeutic response.
Contraindications
Carbidopa, levodopa and entacapone tablets are contraindicated in patients: • Taking nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine and tranylcypromine). These nonselective MAO inhibitors must be discontinued at least two weeks prior to initiating therapy with carbidopa, levodopa and entacapone tablets. • With narrow-angle glaucoma.
Warnings and Precautions
The following adverse reactions described in this section are related to at least one of the components of carbidopa, levodopa and entacapone tablets (i.e., levodopa, carbidopa, and/or entacapone) based upon the safety experience in clinical trials (especially pivotal trials) or in postmarketing reports.
Adverse Reactions
The following adverse reactions are discussed in more detail in the Warnings and Precautions sections of labeling: • Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1)] • Hypotension/Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.2)] • Dyskinesia [see Warnings and Precautions (5.3)] • Depression and suicidality [see Warnings and Precautions (5.4)] • Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions (5.5)] • Impulse Control and/or Compulsive Behaviors [see Warnings and Precautions (5.6)] • Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.7)] • Diarrhea and Colitis [see Warnings and Precautions (5.8)] • Rhabdomyolysis [see Warnings and Precautions (5.9)] • Vitamin B6 Deficiency and Seizures [see Warnings and Precautions (5.10)] • Peptic Ulcer Disease [see Warnings and Precautions (5.13)]
Mechanism of Action
Levodopa Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson’s disease because it does not cross the blood-brain barrier. However, levodopa the metabolic precursor of dopamine, does cross the blood-brain barrier, and is presumably converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves the symptoms of Parkinson’s disease. Carbidopa When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain. Entacapone Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD).