Overview
11 DESCRIPTION Carbidopa, levodopa and entacapone tablets is a combination of carbidopa, levodopa, and entacapone for the treatment of Parkinson’s disease. Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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.
Indications
- 1 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.
Common Doses
- 600 mg
- 50 mg
- 200 mg
- 70 mg
Dosage
2 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. Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.
Contraindications
- 4 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. Concomitant use of nonselective monoamine oxidase (MAO) inhibitors ( 4 ) Narrow-angle glaucoma ( 4 )
Side Effects
- 6 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.
Interactions
- 7 DRUG INTERACTIONS Drugs metabolized by COMT: use with caution ( 5.11 , 7.2 ) Anti-hypertensive agents: dose adjustment may be required ( 7.3 ) Tricyclic antidepressants: risk of hypertension and dyskinesia reported during concomitant use with carbidopa/levodopa ( 7.4 ) Dopamine D2 receptor antagonists, isoniazid, phenytoin, papaverine and iron salts: may reduce efficacy of carbidopa, levodopa and entacapone tablets ( 7.5 , 7.6 , 7.7 , 7.8 , 7.