A triple combination therapy for Parkinson's disease, providing enhanced and sustained dopaminergic stimulation. Levodopa is a dopamine precursor, Carbidopa is a peripheral DOPA decarboxylase inhibitor that reduces peripheral conversion of levodopa, and Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that prolongs the effect of levodopa by reducing its peripheral metabolism. This combination significantly reduces 'off' time and improves motor fluctuations in patients with advanced Parkinson's disease.
Adult: Individualized. Typically 1 tablet (Levodopa 100mg/Carbidopa 25mg/Entacapone 200mg) 3 to 8 times daily. Maximum daily dose of Entacapone is 1600mg (8 tablets). Dose adjustments of levodopa/carbidopa may be needed when adding entacapone; a 20-30% reduction in levodopa dose is often recommended.
Note: Administer with or without food, but consistency is key. High-protein meals can impair absorption. Tablets should be swallowed whole with water. Do not crush or chew. Doses should be spaced approximately 3-6 hours apart while awake. The interval between the last dose of the day and the first dose the next morning should not exceed 8 hours.
This combination addresses the dopamine deficiency in the nigrostriatal pathway of Parkinson's disease through a multi-pronged approach. Levodopa, a dopamine precursor, crosses the blood-brain barrier and is converted to dopamine in the brain. Carbidopa, a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor, prevents the peripheral conversion of levodopa to dopamine, allowing more levodopa to reach the CNS and reducing peripheral side effects like nausea. Entacapone, a reversible, peripherally-acting catechol-O-methyltransferase (COMT) inhibitor, blocks the major peripheral metabolic pathway of levodopa (to 3-O-methyldopa), increasing its bioavailability and plasma half-life, leading to more sustained and stable plasma levels.
Pregnancy: Category C. Animal studies show adverse effects. Use only if potential benefit justifies potential risk to the fetus. Levodopa may inhibit lactation.
Driving: May cause dizziness, syncope, and sudden sleep attacks. Patients should be warned not to drive or operate machinery until their individual response is known.
| Non-selective MAO Inhibitors (Phenelzine, Tranylcypromine) | Risk of hypertensive crisis | Contraindicated |
| Selective MAO-B Inhibitors (Selegiline, Rasagiline) | Enhanced dopaminergic effects, increased risk of dyskinesia and orthostasis. Dose adjustment may be needed. | Major |
| Iron Salts (Ferrous Sulfate) | Reduced bioavailability of levodopa/carbidopa due to chelation | Moderate |
| Antipsychotics (Typical & Atypical e.g., Haloperidol, Risperidone) | Antagonize dopaminergic effect, worsening Parkinsonism | Major |
| Antihypertensives | Additive hypotensive effect | Moderate |
| Isoniazid | May antagonize therapeutic effect of levodopa | Moderate |
| Metoclopramide | Antagonizes dopaminergic effect in CNS | Major |
| Drugs that interfere with catecholamine metabolism (e.g., Epinephrine, Norepinephrine) | Increased risk of arrhythmias and hypertension | Moderate |
| Warfarin | Entacapone may potentiate anticoagulant effect; monitor INR. | Moderate |
Same composition (Levodopa (100mg) + Carbidopa (25mg) + Entacapone (200mg)), different brands: