Products
Entacapone was commercially available in the form of film-coated tablets (Comtan). It was approved in many countries since 1999. In 2017, distribution was discontinued. A fixed combination with levodopa and carbidopa has also been available since 2004 (Stalevo). Generic versions of the combination drug were approved in 2014.
Structure and properties
Entacapone (C14H15N3O5, Mr = 305.3 g/mol) exists as a greenish yellow to yellow powder that is practically insoluble in water. It belongs to the nitrocatechols.
Effects
Entacapone (ATC N04BX02) affects the pharmacokinetics of levodopa. The effects are due to peripheral, selective, and reversible inhibition of the enzyme catechol- methyltransferase (COMT). This reduces the degradation of concomitantly administered levodopa, resulting in higher, longer-lasting and more consistent blood levels. As a result, more dopamine is produced from levodopa in the central nervous system and dopaminergic stimulation is more sustained. Entacapone has high first-pass metabolism and a short half-life of about half an hour.
Indications
For the treatment of Parkinson’s disease in combination with levodopa and a decarboxylase inhibitor (benserazide or carbidopa) for patients with fluctuating motor symptoms (on-off symptoms, end-of-dose).
Dosage
According to the SmPC. Tablets are taken up to ten times daily concomitantly with levodopa combination and independently of meals.
Contraindications
Entacapone is contraindicated in the presence of hypersensitivity, hepatic insufficiency, malignant neuroleptic syndrome, or a history of atraumatic rhabdomyolysis, and pheochromocytoma. Entacapone must not be combined with nonselective MAO inhibitors or concomitantly with an MAO-A and MAO-B inhibitor. For complete precautions, see the drug label.
Adverse effects
The most common possible adverse effects include dyskinesia (movement disorders), discoloration of the urine, and nausea. Rarely, severe side effects such as malignant neuroleptic syndrome, rhabdomyolysis, myocardial infarction, and hepatitis are possible. Entacapone, however, is significantly less toxic to the liver than tolcapone (Tasmar).