Products
Tolcapone is commercially available in the form of film-coated tablets (Tasmar). It has been approved in many countries since 1997.
Structure and properties
Tolcapone (C14H11NO5, Mr = 273.2 g/mol) exists as a yellow, odorless, non-hygroscopic, crystalline powder. It is a nitrobenzophenone.
Effects
Tolcapone (ATC N04BX01) affects the pharmacokinetics of levodopa. The effects are due to 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. Tolcapone is primarily peripherally active, but also entered the central nervous system in small amounts. The half-life is short, lasting about two hours.
Indications
As a second-line agent 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 phenomenon, end-of-dose).
Dosage
According to the SmPC. Tablets are administered three times daily, six hours apart and independent of meals. The first dose is always taken with the levodopa combination.
Contraindications
- Hypersensitivity
- Pre-existing liver damage, evidence of liver disease, elevated liver enzymes
- Malignant neuroleptic syndrome, nontraumatic rhabdomyolysis, or severe dyskinesia in patient history
- Therapy with a nonselective MAO inhibitor, concurrent therapy 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), nausea, sleep disturbances, loss of appetite, and diarrhea. Tolcapone has liver-toxic properties and may rarely cause severe liver injury, including fatalities. The appropriate precautions must be carefully observed (see the SmPC).
