Adult: As adjunct to levodopa combination therapy in patient w/ "end of dose" motor fluctuations: 100 mg tid. 1st daily dose given at the same time w/ levodopa preparation, succeeding doses at 6 and 12 hr later. Max: 200 mg tid as tolerated, discontinue if no clinical benefit is obtained w/in 3 wk. Dose reduction of levodopa may be necessary.
May be taken with or without food.
Elevated liver enzyme, severe dyskinesia, history of neuroleptic malignant syndrome (NMS), symptom complex (e.g. non-traumatic rhabdomyolysis, hyperthermia), phaeochromocytoma. Hepatic impairment. Concomitant use w/ non-selective MAOI(s).
Patients w/ pre-existing dyskinesia or dystonia, major psychotic disorder. Severe renal impairment. Pregnancy and lactation. Avoid abrupt withdrawal or dose reduction.
This drug may cause dizziness and/or sudden sleep disorder, if affected, do not drive or operate machinery.
Perform LFT upon initiation of treatment and monitor every 2 wk for 1st yr; every 4 wk for next 6 mth; every 8 wk thereafter. Discontinue if liver enzyme levels exceed 2 times the upper limit of normal values. Monitor BP, signs and symptoms of mental status.
Symptoms: Nausea, vomiting, dizziness. Management: Symptomatic and supportive treatment. Hospitalization is advised.
May increase the bioavailability of levodopa. Potentially Fatal: May cause severe hypertension w/ non-selective MAOI(s) (e.g. phenelzine, tranylcypromine).
Food delays and decreases the absorption. May enhance CNS depressant effect of alcohol.
Description: Tolcapone is a selective, reversible peripheral inhibitor of catechol-O-methyltransferase (COMT), an enzyme responsible for the breakdown of levodopa and dopamine. Its inhibition allows more levodopa to reach the brain, leading to enhanced dopaminergic activity. Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract. Food delays and decreases the absorption. Absolute bioavailability: Approx 65%. Time to peak plasma concentration: W/in 2 hr. Distribution: Volume of distribution: 9 L. Plasma protein binding: >99%, mainly to albumin. Metabolism: Extensively metabolised in the liver, mainly via conjugation into inactive glucuronide; methylation by COMT into 3-O-methyltolcapone; and by CYP450 isoenzymes CYP3A4 and CYP2A6. Excretion: Mainly via urine (approx 60% as metabolites; 0.5% as unchanged drug); faeces (40%). Elimination half-life: Approx 2-3 hr.