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.
Chống chỉ định
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.
Chỉ số theo dõi
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).
Tương tác với thức ăn
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.