Tolcapone


Concise Prescribing Info
Indications/Uses
Parkinson's disease.
Dosage/Direction for Use
Adult : PO 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.
Dosage Details
Oral
Parkinson's disease
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.
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
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).
Special Precautions
Patients w/ pre-existing dyskinesia or dystonia, major psychotic disorder. Severe renal impairment. Pregnancy and lactation. Avoid abrupt withdrawal or dose reduction.
Adverse Reactions
Significant: Abnormal thinking/behavioural changes (e.g. paranoid ideation, delusions, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, delirium); diarrhoea, hallucinations, impulse control disorders (e.g. restless-leg syndrome, pathological gambling, increased libido, binge eating); melanoma, orthostatic hypotension, pleural/retroperitoneal fibrosis, somnolence, dyskinesia and psychosis exacerbation, NMS associated w/ withdrawal.
Nervous: Drowsiness, sleep disorders, dystonia, increased dream activity, dizziness, confusion, fatigue, loss of balance, paraesthesia, headache.
CV: Syncope, chest pain, hypotension, palpitations.
GI: Nausea, vomiting, anorexia, constipation, abdominal pain, dry mouth, dyspepsia, flatulence.
Resp: Upper resp tract infection, influenza, dyspnoea, sinus congestion.
Hepatic: Jaundice.
Genitourinary: Urine discolouration, UTI, haematuria, urination disorder.
Endocrine: Increased serum transaminases.
Musculoskeletal: Muscle cramps, hyperkinesia, hypokinesia, muscle rigidity, neck pain, arthritis.
Ophthalmologic: Cataract, inflammation.
Dermatologic: Increased sweating, pruritus.
Potentially Fatal: Severe hepatotoxicity (e.g. acute fulminant liver failure).
Patient Counseling Information
This drug may cause dizziness and/or sudden sleep disorder, if affected, do not drive or operate machinery.
MonitoringParameters
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.
Overdosage
Symptoms: Nausea, vomiting, dizziness. Management: Symptomatic and supportive treatment. Hospitalization is advised.
Drug Interactions
May increase the bioavailability of levodopa.
Potentially Fatal: May cause severe hypertension w/ non-selective MAOI(s) (e.g. phenelzine, tranylcypromine).
Food Interaction
Food delays and decreases the absorption. May enhance CNS depressant effect of alcohol.
Action
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.
Chemical Structure

Chemical Structure Image
Tolcapone

Source: National Center for Biotechnology Information. PubChem Database. Tolcapone, CID=4659569, https://pubchem.ncbi.nlm.nih.gov/compound/Tolcapone (accessed on Jan. 23, 2020)

Storage
Store between 20-25°C.
ATC Classification
N04BX01 - tolcapone ; Belongs to the class of other dopaminergic agents used in the management of Parkinson's disease.
References
Anon. Tolcapone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 23/10/2017.

Bausch & Lomb (NZ) Ltd. Tasmar 100 mg Film-Coated Tablets data sheet 19 September 2016. Medsafe. http://www.medsafe.govt.nz/. Accessed 23/10/2017.

Buckingham R (ed). Tolcapone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com/. Accessed 23/10/2017.

Joint Formulary Committee. Tolcapone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 23/10/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Tolcapone. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 23/10/2017.

Preston CL (ed). Tolcapone + Phenelzine. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/11/2017.

Preston CL (ed). Tolcapone + Tranylcypromine. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/11/2017.

Tolcapone Tablets (Oceanside Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 23/10/2017.

Disclaimer: This information is independently developed by MIMS based on Tolcapone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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