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Indications and Dosage
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.
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Hepatic Impairment
Contraindicated.
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Administration
May be taken with or without food.
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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).
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Special Precautions
Patients w/ pre-existing dyskinesia or dystonia, major psychotic disorder. Severe renal impairment. Pregnancy and lactation. Avoid abrupt withdrawal or dose reduction.
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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). |
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Patient Counseling Information
This drug may cause dizziness and/or sudden sleep disorder, if affected, do not drive or operate machinery.
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Monitoring Parameters
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.
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Overdosage
Symptoms: Nausea, vomiting, dizziness. Management: Symptomatic and supportive treatment. Hospitalization is advised.
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Drug Interactions
May increase the bioavailability of levodopa.
Potentially Fatal: May cause severe hypertension w/ non-selective MAOI(s) (e.g. phenelzine, tranylcypromine). |
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Food Interaction
Food delays and decreases the absorption. May enhance CNS depressant effect of alcohol.
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Action
Description:
Mechanism of Action: 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. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Tolcapone, CID=4659569, https://pubchem.ncbi.nlm.nih.gov/compound/Tolcapone (accessed on Jan. 23, 2020) |
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Storage
Store between 20-25°C.
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MIMS Class
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ATC Classification
N04BX01 - tolcapone ; Belongs to the class of other dopaminergic agents used in the management of Parkinson's disease.
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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.
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