Adult: As adjunct to levodopa/carbidopa or levodopa/benserazide therapy in patients with motor fluctuations who failed to respond to or are intolerant of other COMT inhibitors or when other adjunctive therapy is ineffective or inappropriate: 100 mg tid; 1st dose of the day must be given at the same time as the combined levodopa preparation and the subsequent doses given approx 6 and 12 hours later. Max: 200 mg tid (use only in exceptional circumstances, when clinical benefit justifies the increased risk of hepatotoxicity). Discontinue use if no clinical benefit is achieved within 3 weeks of treatment. To optimise individual response, dose reduction of levodopa may be needed upon initiation of tolcapone. Treatment recommendations may vary between countries (refer to specific country guidelines).
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food.
Contraindications
Phaeochromocytoma, severe dyskinesia; history of NMS and/or non-traumatic rhabdomyolysis or hyperthermia; clinical evidence of liver disease, increased liver enzymes or any other evidence of hepatocellular dysfunction. Concomitant use with non-selective MAOIs.
Special Precautions
Patient with pre-existing dystonia; at risk of hypotension or where transient hypotensive episodes would be poorly tolerated (e.g. CV or cerebrovascular disease). Avoid use in patients with psychotic disorders. Severe renal impairment (CrCl <30 mL/min). Pregnancy and lactation.
Adverse Reactions
Significant: Increased hepatic enzymes, orthostatic hypotension, syncope, diarrhoea (occasionally severe), compulsive behaviours and/or loss of impulse control (manifesting as pathological gambling, increased libido or hypersexuality, compulsive spending or buying, and binge eating); psychiatric effects (e.g. confusion, delusions, disorientation, aggressive behaviour, agitation, delirium, hallucinations, paranoid ideation, psychosis), dyskinesia, dystonia; symptom complex resembling NMS (following abrupt withdrawal or dose reduction). Cardiac disorders: Chest pain. Gastrointestinal disorders: Nausea, vomiting, constipation, xerostomia, abdominal pain, dyspepsia. General disorders and administration site conditions: Influenza-like illness, fatigue. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Muscle cramps. Nervous system disorders: Headache, dizziness, somnolence, hypokinesia, loss of balance. Psychiatric disorders: Sleep disorder, excessive dreaming. Renal and urinary disorders: Urine discolouration, UTI, haematuria. Respiratory, thoracic and mediastinal disorders: URTI, dyspnoea. Skin and subcutaneous tissue disorders: Increased sweating. Potentially Fatal: Severe hepatocellular injury including fulminant liver failure.
Patient Counseling Information
This drug may cause drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform LFTs before initiating treatment, then monitor every 2 weeks for the 1st year of treatment, every 4 weeks for the next 6 months and every 8 weeks thereafter. If dose increase to 200 mg tid is needed, perform LFTs before increasing the dose and then monitor at the same frequency as recommended when therapy is started. Monitor blood pressure. Assess mental status and clinical signs and symptoms of hepatic dysfunction.
Overdosage
Symptoms: Nausea, vomiting, dizziness. Management: Supportive and symptomatic treatment. Hospitalisation is advised.
Drug Interactions
Increases the bioavailability and enhances the clinical efficacy of levodopa. May enhance the adverse or toxic effects of non-selective MAOIs (e.g. phenelzine, tranylcypromine, isocarboxazid). May increase the plasma concentrations of benserazide and its active metabolite. May cause additive sedative effects when used concomitantly with CNS depressants.
Food Interaction
Delayed and reduced absorption with food.
Action
Description: Mechanism of Action: Tolcapone is a selective, reversible peripheral inhibitor of catechol-O-methyltransferase (COMT), an enzyme responsible for the metabolism of dopamine and levodopa. By inhibiting COMT, tolcapone prevents the peripheral breakdown of levodopa, leading to more stable plasma levodopa levels and increased central dopaminergic activity. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Food delays and reduces absorption. Bioavailability: Approx 65%. Time to peak plasma concentration: Approx 2 hours. Distribution: Plasma protein binding: >99.9%, mainly to albumin. Metabolism: Extensively metabolised in the liver mainly via conjugation into inactive glucuronide. Additionally, it undergoes methylation by COMT into 3-O-methyltolcapone and metabolism by CYP3A4 and CYP2A6 into primary alcohol, which is subsequently oxidised to carboxylic acid. Excretion: Via urine (60%; 0.5% as unchanged drug); faeces (40%). Elimination half-life: 2-3 hours.
Chemical Structure
Tolcapone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4659569, Tolcapone. https://pubchem.ncbi.nlm.nih.gov/compound/Tolcapone. Accessed Oct. 25, 2024.
N04BX01 - tolcapone ; Belongs to the class of other dopaminergic agents used in the management of Parkinson's disease.
References
Anon. Tolcapone. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 03/09/2024.Brayfield A, Cadart C (eds). Tolcapone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/09/2024.iNova Pharmaceuticals (New Zealand) Limited. Tasmar 100 mg Film-coated Tablets data sheet 19 October 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 03/09/2024.Joint Formulary Committee. Tolcapone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/09/2024.Tasmar 100 mg Film-coated Tablets (Mylan Products Ltd). MHRA. https://products.mhra.gov.uk. Accessed 03/09/2024.Tasmar Tablet, Film Coated (Bausch Health US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 03/09/2024.Tolcapone. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 03/09/2024.
Sign Out
Lanjutkan dengan Google