Tolcapone
Related Subjects:Multiple System Atrophy (MSA)
|Parkinson Plus syndromes
|Parkinsonism
|Idiopathic Parkinson disease
|Progressive Supranuclear Palsy
|Drug Induced Parkinson disease
|Neuroleptic Malignant Syndrome
💊 Tolcapone is a COMT inhibitor used as an adjunct in Parkinson’s disease to prolong the effect of levodopa.
⚠️ It is hepatotoxic and requires strict monitoring. Always check the BNF or SmPC for up-to-date prescribing guidance.
⚙️ Mode of Action
- Inhibits catechol-O-methyltransferase (COMT) 🧬.
- Reduces peripheral breakdown of levodopa → more levodopa reaches the brain 🧠.
- Enhances and prolongs dopamine activity at the synapse → improves “end-of-dose” motor fluctuations.
📌 Indications
- Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease.
- Particularly for patients with “wearing-off” phenomena or “end-of-dose” motor fluctuations.
💊 Dosing
- Initial: 100 mg TDS PO.
- If no clinical improvement within 3 weeks → increase to 200 mg TDS.
- If still ineffective → withdraw tolcapone.
- ⚠️ Most patients on >600 mg levodopa daily require a ~30% dose reduction to avoid dyskinesias.
🔗 Interactions
- Always check BNF for full list.
- May potentiate the effects of other dopaminergic therapies.
- Caution with drugs affecting liver metabolism (CYP2C9, CYP3A4 substrates).
⚠️ Cautions
- 🚨 Hepatotoxicity: Baseline LFTs, then monitor frequently (every 2 weeks for first year, then less often).
- Withdraw if ALT/AST >2 × ULN or if clinical signs of liver dysfunction.
- Use only when entacapone is ineffective or unsuitable.
⛔ Contraindications
- Active liver disease or unexplained elevated LFTs.
- History of neuroleptic malignant syndrome (NMS) or rhabdomyolysis.
- See BNF for full list.
💥 Side Effects
- 💢 Dyskinesias (esp. if levodopa dose not adjusted).
- 😮 Nausea, vomiting, diarrhoea.
- 🧠 Hallucinations, confusion, insomnia.
- 🫀 Orthostatic hypotension.
- 🚨 Hepatotoxicity – potentially fatal.
🧠 Clinical Pearls
- Tolcapone is more potent than entacapone but rarely used due to liver toxicity risks.
- Only prescribe if patients fail to respond to entacapone and require close monitoring.
- Educate patients to report early signs of liver dysfunction (fatigue, anorexia, dark urine, jaundice).
📚 References
