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COMT Inhibitor — Parkinson's Disease Pregnancy: Avoid — limited data

Entacapone

Brand names: Comtess, Stalevo (combined with levodopa/carbidopa)

Adult dose

Dose: 200 mg with each dose of levodopa/carbidopa
Route: Oral
Frequency: With each levodopa dose (up to 10 times daily)
Max: 2000 mg/day (10 × 200 mg doses)
Catechol-O-methyltransferase (COMT) inhibitor — blocks peripheral degradation of levodopa, extending its half-life and increasing CNS bioavailability. Reduces 'wearing-off' fluctuations. Always used ALONGSIDE levodopa — not monotherapy. Available combined as Stalevo (levodopa/carbidopa/entacapone).

Paediatric dose

Route:
Not indicated in children — Parkinson's disease is an adult condition.

Dose adjustments

Renal

No dose adjustment required.

Hepatic

Avoid in hepatic impairment — hepatotoxic potential.

Clinical pearls

  • Orange urine discolouration is expected and harmless — counsel patients to prevent alarm or non-adherence
  • When adding entacapone, levodopa dose often needs to be reduced by 10–30% to avoid peak-dose dyskinesia
  • Stalevo (combined tablet) reduces pill burden — improves adherence in patients on multiple levodopa doses daily

Contraindications

  • Phaeochromocytoma
  • Hypersensitivity to entacapone
  • Hepatic impairment
  • History of neuroleptic malignant syndrome or rhabdomyolysis

Side effects

  • Orange-brown discolouration of urine (harmless — warn patient)
  • Dyskinesia (enhanced levodopa effect — may need levodopa dose reduction)
  • Diarrhoea
  • Nausea
  • Hallucinations
  • Postural hypotension

Interactions

  • Non-selective MAOIs (contraindicated — hypertensive crisis)
  • Drugs metabolised by COMT: adrenaline, isoprenaline (prolonged duration and enhanced effects)
  • Warfarin (modest INR increase — monitor)

Monitoring

  • LFTs at baseline and periodically
  • Dyskinesia assessment
  • 'On' and 'Off' time diary
  • INR if on warfarin

Reference: BNFc; BNF 90; NICE NG71 (Parkinson's Disease); BNFc. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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