carbidopa + entacapone + levodopa: clinical use

Prescribing considerations

• Confirm end-of-dose motor fluctuations and review current levodopa exposure before switching.
• Assess dyskinesia and other levodopa-related adverse effects during transition.
• Use caution with cardiovascular or pulmonary disease, asthma, endocrine disease, peptic-ulcer history, seizures, psychosis, wide-angle glaucoma and severe renal impairment.
• Avoid abrupt reduction or withdrawal because neuroleptic malignant syndrome and rhabdomyolysis may follow.
• Use cautiously in mild-to-moderate hepatic impairment.

Contraindications and cautions

• Hypersensitivity to an active ingredient or excipient
• Severe hepatic impairment
• Narrow-angle glaucoma
• Phaeochromocytoma
• Non-selective MAO inhibition or concurrent selective MAO-A and MAO-B inhibition
• Previous neuroleptic malignant syndrome or non-traumatic rhabdomyolysis

Monitoring

• Motor response, wearing-off and dyskinesia
• Mental state, suicidal thinking, hallucinations and psychosis
• Impulse-control disorders and dopamine dysregulation syndrome
• Somnolence and sudden sleep onset
• Postural blood pressure and cardiovascular status where indicated
• Persistent diarrhoea, appetite and weight
• Periodic hepatic, haematological, cardiovascular and renal assessment during extended treatment
• INR when initiated with warfarin

Clinical pharmacology

Levodopa is converted to dopamine in the central nervous system. Carbidopa inhibits peripheral dopa decarboxylase, while entacapone reversibly inhibits mainly peripheral COMT, increasing and prolonging levodopa exposure.

Formulation and product differences

• Immediate-release, unscored film-coated tablets intended to be swallowed whole.
• Available in several fixed-ratio strengths; the entacapone component remains fixed across the selected range.
• Contains sucrose and is essentially sodium-free.