Levodopa Benserazide

Levodopa with benserazide is the second widely used combination of levodopa and a peripheral decarboxylase inhibitor for Parkinson disease. It has the same efficacy, risks and time-critical importance as levodopa with carbidopa, but different tablet strengths and a ratio of 4 to 1.

Mechanism. Levodopa is converted to dopamine in the brain. Benserazide inhibits peripheral aromatic amino acid decarboxylase and does not cross the blood-brain barrier effectively.

Pharmacokinetics. Levodopa half-life is about 1.5 hours. Absorption is delayed by food and by high-protein meals. Dispersible tablets reach peak levels faster, and modified-release capsules give a smoother, lower peak with about 60 to 70% of the immediate-release bioavailability.

First-line use. Parkinson disease and other parkinsonian syndromes.

• Oral levodopa and benserazide in a 4 to 1 ratio: start 50/12.5 mg (one 62.5 capsule) three or four times daily. Increase by 100/25 mg daily each week until response. Usual maintenance 400 to 800 mg of levodopa daily in 3 to 4 doses. Higher specialist doses may be needed.

• Modified-release capsules: usual starting dose 100/25 mg three times daily, adjusted by response.

• Dispersible tablets: used for morning OFF periods and rapid onset.

Emergency and hospital use. Give doses on time, within 30 minutes of the usual times. If the oral route is not possible, give dispersible tablets by nasogastric tube, or use a rotigotine patch as a bridge under specialist advice. Never stop abruptly.

Kidney, liver, weight and age.

• Kidney and liver: caution in mild impairment; contraindicated when decompensated.

• Older adults: start low and titrate slowly.

Contraindications. Decompensated endocrine, renal, hepatic or cardiac disease, pregnancy and women of childbearing potential not using effective contraception, narrow-angle glaucoma, severe psychiatric illness, age under 25 years (incomplete skeletal development), non-selective monoamine oxidase inhibitors within 14 days, and hypersensitivity.

Serious adverse effects. Severe dyskinesia, hallucinations, psychosis, impulse control disorders, sudden sleep onset, orthostatic hypotension, haemolytic anaemia, and parkinsonism-hyperpyrexia syndrome on abrupt withdrawal.

Common adverse effects. Nausea, vomiting, dyskinesia, orthostatic hypotension, somnolence and confusion.

Interactions. Iron salts reduce absorption, so separate by 2 hours. Antipsychotics (except quetiapine and clozapine), metoclopramide and prochlorperazine antagonise the effect. Antihypertensives add hypotension. Sympathomimetics and non-selective monoamine oxidase inhibitors risk hypertensive crisis.

Common prescribing errors. Missed or delayed doses in hospital. Giving metoclopramide. Prescribing in women of childbearing potential without contraception. Crushing modified-release capsules.

Special groups.

• Pregnancy: contraindicated.

• Breastfeeding: avoid.

• Regional: availability of this combination varies, and it may be the only available dopaminergic drug in some settings.

Formulations. Capsules with levodopa/benserazide of 50/12.5, 100/25 and 200/50 mg. Dispersible tablets 50/12.5 and 100/25 mg. Modified-release capsules 100/25 mg.

Preparation. Take 30 minutes before or 1 hour after meals where possible, with a small snack if nausea occurs. Dispersible tablets are mixed with water.

Monitoring.

• Motor diary, lying and standing blood pressure, mental state, impulse control and weight.

• Blood count, kidney and liver function and glucose periodically. Skin examination for melanoma risk.

Stopping. Do not stop abruptly. Taper gradually under supervision.

Referral and escalation. Refer for motor fluctuations, disabling dyskinesia, psychosis or falls. Refer urgently for suspected parkinsonism-hyperpyrexia syndrome.