Levodopa Preparations

Levodopa preparations deliver the dopamine precursor across the blood-brain barrier where it is converted to dopamine. A peripheral decarboxylase inhibitor (carbidopa or benserazide) is always added to reduce nausea and hypotension and lower the dose needed.

Pharmacokinetics. Absorbed in the proximal small bowel by a saturable amino acid transporter and competes with protein. Plasma half life is 1 to 2 hours, which explains the fluctuations seen in advanced disease. Gastric emptying delays onset.

• Levodopa with carbidopa (ratio 4:1 or 10:1): start 100/25 mg three times daily, increase weekly; usual 300 to 800 mg of levodopa daily in 3 to 4 doses; maximum carbidopa 200 mg daily.
• Levodopa with benserazide (4:1): start 50/12.5 mg three times daily; usual 300 to 800 mg of levodopa daily.
• Controlled release forms: smoother levels, less predictable onset; used at night.
• Dispersible forms: rapid onset for morning off periods and delayed on.
• Inhaled levodopa 84 mg for off episodes, up to 5 doses daily.
• Levodopa with carbidopa intestinal gel or subcutaneous infusions: specialist advanced therapy.

Differences. Carbidopa at a daily dose of 70 to 100 mg is needed to prevent peripheral nausea. Controlled release forms have lower bioavailability.

• Initial treatment: start low, increase every 1 to 2 weeks to the lowest dose with good function.
• Dosing: take 30 minutes before or 60 minutes after meals; if nausea occurs, take with a small carbohydrate snack and add domperidone 10 mg three times daily for 1 to 2 weeks.
• Wearing-off: shorter dosing intervals (every 3 to 4 hours), add entacapone or rasagiline, or use dispersible forms.
• Nil by mouth: nasogastric levodopa or a rotigotine patch.

Selection. Do not delay levodopa from fear of motor complications; untreated disability causes harm.

Contraindications. Non-selective MAO inhibitors (stop 2 weeks before). Narrow-angle glaucoma. Suspicious undiagnosed skin lesions or a history of melanoma.

Adverse effects. Nausea, vomiting, orthostatic hypotension, dyskinesia, hallucinations, vivid dreams, sleepiness and sudden sleep onset, impulse control disorders, dopamine dysregulation syndrome, and dark urine or sweat. Long-term use can cause vitamin B12 deficiency and neuropathy through raised homocysteine.

Interactions. Dopamine antagonists oppose levodopa. Iron salts and high-protein meals reduce absorption. Antihypertensives add to hypotension. Selective MAO-B inhibitors can be combined.

Special groups.

• Pregnancy: avoid unless essential.
• Breastfeeding: may suppress lactation; avoid.
• Older adults: start at the lowest dose; hallucinations and hypotension are more common.
• Kidney and liver impairment: no formal adjustment; titrate carefully.
• Regional: carbidopa-levodopa and benserazide-levodopa generics may differ in availability; do not substitute without review.

Monitoring. Response diary, lying and standing blood pressure, dyskinesia, mental state and impulse control, vitamin B12, and periodic skin examination.

Referral and escalation. Motor fluctuations lasting more than 2 hours off each day or troublesome dyskinesia despite optimised oral therapy need specialist review for advanced therapy.