Section 03 · Monograph
Carbidopa-levodopa
Reviewed Nov 2026FDA label
SinemetDopamine precursor
- Forms
- IR: 10/100, 25/100, 25/250mg | CR: 25/100, 50/200mg | ODT: 10/100-25/250mg
- Dose
- TID-5x/day, titrate to effect
- MOA
- Levodopa→dopamine; carbidopa blocks peripheral breakdown
Indications
- Idiopathic Parkinson's diseaseFDA-labeled
- Postencephalitic parkinsonismFDA-labeled
- Symptomatic parkinsonism following carbon monoxide poisoning or manganese intoxicationFDA-labeled
Mechanism of Action
- Levodopa crosses the blood-brain barrier and is converted to dopamine by dopa-decarboxylase, replenishing striatal dopamine
- Carbidopa is a peripheral dopa-decarboxylase inhibitor that does not cross the blood-brain barrier — blocks peripheral conversion of levodopa to dopamine, reducing peripheral side effects (nausea, hypotension) and increasing levodopa available to the CNS
Full Dosing
Adult / usual
- Immediate-release: start 25/100mg TID, titrate by 1 tablet/day every 1-2 days as needed and tolerated
- Typical maintenance: 300-800mg levodopa/day divided TID to 5x/day
- Take with food if nausea occurs, but high-protein meals may reduce absorption/efficacy in advanced disease — timing relative to meals should be individualized
- Never discontinue abruptly
Pediatric
- Not indicated for pediatric parkinsonism outside of rare specialist-guided use
Contraindications
- Concurrent nonselective MAOI use, or use within 2 weeks of discontinuation — risk of hypertensive crisis
- Narrow-angle glaucoma
- Suspicious undiagnosed skin lesions or history of melanoma — levodopa may activate malignant melanoma
Drug Interactions
- Nonselective MAOIs contraindicated
- Antipsychotics/dopamine antagonists may reduce efficacy and worsen parkinsonism
- High-protein diets and large neutral amino acids can compete for intestinal absorption and blood-brain barrier transport
- Iron salts may reduce bioavailability of levodopa
Adverse Effects
- Nausea, dyskinesia, orthostatic hypotension
- Hallucinations/psychosis, particularly in elderly patients or those with underlying dementia
- Somnolence and sudden sleep onset episodes — caution with driving/operating machinery
- Impulse control disorders: pathological gambling, hypersexuality, compulsive eating or shopping
- Abrupt dose reduction or discontinuation risks a neuroleptic-malignant-like syndrome — hyperthermia, rigidity, altered mental status
Monitoring Parameters
- Motor fluctuations and dyskinesia over time
- Blood pressure, particularly for orthostatic hypotension
- Mental status and impulse-control behaviors
- Periodic liver function tests and CBC with long-term use
Pregnancy & Lactation
- Limited human data available
- Use only if potential benefit justifies potential risk to the fetus