Antiparkinsonian (dopamine precursor)
Levodopa is the most effective treatment for Parkinson's disease: it is converted in the brain into dopamine, the substance that is lacking in this disease, and relieves motor symptoms (tremor, rigidity, slowness). It is usually used in combination with carbidopa to reduce side effects and improve efficacy.
Also known as: Levodopa, L-dopa
Levodopa + metoclopramide: metoclopramide may increase levodopa bioavailability (gastric emptying), but antagonises the antiparkinsonian effect through its dopaminergic antagonist effects (QUADRO 2).
Metoclopramide is a dopaminergic (D2) antagonist and may counteract the therapeutic effect of levodopa in Parkinson's disease patients, worsening motor symptoms; both drugs can also cause dyskinesias. QUADRO 2 of Annex 7 records this interaction in the levodopa section. In parkinsonian patients, avoid metoclopramide as an antiemetic; prefer domperidone (which crosses the blood-brain barrier less) or other non-dopaminergic antiemetics. If metoclopramide is unavoidable, use it for a short period and watch for motor worsening. The risk is higher in patients on high levodopa doses or advanced disease.
Metoclopramide + levodopa: dopaminergic antagonism — reduced antiparkinsonian effect and risk of worsening symptoms; avoid.
Metoclopramide increases gastric motility (increases levodopa absorption) but is a D2 dopaminergic antagonist — it may worsen parkinsonian symptoms (QUADRO 2, Levodopa: agents that alter GI motility may alter the degree of intra-luminal degradation; the combination with dopaminergic antagonist agents may lead to antagonistic effects).
Watch for worsening parkinsonian symptoms.
Worsening tremor/rigidity in a parkinsonian patient taking metoclopramide.
Avoid the combination in Parkinsons disease; use a non-dopaminergic prokinetic (e.g. domperidone has less central passage, but with caution) or an alternative.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Levodopa)
SINEMET label (Drug Interactions): protein-rich meals may reduce levodopa absorption (competition with amino acids at intestinal transport and the blood-brain barrier) — the response to the drug may vary with the protein content of meals.
Inform the patient about possible response variation with protein-rich meals; keep meals consistent and adjust the dose according to clinical response.
DailyMed/FDA (NIH/NLM) — Sinemet, Drug Interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b17b028-964a-473c-823d-81423535bd66
SINEMET label (CONTRAINDICATIONS): contraindicated in narrow-angle glaucoma (dopamine may increase intraocular pressure).
Contraindicated in narrow-angle glaucoma.
DailyMed/FDA (NIH/NLM) — Sinemet, CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b17b028-964a-473c-823d-81423535bd66
SINEMET label (Pregnancy): no teratogenic effects in mice up to 20× the maximum recommended human dose; visceral and skeletal malformations in rabbits at all doses tested; no adequate and well-controlled studies in pregnant women.
Potential risk (malformations in rabbits); use only if benefit justifies risk.
No specific breastfeeding data in the label; assess risk/benefit (levodopa is excreted in human milk — literature data).
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Sinemet label (ORGANON), Pregnancy section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b17b028-964a-473c-823d-81423535bd66 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Levodopa may suppress lactation; it is present in milk; avoid.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Dopamine precursor: crosses the blood-brain barrier and is decarboxylated to dopamine in the brain; carbidopa reduces the required dose by ~75% and increases levodopa plasma levels and half-life (SINEMET label Pharmacokinetics).
Decarboxylation of levodopa to dopamine (DOPA decarboxylase) — central dopaminergic replenishment; carbidopa inhibits peripheral decarboxylase.
Oral absorption; iron salts form chelates with levodopa and carbidopa, reducing bioavailability (Drug Interactions).
Metabolised by decarboxylation and O-methylation (COMT); carbidopa increases the plasma half-life of levodopa from ~50 min to ~1.5 h.
Plasma half-life of levodopa: ~50 minutes without carbidopa; ~1.5 hours with carbidopa (SINEMET label Pharmacokinetics).
