Sinemet
Sinemet
Generic Name
Sinemet
Mechanism
- Levodopa crosses the blood‑brain barrier and is decarboxylated to dopamine in dopaminergic neurons.
- Carbidopa competitively inhibits peripheral Aromatic‑L‑amino‑acid decarboxylase (DOPA‑dec), preventing peripheral levodopa metabolism.
- This dual action restores dopaminergic neurotransmission, improving motor control and reducing PD motor symptoms.
Pharmacokinetics
| Parameter | Typical Value (Levodopa) |
| Absorption | Rapid; peak plasma ~1 h after oral dosing |
| Bioavailability | 30–50 % without carbidopa; ↑ with carbidopa |
| Distribution | Large volume; crosses blood‑brain barrier via LAT1 transporter |
| Protein Binding | ~35 % |
| Metabolism | Decarboxylated to dopamine; metabolized by COMT → 3‑O‑MT |
| Elimination | Renal; half‑life 1.5–2 h (free base) |
| Drug–Drug Interaction | COMT inhibitors (entacapone) prolong levodopa action; MAO‑B inhibitors (selegiline) increase levodopa availability |
Indications
- Early to advanced Parkinson’s disease: alleviates bradykinesia, rigidity, rigidity, and tremor.
- Resting tremor and postural instability when levodopa‑responsive.
- Used adjunctively with dopamine agonists or MAO‑B inhibitors to reduce “off” periods.
Contraindications
- Contraindications: known hypersensitivity to levodopa, carbidopa, or formulation excipients.
- Warnings:
- Cardiovascular disease (e.g., hypertension, arrhythmias): monitor blood pressure.
- Psychiatric disorders: risk of hallucinations, delusions, or behavior disorders, especially in elderly or pre‑existing psychiatric conditions.
- Severe hepatic or renal impairment: dosing adjustment may be required.
- Pregnancy: limited data; use only if benefits outweigh risks.
- Precautions: avoid concomitant drugs that increase dopamine levels (e.g., sympathomimetics) without supervision.
Dosing
| Form | Initial Dose | Titration | Max Daily Dose | Notes |
| Tablet (Levodopa 25 mg / Carbidopa 25 mg) | 1–2 tablets twice daily | ↑ 25 mg tablets every 3–4 days as tolerated | 600–800 mg levodopa / 600 mg carbidopa | Start low to mitigate nausea. |
| Tablet (Levodopa 25 mg / Carbidopa 25 mg) | 1 tablet daily | Increase 1 tablet every 3–4 days | 500 mg levodopa / 500 mg carbidopa | For patients with tolerance. |
| Tablet (Levodopa 200 mg / Carbidopa 50 mg) | 1 tablet twice daily | Increase 1 tablet every 3–5 days | 600 mg levodopa / 150 mg carbidopa | Use for moderate to advanced PD. |
| Extended‑release (Levodopa 200 mg / Carbidopa 50 mg) | 1 tablet twice daily | Adjust every 4 days | 600 mg levodopa / 150 mg carbidopa | Fewer peaks, reduced nausea. |
Administration Tips
• Take with a low‑protein meal or fasting 30 min before/after to optimize absorption.
• Avoid large protein meals within 1–2 h before or after dosing to reduce competition at transporter sites.
• Split daily dosing into 3–4 equal portions to smooth plasma levels.
Adverse Effects
| Category | Examples |
| Common | Nausea, vomiting, dizziness, orthostatic hypotension, constipation, dry mouth, headache |
| Serious | Dyskinesia, wearing‑off phenomenon, hallucinations, impulse control disorders (punding, pathological gambling), neuroleptic sensitivity, serotonin syndrome with MAO‑B inhibitors |
Monitoring
- Motor function: Unified Parkinson’s Disease Rating Scale (UPDRS) part III.
- Blood pressure: at least once per visit, especially when starting or escalating dose.
- Weight & nutritional status: monitor for weight loss due to nausea.
- Psychosis assessment: evaluate for hallucinations or delusions quarterly.
- Drug levels (optional): levodopa plasma concentration to guide dose adjustments in refractory cases.
- Gastrointestinal tolerance: document nausea episodes; consider pro‑emetic prophylaxis if needed.
Clinical Pearls
- Protein–Drug Interaction: Levodopa absorption is inhibited by high‑protein meals; a small snack high in protein should be spaced at least 2 h away from dosing.
- Nausea Mitigation: A 10‑mg dose of ondansetron or 10 mg of prochlorperazine administered 30 min before levodopa can significantly reduce nausea, improving adherence.
- Fluctuations Management: Transitioning to extended‑release formulations can decrease motor “off” time and reduce dosage frequency, improving quality of life.
- Drug–Drug Interactions: When adding a COMT inhibitor (entacapone), double the carbidopa component to maintain the levodopa:carbidopa ratio and avoid peripheral side‑effect reversal.
- Neuroleptic Sensitivity: In patients treated with antipsychotics, the “neuroleptic sensitivity” can exacerbate motor symptoms; monitor closely and consider antipsychotic dose reduction or switch to a dopamine antagonist with a lower affinity.
- Monitoring Dyskinesias: Early dyskinesias may signal the need for dose taper or add a dopamine agonist to mask motor fluctuations.
- Elderly Population: Start at the lowest effective dose and titrate slowly (≈25 mg tablets) because older adults have increased sensitivity to levodopa side effects and a higher risk of psychosis.
> Take‑home: Sinemet’s dual composition optimizes CNS dopamine while minimizing peripheral toxicity. Careful meal timing, gradual titration, and diligent monitoring of motor status and neuropsychiatric symptoms ensure safe, effective therapy for Parkinson’s disease.