STALEVO 200
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STALEVO 200 (STALEVO 200).
STALEVO 200 contains carbidopa, levodopa, and entacapone. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing levodopa availability to the brain. Levodopa is decarboxylated to dopamine in the brain, restoring dopaminergic activity in the striatum. Entacapone inhibits catechol-O-methyltransferase (COMT), reducing peripheral metabolism of levodopa and prolonging its half-life.
| Metabolism | Levodopa is metabolized primarily by aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT). Carbidopa inhibits decarboxylation but is itself metabolized. Entacapone is metabolized via glucuronidation (UGT1A9, UGT2B7) and to a minor extent by COMT. |
| Excretion | Carbidopa: 70% renal (unchanged and metabolites), 30% fecal. Levodopa: 70-80% renal (metabolites), <10% fecal. Entacapone: 90% fecal (unchanged and metabolites), 10% renal. |
| Half-life | Levodopa: 1.3 hours (with carbidopa). Entacapone: 0.4-0.7 hours. Carbidopa: 1-2 hours. Terminal half-life of levodopa is extended to ~1.5-2 hours in combination; clinical dosing is every 4-6 hours. |
| Protein binding | Levodopa: 10-15% bound (albumin). Carbidopa: 36% bound. Entacapone: 98% bound (albumin). |
| Volume of Distribution | Levodopa: 0.9-1.6 L/kg; carbidopa: 1.3 L/kg; entacapone: 0.3 L/kg. Levodopa distributes widely, including CNS. |
| Bioavailability | Oral: levodopa bioavailability 30-40% with carbidopa (vs 10% alone). Carbidopa: 40-70%. Entacapone: 35% (extensive first-pass metabolism). |
| Onset of Action | Oral: levodopa appears in plasma within 0.5-1 hour; clinical effect (motor response) typically 0.5-1 hour. |
| Duration of Action | Oral: levodopa motor response duration 4-6 hours; entacapone extends levodopa half-life and duration by ~1 hour per dose. |
One tablet (levodopa 200 mg, carbidopa 50 mg, entacapone 200 mg) administered orally 3 to 4 times daily, adjusted based on response and tolerability.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (GFR <25 mL/min). For GFR 25–50 mL/min, use with caution; maximum levodopa dose 600 mg/day. No adjustment for GFR >50 mL/min. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce levodopa dose by 25-50%. Child-Pugh Class C: Avoid use (entacapone contraindicated). |
| Pediatric use | Not recommended for pediatric patients (safety and efficacy not established). |
| Geriatric use | Start at lower end of dosing range (e.g., one tablet twice daily) due to increased sensitivity to levodopa and higher risk of dyskinesia, hallucinations, and hypotension; titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STALEVO 200 (STALEVO 200).
| Breastfeeding | Levodopa is excreted in breast milk (M/P ratio not well established); carbidopa and entacapone excretion unknown. Potential for adverse effects in nursing infant (e.g., hypotonia, growth suppression). Decision to breastfeed should consider maternal need for therapy and infant monitoring. |
| Teratogenic Risk | First trimester: Animal studies with levodopa/carbidopa show fetal skeletal malformations at high doses; human data insufficient but risk cannot be excluded. Second/third trimester: Limited human data; potential for fetal distress from maternal hypotension. Entacapone: No teratogenic effects in animal studies; no adequate human studies. Overall risk cannot be ruled out; use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent use with nonselective monoamine oxidase inhibitors (MAOIs)","Narrow-angle glaucoma","History of malignant melanoma","Hypersensitivity to any component of the formulation","Severe cardiovascular or pulmonary disease (relative)","Bronchial asthma (relative)","Endocrine disease (relative)","Peptic ulcer disease (relative)","History of convulsions (relative)"]
| Precautions | ["May cause or exacerbate dyskinesias","May cause orthostatic hypotension","May cause hallucinations and psychotic-like behavior","May cause impulse control disorders","May cause serotonin syndrome when used with serotonergic drugs","May cause withdrawal-emergent hyperpyrexia and confusion with abrupt dose reduction or discontinuation","May cause sleepiness and sudden sleep onset","May cause rhabdomyolysis","May cause gastrointestinal bleeding with concomitant iron salts","Not recommended for patients with narrow-angle glaucoma","May cause melanoma; patients should be monitored","Pregnancy: Use only if clearly needed","Lactation: Caution advised"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of dyskinesia or neuroleptic malignant syndrome. Fetal monitoring via ultrasound for growth and well-being if used in second/third trimester. Assess for neonatal withdrawal symptoms (e.g., irritability, dystonia) after delivery. |
| Fertility Effects | No definitive evidence of impaired fertility in humans. Animal studies with levodopa/carbidopa showed reduced fertility at high doses; entacapone had no effect. Clinical impact uncertain. |