STALEVO 50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STALEVO 50 (STALEVO 50).
Stalevo 50 is a combination of carbidopa, levodopa, and entacapone. Levodopa is converted to dopamine in the brain, replenishing striatal dopamine levels. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing its central availability. Entacapone is a selective, reversible inhibitor of catechol-O-methyltransferase (COMT), reducing peripheral metabolism of levodopa to 3-O-methyldopa, thereby prolonging its half-life.
| Metabolism | Levodopa is metabolized by aromatic L-amino acid decarboxylase (AAAD) and COMT. Carbidopa is primarily excreted unchanged. Entacapone is glucuronidated by UGT1A9 and UGT2B7, with minor cytochrome P450 (CYP2C9, CYP3A4) involvement. |
| Excretion | Renal: ~80% (carbidopa: 70% unchanged, levodopa metabolites: 70-80% as HVA/DOPAC); Fecal: ~20% (entacapone: primarily as glucuronide conjugates via bile). |
| Half-life | Levodopa: 1-3 hours (short half-life necessitates frequent dosing; COMT inhibition by entacapone prolongs elimination half-life by ~1-2 hours vs levodopa alone). Carbidopa: 1-2 hours. Entacapone: 0.4-0.7 hours (terminal half-life in plasma). |
| Protein binding | Levodopa: ~10-33% (albumin); Carbidopa: ~36% (albumin); Entacapone: ~98% (mainly albumin). |
| Volume of Distribution | Levodopa: 0.5-1.2 L/kg (widely distributed, including CNS); Carbidopa: ~0.2 L/kg (limited CNS penetration); Entacapone: 0.3-0.4 L/kg (primarily peripheral). |
| Bioavailability | Oral: Levodopa: 30-50% (when combined with carbidopa, peripheral decarboxylation inhibited, bioavailability increased ~10-fold vs levodopa alone); Carbidopa: 40-70%; Entacapone: 35-45% (taken with levodopa/carbidopa). |
| Onset of Action | Oral: 30-60 minutes (levodopa crosses BBB rapidly; clinical effect on Parkinsonian symptoms). |
| Duration of Action | Oral: 4-6 hours (plasma levodopa levels maintained; entacapone extends duration of therapeutic levodopa levels by ~1 hour compared to levodopa/carbidopa alone). |
One tablet (carbidopa 12.5 mg, levodopa 50 mg, entacapone 200 mg) orally, up to 8 tablets per day in divided doses, adjusting based on individual response. Maximum levodopa dose: 800 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild-to-moderate renal impairment (GFR 30-89 mL/min). Not recommended for severe renal impairment (GFR <30 mL/min) or dialysis due to lack of data. |
| Liver impairment | Contraindicated in Child-Pugh Class C (severe hepatic impairment). For Child-Pugh Class A or B, no specific dose adjustment; use with caution and monitor liver function. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). No dosing guidelines available. |
| Geriatric use | Initiate at low doses and titrate slowly due to increased sensitivity and risk of adverse effects (e.g., hallucinations, falls). Monitor renal function (age-related decline) and avoid in severe renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STALEVO 50 (STALEVO 50).
| Breastfeeding | Levodopa and carbidopa are excreted in breast milk. Infant exposure is low; minimal risk of adverse effects. M/P ratio not established. Caution in breastfeeding; monitor infant for drowsiness or poor feeding. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited data; animal studies show fetal abnormalities (skeletal and visceral malformations) at high doses. Second and third trimester: Increased risk of fetal bradycardia and reduced placental perfusion due to levodopa. Avoid unless benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
Concurrent use with non-selective monoamine oxidase inhibitors (MAOIs); narrow-angle glaucoma; pheochromocytoma; history of malignant melanoma or undiagnosed skin lesions; hypersensitivity to any component.
| Precautions | Falling asleep during activities of daily living; hypotension (postural); hallucinations; psychosis; impulse control disorders; dyskinesias; melanoma risk; neuroleptic malignant syndrome; caution in patients with severe cardiovascular, hepatic, or renal disease; avoid sudden discontinuation. |
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| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate; fetal heart rate monitoring for bradycardia. Assess fetal growth with ultrasound. Observe for signs of preeclampsia or gestational hypertension. |
| Fertility Effects | No evidence of impaired fertility in humans. Animal studies show reduced fertility at high doses. Potential for hormonal changes affecting menstrual regularity. |