STALEVO 100
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STALEVO 100 (STALEVO 100).
Stalevo 100 is a combination of carbidopa, levodopa, and entacapone. Levodopa is a precursor to dopamine that crosses the blood-brain barrier and is converted to dopamine by aromatic L-amino acid decarboxylase (AAAD), thereby increasing dopamine levels in the brain. Carbidopa inhibits peripheral AAAD, reducing the conversion of levodopa to dopamine outside the brain, which increases the amount of levodopa available for CNS entry and decreases side effects. Entacapone is a reversible inhibitor of catechol-O-methyltransferase (COMT), which reduces the metabolism of levodopa to 3-O-methyldopa, prolonging the half-life and duration of action of levodopa.
| Metabolism | Levodopa is metabolized primarily by AAAD and COMT. Carbidopa is metabolized mainly by AAAD. Entacapone is metabolized via glucuronidation (UGT1A9) and to a minor extent by COMT. |
| Excretion | Renal: ~90% (levodopa metabolites), ~80% (carbidopa unchanged and metabolites); biliary/fecal: minimal |
| Half-life | Levodopa: 1.5-2 h (peripherally); with carbidopa: prolongs to ~2.5 h. Carbidopa: 2-3 h. Clinical context: requires continuous dopaminergic stimulation to avoid motor fluctuations. |
| Protein binding | Levodopa: ~10%; Carbidopa: ~36% bound to albumin. Not significantly displaced by other drugs. |
| Volume of Distribution | Levodopa: 0.9-1.6 L/kg; Carbidopa: 0.8-1.2 L/kg. Reflects distribution into total body water and peripheral tissues. |
| Bioavailability | Levodopa: ~99% with carbidopa (vs. 5-10% alone). Carbidopa: ~40-70% after oral administration. |
| Onset of Action | Oral: 30-60 min; clinical effect correlates with peak plasma levodopa concentrations. |
| Duration of Action | Oral: 4-6 h for antiparkinsonian effect; shorter with disease progression (wearing-off). |
One tablet (carbidopa 25 mg / levodopa 100 mg / entacapone 200 mg) orally three to four times daily, maximum 8 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR 30–89 mL/min: No adjustment required. GFR 15–29 mL/min: Use with caution; no specific dose recommendation. GFR <15 mL/min: Not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Use with caution; reduce dose or extend interval. Class C: Contraindicated. |
| Pediatric use | Not recommended in pediatric patients (<18 years) due to lack of safety and efficacy data. |
| Geriatric use | Initiate at lower end of dosing range; monitor for hypotension, hallucinations, and dyskinesias; adjust levodopa component carefully due to increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STALEVO 100 (STALEVO 100).
| Breastfeeding | Levodopa is excreted in breast milk (M/P ratio not established). Carbidopa and entacapone are likely present in low amounts. Limited human data; potential for adverse effects in infant (e.g., drowsiness, poor feeding). Not recommended during breastfeeding unless essential. |
| Teratogenic Risk | First trimester: Limited data; carbidopa/levodopa and entacapone have not been associated with major congenital malformations in animal studies, but human data are insufficient. Second and third trimesters: Potential risk of fetal harm due to maternal hypotension and uterine contractility changes; levodopa may cause fetal metabolic acidosis. Overall, avoid unless benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concurrent use with non-selective MAO inhibitors (e.g., phenelzine, tranylcypromine)","Hypersensitivity to any component of the drug","Narrow-angle glaucoma"]
| Precautions | ["May cause or exacerbate dyskinesia","May cause hypotension, especially orthostatic hypotension","May cause hallucinations or psychotic-like behavior","Impulse control disorders (e.g., pathological gambling, hypersexuality) have been reported","Sudden onset of sleep without warning (somnolence)","Potential for melanoma, monitor skin lesions","Neuroleptic malignant syndrome (NMS) if rapidly withdrawn","Entacapone may cause diarrhea and discoloration of urine, sweat, or feces"] |
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| Fetal Monitoring | Monitor maternal blood pressure, fetal heart rate, and uterine activity. Assess for signs of fetal distress (e.g., decreased movement). Consider fetal growth scans if prolonged use. Monitor mother for symptoms of neuroleptic malignant syndrome. |
| Fertility Effects | Levodopa may dysregulate prolactin secretion, potentially affecting ovulation and menstrual cycles. Animal studies show no significant fertility impairment, but human data are lacking. No known effect on spermatogenesis. |