STALEVO 75
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STALEVO 75 (STALEVO 75).
STALEVO 75 is a combination product containing carbidopa, levodopa, and entacapone. Levodopa is the metabolic precursor of dopamine, which crosses the blood-brain barrier and is converted to dopamine in the brain, thereby ameliorating dopamine deficiency in Parkinson's disease. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing levodopa availability to the brain. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), primarily in the periphery, which prolongs the plasma half-life of levodopa.
| Metabolism | Levodopa is extensively metabolized by decarboxylation via aromatic L-amino acid decarboxylase (AADC) and by O-methylation via catechol-O-methyltransferase (COMT). Carbidopa is metabolized by CYP2D6 and other pathways. Entacapone is primarily metabolized by glucuronidation and to a lesser extent by COMT and CYP2C9. |
| Excretion | Carbidopa: 70% renal (metabolites), 30% fecal. Levodopa: 80% renal (metabolites), 20% fecal. Entacapone: 90% fecal, 10% renal. |
| Half-life | Levodopa: 1.5-2 hours (alone). With carbidopa: 1.5 hours. Entacapone: 0.4-0.7 hours (elimination half-life). Clinical context: Entacapone prolongs levodopa half-life by ~30% via COMT inhibition. |
| Protein binding | Levodopa: <10% bound (plasma proteins). Carbidopa: 36% bound (albumin). Entacapone: 98% bound (primarily albumin). |
| Volume of Distribution | Levodopa: 1.6 L/kg (large, indicates extensive tissue distribution). Carbidopa: Not well documented; limited distribution. Entacapone: 0.3-0.5 L/kg (moderate). |
| Bioavailability | Oral: Levodopa (with carbidopa) ~99% (carbidopa inhibits peripheral decarboxylation). Entacapone: 35% (high first-pass metabolism). |
| Onset of Action | Oral: Levodopa (with carbidopa) clinical benefit begins within 30-60 minutes, peak effect at 1-2 hours. |
| Duration of Action | Oral: Levodopa effect duration 3-6 hours (entacapone extends by ~1.3 hours per dose). Clinical notes: Dosing interval tailored to motor fluctuations. |
Oral, 1 tablet (levodopa 75 mg, carbidopa 18.75 mg, entacapone 200 mg) taken 3 to 4 times daily. Maximum recommended dose: 10 tablets per day (levodopa 750 mg, carbidopa 187.5 mg, entacapone 2000 mg). Dose should be adjusted based on individual response and tolerability.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-80 mL/min: no dose adjustment required. For GFR <30 mL/min: not recommended due to lack of data. Contraindicated in patients undergoing hemodialysis. |
| Liver impairment | Child-Pugh Class A (mild): no dose adjustment. Child-Pugh Class B (moderate): use with caution; dose reduction may be considered. Child-Pugh Class C (severe): contraindicated. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Not recommended for use in patients under 18 years of age. |
| Geriatric use | Elderly patients (≥65 years) may require lower doses due to increased sensitivity to dopaminergic effects and higher risk of adverse events (e.g., hallucinations, orthostatic hypotension). Initiate therapy at the lower end of the dosing range and titrate slowly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STALEVO 75 (STALEVO 75).
| Breastfeeding | Levodopa is excreted into breast milk; carbidopa and entacapone are likely present (no specific M/P ratio available). Milk concentrations of levodopa are low (M/P ratio ~0.2-0.3). Theoretical risk of infant dyskinesia or developmental effects. Manufacturers recommend caution; consider alternative therapy or avoid breastfeeding during treatment, especially for premature or low-birth-weight infants. |
| Teratogenic Risk | STALEVO 75 (carbidopa/levodopa/entacapone) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal abnormalities (skeletal and visceral) at high doses. Second and third trimesters: Risk of fetal harm cannot be excluded; use only if maternal benefit outweighs potential fetal risk. Case reports suggest possible association with fetal levodopa effects (e.g., transient dyskinesia). Entacapone component: Animal studies indicate increased fetal resorptions and reduced fetal weight at maternally toxic doses. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent use of non-selective monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine)","Narrow-angle glaucoma","Suspicious undiagnosed skin lesions or history of melanoma (levodopa may activate malignant melanoma)","History of neuroleptic malignant syndrome (NMS) or non-traumatic rhabdomyolysis related to entacapone","Severe hepatic impairment (entacapone component)","Known hypersensitivity to any component of the product"]
| Precautions | ["May cause falling asleep during activities of daily living, including driving, which may result in accidents","May cause hallucinations and psychosis-like behavior","May cause or exacerbate dyskinesia","Risk of hypotension, especially orthostatic hypotension","May cause impulse control disorders (e.g., compulsive gambling, hypersexuality)","May cause gastrointestinal bleeding (entacapone component)","May cause neuroleptic malignant syndrome (NMS) upon abrupt discontinuation or dose reduction","May cause rhabdomyolysis","Metabolite of entacapone may discolor urine, sweat, and other bodily fluids (reddish-brown)","Avoid abrupt withdrawal to prevent withdrawal-emergent hyperpyrexia and confusion"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, liver function tests, and complete blood counts periodically. Assess for signs of neuroleptic malignant syndrome-like symptoms (e.g., hyperpyrexia, rigidity). Fetal monitoring: Regular ultrasound for growth and anatomy; consider nonstress test/biophysical profile in third trimester if maternal condition unstable. Monitor for fetal movement; report any decrease. |
| Fertility Effects | Levodopa may alter menstrual cyclicity and reduce prolactin levels, potentially affecting fertility transiently. Entacapone has no known direct fertility effects. Carbidopa's effect is minimal. In males, levodopa may improve libido but no specific effect on spermatogenesis. No systematic fertility studies in humans. |