STALEVO 125
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STALEVO 125 (STALEVO 125).
Stalevo 125 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, replenishing striatal dopamine levels. Carbidopa inhibits peripheral decarboxylation of levodopa, increasing its availability to the brain. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), primarily in the periphery, which reduces the metabolism of levodopa to 3-O-methyldopa, prolonging the half-life of levodopa.
| Metabolism | Levodopa is extensively metabolized by aromatic L-amino acid decarboxylase (AAAD) and COMT. Carbidopa is metabolized by AAAD. Entacapone is metabolized via glucuronidation (UGT1A9, UGT2B7) and to a minor extent by CYP2C9 and CYP3A4. |
| Excretion | Levodopa: renal excretion of metabolites (dopamine, DOPAC, HVA) accounts for >70% of dose; <1% unchanged. Carbidopa: renal excretion of unchanged drug (~30%) and metabolites (~70%). Entacapone: primarily fecal excretion (~90%) with ~10% renal; entacapone glucuronide and unchanged drug in urine. |
| Half-life | Levodopa: 1-3 hours (short half-life necessitates frequent dosing with carbidopa to reduce peripheral metabolism). Carbidopa: 1-2 hours (not clinically significant alone). Entacapone: 0.4-0.7 hours (short half-life; acts primarily during absorption phase of levodopa). |
| Protein binding | Levodopa: ~10% bound to plasma proteins (low). Carbidopa: ~36% bound (mainly albumin). Entacapone: ~98% bound (mainly albumin). |
| Volume of Distribution | Levodopa: 1.4-1.7 L/kg (extensive tissue distribution, including CNS via L-amino acid transporter). Carbidopa: 0.43 L/kg (limited to extracellular fluid). Entacapone: 0.27-0.35 L/kg (moderate distribution). |
| Bioavailability | Levodopa: ~80-100% when administered with carbidopa (without carbidopa, bioavailability is ~10% due to peripheral decarboxylation). Carbidopa: ~50% (absorbed but extensively metabolized). Entacapone: ~35% (low absolute bioavailability due to first-pass metabolism). |
| Onset of Action | Oral: 30-60 minutes for motor response (levodopa absorption and central effect). |
| Duration of Action | Oral: 4-6 hours for clinical effect on Parkinsonian symptoms (varies with disease progression; possible 'wearing-off' phenomenon). |
One tablet of STALEVO 125 (levodopa 100 mg, carbidopa 25 mg, entacapone 200 mg) orally, one tablet per dose, up to maximum 10 tablets per day. Frequency: typically every 4-6 hours while awake, adjusted based on response.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment for mild to moderate renal impairment (GFR ≥30 mL/min). Avoid use in severe renal impairment (GFR <30 mL/min) or on dialysis due to lack of data. |
| Liver impairment | Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). Use with caution in moderate impairment (Child-Pugh class B), with dose reduction or extended dosing interval as tolerated. |
| Pediatric use | Not recommended for use in pediatric patients (age <18 years) due to lack of safety and efficacy data. |
| Geriatric use | Start at lower end of dosing range; monitor for increased risk of adverse effects such as orthostatic hypotension, hallucinations, and dyskinesias. Use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STALEVO 125 (STALEVO 125).
| Breastfeeding | Levodopa and carbidopa are excreted in human breast milk. The milk-to-plasma ratio (M/P) for levodopa is approximately 1.0; carbidopa M/P ratio not quantified. Potential for infant exposure and adverse effects (e.g., developmental delay, movement disorders). Discontinue breastfeeding or drug based on necessity. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show developmental toxicity (skeletal abnormalities, reduced fetal weight) at maternally toxic doses. Second/third trimester: Risk of fetal distress due to carbidopa/levodopa effects on maternal blood pressure; avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine)","Narrow-angle glaucoma","Hypersensitivity to any component of the product","History of melanoma or suspicious undiagnosed skin lesions","Severe psychotic or psychiatric disorder"]
| Precautions | ["May cause hypotension, syncope, and orthostatic hypotension","Risk of dyskinesias and motor fluctuations","May cause hallucinations, psychosis, or somnolence","May cause impulse control disorders (e.g., pathological gambling, hypersexuality)","May cause hyperpyrexia and confusion (similar to neuroleptic malignant syndrome) with rapid dose reduction or withdrawal","May cause cardiovascular effects including arrhythmias","May cause gastrointestinal bleeding (particularly in patients with history of peptic ulcer)","May cause melanomas (skin examination recommended)","May cause retinal degeneration and melanoma in animal studies","Avoid abrupt discontinuation"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and for signs of dyskinesia. Fetal monitoring includes ultrasound for growth and well-being, especially if used in third trimester. Assess for neonatal withdrawal or extrapyramidal symptoms at birth. |
| Fertility Effects | No specific human studies on fertility. Levodopa may alter prolactin secretion, potentially affecting ovulation. Animal studies show no significant impairment of fertility at therapeutic doses. |