entacapone/levodopa/carbidopa (Stalevo)
Classes: Antiparkinson Agents, COMT Inhibitors; Antiparkinson Agents, Dopamine Agonists; Decarboxylase Inhibitors
Dosing and uses of Stalevo (entacapone/levodopa/carbidopa)
Dosing Forms & Strength
levodopa/carbidopa/entacapone
tablet
- 50mg/12.5mg/200mg
- 75mg/18.75mg/200mg
- 100mg/25mg/200mg
- 125mg/31.25mg/200mg
- 150mg/37.5mg/200mg
- 200mg/50mg/200mg
Parkinson Disease
Substitute an equal levodopa dose with Stalevo as patient's dose at transfer
Maintenance: Titrate as necessary
Carbidopa should be 70-100 mg/day; not to exceed 200 mg/day
Not to exceed 8 tablets/day divided q4-8hr while awake
Food increases levodopa absorption
Monitor hepatic, hematopoietic, cardiovascular, renal function
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
Parkinson Disease
Substitute an equal levodopa dose with Stalevo as patient's dose at transfer
Maintenance: Titrate as necessary
Carbidopa should be 70-100 mg/day; not to exceed 200 mg/day
Not to exceed 8 tablets/day divided q4-8hr while awake
Food increases levodopa absorption
Monitor hepatic, hematopoietic, cardiovascular, renal function
Stalevo (entacapone/levodopa/carbidopa) adverse (side) effects
>10%
Entacapone
- Dyskinesia (25%)
- Nausea (14%)
- Diarrhea (10%)
- Hyperkinesia (10%)
- Urine discoloration (10%)
1-10%
Entacapone
- Hypokinesia (9%), dizziness (8%), Fatigue (6%), hallucinations (1-4%), anxiety (2%), somnolence (2%), asthenia (2%), agitation (1%)
- Increased sweating (2%)
- Purpura (2%)
- Abdominal pain (8%), constipation (6%), vomiting (4%), dry mouth (3%), dyspepsia (2%), flatulence (2%), taste perversion (1%), gastritis (1%)
- Back pain (4%)
- Dyspnea (3%)
- Bacterial infection (1%)
Frequency not defined
Levodopa/Carbodopa
- Edema
- Agitation, anxiety, ataxia, bruxism, confusion, daytime somnolence decreased attention span, dyskinesia, dystonia, euphoria, insomnia, fainting, fatigue, increased trembling of hands, insouciance, malaise, memory loss, nightmares, nervousness, restlessness, trismus, vivid dreams
- Alopecia, hot flushes, increased &/or dark perspiration, skin eruptions
- Abdominal pain & discomfort, burning feeling in tongue, constipation, diarrhea, dysgeusia, dry mouth, dysphagia, hiccups, meteorism, sialorrhea, nausea, weight loss
- Muscular spasms, muscular cramp
- Hematuria, dark urine, incontinence, priapism, urine retention
- Blurred vision, diplopia, dilated pupil, oculogyric problems
Entacapone
- Postural hypotension
- Insomnia
- Confusion
Warnings
Contradindications
Hypersensitivity
Concurrency with nonselective MAOIs (discontinue 2 weeks before starting treatment)
Narrow angle glaucoma
Undiagnosed skin lesions, history of melanoma
Cautions
Hepatic disease, severe cardiovascular/pulmonary disease, bronchial asthma, renal/endocrine disease, open-angle glaucoma
Age >75 yr
History/active psychoses, history of MI or peptic ulcer
Residual atrial, nodal, ventricular arrhythmias
Risk of uncontrollable sexual, gambling or other urges
May be linked to higher melanoma risk in patient with Parkinson disease
May cause NMS if reduced abruptly or discontinued
Risk of syncope
Risk of developing prostate cancer
Diarrhea may occur and be associated entacapone; may cause weight loss, dehydration, and hypokalemia; if severe, may be a sign of drug-induced microscopic colitis
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Stalevo (entacapone/levodopa/carbidopa)
Mechanism of action
Levodopa: Crosses blood-brain barrier & converts to dopamine
Carbidopa: Inhibits decarboxylation or breakdown of peripheral levodopa
Entacapone: Selective & reversible inhibitor of COMt
Pharmacokinetics
Absorption
- levodopa: rapid
- carbidopa: slightly slower than levodopa/entacapone
- entacapone: rapid
Peak plasma time
- levodopa: 0.6-2.4 hr
- carbidopa: 2.5-3.4 hr
- entacapone: 1-1.2 hr
Half Life
- levodopa: 1.7 hr
- carbidopa: 1.6-2 hr
- entacapone: 0.8-1 hr
Protein Bound
- levodopa: 10-30%
- carbidopa: 36%
- entacapone: 98%
Metabolites
- levodopa: dopamine, homovanillic acid
- carbidopa: alpha-methyl-3-methoxy-4-hydroxyphenyl propionic acid & alpha-methyl-3,4-dihydroxyphenylpropionic acid
- entacapone: cis-isomer
Elimination
- levodopa: urine: 80-85%
- carbidopa: 30% unchanged in urine
- entacapone: Urine (10%); feces (90%)