Stalevo 50 (carbidopa/levodopa/entacapone)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT); concomitant administration of entacapone with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased and more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor.
Levodopa is the levorotatory isomer of dihydroxyphenylalanine and the metabolic precursor of dopamine, and carbidopa is a decarboxylase inhibitor that inhibits the peripheral decarboxylation of levodopa to dopamine.
Entacapone is a selective and reversible inhibitor of COMT that is structurally and pharmacologically related to tolcapone. The drugs are nitrocatechols and are chemically and pharmacologically unrelated to other currently available antiparkinsonian agents (e.g., levodopa, carbidopa, dopamine-receptor agonists, selective MAO-B inhibitors). However, unlike tolcapone, entacapone has not been associated with hepatotoxicity (e.g., drug-induced hepatitis, fatal liver failure).
In humans, entacapone inhibits the COMT enzyme in peripheral tissues. The effects of the drug on central COMT activity in humans have not been studied. For information on COMT, see Pharmacology in Tolcapone 28:36.12.
Concomitant administration of entacapone with levodopa and a decarboxylase inhibitor (e.g., carbidopa) results in increased and more sustained plasma levodopa concentrations compared with administration of levodopa and a decarboxylase inhibitor. Sustained levodopa concentrations presumably result in more consistent dopaminergic stimulation, resulting in greater reduction in the manifestations of parkinson disease. Entacapone lacks antiparkinsonian activity when administered alone.
Entacapone is almost completely metabolized prior to excretion with only 0.2% of a dose excreted unchanged in urine. The main metabolic pathway is isomerization followed by glucuronidation to an inactive conjugate. Biliary excretion apparently is the principal route of elimination of the drug and its metabolites.
USES: This combination medication is used to treat symptoms of Parkinson's disease (such as shakiness, stiffness, difficulty moving). Parkinson's disease is thought to be caused by too little of a naturally occurring substance (dopamine) in the brain. Levodopa changes into dopamine in the brain, helping to control movement.
Carbidopa and entacapone prevent the breakdown of levodopa in the bloodstream so more levodopa can enter the brain. Carbidopa can also reduce some of levodopa's side effects such as nausea and vomiting.
Generic name: carbidopa/levodopa/entacapone
Pronunciation: (KAR-bi-DOE-pa/LEE-vo-DOE-pa/en-TAK-a-pone)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Stalevo 50:
- Idiopathic Parkinsonism
Also known as: Paralysis Agitans, Primary Parkinson's Disease.
Dosing
The recommended dosage of entacapone is 200 mg administered with each levodopa-carbidopa dose up to a maximum of 8 times daily (1.6 g daily). Clinical experience with dosages exceeding 1.6 g daily is limited.
To optimize patient response, reductions in the daily levodopa dosage or frequency of administration may be necessary. In clinical studies, most patients (58%) who were receiving 800 mg or more of levodopa daily or who had moderate or severe dyskinesias before initiating entacapone therapy required a reduction in levodopa dosage; the average reduction in daily levodopa dosage was about 25%.
Levodopa and carbidopa are administered orally as fixed-combination or single-entity (carbidopa only) conventional tablets, orally disintegrating tablets, extended-release tablets, or extended-release capsules. Levodopa also is commercially available as a powder for oral inhalation. Carbidopa-levodopa enteral suspension is administered by direct intestinal infusion through a nasojejunal (NJ) tube or a percutaneous endoscopic gastrojejunostomy (PEG-J) tube.
In patients with moderate to severe motor fluctuations, better global improvement may be achieved in some patients when extended-release rather than conventional tablet preparations of carbidopa-levodopa are used. However, some studies have not found a substantial difference in ''off'' time between extended-release and immediate-release tablet preparations in such patients. In patients without motor fluctuations, the preparations were comparably effective but less frequent dosing was required with the extended-release preparation. Use of the extended-release capsule formulation of carbidopa-levodopa has been shown to improve ''off'' time compared with immediate-release preparations in patients with advanced parkinson disease. (See Absorption under Pharmacokinetics.)
Patients receiving other antiparkinsonian agents may continue taking these drugs while carbidopa-levodopa is administered; however, dosage adjustments of these drugs may be necessary.
Whenever a general anesthetic is required, levodopa may be continued as long as the patient is able to take fluids and medication orally. If therapy is interrupted, the patient should be observed for neuroleptic malignant syndrome and the usual daily dose may be given as soon as the patient can take oral medication.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to entacapone or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 1% or more of patients receiving entacapone and more frequently than placebo include dyskinesia, nausea, hyperkinesia, diarrhea, urine discoloration, hypokinesia, dizziness, abdominal pain, constipation, fatigue, vomiting, back pain, dry mouth, dyspnea, increased sweating, anxiety, somnolence, dyspepsia, flatulence, purpura, asthenia, taste perversion, agitation, gastritis, GI disorder, and bacterial infection.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of entacapone have not been established in pediatric patients.
In animal reproduction studies in which entacapone was administered to pregnant rats and rabbits during the period of organogenesis, no evidence of teratogenicity was observed; however, there was an increased frequency of abortions, resorptions, decreased fetal weights, and fetal variations. When the drug was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies was observed; exposure to the drug during later stages of gestation and throughout lactation produced no evidence of developmental impairment in the offspring.
Entacapone has not been studied in pregnant women; therefore, the drug should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.
There are no adequate and well-controlled studies of levodopa and carbidopa in pregnant women. Reproduction studies in rodents using levodopa and carbidopa at dosages approximately 5 and 2 times greater than the maximum human dosage, respectively, have shown adverse effects on fetal and postnatal growth and viability, and studies in rabbits using the drug alone or in conjunction with carbidopa have shown visceral and skeletal malformations. Levodopa and carbidopa should be administered to pregnant women or women who might become pregnant only when the benefits to the mother outweigh the possible risks to the mother and fetus.
Levodopa is distributed into human milk. Carbidopa is distributed into milk in rats; it is not known whether carbidopa is distributed into human milk. Levodopa-carbidopa should be used with caution in nursing women. The known benefits of breast-feeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the infant from the drug or underlying maternal condition.
Entacapone is distributed into milk in rats; caution is advised if the drug is used in nursing women.
No substantial differences in safety or pharmacokinetics of entacapone have been observed relative to younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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