Parkinson disease: Oral: 200 mg with each dose of levodopa/carbidopa, up to a maximum of 8 times daily (maximum daily dose: 1600 mg daily).
Note: To optimize therapy, the dosage of levodopa may need to be reduced or the dosing interval may need to be extended. Patients taking levodopa ≥800 mg daily or who had moderate-to-severe dyskinesias prior to therapy required an average decrease of 25% in the daily levodopa dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal function was not found to significantly affect the pharmacokinetics of entacapone.
U.S. labeling: There are no dosage adjustments provided in the manufacturer's labeling. Treat with caution and monitor carefully; AUC and Cmax may possibly be doubled.
Canadian labeling: Use is contraindicated.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Comtan: 200 mg [DSC]
Comtan: 200 mg [contains polysorbate 80]
Generic: 200 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Comtan: 200 mg [contains polysorbate 80]
Generic: 200 mg
Always administer in association with levodopa/carbidopa; can be combined with both the immediate and sustained release formulations of levodopa/carbidopa. May be administered without regard to meals. Should not be abruptly withdrawn from patient's therapy due to significant worsening of symptoms.
Parkinson disease: Adjunct to levodopa/carbidopa therapy in patients with idiopathic Parkinson disease who experience “wearing-off” symptoms at the end of a dosing interval
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea (14%)
Neuromuscular & skeletal: Dyskinesia (25%)
1% to 10%:
Cardiovascular: Syncope (1%)
Central nervous system: Dizziness (8%), fatigue (6%), anxiety (2%), drowsiness (2%), agitation (1%), hallucination (≤1%)
Dermatologic: Diaphoresis (increased; 2%)
Gastrointestinal: Diarrhea (10%), abdominal pain (8%), constipation (6%), vomiting (4%), xerostomia (3%), dyspepsia (2%), flatulence (2%), dysgeusia (1%), gastritis (1%), gastrointestinal disease (1%)
Genitourinary: Urine discoloration (brown-orange; 10%)
Hematologic & oncologic: Purpura (2%)
Infection: Bacterial infection (1%)
Neuromuscular & skeletal: Hyperkinesia (10%), hypokinesia (9%), back pain (2% to 4%), weakness (2%)
Respiratory: Dyspnea (3%)
<1%, postmarketing, and/or case reports: Behavioral changes (including psychotic-like behavior), hepatitis (mainly cholestatic features), impulse control disorder (eg, pathological gambling, hypersexuality, spending money), mental status changes, neurological signs and symptoms (hyperpyrexia and confusion [resembling neuroleptic malignant syndrome]), orthostatic hypotension, pulmonary fibrosis, retroperitoneal fibrosis, rhabdomyolysis, sudden onset of sleep
Hypersensitivity to entacapone or any component of the formulation
Canadian labeling: Additional contraindications (not in U.S. labeling): Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, pulmonary (including bronchial asthma), or renal disease; history of neuroleptic malignant syndrome (NMS) and/or nontraumatic rhabdomyolysis; hepatic impairment; narrow-angle glaucoma; pheochromocytoma; in the presence of a suspicious, undiagnosed skin lesion or history of melanoma; concomitant use with a nonselective monoamine oxidase (MAO) inhibitor (eg, tranylcypromine, phenelzine) or concomitant use with both a selective MAO-A and selective MAO-B inhibitor; when administration of a sympathomimetic amine is contraindicated
Concerns related to adverse effects:
• Abnormal thinking/behavioral changes: Abnormal thinking and behavior changes have been reported and may include aggressive behavior, agitation, confusion, delirium, delusions, disorientation, paranoid ideation, and psychotic-like behavior.
• Diarrhea: Has been associated with delayed development of diarrhea (usual onset after 4 to 12 weeks); use with caution in patients with lower gastrointestinal disease or an increased risk of dehydration. Diarrhea may be a sign of drug-induced colitis (primarily lymphocytic). Monitor for weight loss. Discontinue use with prolonged diarrhea.
• Dyskinesia: New-onset or exacerbation of preexisting dyskinesia may occur when used as an adjunct to levodopa. Decreasing the dose of levodopa may ameliorate these side effects in some cases.
• Hallucinations: May cause hallucinations.
• Impulse control disorders: Compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), intense urges to spend money uncontrollably, and other intense urges have been reported. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Melanoma: Risk for melanoma development is increased in Parkinson disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed. The Canadian labeling contraindicates use in patients with suspicious, undiagnosed skin lesions or history of melanoma.
• Neuroleptic malignant syndrome: Entacapone, in conjunction with other drug therapy that alters brain biogenic amine concentrations (eg, MAO inhibitors, SSRIs), has been associated with a syndrome resembling neuroleptic malignant syndrome (hyperpyrexia and confusion - some fatal) on abrupt withdrawal or dosage reduction. Concomitant use of entacapone and nonselective MAO inhibitors should be avoided.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope.
• Pleural/retroperitoneal fibrosis: Dopaminergic agents from the ergot class have been associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or pleural effusion and thickening. These complications may resolve when the drug is discontinued, but complete resolution does not always occur. It is unknown whether nonergot, pro-dopaminergic agents like entacapone confer this risk.
• Rhabdomyolysis: Severe rhabdomyolysis has been reported with use.
• Somnolence: Patients have reported falling asleep while engaging in activities of daily living; this has been reported to occur without significant warning signs and may occur as late as up to 1 year after initiation of treatment. Monitor for daytime somnolence or preexisting sleep disorder. Use caution in the presence of sleep disorders, with other CNS depressants, sedating agents, psychoactive drugs or ethanol. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Cardiovascular disease: The Canadian product labeling notes to use with caution in patients with cardiovascular disease, including a history of myocardial infarction (MI) and arrhythmias; MI and other ischemic adverse events have been observed in clinical trials.
• Hepatic impairment: Use with caution in patients with hepatic impairment or biliary obstruction. The Canadian labeling contraindicates use in hepatic impairment.
• Psychotic disorders: Avoid use in patients with major psychotic disorder due to the risk of exacerbating psychosis. Many treatments for psychosis may exacerbate the symptoms of Parkinson disease and may also decrease the effectiveness of entacapone.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Other warnings/precautions:
• Discontinuation of therapy: Do not withdraw therapy abruptly.
• Urine discoloration: Urine may appear dark in color (brownish orange) during therapy.
Inhibits COMT
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
COMT Substrates: COMT Inhibitors may increase the serum concentration of COMT Substrates. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iron Preparations: May decrease the serum concentration of Entacapone. Management: Consider separating doses of the agents by 2 or more hours to minimize the effects of this interaction. Monitor for decreased therapeutic effects of levodopa during concomitant therapy, particularly if doses cannot be separated. Risk D: Consider therapy modification
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofepramine: Entacapone may enhance the adverse/toxic effect of Lofepramine. Risk X: Avoid combination
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: COMT Inhibitors may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Avoid coadministration of COMT inhibitors and nonselective monoamine oxidase inhibitors (MAOIs) (eg, isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue) whenever possible. Risk D: Consider therapy modification
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pipamperone [INT]: COMT Inhibitors may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of COMT Inhibitors. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Entacapone has been reported to chelate iron and decreasing serum iron levels were noted in clinical trials; however, clinically significant anemia has not been observed.
The incidence of Parkinson disease in pregnancy is relatively rare and information related to the use of entacapone in pregnant women is very limited (Kranick 2010; Tüfekçioğlu 2018).
It is not known if entacapone is present in breast milk.
The manufacturer recommends that caution be exercised when administering entacapone to breast-feeding women.
Signs and symptoms of Parkinson's disease; liver function tests, blood pressure, patient's mental status and impulse control disorders; daytime sleepiness; serum iron (if signs of anemia); weight loss (patients experiencing diarrhea); signs and symptoms of neuroleptic malignant syndrome if abrupt discontinuation required; dermatologic examination (regularly while on therapy).
Canadian labeling (additional monitoring recommendations): Cardiac function with initial dosage adjustments and periodically during prolonged therapy (patients with history of MI or arrhythmia)
Entacapone is a reversible and selective inhibitor of catechol-O-methyltransferase (COMT). When entacapone is taken with levodopa, the pharmacokinetics are altered, resulting in more sustained levodopa serum levels compared to levodopa taken alone. The resulting levels of levodopa provide for increased concentrations available for absorption across the blood-brain barrier, thereby providing for increased CNS levels of dopamine, the active metabolite of levodopa.
Onset of action: Rapid
Absorption: Rapid
Distribution: IV: Vdss: 20 L
Protein binding: 98%, primarily to albumin
Metabolism: Isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer
Bioavailability: 35%
Half-life elimination: Beta phase: 0.4 to 0.7 hours; gamma phase: 2.4 hours
Time to peak, serum: 1 hour
Excretion: Feces (90%); urine (10%)
Hepatic function impairment: AUC and Cmax are approximately 2-fold higher in those with a history of alcoholism and hepatic impairment.
Tablets (Comtan Oral)
200 mg (per each): $9.25
Tablets (Entacapone Oral)
200 mg (per each): $3.95 - $4.54
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