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Pronunciation
(en TA ka pone)
Generic Available (U.S.)
No
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Adjunct to levodopa/carbidopa therapy in patients with idiopathic Parkinson's disease who experience “wearing-off” symptoms at the end of a dosing interval
Pregnancy Risk Factor
C
Pregnancy Considerations
Not recommended
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to entacapone or any of component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Diarrhea: Has been associated with delayed development of diarrhea (usual onset after 4-12 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. Discontinue use with prolonged diarrhea.
• Hallucinations: May cause hallucinations, which may improve with reduction in levodopa therapy.
• Impulse control disorders: Dopaminergic agents used for Parkinson's disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. 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's 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.
• 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 tolcapone and nonselective MAO inhibitors should be avoided.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge; use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson's patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk.
• Pleural/retroperitoneal fibrosis: Dopaminergic agents from the ergot class have been associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or effusion and pleural thickening. It is unknown whether non-ergot, pro-dopaminergic agents like tolcapone confer this risk.
• Rhabdomyolysis: Severe rhabdomyolysis has been reported with use.
Disease-related concerns:
• Dyskinesia: Use with caution in patients with pre-existing dyskinesias; exacerbation of pre-existing dyskinesia has been reported. Levodopa dosage reduction may be required, particularly in patients with levodopa dosages >600 mg daily or with moderate-to-severe dyskinesia prior to initiation.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with severe renal impairment.
Concurrent drug therapy issues:
• Catecholamines: Use caution with agents metabolized by COMT (eg, epinephrine, dopamine, methyldopa) regardless of route of administration; effects may be enhanced when used with entacapone.
• MAO inhibitors: Concomitant use of entacapone and nonselective MAO inhibitors should be avoided. Selegiline is a selective MAO type B inhibitor (when given orally at ≤10 mg/day) and can be taken with entacapone.
Other warnings/precautions:
• Body fluid discoloration: Urine, saliva, or sweat may appear dark in color (red, brown, black) during therapy.
• Discontinuation of therapy: Do not withdraw therapy abruptly.
Adverse Reactions
>10%:
Gastrointestinal: Nausea (14%)
Neuromuscular & skeletal: Dyskinesia (25%), placebo (15%)
1% to 10%:
Cardiovascular: Orthostatic hypotension (4%), syncope (1%)
Central nervous system: Dizziness (8%), fatigue (6%), hallucinations (4%), anxiety (2%), somnolence (2%), agitation (1%)
Dermatologic: Purpura (2%)
Gastrointestinal: Diarrhea (10%), abdominal pain (8%), constipation (6%), vomiting (4%), dry mouth (3%), dyspepsia (2%), flatulence (2%), gastritis (1%), taste perversion (1%)
Genitourinary: Brown-orange urine discoloration (10%)
Neuromuscular & skeletal: Hyperkinesia (10%), hypokinesia (9%), back pain (4%), weakness (2%)
Respiratory: Dyspnea (3%)
Miscellaneous: Bacterial infection (1%), diaphoresis increased (2%)
<1%: Hyperpyrexia and confusion (resembling neuroleptic malignant syndrome), pulmonary fibrosis, rhabdomyolysis, retroperitoneal fibrosis
Metabolism/Transport Effects
Inhibits COMT, CYP1A2 (weak), CYP2A6 (weak), CYP2C19 (weak), CYP2C9 (weak), CYP2D6 (weak), CYP2E1 (weak), CYP3A4 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
COMT Substrates: COMT Inhibitors may decrease the metabolism of COMT Substrates. 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 (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MAO Inhibitors: COMT Inhibitors may enhance the adverse/toxic effect of MAO Inhibitors. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: 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.
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Onset of action: Rapid
Peak effect: 1 hour
Absorption: Rapid
Distribution: I.V.: 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: B phase: 0.4-0.7 hours; Y phase: 2.4 hours
Time to peak, serum: 1 hour
Excretion: Feces (90%); urine (10%)
Dosage
Oral: Adults: 200 mg with each dose of levodopa/carbidopa, up to a maximum of 8 times/day (maximum daily dose: 1600 mg/day). To optimize therapy, the dosage of levodopa may need reduced or the dosing interval may need extended. Patients taking levodopa ≥800 mg/day or who had moderate-to-severe dyskinesias prior to therapy required an average decrease of 25% in the daily levodopa dose.
Dosage adjustment in hepatic impairment: Treat with caution and monitor carefully; AUC and Cmax can be possibly doubled
Administration: Oral
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.
Monitoring Parameters
Signs and symptoms of Parkinson's disease; liver function tests, blood pressure, patient's mental status; serum iron (if signs of anemia)
Dietary Considerations
May be taken without regard to meals.
Patient Education
This drug is prescribed as one part of a multidrug combination; take exactly as directed for full course of therapy. Avoid alcohol. Periodic laboratory tests and skin exams may be required. May cause dizziness, fatigue, sleepiness, postural hypotension, unusual taste, nausea, vomiting, flatulence, upset stomach, or brown- or orange-colored urine (normal). Report any CNS changes (unusual compulsiveness, increased libido, binge eating), any new or increased abnormal skeletal movements or weakness, persistent gastrointestinal problems, hallucinations, changes in the appearance of skin moles, or other unusual skin changes.
Geriatric Considerations
No difference in adverse effects was noted in the elderly. Monitor levodopa dose.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic hypotension and abnormal taste. Dopaminergic therapy in Parkinson's disease (ie, treatment with levodopa) is associated with orthostatic hypotension. Entacapone enhances levodopa bioavailability and may increase the occurrence of hypotension/syncope in the dental patient. The patient should be carefully assisted from the chair and observed for signs of orthostatic hypotension.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Monitor for postural hypotension, increased dyskinesias, and CNS changes (hallucinations, compulsive behaviors). Periodic skin examinations should be performed; risk for melanoma is increased in Parkinson's disease. Taper dose when discontinuing. Teach patient proper timing of multiple medications.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Comtan®: 200 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Comtan)
200 mg (30): $112.99
References
Pahwa R, Factor SA, Lyons KE, et al, “Practice Parameter: Treatment of Parkinson Disease With Motor Fluctuations and Dyskinesia (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology," Neurology, 2006, 66(7):983-95.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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