Entacapone (entacapone)

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%.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Comt Inhibitors/Selected Maois

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Since MAOI's and COMT are the two major enzymes responsible for the metabolism of catecholamines, the combination of entacapone, tolcapone, or opicapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-3)

CLINICAL EFFECTS: Concurrent administration of entacapone, tolcapone, or opicapone with a non-selective MAOI may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The Canadian(4) and UK(1) manufacturers of entacapone state that concomitant use of either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor with entacapone is contraindicated. Nonselective MAOI should be discontinued at least 2 weeks prior to initiating entacapone therapy.(4) The UK manufacturer of tolcapone states that tolcapone should not be coadministered with either a non-selective MAOI or a selective MAO-A inhibitor with a selective MAO-B inhibitor. (5) The US manufacturer of tolcapone states that patients should not ordinarily be treated concomitantly with tolcapone and a non-selective MAOI. Tolcapone may be concurrently administered with a selective MAO-B inhibitor.(2) The Middle East and US manufacturers of opicapone state that concomitant use of opicapone with MAO inhibitors other than those for the treatment of Parkinson's disease is contraindicated.(10,11)

DISCUSSION: Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone, tolcapone, or opicapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1,2) At daily oral doses of 10 mg, selegiline is primarily a selective MAO-B inhibitor; however, at higher doses, selegiline is capable of inhibiting MAO-A.(6) At dosages administered transdermally for the treatment of depression, selegiline is not selective for MAO-B.(7) Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A.(8,9) Metaxalone is a weak inhibitor of MAO.(12,13)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Comt Inhibitors/Rasagiline; Oral Selegiline

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Since MAOIs and COMT are the two major enzymes responsible for the metabolism of catecholamines, the combination of entacapone, tolcapone, or opicapone and a non-selective MAOI may inhibit the majority of catecholamine metabolism pathways.(1-3)

CLINICAL EFFECTS: Concurrent administration of entacapone, tolcapone, or opicapone with a non-selective MAOI may result in elevated levels of catecholamines, which may result in elevated heart rate and blood pressure.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Entacapone(1,4), tolcapone(5), and opicapone(9,10) should not be used with either a non-selective MAOI or the combination of a selective MAO-A inhibitor and a selective MAO-B inhibitor. Nonselective MAOIs should be discontinued at least 2 weeks prior to initiating COMT inhibitor therapy. Entacapone, tolcapone, or opicapone may be used with oral selegiline, provided that the daily dose of selegiline does not exceed 10 mg, and with rasagiline, provided that the daily dose of rasagiline does not exceed 1 mg, and that patients are not also receiving a selective MAO-A inhibitor.

DISCUSSION: Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes systems involved in the metabolism of catecholamines. Therefore, theoretically, the combination of either entacapone or tolcapone with a non-selective MAO inhibitor will result in inhibition of the majority of catecholamine metabolism pathways.(1,2) Rasagiline is selective for MAO-B in humans at recommended dosages of 1 mg per day or less.(6) Rasagiline has been used with entacapone in clinical trials with no reports of adverse effects.(6) Concurrent administration of rasagiline and entacapone increased rasagiline oral clearance by 28%.(7) At daily doses of 10 mg, selegiline is primarily a selective MAO-B inhibitor; however, at higher doses, selegiline is capable of inhibiting MAO-A.(8)

Entacapone/Oral Iron Supplements

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Entacapone may chelate with iron within the gastrointestinal tract, reducing the absorption of both drugs.

CLINICAL EFFECTS: Simultaneous administration of entacapone and orally administered iron may decrease the clinical effects of both medications.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Iron supplements should not be taken within 2-3 hours before or after entacapone to minimize the effects of this interaction.(1) Some multivitamin preparations that contain sufficient quantities of iron may interact and not be properly absorbed as well.

DISCUSSION: Entacapone may form chelates with iron in the gastrointestinal tract, and preparations should be taken at least 2-3 hours apart.(1) Although the impact on the body's iron stores is unknown, clinical studies showed decreasing serum iron concentrations with coadministration of entacapone.(2) In repeated dose toxicity studies, anemia was observed most likely due to the iron chelating properties of entacapone.(1) Prescribing information of entacapone/levodopa/carbidopa states chelation of entacapone with iron may decrease bioavailability of entacapone/levodopa/carbidopa.(3)

Entacapone; Opicapone/Comt-Metabolized Agents

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Entacapone and opicapone are selective and reversible inhibitors of catechol-O-methyltransferase (COMT) and drugs that are metabolized by COMT can not be fully metabolized when given with entacapone or opicapone.(1)

CLINICAL EFFECTS: COMT-metabolized agents can interact with entacapone or opicapone and may result in an increased heart rates, arrhythmias, or an excessive change in blood pressure.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturers of entacapone and opicapone recommend using caution when administering entacapone or opicapone and a COMT-metabolized agent regardless of the route of administration (including inhalation).(1-3)

DISCUSSION: In an interaction study, ventricular tachycardia was observed after epinephrine and entacapone administration.(1) Another study on the effect of entacapone given with isoproterenol and epinephrine concluded that entacapone may potentiate the chronotropic and arrhythmogenic effects of isoproterenol and epinephrine.(4)

Known hypersensitivity to entacapone or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Diarrhea
• Psychotic disorder

• Biliary obstruction
• Disease of liver
• Dyskinesia
• Hallucinations
• Malignant melanoma
• Orthostatic hypotension

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.

More Frequent

• Dyskinesia
• Hallucinations
• Hyperkinesis
• Hypokinesia

Less Frequent

• Bacterial infection
• Orthostatic hypotension
• Syncope

Rare or Very Rare

• Acute cognitive impairment
• Aggressive behavior
• Altered mental status
• Colitis
• Delirium
• Drug-induced psychosis
• Fever
• Hepatitis
• Neuroleptic malignant syndrome
• Paranoid disorder
• Pleural effusions
• Pulmonary fibrosis
• Pulmonary infiltrates
• Retroperitoneal fibrosis
• Rhabdomyolysis
• Sudden onset of sleep

More Frequent

• Acute abdominal pain
• Constipation
• Diarrhea
• Dizziness
• Fatigue
• Nausea
• Urine discoloration

Less Frequent

• Agitation
• Back pain
• Drowsy
• Dysgeusia
• Dyspepsia
• Dyspnea
• Flatulence
• Gastritis
• Hyperhidrosis
• Purpura
• Symptoms of anxiety
• Vomiting
• Xerostomia

Rare or Very Rare

• Anticholinergic toxicity
• Impulse control disorder

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.

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.