Usage
- Entacapone is prescribed as an adjunct therapy to levodopa/carbidopa or levodopa/benserazide for the treatment of patients with Parkinson’s disease experiencing end-of-dose “wearing-off” phenomenon. This “wearing-off” effect is characterized by the return of Parkinson’s disease motor and non-motor symptoms before the next scheduled dose of levodopa.
- Pharmacological Classification: Catechol-O-methyltransferase (COMT) inhibitor.
- Mechanism of Action: Entacapone reversibly and selectively inhibits COMT, an enzyme that degrades levodopa in the peripheral tissues. By inhibiting COMT, entacapone increases the amount of levodopa that reaches the brain, thus prolonging its therapeutic effect and reducing motor fluctuations in Parkinson’s disease.
Alternate Names
- International Nonproprietary Name (INN): Entacapone
- Brand Names: Comtan, Comtess
How It Works
- Pharmacodynamics: Entacapone increases the area under the curve (AUC) of levodopa by approximately 35% and prolongs its time above minimum effective concentration. This leads to a reduction in “off-time,” periods when Parkinson’s disease symptoms reemerge, and improvement in “on-time without troublesome dyskinesias.”
- Pharmacokinetics:
- Absorption: Rapidly absorbed orally, reaching peak plasma concentration in about one hour. Bioavailability is approximately 35%. Food intake does not significantly affect absorption.
- Metabolism: Primarily metabolized by glucuronidation in the liver. COMT does not play a role in entacapone metabolism.
- Elimination: Excreted mainly in urine (approximately 80%) and bile (approximately 20%). Enterohepatic circulation occurs.
- Mode of Action: Entacapone binds reversibly to the active site of the COMT enzyme, preventing it from metabolizing levodopa to 3-O-methyldopa (3-OMD) peripherally. This allows more levodopa to cross the blood-brain barrier.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Entacapone selectively inhibits COMT. It does not directly bind to dopamine receptors or modulate neurotransmitter release.
- Elimination Pathways: Primarily renal excretion of entacapone glucuronide, with some biliary excretion.
Dosage
Standard Dosage
Adults:
- 200 mg orally with each levodopa/carbidopa or levodopa/benserazide dose (up to 10 times per day, not exceeding a total daily dose of 2000 mg).
Children:
- Not recommended for use in children below 18 years. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No dose adjustments needed.
- Patients with Renal Impairment: No dose adjustment generally needed. A longer dosing interval may be considered for patients undergoing dialysis.
- Patients with Hepatic Dysfunction: Contraindicated in patients with hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with severe cardiovascular disease, endocrine disorders, or other serious conditions.
Clinical Use Cases
Entacapone is not specifically dosed for situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its role is as an adjunct therapy to levodopa/carbidopa or levodopa/benserazide for long-term management of Parkinson’s disease.
Dosage Adjustments
Levodopa dose reduction (about 10-30%) may be necessary when initiating or adjusting entacapone therapy due to enhanced levodopa bioavailability.
Side Effects
Common Side Effects
- Dyskinesia (abnormal, involuntary movements)
- Nausea
- Diarrhea
- Urine discoloration (orange-brown)
- Dizziness
- Sleepiness/drowsiness
- Hallucinations
Rare but Serious Side Effects
- Neuroleptic Malignant Syndrome (NMS): Characterized by muscle rigidity, fever, altered mental status, autonomic instability.
- Rhabdomyolysis (muscle breakdown)
- Severe allergic reactions
- Hepatotoxicity
- Impulse control disorders (e.g., compulsive gambling, shopping, eating, or sexual behavior).
- Sudden sleep onset
Long-Term Effects
- Chronic complications from prolonged use may include worsening of dyskinesias and motor fluctuations. Regular monitoring of liver function and impulse control is necessary during long-term therapy.
Adverse Drug Reactions (ADR)
- See “Rare but Serious Side Effects.”
Contraindications
- Hypersensitivity to entacapone.
- Hepatic impairment.
- Phaeochromocytoma (rare adrenal gland tumor).
- Concomitant use of non-selective monoamine oxidase inhibitors (MAOIs) or a combination of selective MAO-A and MAO-B inhibitors.
Drug Interactions
- Non-selective MAOIs: Concomitant use is contraindicated.
- Catecholamines: Use with caution as it may potentiate their effects, leading to cardiovascular complications.
- Iron Supplements: Entacapone can reduce iron absorption; administer at least 2-3 hours apart.
- Warfarin: May enhance the anticoagulant effect of warfarin; monitor INR closely.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA). Risk to the fetus cannot be ruled out. Not recommended for use during pregnancy.
- Breastfeeding: Entacapone is excreted in animal milk. Not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: COMT inhibitor, increasing levodopa bioavailability.
- Side Effects: Dyskinesia, nausea, diarrhea, urine discoloration, dizziness, drowsiness, hallucinations.
- Contraindications: Hepatic impairment, phaeochromocytoma, concurrent non-selective MAOI use.
- Drug Interactions: Non-selective MAOIs, catecholamines, iron supplements, warfarin.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 200 mg with each levodopa dose, up to 10 times/day (2000 mg/day).
- Monitoring Parameters: Motor symptoms, liver function tests, impulse control, signs of NMS/rhabdomyolysis.
Popular Combinations
- Levodopa/carbidopa + entacapone
- Levodopa/benserazide + entacapone
Precautions
- Monitor for signs of NMS, rhabdomyolysis, hepatic dysfunction, and impulse control disorders.
- Screen for underlying cardiovascular, endocrine, hematologic, pulmonary, hepatic, and renal conditions.
- Caution in patients with ischemic heart disease or biliary obstruction.
- Patients should be advised to avoid activities requiring alertness until response to medication is known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Entacapone?
A: The standard dosage is 200 mg taken orally with each dose of levodopa/carbidopa or levodopa/benserazide, up to a maximum of 10 times per day (2000 mg total daily dose).
Q2: How does Entacapone improve Parkinson’s disease symptoms?
A: Entacapone inhibits COMT, prolonging levodopa’s effect and reducing motor fluctuations.
Q3: What are the most common side effects of Entacapone?
A: Common side effects include dyskinesia, nausea, diarrhea, urine discoloration, dizziness, and drowsiness.
Q4: Is Entacapone safe for patients with liver or kidney problems?
A: Entacapone is contraindicated in patients with hepatic impairment. Renal impairment usually does not necessitate dose adjustment.
Q5: Can Entacapone be used during pregnancy or breastfeeding?
A: It’s not recommended for use during pregnancy or breastfeeding due to potential risks to the fetus/infant.
Q6: What medications should be avoided while taking Entacapone?
A: Non-selective MAOIs and a combination of MAO-A and B inhibitors are contraindicated. Caution is advised with catecholamines, iron supplements, and warfarin.
Q7: Are there any long-term side effects of Entacapone use?
A: Long-term use may worsen dyskinesias and motor fluctuations. Impulse control disorders can also occur.
Q8: How should Entacapone be taken?
A: Take it orally with each dose of levodopa/carbidopa or levodopa/benserazide. It can be taken with or without food.
Q9: What should patients do if they miss a dose of Entacapone?
A: They should take the missed dose as soon as they remember, unless it is close to the time of the next dose. They should not double the dose.
