Entapone

Uses

Adjunct to levodopa treatment in Parkinson's disease

Entapone is also used to associated treatment for these conditions: Parkinson's Disease (PD)

How Entapone works

The mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to a greater reduction in the manifestations of parkinsonian syndrome.

Dosage

Entapone dosage

200 mg with each levodopa/dopa decarboxylase inhibitor dose. Max: 200 mg 10 times daily (2,000 mg daily). Gradually reduce levodopa dose by approx 10-30% or increase dosing interval w/in the 1st few wk of starting treatment.

May be taken with or without food.

Side Effects

Abdominal pain, nausea, vomiting, diarrhoea, constipation, colitis, dry mouth, dyskinesia, dizziness, nightmares, insomnia, hallucinations, confusion, fatigue, increased sweating, behavioural disturbances; urine, skin, hair, beard and nail discolourations; cholestatic hepatitis, rhabdomyolysis. Rarely, agitation, urticaria, erythematous or maculopapular rash, anorexia, wt decrease, increased liver enzymes.

Toxicity

Side effect include increase the occurrence of orthostatic hypotension, severe rhabdomyolysis, dyskinesia, hallucinations, hyperkinesia, hypokinesia, dizziness, fatigu,e gastrointestinal effects including abdominal pain constipation diarrhea nausea

Precaution

Patient with biliary obstruction, ischaemic heart disease. Avoid abrupt withdrawal. Pregnancy and lactation.

Interaction

May interfere with metabolism of other drugs metabolised by COMT (e.g. rimiterole). May aggravate levodopa-induced orthostatic hypotension. Risk of dopaminergic effects with dopamine agonists (e.g. bromocriptine), selegiline, amantadine. May form chelates with Fe in the GI tract. Additive sedative effects with other CNS depressants.

Food Interaction

• Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Entapone Drug Interaction

Moderate: pramipexole, pramipexole, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopa, carbidopa / levodopaMinor: rasagiline, rasagilineUnknown: aspirin, aspirin, apixaban, apixaban, polyethylene glycol 3350, polyethylene glycol 3350, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Entapone Disease Interaction

Major: hypotension, psychosisModerate: hepatic impairment

Volume of Distribution

• 20 L

Elimination Route

Entapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.

Half Life

0.4-0.7 hour

Clearance

• 850 mL/min

Elimination Route

Entapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug.

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Phaeochromocytoma, history of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis. Hepatic impairment. Concomitant use w/ non-selective MAOIs.

Acute Overdose

Symptoms: Decreased activity, confusion, somnolence, hypotonia, urticaria, skin discolouration.

Management: Symptomatic treatment.

Storage Condition

Store at 25°C.

Innovators Monograph

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