This side effect is due to entacapone metabolism and excretion in the urine and shown to not be harmful. Sudden sleep onset
People have reported sudden sleep onset while engaging in daily activities without prior warning of drowsiness. In controlled studies, patients on entacapone had a 2% increased risk of somnolence compared to placebo. Low blood pressure
Episodes of orthostatic hypotension have been shown to be more common at the start of entacapone use due to increased levels of levodopa. Behavior problems
Post-marketing data shows that entacapone may change or worsen mental status, leading to behaviors such as delusions, agitation, confusion, and delirium.People taking entacapone may experience increased urges to participate in gambling, sexual activities, money spending, and other stimulating reward behaviors. Interactions
In studies, entacapone has shown a low potential for interaction with other drugs. In theory, it could interact with MAO inhibitors, tricyclic antidepressants and noradrenaline reuptake inhibitors because they also increase catecholamine levels in the body, with drugs being metabolized by COMT (for example  methyldopa, dobutamine, apomorphine, adrenaline, and isoprenaline), with iron because it could form chelates, with substances binding to the same albumin site in the blood plasma (for example diazepam and ibuprofen), and with drugs being metabolized by the liver enzyme CYP2C9 (for example warfarin). None of the medications tested in studies have shown clinically relevant interactions, except perhaps warfarin for which a 13% (CI90: 6–19%) increase in INR was seen when combined with entacapone. Pharmacology
Mechanism of action
Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT).
COMT eliminates biologically active catechols present in catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered with a decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in the periphery.For the treatment of Parkinsons disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa. Entacapone inhibits COMT in the periphery (but not, or at most marginally, in the brain) and the metabolism of levodopa, thus increasing plasma levels of levodopa and causing more constant dopaminergic stimulation in order to reduce the signs and symptoms presented in the disease. Pharmacokinetics
Absorption
The time to highest blood plasma concentrations is approximately one hour. The substance undergoes extensive first-pass metabolism. Absolute oral bioavailability (F) is 35%. Distribution
The volume of distribution  (Vd) after intravenous injection is approximately 20 liters. 98% of the circulating entacapone is bound to serum albumin, which limits its distribution into tissues. Metabolism and elimination
Entacapone is primarily metabolized to its glucuronide in the liver, and 5% are converted into the Z-isomer. It has a half-life of approximately 0.3–0.7 hours, with only 0.2% being excreted unchanged in the urine. References
External links
"Entacapone". Drug Information Portal. U.S. National Library of Medicine.