Entacapone inhibit CYP2C9 in vitro. Entacapone is most probably not an inhibitor or inducer of CYP enzymes in vivo. Risk for gastrointestinal adverse events in the form of nausea, insomnia, diarrhoea, abdominal pain, obstipation and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.

Entacapone is a catechol O-methyltranseferase (COMT) inhibitor.

Entacapone is indicated as an adjunct to standard preparations of levodopa/benserazide or levodopa/carbidopa for use in adult patients with Parkinsons disease and end-of-dose motor fluctuations, who cannot be stabilised on those combinations. Very common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are nausea and urine discoloration. Other common side effects are insomnia, diarrhoea, abdominal pain, obstipation, vomiting and fatigue.

Entacapone is metabolised via glucuronidation (Seeberger 2009 and SPC). In vitro data indicates that entacapone inhibit CYP2C9, but no or little inhibition of CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A4 and CYP2C19 (SPC). Entacapone has been shown to increase the AUC of R-warfarin by 18% when it was co-administered with racemic warfarin. The mechanism is unknown, but the authors suggest that entacapone might compete for binding to one or more of the enzymes that metabolise R-warfarin (Dingemanse 2002). The increase is however, according to the FDA, too low for entacapone to be considered as an inhibitor. No drug-drug interactions with entacapone as perpetrator regarding CYP enzymes are observed (Interaksjoner and Interaktionsdatabasen), which indicate that entacapone is not an inhibitor or inducer of CYP enzymes.

Uneventful use reported in 1 patient with acute porphyria.