Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 2C8 may decrease the plasma concentrations of treprostinil, which is primarily metabolized by the isoenzyme. Human pharmacokinetic studies with an oral formulation of treprostinil indicate that concomitant administration of the CYP450 2C8 inducer rifampin decreases exposure (both Cmax and AUC) to treprostinil. However, it has not been determined if the safety and efficacy of treprostinil administered subcutaneously or intravenously are altered by this interaction.

MANAGEMENT: Pharmacologic response to treprostinil should be monitored more closely whenever a CYP450 2C8 inducer is added to or withdrawn from therapy, and the treprostinil dosage adjusted as necessary. Patients should be advised to notify their physician if they experience worsening of their condition.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.