Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of fruquintinib, which is primarily metabolized by the isoenzyme. Concomitant use with rifampin, a potent CYP450 3A4 inducer, decreased fruquintinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 12% and 65%, respectively. Reduced efficacy of fruquintinib may occur.

MANAGEMENT: Coadministration of fruquintinib with potent CYP450 3A4 inducers should be avoided.

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

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.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.