Drug Interactions between dyphylline / ephedrine / guaifenesin / phenobarbital and everolimus

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the blood concentrations and pharmacologic effects of everolimus. In a study of healthy volunteers, multiple doses of the potent inducer rifampin increased the oral clearance of everolimus by threefold, representing mean decreases in peak blood concentration (Cmax) and systemic exposure (AUC) of 58% and 63%, respectively.

MANAGEMENT: Concomitant use of everolimus with potent CYP450 3A4 and/or P-gp inducers should generally be avoided. Alternative therapeutic agents with less enzyme induction potential should be considered. Some manufacturers recommend that, if concomitant use is unavoidable, the daily everolimus dose should be doubled to achieve the recommended therapeutic range for the condition being treated. Please refer to the manufacturer's labeling for specific dosing information. If the potent CYP450 3A4 and/or P-gp inducer is discontinued, the everolimus dosage should be returned to the dosage used before the potent inducer was commenced after a washout period of approximately 3 to 5 days. Everolimus whole blood trough levels should be closely monitored during treatment, particularly 2 weeks after a dose increase, and 2 weeks after discontinuation of the potent inducers.

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.