Everolimus Use in Children With Tuberous Sclerosis Complex
Everolimus Use in Children With Tuberous Sclerosis Complex
The metabolism of everolimus may be significantly altered by the concomitant use of CYP3A4 or PgP inhibitors. The use of strong CYP3A4 inhibitors, such as atazanivir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, saquinavir, telithromycin, ritonavir, or voriconazole should be avoided. The use of moderate CYP3A4 or PgP inhibitors (amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, or verapamil) may be considered, but requires a reduction in the everolimus dose (see Dosing Recommendations). The use of strong CYP3A4 inducers (carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine) with everolimus is not recommended. If no alternatives are available, the dose of everolimus should be doubled. In any patient requiring the use of an interacting drug, everolimus concentrations should be closely monitored throughout treatment.
Administration of everolimus with oral midazolam may produce an increase in the maximum midazolam concentration of 25%. Use of everolimus with depot octreotide may increase trough octreotide concentrations by 50%. Concomitant administration of everolimus with exemestane in patients with breast cancer may result in increased exemestane concentrations.
Drug Interactions
The metabolism of everolimus may be significantly altered by the concomitant use of CYP3A4 or PgP inhibitors. The use of strong CYP3A4 inhibitors, such as atazanivir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, saquinavir, telithromycin, ritonavir, or voriconazole should be avoided. The use of moderate CYP3A4 or PgP inhibitors (amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, or verapamil) may be considered, but requires a reduction in the everolimus dose (see Dosing Recommendations). The use of strong CYP3A4 inducers (carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine) with everolimus is not recommended. If no alternatives are available, the dose of everolimus should be doubled. In any patient requiring the use of an interacting drug, everolimus concentrations should be closely monitored throughout treatment.
Administration of everolimus with oral midazolam may produce an increase in the maximum midazolam concentration of 25%. Use of everolimus with depot octreotide may increase trough octreotide concentrations by 50%. Concomitant administration of everolimus with exemestane in patients with breast cancer may result in increased exemestane concentrations.
