ximately 2 weeks after commencing treatment, a change in dose, or any change in hepatic function [see Dosage and Administration (2.3, 2.4)].
CYP3A4/P-glycoprotein (PgP) Inhibitors
Avoid the use of concomitant strong CYP3A4/PgP inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) in patients receiving AFINITOR Tablets or AFINITOR DISPERZ [see Warnings and Precautions (5.9) and Drug Interactions (7.1)].
For patients who require treatment with moderate CYP3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem):
•Reduce the AFINITOR Tablets or AFINITOR DISPERZ dose by approximately 50%. Administer every other day if dose reduction is required for patients receiving the lowest available strength and maintain trough concentrations of 5 to 15 ng/mL [see Dosage and Administration (2.3, 2.4)].
•Assess everolimus trough concentrations approximately 2 weeks after dose reduction [see Dosage and Administration (2.3, 2.4)].
•Resume the dose that was used prior to initiating the CYP3A4/PgP inhibitor 2 to 3 days after discontinuation of a moderate inhibitor. Assess the everolimus trough concentration approximately 2 weeks later [see Dosage and Administration (2.3, 2.4)].
Do not ingest foods or nutritional supplements (e.g., grapefruit, grapefruit juice) that are known to inhibit cytochrome P450 or PgP activity.
Strong CYP3A4/PgP Inducers
Avoid the use of concomitant strong CYP3A4/PgP inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) if alternative therapy is available [see Warnings and Precautions (5.9) and Drug Interactions (7.2)]. For patients who require treatment with a strong CYP3A4/PgP inducer:
•Double the dose of AFINITOR Tablets or AFINITOR DISPERZ and assess tolerability [see Dosage and Administration (2.3)].
•Assess the everolimus trough concentration 2 weeks after doubling the dose and adjust the dose if necessary to maintain a trough concentration of 5 to 15 ng/mL [see Dosage and Administration (2.3, 2.4)].
•Return the AFINITOR Tablets or AFINITOR DISPERZ dose to that used prior to initiating the strong CYP3A4/PgP inducer if the strong inducer is discontinued, and assess the everolimus trough concentrations approximately 2 weeks later [see Dosage and Administration (2.3, 2.4)].
Do not ingest foods or nutritional supplements (e.g., St. John’s Wort (Hypericum perforatum)) that are known to induce cytochrome P450 activity.
2.6 Administration of AFINITOR Tablets in SEGA with TSC
Do not combine the 2 dosage forms (AFINITOR Tablets and AFINITOR DISPERZ) to achieve the desired total dose. Use one dosage form or the other.
Administer AFINITOR Tablets orally once daily at the same time every day. Administer either consistently with food or consistently without food [see Clinical Pharmacology (12.3)].
AFINITOR Tablets should be swallowed whole with a glass of water. Do not break or crush tablets.
2.7 Administration and Preparation of AFINITOR DISPERZ in SEGA with TSC
Wear gloves to avoid possible contact with everolimus when preparing suspensions of AFINITOR DISPERZ for another person.
Do not combine the 2 dosage forms (AFINITOR Tablets and AFINITOR DISPERZ) to achieve the |
