Afinitor Dosage
Generic name: everolimus
Dosage form: tablet
This dosage information does not include all the information needed to use Afinitor safely and effectively. See full prescribing information for Afinitor.
The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.
AFINITOR should be administered orally once daily at the same time every day, either consistently with food or consistently without food [see Clinical Pharmacology (12.3)].
AFINITOR tablets should be swallowed whole with a glass of water. For patients unable to swallow tablets, AFINITOR tablet(s) should be dispersed completely in a glass of water (containing approximately 30 mL) by gently stirring, immediately prior to drinking. The glass should be rinsed with the same volume of water and the rinse should be completely swallowed to ensure that the entire dose is administered.
Continue treatment as long as clinical benefit is observed or until unacceptable toxicity occurs.
2.1 Recommended Dose in Advanced PNET, Advanced RCC, and Renal Angiomyolipoma with TSC
The recommended dose of AFINITOR is 10 mg, to be taken once daily.
2.2 Dose Modifications in Advanced PNET, Advanced RCC, and Renal Angiomyolipoma with TSC
​Adverse Reactions
​Management of severe or intolerable adverse reactions may require temporary dose reduction and/or interruption of AFINITOR therapy. If dose reduction is required, the suggested dose is 5 mg daily [see Warnings and Precautions (5.1)].
​Hepatic Impairment
​Hepatic impairment will increase the exposure to everolimus [see Warnings and Precautions (5.7) and Use in Specific Populations (8.7)]. Dose adjustments are recommended:
​- Mild hepatic impairment (Child-Pugh class A) – The recommended dose is 7.5 mg daily; the dose may be decreased to 5 mg if not well tolerated.
​- Moderate hepatic impairment (Child-Pugh class B) – The recommended dose is 5 mg daily; the dose may be decreased to 2.5 mg if not well tolerated.
​- Severe hepatic impairment (Child-Pugh class C) – If the desired benefit outweighs the risk, a dose of 2.5 mg daily may be used but must not be exceeded.
​Dose adjustments should be made if a patient’s hepatic (Child-Pugh) status changes during treatment.
CYP3A4 and/or P-glycoprotein (PgP) Inhibitors
Avoid the use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) [see Warnings and Precautions (5.6) and Drug Interactions (7.1)].
Use caution when co-administered with moderate CYP3A4 and/or PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). If patients require co-administration of a moderate CYP3A4 and/or PgP inhibitor, reduce the AFINITOR dose to 2.5 mg daily. The reduced dose of AFINITOR is predicted to adjust the area under the curve (AUC) to the range observed without inhibitors. An AFINITOR dose increase from 2.5 mg to 5 mg may be considered based on patient tolerance. If the moderate inhibitor is discontinued, a washout period of approximately 2 to 3 days should be allowed before the AFINITOR dose is increased. If the moderate inhibitor is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the moderate CYP3A4 and/or PgP inhibitor.
Strong CYP3A4 Inducers
Avoid the use of concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). If patients require co-administration of a strong CYP3A4 inducer, consider increasing the AFINITOR dose from 10 mg daily up to 20 mg daily , using 5 mg increments. This dose of AFINITOR is predicted, based on pharmacokinetic data, to adjust the AUC to the range observed without inducers. However, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers. If the strong inducer is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer [see Warnings and Precautions (5.6) and Drug Interactions (7.2)].
Grapefruit, grapefruit juice, and other foods that are known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment. St. John’s Wort (Hypericum perforatum) may decrease everolimus exposure unpredictably and should be avoided.
2.3 Recommended Dose in Subependymal Giant Cell Astrocytoma
The recommended starting dose of AFINITOR for treatment of patients with SEGA is according to Table 1:
| Body Surface Area (BSA) | Starting Dose |
| 0.5 m2 to 1.2 m2 | 2.5 mg once daily |
| 1.3 m2 to 2.1 m2 | 5 mg once daily |
| Greater than or equal to 2.2 m2 | 7.5 mg once daily |
Patients receiving AFINITOR may require dose adjustments based on everolimus whole blood trough concentrations achieved, tolerability, individual response, and change in concomitant medications including CYP3A4-inducing antiepileptic drugs [see Warnings and Precautions (5.6) and Drug Interactions (7.1, 7.2)]. Dose adjustments can be made at two week intervals [see Dosage and Administration (2.4, 2.5)].
Evaluate SEGA volume approximately 3 months after commencing AFINITOR therapy and periodically thereafter, with subsequent dose adjustments taking into consideration changes in SEGA volume, corresponding trough concentration, and tolerability. Responses have been observed at trough concentrations as low as 3 ng/mL; as such, once acceptable efficacy has been achieved, additional dose increases may not be necessary.
AFINITOR has not been studied in patients with SEGA < 3 years of age or with BSA < 0.58 m2.
The optimal duration of therapy for patients with SEGA is unknown.
2.4 Dose Modifications in Subependymal Giant Cell Astrocytoma
​Adverse Reactions
​Management of severe or intolerable adverse reactions may require temporary dose reduction and/or interruption of AFINITOR therapy [see Warnings and Precautions (5.1)]. If dose reduction is required for patients receiving 2.5 mg daily, consider alternate day dosing.
​Hepatic Impairment
​Adjustment to the recommended starting dose for patients with SEGA who have mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment may not be needed; however, subsequent dosing should be based on therapeutic drug monitoring (TDM).
​AFINITOR is not recommended for use in patients with SEGA who have severe hepatic impairment (Child-Pugh class C).
​Everolimus whole blood trough concentration should be assessed approximately 2 weeks after commencing treatment or after any change in hepatic status (Child-Pugh). Dosing should be titrated to attain trough concentrations of 5 to 10 ng/mL [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].
CYP3A4 and/or P-glycoprotein (PgP) Inhibitors
Avoid the use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) [see Warnings and Precautions (5.6) and Drug Interactions (7.1)].
Use caution when co-administered with moderate CYP3A4 and/or PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). If patients require co-administration of a moderate CYP3A4 and/or PgP inhibitor, reduce the AFINITOR dose by approximately 50% to maintain trough concentrations of 5 to 10 ng/mL. If dose reduction is required for patients receiving 2.5 mg daily, consider alternate day dosing. Subsequent dosing should be individualized based on therapeutic drug monitoring. Everolimus trough concentrations should be assessed approximately 2 weeks after the addition of a moderate CYP3A4 and/or PgP inhibitor. If the moderate inhibitor is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the moderate CYP3A4 and/or PgP inhibitor and the everolimus trough concentration should be re-assessed approximately 2 weeks later [see Dosage and Administration (2.5), Warnings and Precautions (5.6) and Drug Interactions (7.1)].
Strong CYP3A4 Inducers
Avoid the use of concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). For patients requiring a concomitant strong CYP3A4 inducer, double the AFINITOR dose. Subsequent dosing should be individualized based on therapeutic drug monitoring. If the strong inducer is discontinued, the AFINITOR dose should be returned to the dose used prior to initiation of the strong CYP3A4 inducer and the everolimus trough concentrations should be assessed approximately 2 weeks later [see Dosage and Administration (2.5), Warnings and Precautions (5.6) and Drug Interactions (7.2)].
Grapefruit, grapefruit juice, and other foods that are known to inhibit cytochrome P450 and PgP activity may increase everolimus exposures and should be avoided during treatment. St. John’s Wort (Hypericum perforatum) may decrease everolimus exposure unpredictably and should be avoided.
2.5 Therapeutic Drug Monitoring in Subependymal Giant Cell Astrocytoma
Routine everolimus whole blood therapeutic drug concentration monitoring is recommended for all patients using a validated assay. Trough concentrations should be assessed approximately 2 weeks after commencing treatment. Dosing should be titrated to attain trough concentrations of 5 to 10 ng/mL.
There is limited safety experience with patients having trough concentrations > 10 ng/mL. If concentrations are between 10 and 15 ng/mL, and the patient has demonstrated adequate tolerability and tumor response, no dose reductions are needed. The dose of AFINITOR should be reduced if trough concentrations > 15 ng/mL are observed.
If concentrations are < 5 ng/mL, the daily dose may be increased by 2.5 mg every 2 weeks, subject to tolerability. Daily dose may be reduced by 2.5 mg every 2 weeks to attain a target of 5 to 10 ng/mL. If dose reduction is required for patients receiving 2.5 mg daily, alternate day dosing should be used.
Trough concentrations should be assessed approximately 2 weeks after any change in dose, after an initiation or change in co-administration of CYP3A4 and/or PgP inducers or inhibitors, or after any change in hepatic status (Child-Pugh Classification) [see Dosage and Administration (2.4), Warnings and Precautions (5.6, 5.7), Drug Interactions (7.1, 7.2)].
