Dosing & Administration

AFINITOR^® (everolimus) tablets: convenient, once-daily dosing

Dosing & administration recommendations

• The recommended once-daily dose of AFINITOR is 10 mg
• AFINITOR should be taken orally, once daily at the same time, consistently either with or without food and with a full glass of water
• The tablets should not be chewed or crushed
• The dosage may be reduced to 5 mg daily when appropriate
• If a dose is missed, the patient should not take an additional dose, but take the usual prescribed next dose
• AFINITOR is available as 5 mg and 10 mg tablets with no score

Inhibitors and inducers

Inhibitors of AFINITOR
AFINITOR is a substrate of CYP3A4, and also a substrate and moderate inhibitor of the multidrug efflux pump P-glycoprotein (PgP). Therefore, absorption and subsequent elimination of AFINITOR may be influenced by products that affect CYP3A4 and/or PgP.

• AFINITOR blood concentrations may be increased by substances that inhibit CYP3A4 activity and thus decrease AFINITOR metabolism
• AFINITOR blood concentrations may be increased by inhibitors of PgP that may decrease the efflux of AFINITOR from intestinal cells
• Concurrent treatment with inhibitors of CYP3A4 or PgP should be avoided. These drugs include, but are not limited to:
  • ketoconazole
  • itraconazole, posaconazol, voriconazole
  • clarithromycin, telithromycin
  • ritonavir, atazanavir, saquinavir, darunnavir, indinavir, nelfinavir
• Concomitant treatment with moderate inhibitors of CYP3A4 and PgP requires caution. These drugs include but are not limited to:
• erythromycin
• verapamil
• cyclosporine
• fluconazole
• diltiazem
• Grapefruit, grapefruit juice and other foods that are known to affect cytochrome P450 and PgP activity should be avoided
• If patients require co-administration of a moderate CYP3A4 or PgP inhibitor, dose reduction to 5 mg daily or 5 mg every other day may be considered

Inducers of AFINITOR

Substances that are inducers of CYP3A4 or PgP may decrease AFINITOR blood concentrations by increasing metabolism or efflux of AFINITOR from intestinal cells.

• Concurrent treatment with inducers of CYP3A4 or PgP should be avoided. These drugs include, but are not limited to:
• rifampicin
• carbamazepine, phenobarbital, phenytoin
• St John's Wort
• efavirenz, nevirapine
• Use caution when co-administration of moderate CYP3A4 inhibitors or PgP inhibitors cannot be avoided. If patients require co-administration of a potent CYP3A4 inducer, an AFINITOR dose increase from 10 mg daily up to 20 mg daily should be considered using 5 mg increments applied on Day 4 and 8 following start of the inducer

Additional Dosage Considerations

• Management of severe and/or intolerable suspected 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
• For patients with moderate hepatic impairment (Child-Pugh class B), the dose should be reduced to 5 mg daily. AFINITOR has not been evaluated in patients with severe hepatic impairment (Child- Pugh class C) and is not recommended for use in this patient population

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