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Printer friendlyAfinitor® (everolimus) tablets allow patients to continue receiving a convenient oral therapy
Once-daily oral therapy after failure of either sunitinib or sorafenib
Please see Important Safety Information below
- The recommended dose is one 10-mg Afinitor tablet once daily with or without food1
- A 5-mg tablet is also available if dose reduction is necessary1
- Management of severe and/or intolerable adverse events may require temporary dose reduction and/or interruption of Afinitor therapy1
Dosing and administration recommendations
- Afinitor tablets should be swallowed whole with a glass of water
- The tablets should not be chewed or crushed
CPY3A4 and PgP Inhibitors and inducers
CPY3A4 and PgP Inhibitors
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 use with strong or moderate inhibitors of CYP3A4 or PgP should be avoided where possible. These include but are not limited to: ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, fosamprenavir, voriconazole, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil or diltazem
CPY3A4 and PgP Inducers
Substances that are inducers of CYP3A4 or PgP may decrease Afinitor blood concentrations by increasing metabolism or efflux of Afinitor from intestinal cells, respectively
- An increase in the Afinitor dose is recommended when co-administered with a strong CYP3A4 inducer. These drugs include but are not limited to:
- Dexamethasone
- Phenytoin
- Carbamazapine
- Rifampin
- Rifabutin
- Phenobarbital
Hepatic Impairment
- 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 should not be used in this patient population
Download the Afinitor dosing card to help patients better understand dosing considerations.
Afinitor is indicated for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.
Important Safety Information
Afinitor is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients.
Non-infectious pneumonitis is a class effect of rapamycin derivatives, including Afinitor. Fatal outcomes have been observed. If symptoms are moderate or severe, patients should be managed with dose interruption until symptoms improve or discontinuation, respectively. Corticosteroids may be indicated. Afinitor may be reintroduced at 5 mg daily depending on the individual clinical circumstances.
Afinitor has immunosuppressive properties and may predispose patients to infections. Localized and systemic infections (bacterial and invasive fungal infections) have occurred. Some of these infections have been severe or fatal. Complete treatment of pre-existing invasive fungal infections prior to starting treatment. If a diagnosis of invasive systemic fungal infection is made, discontinue Afinitor and treat with appropriate antifungal therapy.
Oral ulcerations have occurred in patients treated with Afinitor. In such cases, topical treatments are recommended, but alcohol- or peroxide-containing mouthwashes should be avoided. Antifungal agents should not be used unless fungal infection has been diagnosed.
Elevations of serum creatinine, glucose, lipids, and triglycerides and reductions of hemoglobin, lymphocytes, neutrophils and platelets have been reported in clinical trials. Renal function, hematological parameters, blood glucose, and lipids should be evaluated prior to treatment and periodically thereafter. When possible, optimal glucose and lipid control should be achieved before starting a patient on Afinitor.
Co-administration with strong or moderate inhibitors of CYP3A4 or PgP should be avoided. Increase in the Afinitor dose is recommended when co-administered with a strong CYP3A4 inducer.
Afinitor should not be used in patients with severe hepatic impairment.
The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with Afinitor.
Fetal harm can occur if Afinitor is administered to a pregnant woman.
The most common adverse reactions (incidence ≥30%) were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), cough (30%), and diarrhea (30%). The most common grade 3/4 adverse reactions (incidence ≥3%) were infections (9%), dyspnea (8%), fatigue (5%), stomatitis (4%), dehydration (4%), pneumonitis (4%), abdominal pain (3%), and asthenia (3%). The most common laboratory abnormalities (incidence ≥50%) were anemia (92%), hypercholesterolemia (77%), hypertriglyceridemia (73%), hyperglycemia (57%), lymphopenia (51%), and increased creatinine (50%). The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia (18%), hyperglycemia (16%), anemia (13%), hypophosphatemia (6%), and hypercholesterolemia (4%). Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the Afinitor arm.
Full Prescribing Information about Afinitor.
References
- Afinitor [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009.
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