Afinitor by Novartis Pharmaceuticals, Inc

Specialty Pharmacy TimesMay/June 2015
Volume 6
Issue 3

Afinitor (everolimus) is approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.

Afinitor (everolimus) is approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.

In 2009, Novartis Pharmaceuticals received FDA approval for Afinitor (everolimus) tablets. Currently, the medication is indicated for several conditions, including the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in postmenopausal women who have failed to achieve treatment response with letrozole or anastrozole. The FDA approved this indication on July 20, 2012. Contraindications for use include hypersensitivity to everolimus, other rapamycin derivatives, or any excipients.1,2

Mechanism of Action

Everolimus is thought to inhibit a specific protein, known as mammalian target of rapamycin, which ultimately reduces estrogen-receptor activation and vascular endothelial growth factor expression. Consequently, the use of everolimus is thought to reduce cell proliferation, angiogenesis, and glucose uptake.2

Dosage and Administration

Afinitor tablets are available in 2.5-, 5-, 7.5-, and 10-mg strengths. The medication should be taken consistently with food or consistently without food and should always be taken with a full glass of water. Patients should never break, crush, or split tablets.2

In patients with breast cancer, progressive neuroendocrine tumors of pancreatic origin, renal cell carcinoma, or renal angiomyolipoma with tuberous sclerosis complex, the usual dose of Afinitor is 10 mg daily. The dosage may be reduced, however, in patients with hepatic impairment and in patients taking moderate CYP3A4/P-glycoprotein (PgP) inhibitors.2

Pharmacology and Pharmacokinetics

The elimination half-life of the active medication in Afinitor is approximately 30 hours. Excretion occurs primarily hepatically, with minimal renal excretion. As a result, the maximum dose should be limited to 7.5 mg daily, 5 mg daily, and 2.5 mg daily in Child-Pugh class A, B, and C hepatic impairment, respectively. In addition, everolimus levels should be monitored periodically in patients with hepatic impairment.2

Clinical Trials: Breast Cancer

In clinical studies, a combination of Afinitor and exemestane was administered to patients with advanced HR-positive, HER2-negative breast cancer that has progressed or recurred despite treatment with letrozole or anastrozole. A total of 724 postmenopausal women involved in the trial were randomized in a 2:1 ratio to receive active treatment (Afinitor 10 mg daily plus exemestane 25 mg daily) or placebo (placebo plus exemestane 25 mg daily).2,3

Median progression-free survival was significantly (P <.0001) longer in patients receiving Afinitor plus exemestane (7.8 months) compared with patients receiving placebo plus exemestane (3.2 months). Rates of objective response were 12.6% in the active treatment group compared with 1.7% in the placebo group. However, after 39.3 months of follow-up, investigators did not detect any significant improvement in overall survival between groups (HR 0.89; 95% CI; 0.73-1.10).2,3

Warnings and Precautions

In patients taking Afinitor, CYP3A4/PgP inhibitors or inducers may change therapeutic levels of everolimus, the active medication in Afinitor. As a result, patients should avoid using CYP3A4/PgP inhibitors or inducers with Afinitor. In addition, patients taking Afinitor should not receive live vaccines and should avoid close contact with individuals who have received live vaccines.2

Afinitor is a Pregnancy Category D medication. Everolimus has caused embryo-fetal toxicities in animals at equivalent doses lower than those used in humans. Women who are breastfeeding should not take Afinitor.2

Patients taking Afinitor should be monitored for signs and symptoms of pneumonitis, infection, angioedema, and oral ulceration, and changes in renal function. In addition, blood glucose levels, lipid levels, and other hematologic parameters should be assessed regularly. Depending on the seriousness of the adverse event (AE), dose reductions or complete discontinuation of Afinitor therapy may be necessary in patients with pneumonitis, stomatitis, nonhematologic toxicities, or metabolic events.2

AEs of any grade occurring in at least 30% of patients in the active treatment group (Afinitor plus exemestane) included stomatitis, infections, rash, fatigue, diarrhea, and decreased appetite. For a complete discussion of potential AEs, please consult the product package insert.2 SPT


  • FDA approves Afinitor for advanced breast cancer [press release]. Silver Spring, MD: FDA. July 20, 2012. Accessed April 2015.
  • Afinitor (everolimus) tablets [package insert]. East Hanover, NJ: Novartis; 2015.
  • Rugo HS, Pritchard KI, Gnant M, et al. Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2. Ann Oncol. 2014;25(4):808-815. doi: 10.1093/annonc/mdu009.

About the Author

Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.

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