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Printer friendlyAfinitor Safety Information
In clinical trials, non-infectious pneumonitis was reported in 14% of patients treated with Afinitor (4% Grade 3, 0% Grade 4).1 Symptoms of moderate–severe pneumonitis should be managed with dose interruption or discontinuation respectively, until symptoms resolve. Corticosteroids may be considered. Approximately 44% of patients treated with Afinitor developed stomatitis. Most cases were Grades 1 and 2. Physicians should be aware of increased risk of infection (37%) and institute appropriate treatment promptly. Other adverse reactions, such as hypertension, cardiac disorders, and hand-foot syndrome, were reported in <10% of patients.1
| Adverse reactions reported in at least 10% of patients and at a higher rate in the Afinitor arm than in the placebo arm1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| CTCAE§ Version 3.0 *Stomatitis (including aphthous stomatitis), and mouth and tongue ulceration. † Includes all preferred terms within the ‘infections and infestations’ system organ class, the most common being nasopharyngitis (6%), pneumonia (6%), urinary tract infection (5%), bronchitis (4%), and sinusitis (3%), and also including aspergillosis (<1%), candidiasis (<1%), and sepsis (<1%). ‡ Includes pneumonitis, interstitial lung disease, lung infiltration, pulmonary alveolar hemorrhage, pulmonary toxicity, and alveolitis. § Common Terminology Criteria for Adverse Events. |
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When administering Afinitor to treat advanced renal cell carcinoma, dose reduction is recommended in patients with moderate hepatic impairment. Treatment of patients with severe hepatic impairment is not recommended. The dose of Afinitor should be increased when co-administering a strong CYP3A4 inducer (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, or phenobarbital). When use of strong CYP3A4 inducers cannot be avoided, Afinitor dosage should be increased. Concomitant treatment of strong and moderate CYP3A4 and PgP inhibitors should be avoided. Women who could become pregnant should be advised to use an effective method of contraception while using Afinitor and up to 8 weeks after ending treatment.1
Renal function
Elevations of serum creatinine, usually mild, have been reported in clinical trials. Monitoring of renal function, including measurement of blood urea nitrogen (BUN) or serum creatinine, is recommended prior to the start of Afinitor therapy and periodically thereafter.
Blood glucose and lipids
Hyperglycemia, hyperlipidemia, and hypertriglyceridemia have been reported in clinical trials. Monitoring of fasting serum glucose and lipid profile is recommended prior to the start of Afinitor therapy and periodically thereafter. When possible, optimal glucose and lipid control should be achieved before starting a patient on Afinitor.
Hematological parameters
Decreased hemoglobin,lymphocytes, neutrophils, and platelets have been reported in clinical trials. Monitoring of complete blood count is recommended prior to the start of Afinitor therapy and periodically thereafter.
| Key laboratory abnormalities reported at a higher rate in the Afinitor arm than the placebo arm1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| CTCAE† Version 3.0 * Includes reports of anemia, leukopenia, lymphopenia, neutropenia, pancytopenia, and thrombocytopenia. † Common Terminology Criteria for Adverse Events. |
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Find support resources to download for your patients with advanced renal cell carcinoma by clicking here.
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.
