h AFINITOR. Complete treatment of pre-existing invasive fungal infections prior to starting treatment with AFINITOR. While taking AFINITOR, be vigilant for signs and symptoms of infection; if a diagnosis of an infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of AFINITOR. If a diagnosis of invasive systemic fungal infection is made, discontinue AFINITOR and treat with appropriate antifungal therapy.
Pneumocystis jiroveci pneumonia, some with a fatal outcome, has been reported in patients who received everolimus. This may be associated with concomitant use of corticosteroids or other immunosuppressive agents. Prophylaxis for PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required.
5.3 Angioedema with Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors
Patients taking concomitant ACE inhibitor therapy may be at increased risk for angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment). In a pooled analysis of randomized double-blind oncology clinical trials, the incidence of angioedema in patients taking everolimus with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor.
5.4 Oral Ulceration
Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44%-78% across the clinical trial experience. Grade 3 or 4 stomatitis was reported in 4%-9% of patients [see Adverse Reactions (6.1, 6.2, 6.3, 6.4, 6.5)]. In such cases, topical treatments are recommended, but alcohol-, hydrogen peroxide-, iodine-, or thyme- containing mouthwashes should be avoided as they may exacerbate the condition. Antifungal agents should not be used unless fungal infection has been diagnosed [see Drug Interactions (7.1)].
5.5 Renal Failure
Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR [see Laboratory Tests and Monitoring (5.8)].
5.6 Impaired Wound Healing
Everolimus delays wound healing and increases the occurrence of wound-related complications like wound dehiscence, wound infection, incisional hernia, lymphocele, and seroma. These wound-related complications may require surgical intervention. Exercise caution with the use of AFINITOR in the peri-surgical period.
5.7 Geriatric Patients
In the randomized advanced hormone receptor-positive, HER2-negative breast cancer study, the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥ 65 years of age compared to 2% in patients < 65 years of age. Adverse reactions leading to permanent treatment discontinuation occurred in 33% of patients ≥ 65 years of age compared to 17% in patients < 65 years of age. Careful monitoring and appropriate dose adjustments for adverse reactions are recommended [see Dosage and Administration (2.2), Use in Specific Populations (8.5)].
5.8 Laboratory Tests and Monitoring
Renal Function
Elevations of serum creatinine and proteinuria have been reported in patients taking AFINITOR [see Adverse Reactions (6.1, 6.2, 6.3, 6.4, 6.5)]. Monitoring of renal function, including measurement of blood urea |
