Important Safety Information
Important note: Before prescribing, consult the full prescribing information.
Presentation: Tablets containing 2.5 mg, 5 mg or 10 mg of everolimus.
Indications: AFINITOR is indicated for the treatment of hormone receptor-positive, HER2/neu negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a nonsteroidal aromatase inhibitor. ♦AFINITOR is indicated for the treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease. ♦AFINITOR is indicated for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease. ♦AFINITOR is indicated for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy.
Dosage: AFINITOR 10 mg dose once daily. ♦The daily dose should be taken orally at the same time every day, either consistently with or consistently without food. ♦Dose modification: Management of adverse reactions may require dose reduction, temporary dose interruption, or discontinuation of AFINITOR therapy. Dose modifications may be required due to use of moderate CYP3A4/PgP inhibitors or strong CYP3A4 inducers or hepatic status (Child-Pugh). ♦Children: Not recommended for use in children or adolescents. ♦Patients with hepatic impairment: The recommended dose is 7.5 mg daily in patients with mild hepatic impairment (Child-Pugh A); 5 mg daily in patients with moderate hepatic impairment (Child-Pugh B); not recommended in patients with severe hepatic impairment (Child-Pugh C), unless benefit outweighs the risk. In the latter case, a dose of 2.5 mg daily must not be exceeded. Dose adjustments should be made if a patient’s hepatic (Child-Pugh) status changes during treatment.
Contraindications: Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients.
Warnings and Precautions: ♦Non-infectious pneumonitis: Cases have been described in patients taking AFINITOR, some of these have been severe and on rare occasions, a fatal outcome was observed. A diagnosis of non-infectious pneumonitis should be considered in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough or dyspnoea, and in whom infectious, neoplastic, and other non-medicinal causes have been excluded. Opportunistic infections such as pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) should be ruled out in the differential diagnosis of non-infectious pneumonitis. Management of pneumonitis may require interruption or discontinuation of treatment. The use of corticosteroids may be indicated. For patients who require use of corticosteroids for the treatment of non-infectious pneumonitis, prophylaxis for PJP/PCP may be considered. AFINITOR may be reinitiated at a lower dose. ♦Infections: AFINITOR is immunosuppressive. Localized and systemic bacterial, fungal, viral, or protozoal infections (e.g. pneumonia, aspergillosis, candidiasis, or PJP/PCP and hepatitis B reactivation) have been described in patients taking AFINITOR; some of these have been severe and occasionally fatal. Pre-existing infections should be resolved prior to starting treatment with AFINITOR. Be vigilant for symptoms or signs of infection during treatment with AFINITOR. In case of emergent infections, 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. Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. ♦Hypersensitivity reactions: have been observed with everolimus. ♦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). ♦Stomatitis: Stomatitis is the most commonly reported adverse reaction in patients treated with AFINITOR and mostly occurs within the first 8 weeks of treatment. Management may require temporary dose interruption, dose reduction or discontinuation. Management may also include prophylactic and/or therapeutic use of topical treatments, such as an alcohol-free corticosteroid oral solution as a mouthwash. However, products containing alcohol, hydrogen peroxide, iodine, and thyme derivatives should be avoided. Monitoring for and treatment of fungal infection is recommended, especially in patients being treated with steroid-based medications. Antifungal agents should not be used unless fungal infection has been diagnosed. ♦Renal failure: Cases of renal failure (including acute renal failure), some fatal, have been observed in patients treated with AFINITOR. Renal function of patients should be monitored particularly where patients have additional risk factors that may further impair their renal function. ♦Laboratory tests and monitoring: Renal function, blood glucose, blood lipids, and complete blood counts are recommended prior to initiation of and periodically during treatment. ♦Functional carcinoid tumours: The safety and efficacy of AFINITOR in patients with functional carcinoid tumours have not been established. ♦Prognostic factors in neuroendocrine tumors of gastrointestinal or lung origin: In patients with non-functional gastrointestinal or lung neuroendocrine tumours and good prognostic baseline factors, e.g. ileum as primary tumour origin and normal chromogranin A values or without bone involvement, an individual benefit-risk assessment should be performed prior to the start of AFINITOR therapy. A limited evidence of PFS benefit was reported in the subgroup of patients with ileum as primary tumour origin. ♦Interactions: Co administration with inhibitors and inducers of CYP3A4 and/or PgP should be avoided. If co administration of a moderate CYP3A4 and/or PgP inhibitor or inducer cannot be avoided, dose adjustments of AFINITOR can be taken into consideration based on predicted AUC. Concomitant treatment of AFINITOR and potent inhibitors is not recommended. Caution should be exercised when AFINITOR is taken in combination with orally administered CYP3A4 substrates with a narrow therapeutic index; the patient should be monitored for undesirable effects described in the product information of the orally administered CYP3A4 substrate. ♦Hepatic Impairment: Not recommended in patients with severe severe hepatic impairment (Child-Pugh C) unless the potential benefit outweighs the risk. ♦Vaccination: Avoid use of live vaccines and close contact with people who have received live vaccines. ♦Lactose: Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take AFINITOR. ♦Wound healing complications: Caution should be exercised with use of AFINITOR in peri-surgical period.
♦Pregnancy: AFINITOR is not recommended during pregnancy and in women of childbearing potential not using contraception. Male patients taking AFINITOR should not be prohibited from attempting to father children. ♦Women of childbearing potential: Use highly effective contraception methods while receiving AFINITOR and for up to 8 weeks after ending treatment. ♦Breast-feeding: Women taking AFINITOR should not breast-feed during treatment and for 2 weeks after the last dose. ♦Fertility: Male and female fertility may be compromised by treatment with AFINITOR.
Interactions: See “Interactions” subsection of Warnings and Precautions.
Adverse drug reactions: ♦Very common (≥10%): Infections, anemia, decreased appetite, hyperglycemia, hypercholesterolemia, dysgeusia, headache, pneumonitis, epistaxis, cough, stomatitis, diarrhea, nausea, rash, pruritus, fatigue, asthenia, edema peripheral, weight decreased. ♦Common (≥1 to <10%): Thrombocytopenia, neutropenia, leukopenia, lymphopenia, hypertriglyceridemia, hypophosphatemia, diabetes mellitus, hyperlipidemia, hypokalemia, dehydration, hypocalcemia, insomnia, eyelid edema, hemorrhage, hypertension, dyspnea, vomiting, dry mouth, abdominal pain, mucosal inflammation, oral pain, dyspepsia, dysphagia, aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, dry skin, nail disorders, mild alopecia, acne, erythema, onychoclasis, palmar plantar erythrodysaesthesia syndrome, skin exfoliation, skin lesion, arthralgia, proteinuria, blood creatinine increased, renal failure, menstruation irregular, pyrexia. ♦Uncommon (≥0.1 to <1%): Pancytopenia, hypersensitivity, ageusia, conjunctivitis, congestive cardiac failure, flushing, deep vein thrombosis, hemoptysis, pulmonary embolism, increased daytime urination, acute renal failure, amenorrhea, non-cardiac chest pain, impaired wound healing. ♦Rare (<0.1%): Pure red cell aplasia, acute respiratory distress syndrome, angioedema. ♦In clinical trials and post-marketing reports, everolimus has been associated with serious cases of hepatitis B reactivation, including fatal outcome. Reactivation of infections is an expected event during periods of immunosuppression. In clinical trials and post-marketing spontaneous reports, everolimus has been associated with renal failure events (including fatal outcome), proteinuria, and cases of amenorrhea (secondary amenorrhea and other menstrual irregularities). In clinical studies and post marketing spontaneous reports, everolimus has been associated with cases of PJP/PCP, some with fatal outcome. In clinical trials and post-marketing spontaneous reports, angioedema has been reported with and without concomitant use of ACE inhibitors.
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