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warnings and cautions
5 WARNINGS AND PRECAUTIONS Non-Infectious Pneumonitis : Monitor for clinical symptoms or radiological changes. Withhold or permanently discontinue based on severity. ( 2.9 , 5.1 ) Infections : Monitor for signs and symptoms of infection. Withhold or permanently discontinue based on severity. ( 2.9 , 5.2 ) Severe Hypersensitivity Reactions : Permanently discontinue for clinically significant hypersensitivity. ( 5.3 ) Angioedema : Patients taking concomitant angiotensin-converting-enzyme (ACE) inhibitors may be at increased risk for angioedema. Permanently discontinue for angioedema. ( 5.4 , 7.2 ) Stomatitis : Initiate dexamethasone alcohol-free mouthwash when starting treatment. ( 5.5 , 6.1 ) Renal Failure : Monitor renal function prior to treatment and periodically thereafter. ( 5.6 ) Risk of Impaired Wound Healing : Withhold for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of treatment after resolution of wound healing complications has not been established. ( 5.7 ) Geriatric Patients : Monitor and adjust dose for adverse reactions. ( 5.8 ) Metabolic Disorders : Monitor serum glucose and lipids prior to treatment and periodically thereafter. Withhold or permanently discontinue based on severity. ( 2.9 , 5.9 ) Myelosuppression : Monitor hematologic parameters prior to treatment and periodically thereafter. Withhold or permanently discontinue based on severity. ( 2.9 , 5.10 ) Risk of Infection or Reduced Immune Response with Vaccination : Avoid live vaccines and close contact with those who have received live vaccines. Complete recommended childhood vaccinations prior to starting treatment. ( 5.11 ) Radiation Sensitization and Radiation Recall : Severe radiation reactions may occur. ( 5.12 , 6.2 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.13 , 8.1 , 8.3 ) 5.1 Non-infectious Pneumonitis Non-infectious pneumonitis is a class effect of rapamycin derivatives. Non-infectious pneumonitis was reported in up to 19% of patients treated with AFINITOR/AFINITOR DISPERZ in clinical trials, some cases were reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event. The incidence of Grade 3 and...
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adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Non-Infectious Pneumonitis [see Warnings and Precautions (5.1)] Infections [see Warnings and Precautions (5.2)] Severe Hypersensitivity Reactions [see Warnings and Precautions (5.3)] Angioedema with Concomitant Use of ACE inhibitors [see Warnings and Precautions (5.4)] Stomatitis [see Warnings and Precautions (5.5)] Renal Failure [see Warnings and Precautions (5.6)] Impaired Wound Healing [see Warnings and Precautions (5.7)] Metabolic Disorders [see Warnings and Precautions (5.9)] Myelosuppression [see Warnings and Precautions (5.10)] Radiation Sensitization and Radiation Recall [see Warnings and Precautions (5.12)] Breast cancer, NET, RCC : Most common adverse reactions (incidence ≥ 30%) include stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, fever, asthenia, cough, headache, and decreased appetite. ( 6.1 ) TSC-Associated Renal Angiomyolipoma : Most common adverse reaction (incidence ≥ 30%) is stomatitis. ( 6.1 ) TSC-Associated SEGA : Most common adverse reactions (incidence ≥ 30%) are stomatitis and respiratory tract infection. ( 6.1 ) TSC-Associated Partial-Onset Seizures : Most common adverse reaction (incidence ≥ 30%) is stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. Hormone Receptor-Positive, HER2-Negative Breast Cancer The safety of AFINITOR (10 mg orally once daily) in combination with exemestane (25 mg orally once daily) (n = 485) vs. placebo in combination with exemestane (n = 239) was evaluated in a randomized, controlled trial (BOLERO-2) in patients with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The median age of patients was 61 years (28 to 93 years), and 75% were white. The median follow-up was approximately 13 months. The most common adverse reactions (incidence ≥ 30%) were stomatitis, infections, rash, fatigue, diarrhea, and decreased appetite. The most common Grade 3-4 adverse reactions (incidence ≥ 2...
adverse reactions table
Table 7: Adverse Reactions Reported in ≥ 10% of Patients With Hormone Receptor-Positive Breast Cancer in BOLERO-2Grading according to NCI CTCAE Version 3.0. aIncludes stomatitis, mouth ulceration, aphthous stomatitis, glossodynia, gingival pain, glossitis, and lip ulceration. bIncludes all reported infections, including but not limited to, urinary tract infections, respiratory tract (upper and lower) infections, skin infections, and gastrointestinal tract infections. cIncludes pneumonitis, interstitial lung disease, lung infiltration, and pulmonary fibrosis. dNo Grade 4 adverse reactions were reported. AFINITOR with Exemestane N = 482Placebo with Exemestane N = 238All GradesGrade 3-4All GradesGrade 3-4%%%%Gastrointestinal Stomatitisa678d110.8 Diarrhea332180.8 Nausea290.4281 Vomiting171120.8 Constipation140.4d130.4 Dry mouth11070General Fatigue364271d Edema peripheral191d60.4d Pyrexia150.2d70.4d Asthenia13240Infections Infectionsb506252dInvestigations Weight loss251d60Metabolism and nutrition Decreased appetite301d120.4d Hyperglycemia14520.4dMusculoskeletal and connective tissue Arthralgia200.8d170 Back pain140.2d100.8d Pain in extremity90.4d112dNervous system Dysgeusia220.2d60 Headache210.4d140Psychiatric Insomnia130.2d80Respiratory, thoracic and mediastinal Cough240.6d120 Dyspnea214111 Epistaxis17010 Pneumonitisc1940.40Skin and subcutaneous tissue Rash391d60 Pruritus130.2d50 Alopecia10050Vascular Hot flush60140