besremi

Important safety information

Depression and Suicide: Monitor for symptoms and need for treatment. ( 5.1 ) • Endocrine Toxicity: Discontinue if endocrine disorders occur that cannot be medically managed. ( 5.2 ) • Cardiovascular Toxicity: Avoid use in patients with severe or unstable cardiovascular disease. Monitor patients with history of cardiovascular disorders more frequently. ( 5.3 ) • Hematologic and Hemorrhagic Disorders: Perform blood counts at baseline, every 2 weeks during titration, and at least every 3-6 months during maintenance treatment. ( 5.4 ) • Hypersensitivity Reactions: Stop treatment and immediately manage reaction. ( 5.5 ) • Pancreatitis: Consider discontinuation if confirmed pancreatitis. ( 5.6 ) • Colitis: Discontinue if signs or symptoms of colitis. ( 5.7 ) • Pulmonary Toxicity: Discontinue if pulmonary infiltrates or pulmonary function impairment. ( 5.8 ) • Ophthalmologic Toxicity: Monitor for ocular toxicity. Promptly evaluate eye symptoms and discontinue if new or worsening eye disorders. ( 5.9 ) • Hyperlipidemia: Monitor serum triglycerides before BESREMi treatment and intermittently during therapy and manage when elevated. ( 5.10 ) • Hepatotoxicity: Monitor liver enzymes and hepatic function at baseline and during treatment. Reduce dose or discontinue depending on severity. ( 5.11 ) • Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Discontinue if severe renal impairment develops. ( 5.12 ) • Dental and Periodontal Toxicity: Advise on good oral hygiene and regular dental examinations. ( 5.13 ) • Dermatologic Toxicity: Consider discontinuing if clinically significant dermatologic toxicity. ( 5.14 ) • Driving and Operating Machinery: Advise patients to avoid driving or using machinery if they experience dizziness, somnolence, or hallucination. ( 5.15 ) • Embryo-Fetal Toxicity: Can cause fetal harm. ( 5.16 ) 5.1 Depression and Suicide Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving interferon alfa products, including BESREMi. These reactions may occur in patients with and without previous psychiatric illness. Psychiatric reactions have been observed in 10% of BESREMi-treated patients with essential thrombocythemia including depression, adjustment disorder with depressed mood, and depressed mood. Serious neuropsychiatric reactions have been observed in 3% of BESREMi-treated patients with polycythemia vera, including depression, depressive symptoms, depressed mood, and listlessness. Of these cases, 3.4% of the patients recovered with temporary drug interruption and 2.8% stopped BESREMi treatment. Other central nervous system effects, including suicidal ideation, attempted suicide, aggression, bipolar disorder, mania and confusion have been observed with other interferon alfa products. BESREMi is contraindicated in patients with a history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt [see Contraindications ( 4 )] . Closely monitor patients for any symptoms of psychiatric disorders and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue BESREMi therapy. 5.2 Endocrine Toxicity Endocrine toxicity has occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include worsening hypothyroidism and hyperthyroidism. Autoimmune thyroiditis and hyperglycemia, including new onset type 1 diabetes, have been reported in patients receiving interferon alfa-2b products. Endocrine toxicities included hyperthyroidism (1.1%), hypothyroidism (1.1%), autoimmune thyroiditis (0.5%), and thyroiditis (0.5%) in BESREMi-treated patients with essential thrombocythemia. Endocrine toxicities included hyperthyroidism (4.5%), hypothyroidism (3.9%), and autoimmune thyroiditis/thyroiditis (2.8%) in BESREMi-treated patients with polycythemia vera. Do not use BESREMi in patients with active serious or untreated endocrine disorders associated with autoimmune disease [see Contraindications ( 4 )] . Evaluate thyroid function in patients who develop symptoms suggestive of thyroid disease during BESREMi therapy. Discontinue BESREMi in patients who develop endocrine disorders that cannot be adequately managed during treatment with BESREMi. 5.3 Cardiovascular Toxicity Cardiovascular toxicity has occurred in patients receiving interferon alfa products, including BESREMi. Toxicities may include cardiomyopathy, myocardial infarction, atrial fibrillation, coronary artery ischemia, and acute coronary syndrome [see Adverse Reactions ( 6.1 )] . Three thrombotic events of transient ischemic attack (grade 2, 1 patient), pulmonary embolism (grade 3, 1 patient), and peripheral vein thrombosis (grade 2, 1 patient) occurred in the essential thrombocythemia Phase 3 SURPASS ET study. Patients with a history of cardiovascular disorders and/or thrombotic events should be closely monitored for cardiovascular toxicity and/or thrombotic events during BESREMi therapy. Avoid use of BESREMi in patients with severe or unstable cardiovascular disease (e.g., uncontrolled hypertension, congestive heart failure (≥ NYHA class 2), serious cardiac arrhythmia, significant coronary artery stenosis, unstable angina) or recent stroke or myocardial infarction. 5.4 Hematologic and Hemorrhagic Disorders Decreased peripheral blood counts have occurred in patients receiving interferon alfa products, including BESREMi. These toxicities may include thrombocytopenia (increasing the risk of bleeding), anemia, and leukopenia (increasing the risk of infection). In BESREMi-treated patients with essential thrombocythemia, anemia of grade 3 or greater occurred in 1% of patients. Leukopenia of grade 3 or greater occurred in 2% of patients. Infection occurred in 45% of patients, while serious infections occurred in 4% of patients. Essential thrombocythemia-related hemorrhagic cases occurred in 6% of patients and included gingival bleeding, tongue hemorrhage, epistaxis, purpura, and retinal hemorrhage. In BESREMi-treated patients with polycythemia vera, thrombocytopenia of grade 3 (platelet counts <50,000 – 25,000/mm 3 ) or greater occurred in 2% of patients. Anemia of grade 3 (Hgb <8 g/dL) or greater occurred in 1% of patients. Leukopenia of grade 3 (WBC counts <2,000 – 1,000/mm 3 ) or greater occurred in 2% of patients. Infection occurred in 48% of patients, while serious infections occurred in 8% of patients. Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of infection or bleeding. 5.5 Hypersensitivity Reactions Hypersensitivity reactions have occurred in patients receiving interferon alfa products, including BESREMi. BESREMi is contraindicated in patients with hypersensitivity reactions to interferon products or any of the inactive ingredients in BESREMi [see Contraindications ( 4 )] . Toxicities may include serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis, drug eruption). If such reactions occur, discontinue BESREMi and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment. 5.6 Pancreatitis Pancreatitis has occurred in patients receiving interferon alfa products, including BESREMi. Pancreatitis was reported in 2.2% of patients receiving BESREMi for polycythemia vera. Symptoms may include nausea, vomiting, upper abdominal pain, bloating, and fever. Patients may experience elevated lipase, amylase, white blood cell count, or altered renal/hepatic function. Interrupt BESREMi treatment in patients with possible pancreatitis and evaluate promptly. Consider discontinuation of BESREMi in patients with confirmed pancreatitis. 5.7 Colitis Serious and, in very rare cases potentially life-threatening ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving interferon alfa…