retevmo

Important safety information

Hepatotoxicity: Monitor ALT and AST prior to initiating RETEVMO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.1 ) Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. Withhold, reduce the dose or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.2 ) Hypertension: Do not initiate RETEVMO in patients with uncontrolled hypertension. Optimize blood pressure (BP) prior to initiating RETEVMO. Monitor BP after 1 week, at least monthly thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.3 ) QT Interval Prolongation: Monitor patients who are at significant risk of developing QTc prolongation. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment. Monitor QT interval more frequently when RETEVMO is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and reduce the dose or permanently discontinue RETEVMO based on severity. ( 2.5 , 5.4 ) Hemorrhagic Events: Permanently discontinue RETEVMO in patients with severe or life-threatening hemorrhage. ( 2.5 , 5.5 ) Hypersensitivity: Withhold RETEVMO and initiate corticosteroids. Upon resolution, resume at a reduced dose and increase dose by 1 dose level each week until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. ( 2.5 , 5.6 ) Tumor Lysis Syndrome: Closely monitor patients at risk and treat as clinically indicated. ( 5.7 ) Risk of Impaired Wound Healing: Withhold RETEVMO for at least 7 days 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 RETEVMO after resolution of wound healing complications has not been established. ( 5.8 ) Hypothyroidism: Monitor thyroid function before treatment with RETEVMO and periodically during treatment. Withhold until clinically stable or permanently discontinue based on severity. ( 5.9 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the possible risk to a fetus and to use effective contraception. ( 5.10 , 8.1 , 8.3 ) Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis (SCFE/SUFE) in Pediatric Patients: Monitor patients for symptoms indicative of SCFE/SUFE and treat as medically and surgically appropriate ( 5.11 , 6.1 ) 5.1 Hepatotoxicity Serious hepatic adverse reactions occurred in 4.6% of patients treated with RETEVMO. Increased AST occurred in 62% of patients, including Grade 3 or 4 events in 11% and increased ALT occurred in 58% of patients, including Grade 3 or 4 events in 13% [see Adverse Reactions ( 6.1 )] . The median time to first onset for increased AST was 5 weeks (range: 4.9 days to 6 years) and increased ALT was 4.9 weeks (range: 6 days to 5 years). Monitor ALT and AST prior to initiating RETEVMO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce the dose or permanently discontinue RETEVMO based on the severity [see Dosage and Administration ( 2.5 )] . 5.2 Interstitial Lung Disease/Pneumonitis Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with RETEVMO. ILD/pneumonitis occurred in 3% of patients who received RETEVMO, including 0.3% with Grade 3 or 4 events, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold RETEVMO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce the dose or permanently discontinue RETEVMO based on severity of confirmed ILD [ see Dosage and Administration ( 2.5 ) ]. 5.3 Hypertension Hypertension occurred in 43% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient [see Adverse Reactions ( 6.1 )] . Overall, 6.4% had their dose interrupted, 1.5% had their dose reduced, and 0.2% discontinued RETEVMO for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate RETEVMO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating RETEVMO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce the dose, or permanently discontinue RETEVMO based on the severity [see Dosage and Administration ( 2.5 )] . 5.4 QT Interval Prolongation RETEVMO can cause concentration-dependent QT interval prolongation [see Clinical Pharmacology ( 12.2 )] . An increase in QTcF interval to >500 ms was measured in 8% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 22% of patients [see Adverse Reactions ( 6.1 )] . RETEVMO has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating RETEVMO and during treatment. Monitor the QT interval more frequently when RETEVMO is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and reduce the dose or permanently discontinue RETEVMO based on the severity [see Dosage and Administration ( 2.5 )] . 5.5 Hemorrhagic Events Serious including fatal hemorrhagic events can occur with RETEVMO. Grade ≥3 hemorrhagic events occurred in 4.3% of patients treated with RETEVMO, including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n = 2), tracheostomy site hemorrhage, and hemoptysis (1 each). Permanently discontinue RETEVMO in patients with severe or life-threatening hemorrhage [see Dosage and Administration ( 2.5 )] . 5.6 Hypersensitivity RETEVMO can cause hypersensitivity, including severe skin reactions such as Stevens-Johnson Syndrome. All grade hypersensitivity occurred in 6% of patients receiving RETEVMO, including Grade 3 in 2%. The median time to onset was 1.9 weeks (range: 5 days to 6.5 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. Stevens Johnsons Syndrome has been observed in the post-marketing setting [see Adverse Reactions ( 6.2 )]. Discontinue RETEVMO in patients with Stevens Johnson Syndrome. If hypersensitivity occurs, withhold RETEVMO and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume RETEVMO at a reduced dose and increase the dose of RETEVMO by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity [see Dosage and Administration ( 2.5 )] . Continue steroids until patient reaches target dose and then taper. Permanently discontinue RETEVMO for recurrent hypersensitivity. 5.7 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) occurred in 0.9% of patients with medullary thyroid carcinoma and 0.3% of patients with non-small cell lung cancer receiving RETEVMO [see Adverse Reactions ( 6.1 )] . Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate…