Sepanix 40

Warnings & Precautions

Hepatotoxicity: Serious liver reactions occurred in 2.6% of patients treated with Selpercatinib. ALT and AST should be checked before starting the medicine, every 2 weeks during the first 3 months, then monthly, and whenever clinically indicated. Depending on how severe the reaction is, the doctor may withhold the medicine, reduce the dose or stop it permanently. Hypertension: Hypertension occurred in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one patient (0.1%). In all, 4.6% had their dose interrupted and 1.3% had their dose reduced because of hypertension. Hypertension that appeared during treatment was most often managed with anti-hypertension medicines. Don't start Selpercatinib in patients whose hypertension is uncontrolled, and bring blood pressure under the best control possible before starting. Check blood pressure after 1 week, then at least monthly and as clinically indicated. Start or adjust anti-hypertensive therapy as appropriate. Withhold, reduce the dose or stop the medicine permanently, based on severity. QT Interval Prolongation: Selpercatinib can cause QT interval prolongation that depends on the concentration of the medicine. The QTcF interval rose to >500 ms in 6% of patients, and it rose by at least 60 ms over baseline in 15% of patients. The medicine has not been studied in patients with clinically significant active cardiovascular disease or a recent myocardial infarction. Patients at significant risk of QTc prolongation need monitoring, including those with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess the QT interval, electrolytes and TSH at baseline and periodically during treatment, and adjust how often based on risk factors, including diarrhea. Correct hypokalemia, hypomagnesemia and hypocalcemia before starting and during treatment. Monitor the QT interval more often when Selpercatinib is given together with strong and moderate CYP3A inhibitors or with drugs known to prolong the QTc interval. Withhold and reduce the dose, or stop permanently, based on severity. Hemorrhagic Events: Serious hemorrhagic events, including fatal ones, can occur with Selpercatinib. Grade >3 hemorrhagic events occurred in 2.3% of patients, and 3 patients (0.4%) had fatal events: one case each of cerebral hemorrhage, tracheostomy site hemorrhage and hemoptysis. Stop the medicine permanently in patients with severe or life-threatening hemorrhage. Hypersensitivity: Hypersensitivity occurred in 4.3% of patients, including Grade 3 hypersensitivity in 1.6%. The median time to onset was 1.7 weeks (range: 6 days to 1.5 years). Signs and symptoms included fever, rash, and arthralgias or myalgias with decreased platelets or transaminitis at the same time. If hypersensitivity occurs, withhold Selpercatinib and start corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Once the event has resolved, restart at a reduced dose, then raise the dose by 1 dose level each week as tolerated until the patient is back to the dose taken before the reaction. Continue the steroids until the target dose is reached, and then taper them. Stop permanently if hypersensitivity recurs. Tumor Lysis Syndrome: Tumor lysis syndrome (TLS) occurred in 1% of patients with medullary thyroid carcinoma receiving Selpercatinib. Patients with rapidly growing tumors, a high tumor burden, renal dysfunction or dehydration may be at risk. Monitor these patients closely, consider suitable prophylaxis including hydration, and treat as clinically indicated.