Selpercatinib Disease Interactions

Serious including fatal hemorrhagic events can occur with the use of selpercatinib. Care should be exercised when using this agent in patients with bleeding disorders. It is recommended to permanently discontinue treatment in patients with severe or life-threatening hemorrhage.

Selpercatinib may cause hypertension and therapy should not be initiated in patients with uncontrolled hypertension. Care should be exercised when using this agent in hypertensive patients. Optimize blood pressure before starting treatment. It is recommended to monitor blood pressure after 1 week, and regularly as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue treatment based on the severity.

Selpercatinib may cause severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis. Monitor for new or worsening pulmonary symptoms. Withhold therapy and promptly investigate acute or worsening respiratory symptoms suggestive of ILD/pneumonitis (e.g., dyspnea, cough, and fever).

Selpercatinib is metabolized predominantly by CYP450 3A4. The dose of selpercatinib should be reduced in patients with severe hepatic impairment. No dosage modification is recommended for patients with mild or moderate hepatic impairment. Serious hepatic adverse reactions have been reported in patients treated with selpercatinib. Monitor ALT and AST before starting therapy with selpercatinib, every two weeks during the first three months, then monthly thereafter and as clinically indicated. It is recommended to withhold, reduce dose or permanently discontinue treatment based on the severity of selpercatinib-related adverse reactions in patients with hepatic impairment.

Tumor lysis syndrome has been reported with use of selpercatinib in patients with medullary thyroid carcinoma. Patients with rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration who take selpercatinib may be at increased risk. Closely monitor at-risk patients and consider appropriate prophylaxis, including hydration.

Selpercatinib can cause concentration-dependent QT interval prolongation. 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. This drug has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Assess QT interval, electrolytes, and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors, including diarrhea or drug interactions. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating therapy.

A recommended dose of selpercatinib has not been established for patients with end-stage renal disease. No dosage modification is recommended for patients with mild to severe renal impairment. The use of selpercatinib may increase serum creatinine. It is recommended to consider alternative markers of renal function if persistent elevations in serum creatinine are observed.