Selpercatinib requires clinical monitoring because its pharmacologic activity and drug interactions can produce clinically important toxicity.
Hepatotoxicity
Liver injury is a major safety concern. Current U.S. labeling recommends measuring ALT and AST before treatment, every two weeks during the first three months, then monthly and as clinically indicated. Dose interruption, reduction or permanent discontinuation may be required depending on severity.
Interstitial lung disease and pneumonitis
ILD/pneumonitis can be severe, life-threatening or fatal. New or worsening dyspnea, cough or fever should be evaluated promptly because these symptoms may indicate pulmonary toxicity.
Hypertension
Uncontrolled hypertension should be addressed before treatment. Blood pressure should be checked after one week and at least monthly thereafter under the current U.S. label.
QT prolongation
Selpercatinib can cause concentration-dependent QT prolongation. Current labeling recommends ECG, electrolyte and TSH monitoring in patients at significant risk, with additional monitoring when interacting medicines are required.
Hemorrhagic events
Serious, including fatal, hemorrhagic events can occur. Patients with relevant bleeding risks require clinical consideration and monitoring.
Hypersensitivity
Hypersensitivity reactions can occur, including fever, rash and muscle or joint pain. These reactions may be particularly relevant during the early treatment period.
Tumor lysis syndrome
Rapid breakdown of tumor cells can produce tumor lysis syndrome, which can cause metabolic abnormalities and kidney or cardiac complications. Monitoring may be appropriate in patients at risk.
Drug interactions
Important interactions include:
- PPIs, H2-receptor antagonists and antacids.
- Strong and moderate CYP3A inhibitors.
- Strong and moderate CYP3A inducers.
- Certain CYP2C8 and CYP3A substrates.
- Certain P-gp and BCRP substrates.
- Other medicines that prolong QT.
Pregnancy
Selpercatinib can cause fetal harm based on animal data. Pregnancy status should be verified before treatment in females of reproductive potential. Effective contraception is recommended during treatment and for one week after the last dose under current U.S. labeling.
Breastfeeding
Women are advised not to breastfeed during treatment and for one week after the last dose because of the potential for serious adverse reactions in breastfed children.