selpercatinib: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
selpercatinib: clinical details
Prescribing considerations
- Confirm an eligible RET fusion or mutation using a validated test before treatment.
- Treatment should be initiated and supervised by clinicians experienced in anticancer therapy.
- Review pulmonary disease, hypertension, QT-prolongation risk, thyroid disease, hepatic impairment, bleeding history, tumour-lysis risk and interacting medicines.
- Discuss contraception and potential impairment of male and female fertility; offer fertility-preservation advice where appropriate.
- In adolescents, monitor open growth plates and investigate unexplained hip or knee pain or limping.
Contraindications and cautions
- Hypersensitivity to selpercatinib or any formulation excipient.
- Do not restart selpercatinib after a severe cutaneous adverse reaction such as Stevens–Johnson syndrome attributed to treatment.
Monitoring
- RET alteration status before treatment.
- ALT and AST before and regularly during treatment.
- Blood pressure before treatment and throughout therapy.
- ECG and potassium, magnesium and calcium, with increased surveillance where QT risk is higher.
- Baseline and periodic thyroid function.
- New or worsening respiratory symptoms, hypersensitivity, bleeding and tumour-lysis syndrome.
- Growth-plate complications in adolescents with open growth plates.
Clinical pharmacology
Selpercatinib selectively inhibits wild-type and altered RET receptor tyrosine kinase. It is metabolised mainly through CYP3A4, inhibits CYP2C8 and CYP3A4, and can inhibit P-glycoprotein, BCRP and MATE1; MATE1 inhibition may raise serum creatinine without a corresponding reduction in glomerular filtration.
Formulation and product differences
- Selected products include film-coated tablets and hard gelatin capsules for oral use.
- Both formulations must be swallowed whole and are considered bioequivalent.
- The film-coated tablets may be taken as multiple smaller tablets when the larger tablet cannot be swallowed; this should follow the prescribed amount.
- Current eMC listings mark the hard-capsule presentations as discontinued, while film-coated tablet presentations remain listed.
selpercatinib preparations and strengths
Tablet
Route: Oral
Strengths: 40 mg, 80 mg
selpercatinib interactions
The oncology team should review prescription medicines, over-the-counter products and herbal remedies before and during treatment.
Strong CYP3A4 inducers, including rifampicin, carbamazepine, phenytoin, phenobarbital and St John’s wort
Can substantially lower selpercatinib exposure and reduce its effectiveness, so concurrent use should be avoided.
Strong CYP3A or P-glycoprotein inhibitors, including itraconazole, voriconazole, posaconazole and ritonavir
Can increase selpercatinib exposure and toxicity, requiring specialist review and possible treatment adjustment.
Proton-pump inhibitors, such as omeprazole
Reduce absorption when selpercatinib is taken fasting; selpercatinib must be taken with a meal if both are required.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.