Selpercatinib
TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
TRK and RET inhibitors (tumour-agnostic kinase inhibitors)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Oral selective RET inhibitor for RET-fusion lung and thyroid cancers and RET-mutant medullary thyroid cancer. Watch the liver, blood pressure and QT.
Quick facts
- Group
- TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
- Target
- RET receptor tyrosine kinase (fusions and activating mutations)
- Used for
- Locally advanced
- Key effects
- Dry mouth · Diarrhoea · Hypertension
- Monitor
- Liver tests closely · Blood pressure before
- ATC
- L01EX22
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal structure shows selpercatinib in the kinase domain of human RET.
Selpercatinib inhibits wild-type RET and its oncogenic forms: RET fusion proteins (in some lung, papillary thyroid and other cancers) and RET point mutations (in medullary thyroid carcinoma). It occupies the kinase site and stops the constant RET signal that drives these tumours; at higher concentrations it also inhibits VEGF and FGF receptors.
- A RET fusion or mutation keeps RET switched on
- Selpercatinib blocks the RET kinase site
- Downstream growth signals stop
- RET-driven tumour cells stop dividing
Indications
- Locally advanced or metastatic non-small cell lung cancer with a RET gene fusion, in adults. Lung cancer →
- Advanced or metastatic RET-mutant medullary thyroid cancer needing systemic therapy, in adults and children aged 2 or older. Medullary thyroid carcinoma →
- Advanced or metastatic RET fusion-positive thyroid cancer needing systemic therapy, including when radioactive iodine no longer works. Thyroid cancer (papillary) →
- Other advanced RET fusion-positive solid tumours that progressed after, or have no alternative to, systemic therapy (accelerated approval).
Adverse effects
Common
- Dry mouth, mouth sores
- Diarrhoea, constipation, nausea, abdominal pain
- Hypertension
- Fatigue, headache
- Swelling of the limbs, rash
Contraindications
- Severe allergy to the drug
- Caution in long QT, uncontrolled hypertension and liver disease; stopped before planned surgery
Key interactions
- Proton pump inhibitors
- Lower absorption; if needed, selpercatinib is taken with food.
- H2 blockers and antacids
- Lower absorption; doses are separated in time.
- Strong CYP3A4 inhibitors and inducers (including grapefruit and St John's wort)
- Raise or lower selpercatinib levels.
- Other QT-prolonging drugs
- Add to the risk of arrhythmia.
What is monitored
- Test showing a RET alteration before starting
- Liver tests closely, especially early in treatment
- Blood pressure before and during treatment
- ECG and electrolytes
- Thyroid function
- Growth and hip or knee pain in children
Administration and safety
- Oral, swallowed whole; a dose vomited is not repeated.
- Check acid-reducing medicines: the timing rules for PPIs, H2 blockers and antacids differ.
- Held before elective surgery because of the risk of poor wound healing.
- Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.
Pregnancy and breastfeeding
May harm the fetus; effective contraception is used by patients and partners during and shortly after treatment; breastfeeding is not advised.
Nursing care
- Measure blood pressure at each visit and report rises.
- Review liver tests and the ECG before refills.
- Ask about palpitations, fainting, bleeding, cough and breathlessness.
- Teaching: report yellow skin, dark urine, severe headache or bleeding; tell any surgeon about the treatment; teenagers report hip or knee pain or a limp.
Pharmacokinetics
- Absorption
- Oral capsules or tablets, with or without food; acid-reducing drugs can lower absorption.
- Metabolism
- Mainly by CYP3A4.
- Half-life
- About 32 hours.
Test yourself
Think of the answer, then tap the question to see it.
Which kinase does selpercatinib target?
RET (fusions and activating mutations).
Which thyroid cancer carries RET point mutations?
Medullary thyroid carcinoma.
Which three monitoring checks are typical with selpercatinib?
Liver tests, blood pressure and the ECG (QT), plus thyroid function.
Why are proton pump inhibitors a problem for selpercatinib?
They lower its absorption; if they are needed, selpercatinib is taken with food.
Connections
← Back to the class: TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Selpercatinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Selpercatinib - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.