Active Ingredient: Selpercatinib
Selpercatinib as monotherapy is indicated for the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: In case that patient weight is ≤ 50 kg, oral, 120 milligrams selpercatinib, 2 times daily.
Regimen B: In case that patient weight is ≥ 50 kg, oral, 160 milligrams selpercatinib, 2 times daily.
The presence of a RET gene fusion should be confirmed by a validated test prior to initiation of treatment with selpercatinib.
The recommended dose of selpercatinib based on body weight is:
If a patient vomits or misses a dose, the patient should be instructed to take the next dose at its scheduled time; an additional dose should not be taken.
Treatment should be continued until disease progression or unacceptable toxicity.
The current selpercatinib dose should be reduced by 50% if co-administering with a strong CYP3A inhibitor. If the CYP3A inhibitor is discontinued, the selpercatinib dose should be increased (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.
Based on results from a preclinical study, open growth plates in adolescent patients should be monitored. Dose interruption or discontinuation should be considered based on the severity of any growth plate abnormalities and an individual risk-benefit assessment.
Management of some adverse reactions may require dose interruption and/or dose reduction. Selpercatinib dose modifications are summarised in Table 1 and Table 2.
Table 1. Recommended dose modifications for selpercatinib for adverse reactions based on body weight:
| Dose modification | Adults and adolescents ≥50 Kg | Adults and adolescents <50 Kg |
|---|---|---|
| Starting dose | 160 mg orally twice daily | 120 mg orally twice daily |
| First dose reduction | 120 mg orally twice daily | 80 mg orally twice daily |
| Second dose reduction | 80 mg orally twice daily | 40 mg orally twice daily |
| Third dose reduction | 40 mg orally twice daily | Not applicable |
Table 2. Recommended dose modifications for adverse reactions:
| Adverse drug reaction (ADR) | Dose modification | |
|---|---|---|
| Increased ALT or AST | Grade 3 or Grade 4 | • Suspend dose until toxicity resolves to baseline. Resume at a dose reduced by 2 levels. • If after at least 2 weeks selpercatinib is tolerated without recurrent increased ALT or AST, increase dosing by 1 dose level. • If selpercatinib is tolerated without recurrence for at least 4 weeks, increase to dose taken prior to the onset of Grade 3 or 4 increased AST or ALT. • Permanently discontinue selpercatinib if Grade 3 or 4 ALT or AST increases recur despite dose modifications. |
| Hypersensitivity | All Grades | • Suspend dose until toxicity resolves and begin corticosteroids at a dose of 1 mg/kg. Resume selpercatinib at 40 mg twice daily while continuing steroid treatment. Discontinue selpercatinib for recurrent hypersensitivity. • If after at least 7 days, selpercatinib is tolerated without recurrent hypersensitivity, incrementally increase the selpercatinib dose by 1 dose level each week, until the dose taken prior to the onset of hypersensitivity is reached. Taper steroid dose after selpercatinib has been tolerated for at least 7 days at the final dose. |
| QT interval prolongation | Grade 3 | • Suspend dose for QTcF intervals >500 ms until the QTcF returns to <470 ms or baseline. • Resume selpercatinib treatment at the next lower dose level. |
| Grade 4 | • Permanently discontinue selpercatinib if QT prolongation remains uncontrolled after two dose reductions or if the patient has signs or symptoms of serious arrhythmia. | |
| Hypertension | Grade 3 | • Patient blood pressure should be controlled before starting treatment. • Selpercatinib should be suspended temporarily for medically significant hypertension until controlled with antihypertensive therapy. Dosing should be resumed at the next lower dose if clinically indicated. |
| Grade 4 | • Selpercatinib should be discontinued permanently if medically significant hypertension cannot be controlled. | |
| Haemorrhagic events | Grade 3 or Grade 4 | • Selpercatinib should be suspended until recovery to baseline. • Discontinue selpercatinib for severe or life-threatening haemorrhagic events. |
| Interstitial lung disease (ILD)/Pneumonitis | Grade 2 | • Withhold selpercatinib until resolution. • Resume at a reduced dose. • Discontinue selpercatinib for recurrent ILD/pneumonitis |
| Grade 3 or Grade 4 | • Discontinue selpercatinib. | |
| Other adverse reactions | Grade 3 or Grade 4 | • Selpercatinib should be suspended until recovery to baseline. • Discontinue selpercatinib for severe or life-threatening events |
No dose adjustment is required based on age.
No overall differences were observed in the treatment emergent adverse events or effectiveness of selpercatinib between patients who were ≥65 years of age and younger patients. Limited data are available in patients ≥75 years.
It can be taken with or without food.
Patients should take the doses at approximately the same time every day.
Retsevmo must be accompanied by a meal if used concomitantly with a proton pump inhibitor.
Retsevmo should be administered 2 hours before or 10 hours after H2 receptor antagonists.
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