Active Ingredient: Selpercatinib
Selpercatinib as monotherapy is indicated for the treatment of adults and adolescents 12 years and older with advanced RET fusion-positive thyroid cancer who are radioactive iodine-refractory (if radioactive iodine is appropriate).
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.
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 | Adultsa nd 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.
Selpercatinib must be accompanied by a meal if used concomitantly with a proton pump inhibitor.
Selpercatinib should be administered 2 hours before or 10 hours after H2 receptor antagonists.
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