Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Eli Lilly Nederland B.V., Papendorpseweg 83, 3528BJ Utrecht, The Netherlands
Retsevmo as monotherapy is indicated for the treatment of adults with:
Retsevmo as monotherapy is indicated for the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC).
Retsevmo therapy should be initiated and supervised by physicians experienced in the use of anti-cancer therapies.
The presence of a RET gene fusion (NSCLC and non-medullary thyroid cancer) or mutation (MTC) should be confirmed by a validated test prior to initiation of treatment with Retsevmo.
The recommended dose of Retsevmo 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. Retsevmo dose modifications are summarised in Table 1 and Table 2.
Table 1. Recommended dose modifications for Retsevmo 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 (see sections 4.4 and 4.8). 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 (see sections 4.4 and 4.8). 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 (see section 4.4). • 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 (see sections 4.4 and 4.8). |
| 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 (see section 5.2).
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.
Dose adjustment is not necessary in patients with mild, moderate or severe renal impairment. There are no data in patients with end stage renal disease, or in patients on dialysis (section 5.2).
Close monitoring of patients with impaired hepatic function is important. No dose adjustment is required for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. Patients with severe (Child-Pugh class C) hepatic impairment should be dosed with 80 mg selpercatinib twice daily (section 5.2).
Retsevmo should not be used in children aged less than 12 years. There is no data in children or adolescents with RET fusion-positive NSCLC or thyroid cancer. Retsevmo is intended to be used from the age of 12 years for the treatment of patients with RET-mutant MTC (see section 5.1). In RET-mutant MTC, there are very limited data available in children or adolescents aged less than 18 years. Patients should be dosed according to body weight (see section 4.2). Based on results from a preclinical study (see section 5.3), 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.
Retsevmo is for oral use.
The capsules should be swallowed whole (patients should not open, crush, or chew the capsule before swallowing) and 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 (see section 4.5).
Retsevmo should be administered 2 hours before or 10 hours after H2 receptor antagonists (see section 4.5).
Symptoms of overdose have not been established. In the event of suspected overdose, supportive care should be provided.
2 years.
This medicinal product does not require any special storage conditions.
Each pack contains 1 HDPE bottle with a plastic screw cap.
Retsevmo 40 mg hard capsules: Retsevmo 40 mg hard capsules is supplied as a 60 count HDPE bottle.
Retsevmo 80 mg hard capsules: Retsevmo 80 mg hard capsules is supplied as 60 count HDPE bottle or 120 count HDPE bottle.
Retsevmo 40 mg hard capsules: Supplied as PCTFE/PVC blisters sealed with an aluminium foil in a blister card, in packs of 14, 42, 56 or 168 hard capsules.
Retsevmo 80 mg hard capsules: Supplied as PCTFE/PVC blisters sealed with an aluminium foil in a blister card, in packs of 14, 28, 56 or 112 hard capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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