Selpercatinib (Specialist drug)

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) must be confirmed by a validated test prior to initiation. If a patient vomits or misses a dose, take the next dose at its scheduled time — do not take an additional dose. Reduce the current dose by 50% if co-administering with a strong CYP3A inhibitor; when the inhibitor is discontinued, increase back (after 3-5 half-lives of the inhibitor) to the pre-inhibitor dose. Retsevmo must be accompanied by a meal if used concomitantly with a proton pump inhibitor, and should be administered 2 hours before or 10 hours after H2 receptor antagonists. Dose reduction levels for adults and adolescents >= 50 kg: starting 160 mg twice daily, first reduction 120 mg twice daily, second 80 mg twice daily, third 40 mg twice daily. For adults and adolescents < 50 kg: starting 120 mg twice daily, first reduction 80 mg twice daily, second 40 mg twice daily, no third reduction. Grade 3/4 ALT or AST rise: suspend until resolved to baseline then resume reduced by 2 levels, escalating stepwise if tolerated; permanently discontinue if it recurs despite dose modification. Hypersensitivity (all grades): suspend until resolved and start corticosteroids at 1 mg/kg, resume at 40 mg twice daily while continuing steroids, then increase by 1 dose level each week; discontinue for recurrent hypersensitivity. Grade 3 QT prolongation: suspend for QTcF >500 ms until QTcF returns to <470 ms or baseline, resume at the next lower dose level; permanently discontinue for Grade 4, for uncontrolled QT prolongation after two dose reductions, or for signs/symptoms of serious arrhythmia. Grade 3 hypertension: control blood pressure before starting, suspend for medically significant hypertension until controlled, resume at the next lower dose; discontinue permanently (Grade 4) if it cannot be controlled. Grade 3 haemorrhage: suspend until recovery to baseline, resume reduced; discontinue for Grade 4 or recurrent Grade 3. Grade 2 ILD/pneumonitis: withhold until resolution then resume reduced; discontinue for Grade 3/4 or recurrent ILD. Other Grade 3/4 reactions: suspend until recovery to baseline then resume reduced. Hepatic impairment: no dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B); severe (Child-Pugh C) should be dosed with 80 mg twice daily. PAEDIATRIC (non per-kg, so not given as a structured paediatric dose): Retsevmo should not be used in children aged less than 12 years. It is intended to be used from the age of 12 years for RET-mutant MTC and RET fusion-positive thyroid cancer, dosed according to the same body-weight bands as adults (<50 kg: 120 mg twice daily; >=50 kg: 160 mg twice daily). There are very limited data in children or adolescents aged less than 18 years and no data in children or adolescents with RET fusion-positive NSCLC. Open growth plates in adolescent patients should be monitored, and dose interruption or discontinuation considered based on the severity of any growth plate abnormalities and an individual risk-benefit assessment.