Retsevmo

Selpercatinib

Monotherapy for adults w/ advanced RET fusion +ve NSCLC not previously treated w/ RET inhibitor; advanced RET fusion +ve thyroid cancer who require systemic therapy following prior treatment w/ sorafenib &/or lenvatinib. Monotherapy for adults & adolescents ≥12 yr w/ advanced RET-mutant medullary thyroid cancer.

Patient weighing ≥50 kg 160 mg bd, <50 kg 120 mg bd. Patient w/ severe hepatic impairment (Child-Pugh class C) 80 mg bd. Co-administration w/ strong CYP3A inhibitor Reduce dose by 50%.

May be taken with or without food: Swallow whole, do not open/crush/chew. Take w/ meals if used concomitantly w/ PPI.

Hypersensitivity.

Suspend treatment if hypersensitivity occurs & permanently discontinue for recurrent hypersensitivity. Reports of severe, life-threatening, or fatal cases of ILD/pneumonitis; grade ≥3 increased ALT & AST; HTN; QT interval prolongation; hypothyroidism; serious including fatal haemorrhagic events. W/hold treatment in case of acute or worsening resp symptoms indicative of ILD. Monitor ALT & AST prior to start of therapy, every 2 wk during the 1st 3 mth of treatment, mthly for the next 3 mth of treatment & otherwise as clinically indicated. BP should be controlled before starting treatment & monitored during treatment. Permanently discontinue treatment if medically significant HTN cannot be controlled w/ antihypertensive therapy. Caution in patients w/ congenital or acquired long QT syndrome or other clinical conditions that predispose to arrhythmias. Monitor ECG & serum electrolytes in all patients after 1 wk of treatment, at least mthly for the 1st 6 mth & otherwise as clinically indicated. Correct hypokalaemia, hypomagnesaemia & hypocalcaemia prior to initiating & during treatment. Baseline lab measurement of thyroid function is recommended in all patients. Closely observe all patients for signs & symptoms of thyroid dysfunction during treatment. Permanently discontinue treatment in patients w/ life-threatening or recurrent severe haemorrhage. Risk of tumour lysis syndrome. Avoid concomitant use of strong CYP3A4 inducers. Minor influence on ability to drive & use machines. Women of childbearing potential & men w/ female partners of childbearing potential must use highly effective contraception during treatment & for at least 1 wk after the last dose. Male & female fertility may be compromised by Retsevmo treatment. Not recommended during pregnancy & in women of childbearing potential not using contraception. Discontinue breast-feeding during treatment & for at least 1 wk after the last dose. Do not use in childn <12 yr.

Hypothyroidism; decreased appetite; headache, dizziness; prolonged ECG QT; haemorrhage, HTN; abdominal pain, diarrhoea, nausea, vomiting, constipation, dry mouth; rash; pyrexia, fatigue, oedema; increased AST, ALT & creatinine, decreased platelets, lymphocyte count & Mg. Hypersensitivity; ILD/pneumonitis, chylothorax; chylous ascites.

Increased plasma conc w/ strong CYP3A &/or P-gp inhibitors eg, ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole, nefazodone. Decreased plasma conc w/ strong CYP3A4 inducers eg, carbamazepine, phenobarb, phenytoin, rifabutin, rifampicin, St. John's wort (Hypericum perforatum). Increased plasma conc of sensitive CYP2C8 substrates (eg, odiaquine, cerivastatin, enzalutamide, paclitaxel, repaglinide, torasemide, sorafenib, rosiglitazone, buprenorphine, selexipag, dasabuvir, montelukast); sensitive CYP3A4 substrates (eg, alfentanil, avanafil, buspirone, conivaptan, darifenacin, darunavir, ebastine, lomitapide, lovastatin, midazolam, naloxegol, nisoldipine, saquinavir, simvastatin, tipranavir, triazolam, vardenafil); sensitive P-gp substrates (eg, fexofenadine, dabigatran etexilate, colchicine, saxagliptin) & particularly those w/ narrow therapeutic index (eg, digoxin). Decreased AUC_0-INF & C_max w/ multiple daily doses of omeprazole when selpercatinib was administered fasting. In vivo interactions w/ clinically relevant MATE1 substrates (eg, creatinine) may occur. Insufficient response to levothyroxine substitution.

Targeted Cancer Therapy

L01EX22 - selpercatinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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