Tanstrive

Monotherapy in adults w/ advanced rearranged during transfection (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 in adults & adolescents ≥12 yr w/ advanced RET-mutant medullary thyroid cancer.

Adult & adolescent weighing ≥50 kg 160 mg bid, <50 kg 120 mg bid. Continue until disease progression or unacceptable toxicity. Co-administration w/ strong CYP3A inhibitor Reduce current dose by 50%. Increase to original starting dose after CYP3A inhibitor discontinuation. Dose adjustment: 1st dose reduction: Adult & adolescent ≥50 kg 120 mg bid, <50 kg 80 mg bid; 2nd dose reduction: ≥50 kg 80 mg bid, <50 kg 40 mg bid; 3rd dose reduction: ≥50 kg 40 mg bid. Severe (Child-Pugh class C) hepatic impairment 80 mg bid.

May be taken with or without food: Swallow whole, do not open, crush, or chew.

Hypersensitivity.

Hypersensitivity including fever, rash & arthralgias or myalgias w/ concurrent decreased platelets or elevated aminotransferases. Permanently discontinue treatment for recurrent hypersensitivity; in patients w/ life-threatening or recurrent severe haemorrhage; if medically significant HTN cannot be controlled w/ antihypertensive therapy. Interrupt, reduce dose, or permanently discontinue treatment based on severity of ILD/pneumonitis. Withhold treatment & promptly investigate patients for ILD if they present w/ acute or worsening of resp symptoms which may be indicative of ILD (eg, dyspnoea, cough, & fever). Suspend treatment if hypersensitivity occurs, & begin steroid treatment. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis; w/ risk factors for tumour lysis syndrome including high tumour burden, pre-existing chronic renal insufficiency, oliguria, dehydration, hypotension, & acidic urine (consider treatment & appropriate prophylaxis including hydration). Closely observe patients for signs & symptoms of thyroid dysfunction during treatment. Severe, life-threatening, or fatal cases of ILD/pneumonitis; grade ≥3 increased ALT & AST; HTN; QT interval prolongation; hypothyroidism; serious including fatal haemorrhagic events; tumour lysis syndrome. Patients w/ congenital long QT syndrome or acquired long QT syndrome or other clinical conditions predisposing to arrhythmias; NSCLC previously treated w/ anti-PD-1/PD-L1 immunotherapy. Monitor ALT & AST prior to start of therapy, every 2 wk during 1st 3 mth, mthly for the next 3 mth of treatment, & otherwise as clinically indicated; BP during treatment & treat as needed w/ standard antihypertensive therapy; ECGs & serum electrolytes after 1 wk of treatment, at least mthly for 1st 6 mth & otherwise as clinically indicated; QT interval w/ ECGs more frequently in patients who require treatment w/ concomitant medications known to prolong QT interval; thyroid function periodically throughout treatment. Baseline lab measurement of thyroid function is recommended in all patients. Control BP before starting treatment. Ensure QTcF interval of ≤470 ms & serum electrolytes w/in normal range before starting treatment. Correct hypokalaemia, hypomagnesaemia & hypocalcaemia prior to initiating & during treatment. Treat pre-existing hypothyroidism prior to start of treatment. Confirm presence of RET gene fusion (NSCLC & non-medullary thyroid cancer) or mutation MTC by validated test prior to treatment initiation. Avoid concomitant use w/ strong CYP3A4 inducers due to risk of decreased efficacy. May inhibit conversion of levothyroxine to triiodothyronine (supplementation w/ liothyronine may be needed). Minor influence on ability to drive & use machines. ESRD or patients on dialysis. Closely monitor patients w/ hepatic impairment. Women of childbearing potential & men w/ female partners of childbearing potential must use highly effective contraception during treatment & for at least 1 wk after last dose. Men & women should seek advice on fertility preservation before treatment. Not recommended during pregnancy & in women of childbearing potential not using contraception. Discontinue breast-feeding during treatment & for at least 1 wk after last dose. Not to be used in childn <12 yr. Childn <18 yr. Childn or adolescents w/ RET fusion +ve NSCLC or thyroid cancer. Monitor open growth plates in adolescents. Elderly ≥75 yr.

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

Minimal increase in exposure w/ P-gp inhibitor rifampicin. Increased C_max & AUC w/ strong CYP3A &/or P-gp inhibitor eg, ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole & nefazodone. Decreased AUC & C_max w/ strong CYP3A4 inducers eg, carbamazepine, phenobarb, phenytoin, rifabutin, rifampicin & St. John's wort (Hypericum perforatum). Increased C_max & AUC 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 substrate (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. 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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