Gavreto

Pralsetinib

Adults w/ advanced or metastatic NSCLC rearranged during transfection (RET) fusion +ve. Adult & ped patients ≥12 yr w/ advanced or metastatic RET-mutant medullary thyroid cancer (MTC) requiring systemic therapy; advanced or metastatic RET-fusion positive thyroid cancer requiring systemic therapy & w/ radioactive iodine-refractory when appropriate.

400 mg once daily. May reduce dose by 100 mg decrements to min dose of 100 mg once daily.

Should be taken on an empty stomach: Swallow whole w/ a glass of water. Do not eat at least 2 hr before & at least 1 hr after intake.

Hypersensitivity.

Interrupt, reduce dose or discontinue permanently based on severity of confirmed pneumonitis/ILD; HTN; transaminase elevation observed during treatment. Not to be initiated in patients w/ uncontrolled HTN. Discontinue permanently in life-threatening or recurrent severe haemorrhage; life-threatening arrhythmia; recurrent Grade 4 adverse reactions. Patients w/ medical history of cardiac arrhythmias or QT interval prolongation & on strong CYP3A4 inhibitors or QT/QTc-prolonging medicinal products. Control preexisting HTN before starting treatment. Monitor BP after 1 wk & at least mthly thereafter; ALT & AST every 2 wk during the 1st 3 mth, then mthly thereafter; ECG & serum electrolytes at the end of 1st wk & of 1st mth of treatment, then periodically. Check QTc interval ≤470 ms & serum electrolytes w/in normal range before starting treatment. Correct hypokalaemia, hypomagnesaemia & hypocalcaemia prior & during treatment. Avoid co-administration w/ strong CYP3A4 inhibitors & inducers or combined P-gp & strong CYP3A4 inhibitors. May affect ability to drive & use machines. Severe renal impairment (CrCl 15-29 mL/min) or ESRD (CrCl <15 mL/min). Not recommended in moderate or severe hepatic impairment. Pregnancy status of women of childbearing potential should be verified prior to initiation of treatment. Women of childbearing potential should use highly effective non-hormonal contraception during treatment & for at least 2 wk following last dose of treatment. Males w/ female partners of childbearing potential should use effective contraception during treatment & for at least 1 wk following last dose of treatment. Men & women should seek advice on effective fertility preservation before treatment. Not to be used during pregnancy. Discontinue breastfeeding during treatment & for 1 wk following final dose. May cause foetal harm. Paed <18 yr w/ RET fusion +ve advanced NSCLC; <12 yr w/ RET-mutant MTC & RET-fusion positive thyroid cancer.

Pneumonia, UTI; anaemia, neutropenia, leukopenia, lymphopenia, thrombocytopenia; hypocalcaemia, hypo-/hyperphosphataemia, hypoalbuminaemia, hyponatraemia; taste disorder, headache; HTN, haemorrhage; cough, dyspnoea, pneumonitis; constipation, diarrhoea, dry mouth, nausea, abdominal pain, vomiting; increased AST & ALT, hyperbilirubinaemia; rash; musculoskeletal pain, increased blood creatine phosphokinase; fatigue, oedema, pyrexia; increased blood creatinine & alkaline phosphatase. Stomatitis; QT prolongation.

Increased plasma conc w/ strong CYP3A4 inhibitors or combined P-gp & strong CYP3A4 inhibitors eg, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, grapefruit or Seville oranges. Increased C_max & AUC_0-∞ w/ itraconazole 200 mg once daily. Decreased plasma conc w/ strong CYP3A4 inducers eg, carbamazepine, phenobarb, phenytoin, rifabutin, rifampicin & St. John's wort. Decreased C_max & AUC_0-∞ w/ rifampin 600 mg once daily. Altered exposure of sensitive substrates of CYP enzymes (CYP3A4, CYP2C8 & CYP2C9) & transporters (P-gp, BCRP, OATP1B1, OATP1B3, OAT1, MATE1 & MATE2-K). Avoid substrate drugs of CYP enzymes & transporters w/ narrow therapeutic index eg, cyclosporine, paclitaxel & warfarin.

Targeted Cancer Therapy

L01EX23 - pralsetinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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