Pralsetinib (Specialist drug)

PATIENT SELECTION: select patients based on the presence of a RET gene fusion (non-small cell lung cancer or thyroid cancer). MISSED DOSE: a missed dose can be taken as soon as possible on the same day, then resume the regular daily schedule the next day; do not take an additional dose if vomiting occurs, but continue with the next dose as scheduled. DOSE REDUCTION LADDER for adverse reactions: first reduction 300 mg once daily, second 200 mg once daily, third 100 mg once daily; permanently discontinue in patients unable to tolerate 100 mg once daily. DOSE MODIFICATIONS: serious infections including opportunistic infections — Grade 2 or 3, withhold until resolution and resume at a reduced dose; Grade 4, permanently discontinue. ILD/pneumonitis — Grade 1 or 2, withhold until resolution and resume at a reduced dose, permanently discontinuing for recurrent ILD/pneumonitis; Grade 4, permanently discontinue. Hypertension — Grade 3 persisting despite optimal antihypertensive therapy, withhold and resume at a reduced dose once controlled; Grade 4, discontinue. Hepatotoxicity — Grade 3 or 4, withhold and monitor AST/ALT weekly until resolution to Grade 1 or baseline then resume at a reduced dose, discontinuing for recurrent Grade 3 or higher events. Haemorrhagic events — Grade 3 or 4, withhold until recovery to baseline or Grade 0-1, and discontinue for severe or life-threatening haemorrhage. Other adverse reactions — Grade 3 or 4, withhold until improvement to Grade 2 or less then resume at a reduced dose, permanently discontinuing for recurrent Grade 4 reactions. CYP3A AND P-gp INHIBITORS: avoid strong CYP3A inhibitors, moderate CYP3A inhibitors, P-gp inhibitors, and combined P-gp with strong or moderate CYP3A inhibitors. If unavoidable, reduce the dose — with a combined P-gp and strong CYP3A inhibitor: 400 mg to 200 mg, 300 mg to 200 mg, 200 mg to 100 mg once daily; with a strong CYP3A inhibitor, moderate CYP3A inhibitor, P-gp inhibitor or combined P-gp and moderate CYP3A inhibitor: 400 mg to 300 mg, 300 mg to 200 mg, 200 mg to 100 mg once daily. Resume the prior dose after the inhibitor has been discontinued for 3 to 5 elimination half-lives. CYP3A INDUCERS: avoid strong and moderate CYP3A inducers. If unavoidable, increase the dose starting on Day 7 of coadministration — with a strong CYP3A inducer: 400 mg to 800 mg, 300 mg to 600 mg, 200 mg to 400 mg once daily; with a moderate CYP3A inducer: 400 mg to 600 mg, 300 mg to 500 mg, 200 mg to 300 mg once daily. Resume the prior dose after the inducer has been discontinued for at least 14 days. PAEDIATRIC: safety and effectiveness have been established in patients aged 12 years and older for RET fusion-positive thyroid cancer, at the same 400 mg once daily dose (a fixed dose, not weight-based); they have not been established in paediatric patients with RET fusion-positive NSCLC or in patients younger than 12 years with RET fusion-positive thyroid cancer. In a 4-week repeat-dose non-human primate study physeal dysplasia in the femur occurred at exposures similar to the human exposure at 400 mg. ELDERLY: no overall differences in pharmacokinetics, safety or effectiveness were observed between patients aged 65 and over and younger patients. SURGERY: withhold for at least 5 days prior to elective surgery (risk of impaired wound healing). SOURCE: NO UK SPC WAS AVAILABLE IN THIS BUNDLE (the eMC provider is null) — this draft is distilled entirely from the US GAVRETO prescribing information and must be verified against UK labelling before publication. No renal dose adjustment statement was present in the fetched sections.