Ivacaftor with tezacaftor and elexacaftor

SOURCE: eMC UK SPC, productName 'Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets' (https://www.medicines.org.uk/emc/product/13216/smpc), §4.2 Table 1. NOTE THE REGIMEN IS A COMBINATION PACK: the evening dose is a separate ivacaftor-only tablet, so this page must not present a single twice-daily triple-combination dose. PRESCRIBING RESTRICTION: 'Kaftrio should only be prescribed by healthcare professionals with experience in the treatment of CF.' GENOTYPE: if the patient's genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of at least one F508del mutation. MONITORING: transaminases (ALT and AST) and total bilirubin are recommended for all patients prior to initiating treatment, every 3 months during the first year and annually thereafter; more frequent monitoring should be considered in patients with a history of liver disease or transaminase elevations. Interrupt dosing if ALT or AST >5 x ULN, or ALT or AST >3 x ULN with total bilirubin >2 x ULN (§4.4). PAEDIATRIC (weight-banded, NOT per-kg — hence paedDose is null): 6 to <12 years and <30 kg — morning two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets, evening one ivacaftor 75 mg tablet; 6 to <12 years and >=30 kg — morning two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets, evening one ivacaftor 150 mg tablet. 'The safety and efficacy of Kaftrio in combination with ivacaftor in children aged less than 2 years have not yet been established. No data are available.' MISSED DOSE: if 6 hours or less have passed since the missed morning or evening dose, take it as soon as possible and continue on the original schedule. If more than 6 hours have passed since the missed MORNING dose, take it as soon as possible and do NOT take the evening dose (next scheduled morning dose at the usual time); if more than 6 hours have passed since the missed EVENING dose, do NOT take it (next scheduled morning dose at the usual time). CYP3A INHIBITOR DOSE REDUCTION (§4.2 Table 2): with MODERATE CYP3A inhibitors (e.g. fluconazole, erythromycin, verapamil) alternate each day — two IVA/TEZ/ELX tablets on the first day, one ivacaftor tablet on the next day, with no evening ivacaftor dose. With STRONG CYP3A inhibitors (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin) — two IVA/TEZ/ELX tablets twice a week, approximately 3 to 4 days apart, with no evening ivacaftor dose. No dose adjustment is recommended with concomitant ciprofloxacin. ELDERLY: no dose adjustment recommended. HEPATIC IMPAIRMENT (§4.2 Table 3): mild (Child-Pugh A) — no dose adjustment. Moderate (Child-Pugh B) — use not recommended; only consider when there is a clear medical need and benefits are expected to outweigh the risks, and if used, use with caution at a reduced dose of Day 1 two IVA/TEZ/ELX tablets in the morning, Day 2 one IVA/TEZ/ELX tablet in the morning, continuing to alternate, with the evening ivacaftor tablet NOT taken. Severe (Child-Pugh C) — should not be used. TRANSPLANT: use in patients who have undergone organ transplantation is not recommended (§4.4). GRAPEFRUIT: food or drink containing grapefruit should be avoided during treatment. SOURCE SELECTION: the openFDA record in this bundle is for KALYDECO (ivacaftor monotherapy, Vertex, label date 2026-03-23) — a DIFFERENT product that does not describe this fixed combination, so it was NOT used for the dose. §4.5 was not retrieved in this bundle; the interaction entries below come from §4.2/§4.4 and are not a complete list. §4.4 and §4.8 were truncated at the source-fetch limit.