Elexacaftor / Tezacaftor / Ivacaftor

SOURCE: UK SPC for Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets (https://www.medicines.org.uk/emc/product/13216/smpc). The regimen above is the full combination as labelled — Kaftrio (IVA/TEZ/ELX) in the morning taken together with a separate ivacaftor tablet in the evening. PRESCRIBING RESTRICTION: should only be prescribed by healthcare professionals with experience in the treatment of CF; 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 of treatment and annually thereafter; more frequent monitoring should be considered for 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. PAEDIATRIC (weight-band, not per-kg — not expressed as a mg/kg dose): 6 to <12 years and <30 kg — two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets in the morning plus one ivacaftor 75 mg tablet in the evening; 6 to <12 years and >=30 kg — two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets in the morning plus one ivacaftor 150 mg tablet in the evening. Safety and efficacy in children aged less than 2 years have not yet been established; no data are available. Verify any under-18 use against a children's formulary. MISSED DOSE: if 6 hours or less have passed since the missed morning or evening dose, take the missed dose as soon as possible and continue on the original schedule; if more than 6 hours have passed since the missed MORNING dose, take the missed dose as soon as possible and do not take the evening dose, with the next scheduled morning dose taken at the usual time; if more than 6 hours have passed since the missed EVENING dose, do not take the missed dose and take the next scheduled morning dose at the usual time. CONCOMITANT 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; no evening ivacaftor tablet dose. CONCOMITANT 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; no evening ivacaftor tablet dose. No dose adjustment is recommended with concomitant ciprofloxacin. HEPATIC IMPAIRMENT: mild (Child-Pugh A) — no dose adjustment; moderate (Child-Pugh B) — use not recommended, and if used after a clear medical need and benefit/risk assessment, use with caution at a reduced dose of two IVA/TEZ/ELX tablets in the morning on Day 1 and one IVA/TEZ/ELX tablet in the morning on Day 2, continuing to alternate thereafter, with the evening ivacaftor tablet dose not taken; severe (Child-Pugh C) — should not be used. ELDERLY: no dose adjustment recommended. Food or drink containing grapefruit should be avoided during treatment. Examples of fat-containing meals or snacks given in the SPC are those prepared with butter or oils, or containing eggs, cheeses, nuts, whole milk or meats. Use in patients who have undergone organ transplantation is not recommended. NOTE: §4.5 (interactions) was not retrieved in this bundle and the fetched §4.4 and §4.8 are truncated at the source-fetch limit — verify the complete SPC.