Deutivacaftor with tezacaftor and vanzacaftor

VERBATIM UK SPC §4.2 (ALYFTREK 50 MG/20 MG/4 MG FILM-COATED TABLETS SPC, PL223520024, Vertex Pharmaceuticals (Europe) Limited): 'Adults and paediatrics aged 6 years and older should be dosed according to Table 1.' Table 1 (Age | Weight | Daily Dose (once daily)): '6 to < 12 years < 40 kg Three tablets of deutivacaftor 50 mg/tezacaftor 20 mg/vanzacaftor 4 mg (total dose of deutivacaftor 150 mg/tezacaftor 60 mg/vanzacaftor 12 mg)'; '6 to < 12 years ≥ 40 kg ≥ 12 years Any weight Two tablets of deutivacaftor 125 mg/ tezacaftor 50 mg/ vanzacaftor 10 mg (total dose of deutivacaftor 250 mg/tezacaftor 100 mg/vanzacaftor 20 mg)'. TABLE READING (stated openly): in the extracted PDF text the second dose cell is printed ONCE, after the two row labels '6 to < 12 years / ≥ 40 kg' and '≥ 12 years / Any weight', i.e. one merged table cell covering both rows; the same shared-cell layout is used in Table 2. The ≥ 12 years dose is read from that shared cell. 'Each dose should be taken in its entirety with fat-containing food once daily at approximately the same time each day.' §4.1: 'Alyftrek is indicated for the treatment of cystic fibrosis (CF) in people aged 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.' STRENGTHS: the SPC's §2 as fetched prints only the 50 mg/20 mg/4 mg tablet (each tablet contains 50 mg deutivacaftor, 20 mg tezacaftor and vanzacaftor calcium dihydrate equivalent to 4 mg vanzacaftor); the 125 mg/50 mg/10 mg strength is named in the §4.2 tables. The SPC prints no separate maximum dose. PRESCRIBING (§4.2): only by healthcare professionals experienced in treating CF; if genotype is unknown use an accurate validated genotyping method to confirm at least one F508del or another responsive mutation. MISSED DOSE (§4.2): if 6 hours or less have passed take it as soon as possible and continue the original schedule the next day; if more than 6 hours have passed skip it and continue the original schedule the next day. CYP3A INHIBITORS (§4.2 Table 2, ≥ 12 years any weight): with moderate CYP3A inhibitors (e.g. fluconazole, erythromycin) one tablet of deutivacaftor 125 mg/tezacaftor 50 mg/vanzacaftor 10 mg every other day; with strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin) one such tablet once a week. No adjustment with ciprofloxacin. Moderate or strong CYP3A inducers: co-administration not recommended (§4.4/§4.5). Avoid food or drink containing grapefruit. ELDERLY: clinical studies did not include enough people aged 65 years and older to determine whether they respond differently. CHILDREN: figures for 6 to under 12 years are in paedDose; safety and efficacy in children under 6 years are not established (no data). Some sections of the product information we used were incomplete — check the full SPC.

THESE ARE THE LABEL'S OWN PAEDIATRIC FIGURES (UK SPC §4.2 Table 1), NOT SCALED ADULT DOSES, AND ARE FIXED TABLET COUNTS BY AGE AND WEIGHT BAND, NOT A PER-KG REGIMEN. VERBATIM: '6 to < 12 years < 40 kg Three tablets of deutivacaftor 50 mg/tezacaftor 20 mg/vanzacaftor 4 mg (total dose of deutivacaftor 150 mg/tezacaftor 60 mg/vanzacaftor 12 mg)'; '6 to < 12 years ≥ 40 kg ... Two tablets of deutivacaftor 125 mg/ tezacaftor 50 mg/ vanzacaftor 10 mg (total dose of deutivacaftor 250 mg/tezacaftor 100 mg/vanzacaftor 20 mg)'. CYP3A inhibitors (Table 2): 6 to under 12 years and under 40 kg - two tablets of the 50 mg/20 mg/4 mg strength every other day with moderate inhibitors, or once a week with strong inhibitors; 6 to under 12 years and 40 kg or more - one tablet of the 125 mg/50 mg/10 mg strength every other day (moderate) or once a week (strong). The SPC states: 'The safety and efficacy of Alyftrek in children aged less than 6 years have not yet been established. No data are available.' No figure is given for children under 6 years or for neonates. Baseline and follow-up ophthalmological examinations are recommended in people aged less than 18 years initiating treatment (§4.4, cataract risk). Verify any under-18 dose against a children's formulary before use.