Ivacaftor

No per-kg dose is stated: the SPC doses by fixed weight bands, so paedDose has been left null and the full band table is given above. Ivacaftor should only be prescribed by physicians with experience in the treatment of cystic fibrosis; confirm an indicated CFTR mutation in at least one allele by validated genotyping before starting. Not recommended for use in children under 1 month of age; use in patients aged 1 to less than 6 months born at a gestational age under 37 weeks has not been evaluated. Safety and efficacy have not been established in children less than 1 month as monotherapy, or in children less than 2 years in combination with ivacaftor/tezacaftor/elexacaftor; limited data in patients under 6 years with an R117H mutation. COMBINATION REGIMEN with ivacaftor/tezacaftor/elexacaftor, 2 years to less than 6 years: under 14 kg = one sachet of ivacaftor 60 mg/tezacaftor 40 mg/elexacaftor 80 mg granules in the morning and one sachet of ivacaftor 59.5 mg granules in the evening; 14 kg and over = one sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg granules in the morning and one sachet of ivacaftor 75 mg granules in the evening. MODERATE OR STRONG CYP3A INHIBITORS (monotherapy): 4 months to less than 6 months - not recommended unless benefits outweigh risks; if used, one 25 mg sachet twice weekly or less frequently, no evening dose. 6 months and older: 5 to less than 7 kg = 25 mg once daily (moderate) or 25 mg twice weekly (strong), no evening dose; 7 to less than 14 kg = 50 mg once daily (moderate) or 50 mg twice a week (strong), no evening dose; 14 to less than 25 kg = 75 mg once daily (moderate) or 75 mg twice a week (strong), no evening dose. Not recommended in patients aged 1 month to less than 4 months taking concomitant strong or moderate CYP3A inhibitors. MODERATE HEPATIC IMPAIRMENT (Child-Pugh B, monotherapy, 6 months and older): 5 to less than 7 kg = 25 mg once daily; 7 to less than 14 kg = 50 mg once daily; 14 to less than 25 kg = 75 mg once daily, no evening dose. Severe (Child-Pugh C): not recommended unless benefits outweigh risks; if used, the same sachet strength every other day with intervals modified to clinical response. Not recommended in patients aged 1 month to less than 4 months with any level of hepatic impairment. Missed dose: if 6 hours or less have passed, give as soon as possible then give the next dose at the regularly scheduled time; if more than 6 hours have passed, wait until the next scheduled dose. Avoid food or drink containing grapefruit. Liver monitoring: ALT, AST and total bilirubin before starting, every 3 months during the first year and annually thereafter. Verify against a children's formulary before prescribing. Cross-check only (openFDA, US Kalydeco labelling): 1 month to less than 2 months and 3 kg or greater = one 5.8 mg packet every 12 hours - note the US label includes a 5.8 mg strength for the youngest band where the UK SPC specifies 13.4 mg; clinician to reconcile.