Tezacaftor with ivacaftor

SCOPE: this is the page's primary and only route and indication. Every component of the fixed combination is quantified: the morning tablet is tezacaftor 100 mg WITH ivacaftor 150 mg; the evening tablet is ivacaftor 150 mg alone (ivacaftor is supplied as a separate tablet, not contained in the Symkevi tablet). VERBATIM §4.2 Table 1 (Dosing recommendations for patients aged 6 years and older), the ≥ 12 years row: 'Morning (1 tablet): tezacaftor 100 mg/ivacaftor 150 mg; Evening (1 tablet): ivacaftor 150 mg.' VERBATIM §4.2: 'The morning and evening dose should be taken approximately 12 hours apart with fat-containing food.' METHOD OF ADMINISTRATION, VERBATIM §4.2: 'For oral use. Patients should be instructed to swallow the tablets whole. The tablets should not be chewed, crushed, or broken before swallowing because there are no clinical data currently available to support other methods of administration. Both Symkevi and ivacaftor tablets should be taken with fat-containing food, such as food recommended in standard nutritional guidelines. Food or drink containing grapefruit should be avoided during treatment.' MISSED DOSE, VERBATIM §4.2: 'If 6 hours or less have passed since the missed morning or evening dose, the patient should 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 or evening dose, the patient should not take the missed dose. The next scheduled dose can be taken at the usual time. More than one dose of either tablet should not be taken at the same time.' CYP3A INHIBITOR DOSE REDUCTIONS (§4.2 Table 2), 12 years and older, VERBATIM — moderate CYP3A inhibitors (e.g. fluconazole, erythromycin, verapamil): 'Alternate each morning: - one tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily on the first day - one tablet of ivacaftor 150 mg on the next day. Continue alternating tablets each day. No evening dose.'; strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin): 'One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg twice a week, approximately 3 to 4 days apart. No evening dose.' PRESCRIBING AND GENOTYPE, VERBATIM §4.2: 'Symkevi should only be prescribed by physicians 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 an indicated mutation using a genotyping assay.' ELDERLY, VERBATIM §4.2: 'The safety, efficacy and pharmacokinetics of Symkevi have been examined in a limited number of elderly patients. No dose adjustment specific to this patient population is required.' maxDose left empty deliberately: no maximum daily dose, and no ceiling of any kind, is stated in the fetched sections. The only ceiling-shaped sentence is the missed-dose instruction 'More than one dose of either tablet should not be taken at the same time', which is a co-administration instruction, not a dose limit. PROVENANCE: this draft supersedes an earlier draft of the same bundle that left the dose field empty; the regimen above was already quoted verbatim in that draft's notes, and the SPC doses this page's exact product, route and indication with both components quantified, so the dose field is now populated from it.

dosePerKg is null because the paediatric regimen is WEIGHT-BANDED with fixed milligram tablet strengths, not a per-kilogram calculation; concentration is null because these are tablets, not a liquid, so no mg/mL figure exists. VERBATIM §4.2 Table 1 (Dosing recommendations for patients aged 6 years and older): '6 to < 12 years weighing < 30 kg — Morning (1 tablet): tezacaftor 50 mg/ivacaftor 75 mg; Evening (1 tablet): ivacaftor 75 mg.' '6 to < 12 years weighing ≥ 30 kg — Morning (1 tablet): tezacaftor 100 mg/ivacaftor 150 mg; Evening (1 tablet): ivacaftor 150 mg.' '≥ 12 years — Morning (1 tablet): tezacaftor 100 mg/ivacaftor 150 mg; Evening (1 tablet): ivacaftor 150 mg' (i.e. from 12 years the adult regimen applies). AGE LIMIT, VERBATIM §4.2 Paediatric population: 'The safety and efficacy of Symkevi in children aged less than 6 years has not yet been established. No data are available.' CYP3A INHIBITORS, 6 to < 12 years (§4.2 Table 2), VERBATIM — moderate inhibitors, < 30 kg: 'Alternate each morning: - one tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily on the first day - one tablet of ivacaftor 75 mg on the next day. Continue alternating tablets each day. No evening dose.'; ≥ 30 kg: the same alternating pattern at tezacaftor 100 mg/ivacaftor 150 mg and ivacaftor 150 mg. Strong inhibitors, < 30 kg: 'One morning tablet of tezacaftor 50 mg/ivacaftor 75 mg twice a week, approximately 3 to 4 days apart. No evening dose.'; ≥ 30 kg: the same twice-weekly pattern at tezacaftor 100 mg/ivacaftor 150 mg. HEPATIC IMPAIRMENT, 6 to < 12 years (§4.2 Table 3), VERBATIM — moderate (Child-Pugh Class B), < 30 kg: 'One morning tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily. No evening dose.'; ≥ 30 kg: 'One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily. No evening dose.'; severe (Child-Pugh Class C): the same morning tablet 'once daily or less frequently. Dosing intervals should be modified according to clinical response and tolerability. No evening dose.' SAFETY, §4.4: 'Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with ivacaftor-containing regimens' — this paragraph is cut at the source-fetch limit, so any eye-examination requirement that follows it was NOT retrieved. maxDose left empty deliberately: no maximum dose is stated for any paediatric band. Verify any under-18 dose against a children's formulary and current prescribing references before prescribing.