Lumacaftor with ivacaftor

SOURCE: eMC UK SPC, productName 'Orkambi 100 mg/125 mg film coated tablets' (https://www.medicines.org.uk/emc/product/8952/smpc), §4.2 Table 1. VERBATIM TABLE ROW: '12 years and older | lumacaftor 200 mg/ivacaftor 125 mg | Morning 2 tablets | Evening 2 tablets', under the heading 'Dose (every 12 hours)'. The SPC expresses the dose as tablets of a stated per-tablet strength — the daily total has deliberately NOT been calculated here; report it as tablets. PRESCRIBING RESTRICTION: 'Orkambi should only be prescribed by physicians 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 the F508del mutation on BOTH alleles of the CFTR gene. Patients may start treatment on any day of the week. PAEDIATRIC (tablet-strength band, NOT per-kg — hence paedDose is null): 6 to <12 years — lumacaftor 100 mg/ivacaftor 125 mg tablets, 2 tablets in the morning and 2 tablets in the evening. 'The safety and efficacy of Orkambi in children aged less than 1 year have not yet been established. No data are available.' MISSED DOSE: if less than 6 hours have passed since the missed dose, take the scheduled dose with fat-containing food; if more than 6 hours have passed, wait until the next scheduled dose. A double dose should not be taken to make up for a forgotten dose. STRONG CYP3A INHIBITORS (§4.2 Table 2): no dose adjustment is necessary when a CYP3A inhibitor is started in a patient already taking Orkambi; but when INITIATING Orkambi in a patient already taking a strong CYP3A inhibitor, reduce to one tablet daily for the first week, then from day 8 give the recommended full daily dose. The same one-tablet-daily first week applies if treatment is interrupted for more than one week and re-initiated while on a strong CYP3A inhibitor. HEPATIC IMPAIRMENT (§4.2 Table 3): mild (Child-Pugh A) — no dose adjustment. Moderate (Child-Pugh B) — reduce to 2 tablets in the morning and 1 tablet 12 hours later. Severe (Child-Pugh C) — no experience and exposure expected to be higher; after weighing risks and benefits, use with caution at a reduced dose of 1 tablet in the morning and 1 tablet 12 hours later, or a reduced daily dose. NOT EFFECTIVE / NOT TO BE USED (§4.4): not effective in patients heterozygous for F508del whose second allele carries a mutation predicted to result in a lack of CFTR production or not responsive to ivacaftor in vitro; should not be used in patients with a gating (Class III) mutation, because ivacaftor exposure is very significantly reduced when dosed in combination with lumacaftor. Initiating treatment in a patient having a pulmonary exacerbation is not advisable. Blood pressure should be monitored periodically in all patients. SECTION COVERAGE: §4.5 was not retrieved in this bundle; the interaction entries below come from §4.2 and are not a complete list. §4.4 and §4.8 were truncated at the source-fetch limit.