Indications And Dose
Cystic fibrosis (specialist use only) ▶BY MOUTH USING TABLETS ▶Adult: 400/250 mg every 12 hours
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Drug reference
Cystic fibrosis (specialist use only) ▶BY MOUTH USING TABLETS ▶Adult: 400/250 mg every 12 hours
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DUE TO INTERACTIONS ▶Manufacturer advises reduce initial dose to 200/125 mg daily for the first week in those also taking a potent inhibitor of CYP3A4. DOSE EQUIVALENCE AND CONVERSION ▶Dose expressed as x/y mg of lumacaftor/ivacaftor.
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Forced expiratory volume in 1 second (FEV1) less than 40% of the predicted normal value—additional monitoring recommended at initiation of treatment. pulmonary exacerbation—no information available
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If the patient’s genotype is unknown, a validated genotyping method should be performed to confirm the presence of the F508del mutation on both alleles of the CFTR gene before starting treatment.
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NICE decisions ▶Lumacaftor with ivacaftor for treating cystic fibrosis homozygous for the F508del mutation (July 2016) NICE TA398 Lumacaftor with ivacaftor (Orkambi ®) is not recommended, within its marketing authorisation, for treating cystic fibrosis in patients aged 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they (or their carers) and their NHS Respiratory system clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta398 Scottish Medicines Consortium (SMC) decisions SMC No. 1136/16 The Scottish Medicines Consortium has advised (May 2016) that lumacaftor with ivacaftor (Orkambi ®) is not recommended within NHS Scotland for the treatment of cystic fibrosis in patients aged 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, as the economic case was not demonstrated.
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→Appendix 1: ivacaftor. lumacaftor
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▶Common or very common Breast abnormalities. diarrhoea. dizziness. ear discomfort. flatulence. gastrointestinal discomfort. headache. menstrual cycle irregularities. nausea. ototoxicity. rash. tympanic membrane hyperaemia. vomiting ▶Uncommon Gynaecomastia. hepatic encephalopathy. hepatitis cholestatic. hypertension SIDE-EFFECTS, FURTHER INFORMATION Manufacturer advises interrupt treatment if transaminase levels more than 5 times the upper limit of normal or transaminase levels more than 3 times the upper limit of normal and blood bilirubin more than twice the upper limit of normal—consult product literature.
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Manufacturer advises caution in moderate to severe impairment (risk of increased exposure). Dose adjustments Manufacturer advises dose reduction of evening dose to 200/125 mg in moderate impairment; in severe impairment, dose reduction to 200/125 mg every 12 hours is advised.
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Manufacturer advises monitor blood pressure periodically during treatment. l EFFECT ON LABORATORY TESTS False positive urine screening tests for tetrahydrocannabinol have been reported—manufacturer advises consider alternative confirmatory method.
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Tablets should be taken with fat-containing food.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 25 EXCIPIENTS: May contain Propylene glycol ▶Orkambi (Vertex Pharmaceuticals (UK) Ltd) A Lumacaftor 100 mg, Ivacaftor 125 mg Orkambi 100mg/125mg tablets | 112 tablet P £8,000.00 (Hospital only) Ivacaftor 125 mg, Lumacaftor 200 mg Orkambi 200mg/125mg tablets | 112 tablet P £8,000.00 (Hospital only)
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Patients or carers should be given advice on how to administer tablets. Missed doses Manufacturer advises if a dose is more than 6 hours late, the missed dose should not be taken and the next dose should be taken at the normal time.
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400/250 mg every 12 hours
First-line fragment. Read the complete Indications and Dose section above.
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