ORKAMBI

Lumacaftor 200mg, Ivacaftor 125mg, Oral tablet

Grapefruit juice

· Severity: Major

· Notes for Consumers: Do not take Lumacaftor; ivacaftor and grapefruit juice together without approval from your prescriber. Grapefruit juice may increase the amount of Lumacaftor; ivacaftor in your blood. Contact your health care provider immediately if you experience dark yellow or brown urine, general ill feeling or flu-like symptoms, light-colored stools, loss of appetite, nausea, right upper belly pain, yellowing of the eyes or skin, or become unusually weak or tired.

· Notes for Professionals: It may be prudent to avoid consumption of grapefruit or grapefruit juice with lumacaftor; ivacaftor if possible. If a patient has taken lumacaftor; ivacaftor uninterrupted for more than 1 week, grapefruit consumption may be acceptable. However, when initiating lumacaftor; ivacaftor, avoid consumption of grapefruit and/or its juice for a minimum of 1 week. If lumacaftor; ivacaftor therapy is interrupted for more than 1 week, consumption of grapefruit and/or its juice should be avoided until lumacaftor; ivacaftor therapy is reinstated for a minimum of 1 week. The 1-week lead-in period allows for lumacaftor's induction of CYP3A to reach steady state. Grapefruit is a potent CYP3A inhibitor, ivacaftor is a CYP3A substrate, and lumacaftor is a potent CYP3A inducer. The inhibitory effects of grapefruit and its juice may increase the systemic exposure of ivacaftor. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with once-daily itraconazole, a strong CYP3A inhibitor, increased ivacaftor exposure by 4.3-fold. However, because lumacaftor is a strong inducer of CYP3A, the net exposure of ivacaftor at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours).

<b>DISCLAIMER:</b><em> This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Drug information is sourced from GSDD (Gold Standard Drug Database ) provided by Elsevier.</em>