Drug Interactions between ivacaftor / lumacaftor and Posicor

Mibefradil may significantly increase the blood levels of ivacaftor. This may increase the risk and/or severity of serious side effects such as liver damage. A dosage adjustment is normally recommended for ivacaftor. Talk to your doctor if you have any questions or concerns, or if you do not know whether your dosage has already been adjusted. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Consumer information for this interaction is not currently available.

GENERALLY AVOID: Potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of most calcium channel blockers (CCBs), as CYP450 3A4 is the primary isoenzyme responsible for their metabolism. Some drug interaction studies have reported a significant reduction in plasma levels for certain CCBs. For example, when a single dose of nimodipine (60 mg) was administered to patients with epilepsy (n=8) who were also receiving chronic treatment with a potent CYP450 3A4-inducing antiepileptic agent (phenytoin, phenobarbital and/or carbamazepine), the mean areas under the plasma nimodipine concentration curve (AUC) were lowered by about 7-fold compared to the control group. In another drug interaction study comparing nisoldipine pharmacokinetics in epileptic patients on concurrent phenytoin therapy (n=12) to healthy controls (n=12), the AUC of nisoldipine was approximately 90% lower (1.6 vs 15.2 mcg/L/h) in patients on concomitant phenytoin therapy. Clinical data for all calcium channel blockers with potent CYP450 3A4 inducers are not available.

MANAGEMENT: Concomitant use of calcium channel blockers (CCBs) primarily metabolized by CYP450 3A4 with potent CYP450 3A4 inducers should generally be avoided. Additional monitoring and dose adjustments may be required if coadministration is necessary, particularly during initiation, titration, or discontinuation of the CYP450 3A4 inducer. Individual product labeling for the CCB should be consulted for further guidance.