Drug Interactions with KALYDECO® (ivacaftor)
Drug-Drug interaction profiles1
KALYDECO is supplied as tablets (150 mg) for patients 6 years and older and as oral granules (25-mg, 50-mg, and 75-mg packets) for patients age 4 months to less than 6 years
Concomitant use of strong or moderate CYP3A inhibitors is not recommended for patients age 4 to <6 months.1
CYP3A substrate2
Alprazolam XANAX®
One dose every 12 hours
Carbamazepine TEGRETOL®, EQUETRO®, CARBATROL®
Ciprofloxacina CIPRO®
Clarithromycin BIAXIN®
One dose twice a week
Dose adjustment
CYP2D6 substrate3
Desipraminea NORPRAMIN®
One dose every 12 hours
CYP3A substrate2
Diazepam VALIUM®
One dose every 12 hours
Digoxinb LANOXIN®
Increased exposure of digoxinb
One dose every 12 hours
Erythromycin ERYC®, ERY-TAB®
One dose once daily
Dose adjustment
Fluconazolea,c DIFLUCAN®
Increased KALYDECO exposurec
One dose once daily
Dose adjustment
Itraconazole SPORANOX®
One dose twice a week
Dose adjustment
Ketoconazolea,dNIZORAL®, EXTINA®, XOLEGEL®
Increased KALYDECO exposured
One dose twice a week
Dose adjustment
Midazolama,e
Increased exposure of midazolame
One dose every 12 hours
CYP3A substrate2,4
Oral contraceptivea Numerous brand names available
One dose every 12 hours
No dose adjustment
Phenytoin DILANTIN®
Posaconazole NOXAFIL®
One dose twice a week
Dose adjustment
Rifabutin MYCOBUTIN®
Rifampina,f RIFADIN®
Decreased KALYDECO exposuref
CYP2C8 substrate2
Rosiglitazonea AVANDIA®
One dose every 12 hours
No dose adjustment
Tacrolimus PROGRAF®
One dose every 12 hours
One dose twice a week
Dose adjustment
CYP3A substrate2
Triazolam HALCION®
One dose every 12 hours
Voriconazole VFEND®
One dose twice a week
Dose adjustment
CYP2C9 substrate2
Warfarin COUMADIN®, JANTOVEN®
One dose every 12 hours
This is a representative list of drugs and common brand names and is not intended to be exhaustive.
Dose=one tablet or one packet of oral granules.
aThese interactions have been studied.
bCo-administration with digoxin increased digoxin exposure by 1.3-fold.
cCo-administration with fluconazole increased KALYDECO exposure (AUC) by 3-fold.
dCo-administration with ketoconazole significantly increased KALYDECO exposure (AUC) by 8.5-fold.
eKALYDECO increased midazolam exposure by 1.5-fold.
fCo-administration with rifampin significantly decreased KALYDECO exposure (AUC) by approximately 9-fold.
AUC, area under the curve; INR, international normalized ratio.
Potential drug interactions with KALYDECO
Inhibitors of CYP3A1
- Ivacaftor is a sensitive CYP3A substrate. Co-administration with ketoconazole, a strong CYP3A inhibitor, significantly increased ivacaftor exposure [measured as area under the curve (AUC)] by 8.5-fold. Based on simulations of these results, a reduction of the KALYDECO dose is recommended when co-administered with strong CYP3A inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin
- Co-administration with fluconazole, a moderate inhibitor of CYP3A, increased ivacaftor exposure by 3-fold. Therefore, a reduction of the KALYDECO dose is recommended for patients taking concomitant moderate CYP3A inhibitors, such as fluconazole and erythromycin
- Co-administration of KALYDECO with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of ivacaftor. Therefore, food containing grapefruit should be avoided during treatment with KALYDECO
Inducers of CYP3A1
Co-administration with rifampin, a strong CYP3A inducer, significantly decreased ivacaftor exposure (AUC) by approximately 9-fold. Therefore, co-administration with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort is not recommended.
Ciprofloxacin1
Co-administration of KALYDECO with ciprofloxacin had no effect on the exposure of ivacaftor. Therefore, no dose adjustment is necessary during concomitant administration of KALYDECO with ciprofloxacin.
Potential for KALYDECO to affect other drugs1
CYP2C9 Substrates
Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) during co-administration of KALYDECO with warfarin is recommended. Other medicinal products for which exposure may be increased by KALYDECO include glimepiride and glipizide; these medicinal products should be used with caution.
CYP3A and/or P-gp substrates1
Ivacaftor and its M1 metabolite have the potential to inhibit CYP3A and P-gp. Co-administration with midazolam, a sensitive CYP3A substrate, increased midazolam exposure 1.5-fold, consistent with weak inhibition of CYP3A by ivacaftor. Co-administration with digoxin, a sensitive P-gp substrate, increased digoxin exposure by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor. Administration of KALYDECO may increase systemic exposure of drugs that are substrates of CYP3A and/or P-gp, which may increase or prolong their therapeutic effect and adverse events. Therefore, caution and appropriate monitoring are recommended when co-administering KALYDECO with sensitive CYP3A and/or P-gp substrates, such as digoxin, cyclosporine, and tacrolimus.