This site is intended for
US Healthcare Professionals only.

Drug Interactions With ORKAMBI® (lumacaftor/ivacaftor)

Drug-Drug Interactions Tool

The Drug-Drug Interactions (DDI) Tool provides the established or predicted effect of ORKAMBI on other medicinal products or effect of other medicinal products on ORKAMBI1-3

  • The clinical comments are based on drug interaction studies, clinical relevance, or predicted interactions due to elimination pathways
  • Drugs shown within a therapeutic class do not represent all possible drugs within the class. Drugs within a therapeutic class may have different metabolic profiles and, therefore, clinical recommendations apply only to the indicated drugs and not the class. The table does not represent all possible drugs or drug classes that a patient could be receiving. For further information, contact your clinical pharmacist

Choose or Begin Typing the Brand or Generic Drug Name or Drug Class to Learn More About Potential DDIs

Choose or begin typing the brand or generic drug name or drug class to learn more about potential DDIs

Search by:

Drug Name

Drug Name

Abilify®

Advil®

Afinitor®

Afirmelle®

Alesse®

Alprazolam

Altavera®

Amaryl®

Antacids

Aripiprazole

Atorvastatin

Aviane®

Ayuna®

Azithromycin

Biaxin®

Carbamazepine

Carbatrol®

Celexa®

Cipro®

Ciprofloxacin

Citalopram

Clarithromycin

Clonazepam

Clozapine

Clozaril®

Coumadin®

Crestor®

Cyclosporine

Cymbalta®

Dexamethasone

Diazepam

Diflucan®

Digoxin

Dilantin®

Duloxetine

Enpresse®

Equetro®

Erythromycin

Ery-Tab®

Escitalopram

Esomeprazole

Ethinyl estradiol/Levonorgestrel

Ethinyl estradiol/Norethindrone

Everolimus

Ezallor®

Falmina®

Flolipid®

Fluconazole

Fluvastatin

Fluoxetine

Glimepiride

Glipizide

Glucotrol®

Glumetza®

Halcion®

Ibuprofen

Itraconazole

Jantoven®

Ketoconazole

Klonopin®

Kurvelo®

Lanoxin®

Lansoprazole

Lescol®

Lessina®

Levora®

Lexapro®

Lipitor®

Livalo®

Loestrin®

Lovastatin

Marlissa®

Medrol®

Metformin

Methylprednisolone

Midazolam

Mirtazapine

Montelukast

Motrin®

Mycobutin®

Myzilra®

Nateglinide

Nexium®

Nizoral®

Nordette®

Noxafil®

Omeprazole

Orsythia®

Paroxetine

Paxil®

PCE

Perseris®

Phenobarbital

Phenytoin

Pitavastatin

Portia-28®

Posaconazole

Pravachol®

Pravastatin

Prednisone

Prednisone Intensol®

Prevacid®

Prilosec®

Prograf®

Prozac®

Quetiapine

Ranitidine

Rapamune®

Rayos®

Remeron®

Repaglinide

Rifabutin

Rifadin®

Rifampin

Riomet®

Risperdal®

Risperidone

Rosuvastatin

Sandimmune®

Seroquel®

Sertraline

Simvastatin

Singulair®

Sirolimus

Sporanox®

Starlix®

St. John's wort

Tacrolimus

Tegretol®

Telithromycin

Trazodone

Triazolam

Trivora-28®

Valium®

Vfend®

Vienva®

Voriconazole

Warfarin

Xanax®

Zantac®

Zithromax®

Zocor®

Zoloft®

Zortress®

Zypitamag®

OR

Drug Class

Antacids

Anti-allergics

Anti-arrhythmics

Antibiotics, macrolides

Antibiotics, quinolone

Anticoagulants

Anticonvulsants

Antifungals

Anti-inflammatories

Antimycobacterials

Antipsychotics

Benzodiazepines

Corticosteroids (systemic)

Herbals

HMG-CoA Reductase Inhibitors (Statins)

Hormonal contraceptives

H2 blockers

Immunosuppressants

Oral hypoglycemics

Proton pump inhibitors

SNRIs

SSRIs

Tetracyclic antidepressants

Drug names in the table that are bold are listed in the full Prescribing Information for SYMDEKO.

Drug names in the table that are BOLD are listed in the full Prescribing Information for ORKAMBI.

 

POTENTIAL FOR OTHER DRUGS TO AFFECT ORKAMBI

Inhibitors of CYP3A1

  • Co-administration of lumacaftor/ivacaftor with itraconazole, a strong CYP3A inhibitor, did not impact the exposure of lumacaftor, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state, the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg every 12 hours (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking ORKAMBI
  • However, when initiating ORKAMBI in patients taking strong CYP3A inhibitors, reduce the ORKAMBI dose to 1 tablet daily or 1 packet every other day (patients age 2 through 5 years) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. Examples of strong CYP3A inhibitors include
    • Ketoconazole, itraconazole, posaconazole, and voriconazole
    • Telithromycin, clarithromycin
  • No dose adjustment is recommended when used with moderate or weak CYP3A inhibitors

Inducers of CYP3A1

  • Co-administration of lumacaftor/ivacaftor with rifampin, a strong CYP3A inducer, had minimal effect on the exposure of lumacaftor, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort (Hypericum perforatum) is not recommended
  • No dose adjustment is recommended when used with moderate or weak CYP3A inducers

 

POTENTIAL FOR ORKAMBI TO AFFECT OTHER DRUGS

CYP3A Substrates1

  • Lumacaftor is a strong inducer of CYP3A. Co-administration of lumacaftor with ivacaftor, a sensitive CYP3A substrate, decreased ivacaftor exposure by approximately 80%. Administration of ORKAMBI may decrease systemic exposure of medicinal products which are substrates of CYP3A, thereby decreasing the therapeutic effect of the medicinal product
  • Co-administration of ORKAMBI is not recommended with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index such as 
    • Benzodiazepines: midazolam, triazolam (consider an alternative to these benzodiazepines)
    • Immunosuppressants: cyclosporine, everolimus, sirolimus, and tacrolimus (avoid the use of ORKAMBI)

CYP2B6 and CYP2C Substrates1

  • In vitro studies suggest that lumacaftor has the potential to induce CYP2B6, CYP2C8, CYP2C9, and CYP2C19; inhibition of CYP2C8 and CYP2C9 has also been observed in vitro. Additionally, in vitro studies suggest that ivacaftor may inhibit CYP2C9. Therefore, concomitant use of ORKAMBI with CYP2B6, CYP2C8, CYP2C9, and CYP2C19 substrates may alter the exposure of these substrates

Digoxin and Other P-gp Substrates1

  • Based on in vitro results, which showed P-gp inhibition and pregnane-X-receptor (PXR) activation, lumacaftor has the potential to both inhibit and induce P-gp. Additionally, a clinical study with ivacaftor monotherapy showed that ivacaftor is a weak inhibitor of P-gp. Therefore, concomitant use of ORKAMBI with P-gp substrates may alter the exposure of these substrates
  • Monitor the serum concentration of digoxin and titrate the digoxin dose to obtain the desired clinical effect

Anti-allergics and Systemic Corticosteroids

  • ORKAMBI may decrease the exposure of montelukast, which may reduce its efficacy. No dose adjustment for montelukast is recommended. Employ appropriate clinical monitoring, as is reasonable, when co-administered with ORKAMBI
  • Concomitant use of ORKAMBI may reduce the exposure and effectiveness of prednisone and methylprednisolone. A higher dose of these systemic corticosteroids may be required to obtain the desired clinical effect

Antibiotics1

  • Concomitant use of ORKAMBI may decrease the exposure of clarithromycin, erythromycin, and telithromycin, which may reduce the effectiveness of these antibiotics. Consider an alternative to these antibiotics, such as ciprofloxacin, azithromycin, and levofloxacin

Antifungals1

  • Concomitant use of ORKAMBI may reduce the exposure and effectiveness of itraconazole, ketoconazole, posaconazole, and voriconazole. Concomitant use of ORKAMBI with these antifungals is not recommended. Monitor patients closely for breakthrough fungal infections if such drugs are necessary. Consider an alternative such as fluconazole

Anti-inflammatories1

  • Concomitant use of ORKAMBI may reduce the exposure and effectiveness of ibuprofen. A higher dose of ibuprofen may be required to obtain the desired clinical effect

Antidepressants1

  • Concomitant use of ORKAMBI may reduce the exposure and effectiveness of citalopram, escitalopram, and sertraline. A higher dose of these antidepressants may be required to obtain the desired clinical effect

Hormonal Contraceptives1

  • ORKAMBI may decrease hormonal contraceptive exposure, reducing the effectiveness. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI
  • Concomitant use of ORKAMBI with hormonal contraceptives increased the menstrual abnormality events. Avoid concomitant use unless the benefit outweighs the risks

Oral Hypoglycemics1

  • Concomitant use of ORKAMBI may reduce the exposure and effectiveness of repaglinide and may alter the exposure of sulfonylurea. A dose adjustment may be required to obtain the desired clinical effect. No dose adjustment is recommended for metformin

Proton Pump Inhibitors, H2 Blockers, Antacids1

  • ORKAMBI may reduce the exposure and effectiveness of proton pump inhibitors such as omeprazole, esomeprazole, and lansoprazole, and may alter the exposure of ranitidine. A dose adjustment may be required to obtain the desired clinical effect. No dose adjustment is recommended for calcium carbonate antacid

Warfarin1

  • ORKAMBI may alter the exposure of warfarin. Monitor the international normalized ratio (INR) when warfarin co-administration with ORKAMBI is required

Concomitant Drugs That Do Not Need Dose Adjustment1

  • No dosage adjustment of ORKAMBI or concomitant drug is recommended when ORKAMBI is given with the following: azithromycin, aztreonam, budesonide, ceftazidime, cetirizine, ciprofloxacin, colistimethate, colistin, dornase alfa, fluticasone, ipratropium, levofloxacin, pancreatin, pancrelipase, salbutamol, salmeterol, sulfamethoxazole and trimethoprim, tiotropium, and tobramycin. Based on the metabolism and route of elimination, ORKAMBI is not expected to impact the exposure of these drugs