Drug-Drug Interaction Tool

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

  • 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

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Drug Class:

Aripiprazole
(Abilify®)1,2

Antipsychotics

Decreased ↓

  • A higher dose of this antipsychotic may be required to obtain the desired clinical effect
Ibuprofen
(Advil®, Motrin®)1
Anti-inflammatories
Decreased ↓
  • A higher dose of ibuprofen may be required to obtain the desired clinical effect
Cyclosporine
(Sandimmune®)1
Immunosuppressants

Decreased ↓

  • Concomitant use not recommended
  • Avoid the use of ORKAMBI

Alprazolam
(Xanax®)1,5

Benzodiazepines

Decreased ↓

  • A higher dose of this benzodiazepine may be required to obtain the desired clinical effect

Antacids1

Antacids

Increased ↑ or
decreased ↓

  • No dose adjustment is recommended for calcium carbonate antacid

Clarithromycin
(Biaxin®)1

Antibiotics, macrolides

Decreased ↓

  • Consider an alternative, such as ciprofloxacin, azithromycin, and levofloxacin
  • No dose adjustment recommended for ORKAMBI when this antibiotic is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antibiotic, reduce ORKAMBI dose to 1 tablet daily for first week, then 2 tablets every 12 hours
Carbamazepine
(Tegretol®, Equetro®, Carbatrol®)1
Anticonvulsants
Decreased ↓
  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI
Fluoxetine
(Prozac®)1,4,9
Selective serotonin reuptake inhibitors (SSRIs)
No effect predicted
  • No effect predicted

Clonazepam
(Klonopin®)1,6

Benzodiazepines

Decreased ↓

  • A higher dose of this benzodiazepine may be required to obtain the desired clinical effect

Clozapine
(Clozaril®)1,3

Antipsychotics

Decreased ↓

  • A higher dose of this antipsychotic may be required to obtain the desired clinical effect

Warfarin
(Coumadin®, Jantoven®)1

Anticoagulants

Increased ↑ or
decreased ↓

  • Monitor international normalized ratio when co-administration with ORKAMBI is required
Everolimus
(Zortress®, Afinitor®)1
Immunosuppressants

Decreased ↓

  • Concomitant use not recommended
  • Avoid the use of ORKAMBI

Duloxetine
(Cymbalta®)1,9,10

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

No effect predicted

  • No effect predicted
Mirtazapine
(Remeron®)1,12
Tetracyclic antidepressants

Decreased ↓

  • A higher dose of this antidepressant may be required to obtain the desired clinical effect

Diazepam
(Valium®)1,7

Benzodiazepines

Decreased ↓

  • A higher dose of this benzodiazepine may be required to obtain the desired clinical effect

Digoxin
(Lanoxin®)1

Anti-arrhythmics

Increased ↑ or
decreased ↓

  • Monitor the serum concentration and titrate the dose to obtain the desired clinical effect
Phenobarbital
(Luminal®)1
Anticonvulsants
Decreased ↓
  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI

Erythromycin
(Eryc®, Ery-Tab®, PCE®)1

Antibiotics, macrolides

Decreased ↓

  • Consider an alternative, such as ciprofloxacin, azithromycin, and levofloxacin
  • No dose adjustment recommended for ORKAMBI when this antibiotic is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antibiotic, reduce ORKAMBI dose to 1 tablet daily for first week, then 2 tablets every 12 hours
Citalopram
(Celexa®)1
Selective serotonin reuptake inhibitors (SSRIs)
Decreased ↓
  • A higher dose of this antidepressant may be required to obtain the desired clinical effect

Esomeprazole
(Nexium®)1

Proton pump inhibitors

Decreased ↓

  • A dose adjustment may be required to obtain the desired clinical effect
  • No dose adjustment is recommended for calcium carbonate antacid

Estrogen,
Progestins1,8

Hormonal contraceptives

Decreased ↓

  • Do not rely on hormonal contraceptives, including oral, injectable, transdermal, and implantable, as an effective method of contraception
  • Concomitant use of ORKAMBI with hormonal contraceptives increased menstrual abnormality events
  • Avoid concomitant use unless the benefits outweigh the risks
Escitalopram
(Lexapro®)1
Selective serotonin reuptake inhibitors (SSRIs)
Decreased ↓
  • A higher dose of this antidepressant may be required to obtain the desired clinical effect
Midazolam
(Versed®)1,4
Benzodiazepines

Decreased ↓

  • Concomitant use not recommended
  • Consider an alternative to this benzodiazepine

Telithromycin
(Ketek®)1

Antibiotics, macrolides

Decreased ↓

  • Consider an alternative, such as ciprofloxacin, azithromycin, and levofloxacin
  • No dose adjustment recommended for ORKAMBI when this antibiotic is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antibiotic, reduce ORKAMBI dose to 1 tablet daily for first week, then 2 tablets every 12 hours
Ketoconazole
(Nizoral®)1
Antifungals
Decreased ↓
  • Concomitant use not recommended
  • Monitor closely for breakthrough fungal infections if use is necessary
  • Consider an alternative, such as fluconazole
  • No dose adjustment recommended for ORKAMBI when this antifungal is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antifungal, reduce dose to 1 tablet daily for first week, then 2 tablets every 12 hours

Lansoprazole
(Prevacid®)1

Proton pump inhibitors

Decreased ↓

  • A dose adjustment may be required to obtain the desired clinical effect
  • No dose adjustment is recommended for calcium carbonate antacid
Phenytoin
(Dilantin®)1
Anticonvulsants
Decreased ↓
  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI

Methylprednisolone
(Solu-Medrol®)1

Corticosteroids (systemic)

Decreased ↓

  • A higher dose of this systemic corticosteroid may be required to obtain the desired clinical effect

Triazolam
(Halcion®)1,4

Benzodiazepines

Decreased ↓

  • Concomitant use not recommended
  • Consider an alternative to this benzodiazepine
Trazodone
(Desyrel®)1,13
Tetracyclic antidepressants

Decreased ↓

  • A higher dose of this antidepressant may be required to obtain the desired clinical effect

Montelukast
(Singulair®)1

Anti-allergics

Decreased ↓

  • No dose adjustment recommended
  • Appropriate clinical monitoring, as is reasonable

Rifabutin
(Mycobutin®)1

Antimycobacterials

Decreased ↓

  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI
Posaconazole
(Noxafil®)1
Antifungals
Decreased ↓
  • Concomitant use not recommended
  • Monitor closely for breakthrough fungal infections if use is necessary
  • Consider an alternative, such as fluconazole
  • No dose adjustment recommended for ORKAMBI when this antifungal is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antifungal, reduce dose to 1 tablet daily for first week, then 2 tablets every 12 hours

Omeprazole
(Prilosec®)1

Proton pump inhibitors

Decreased ↓

  • A dose adjustment may be required to obtain the desired clinical effect
  • No dose adjustment is recommended for calcium carbonate antacid
Paroxetine
(Paxil®)1,11
Selective serotonin reuptake inhibitors (SSRIs)
Decreased ↓
  • A higher dose of this antidepressant may be required to obtain the desired clinical effect

Repaglinide
(Prandin®)1

Oral hypoglycemics

Decreased ↓

  • A dose adjustment for this agent may be required to obtain the desired clinical effect
  • No dose adjustment is recommended for metformin

Prednisone
(Prednisone Intensol®, Rayos®)1

Corticosteroids (systemic)

Decreased ↓

  • A higher dose of this systemic corticosteroid may be required to obtain the desired clinical effect
Sirolimus
(Rapamune®)1
Immunosuppressants

Decreased ↓

  • Concomitant use not recommended
  • Avoid the use of ORKAMBI
Ranitidine
(Zantac®)1
H2 blockers
Increased ↑ or
decreased ↓
  • A dose adjustment may be required to obtain the desired clinical effect
Tacrolimus
(Prograf®)1
Immunosuppressants

Decreased ↓

  • Concomitant use not recommended
  • Avoid the use of ORKAMBI

Rifampin*
(Rifadin®)1

Antimycobacterials

Decreased ↓

  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI
* Based on clinical drug-drug interaction studies. All other drug interactions shown are predicted based on elimination pathways. Co-administration with rifampin had minimal effect on the exposure of lumacaftor but decreased ivacaftor exposure (AUC) by 57%.

Quetiapine
(Seroquel®)1,4

Antipsychotics

Decreased ↓

  • A higher dose of this antipsychotic may be required to obtain the desired clinical effect
Sertraline
(Zoloft®)1
Selective serotonin reuptake inhibitors (SSRIs)
Decreased ↓
  • A higher dose of this antidepressant may be required to obtain the desired clinical effect

St. John's wort
(Hypericum perforatum)1

Herbals

Decreased ↓

  • Concomitant use not recommended
  • Decreased ivacaftor exposure; may reduce the effectiveness of ORKAMBI

Sulfonylureas1

Oral hypoglycemics

Increased ↑ or
decreased ↓

  • A dose adjustment for this agent may be required to obtain the desired clinical effect
  • No dose adjustment is recommended for metformin
Voriconazole
(Vfend®)1
Antifungals
Decreased ↓
  • Concomitant use not recommended
  • Monitor closely for breakthrough fungal infections if use is necessary
  • Consider an alternative, such as fluconazole
  • No dose adjustment recommended for ORKAMBI when this antifungal is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antifungal, reduce dose to 1 tablet daily for first week, then 2 tablets every 12 hours
Itraconazole*
(Sporanox®)1
Antifungals
Decreased ↓
  • Concomitant use not recommended
  • Monitor closely for breakthrough fungal infections if use is necessary
  • Consider an alternative, such as fluconazole
  • No dose adjustment recommended for ORKAMBI when this antifungal is initiated in patients currently taking ORKAMBI
  • When initiating ORKAMBI in patients taking this antifungal, reduce dose to 1 tablet daily for first week, then 2 tablets every 12 hours
*
Based on clinical drug-drug interaction studies. All other drug interactions shown are predicted based on elimination pathways. Co-administration with itraconazole did not impact the exposure of lumacaftor but increased ivacaftor exposure by 4.3-fold.
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ORKAMBI® (lumacaftor/ivacaftor) INDICATIONS AND USAGE

ORKAMBI is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.


Limitations of Use

The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation.

IMPORTANT SAFETY INFORMATION

Use in Patients With Advanced Liver Disease

  • Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported in some patients with CF while receiving ORKAMBI
  • Use ORKAMBI with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dose should be reduced

Liver-related Events

  • Serious adverse reactions related to elevated transaminases have been reported in patients with CF receiving ORKAMBI. In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin
  • It is recommended that ALT, AST, and bilirubin be assessed prior to initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered
  • Patients who develop increased ALT, AST, or bilirubin should be closely monitored until the abnormalities resolve
  • Dosing should be interrupted in patients with ALT or AST greater than 5 x upper limit of normal (ULN) when not associated with elevated bilirubin. Dosing should also be interrupted in patients with ALT or AST elevations greater than 3 x ULN when associated with bilirubin elevations greater than 2 x ULN
  • Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing

Respiratory Events

  • Respiratory events (e.g., chest discomfort, dyspnea, and respiration abnormal) were observed more commonly in patients during initiation of ORKAMBI compared to those who received placebo. Clinical experience in patients with percent predicted FEV1 (ppFEV1) <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy

Effect on Blood Pressure

  • Increased blood pressure has been observed in some patients treated with ORKAMBI. Blood pressure should be monitored periodically in all patients being treated with ORKAMBI

Drug Interactions

Substrates of CYP3A

  • Lumacaftor is a strong inducer of CYP3A. Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect. Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended
  • ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI

Strong CYP3A Inducers

  • Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Use of ORKAMBI with strong CYP3A inducers, such as rifampin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers is not recommended

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with ORKAMBI

Adverse Reactions

  • Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with ORKAMBI included pneumonia, hemoptysis, cough, increased blood creatine phosphokinase, and transaminase elevations. These occurred in 1% or less of patients
  • The most common adverse reactions in patients age 12 years and older in Phase 3 trials (Trials 1 and 2) occurring in ≥5% of patients treated with ORKAMBI (N=369) vs placebo (N=370) and at a rate higher than placebo were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, and influenza
  • The safety profile for patients age 6 through 11 years in an open-label Phase 3 trial (Trial 3; N=58) was similar to that observed in Trials 1 and 2

Click here to access full Prescribing Information.

×
+

ORKAMBI® (lumacaftor/ivacaftor) INDICATIONS AND USAGE

ORKAMBI is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.


Limitations of Use

The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation.

IMPORTANT SAFETY INFORMATION

Use in Patients With Advanced Liver Disease

  • Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported in some patients with CF while receiving ORKAMBI
  • Use ORKAMBI with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dose should be reduced

Liver-related Events

  • Serious adverse reactions related to elevated transaminases have been reported in patients with CF receiving ORKAMBI. In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin
  • It is recommended that ALT, AST, and bilirubin be assessed prior to initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered
  • Patients who develop increased ALT, AST, or bilirubin should be closely monitored until the abnormalities resolve
  • Dosing should be interrupted in patients with ALT or AST greater than 5 x upper limit of normal (ULN) when not associated with elevated bilirubin. Dosing should also be interrupted in patients with ALT or AST elevations greater than 3 x ULN when associated with bilirubin elevations greater than 2 x ULN
  • Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing

Respiratory Events

  • Respiratory events (e.g., chest discomfort, dyspnea, and respiration abnormal) were observed more commonly in patients during initiation of ORKAMBI compared to those who received placebo. Clinical experience in patients with percent predicted FEV1 (ppFEV1) <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy

Effect on Blood Pressure

  • Increased blood pressure has been observed in some patients treated with ORKAMBI. Blood pressure should be monitored periodically in all patients being treated with ORKAMBI

Drug Interactions

Substrates of CYP3A

  • Lumacaftor is a strong inducer of CYP3A. Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect. Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended
  • ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI

Strong CYP3A Inducers

  • Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Use of ORKAMBI with strong CYP3A inducers, such as rifampin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers is not recommended

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with ORKAMBI

Adverse Reactions

  • Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with ORKAMBI included pneumonia, hemoptysis, cough, increased blood creatine phosphokinase, and transaminase elevations. These occurred in 1% or less of patients
  • The most common adverse reactions in patients age 12 years and older in Phase 3 trials (Trials 1 and 2) occurring in ≥5% of patients treated with ORKAMBI (N=369) vs placebo (N=370) and at a rate higher than placebo were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, and influenza
  • The safety profile for patients age 6 through 11 years in an open-label Phase 3 trial (Trial 3; N=58) was similar to that observed in Trials 1 and 2

Click here to access full Prescribing Information.