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DRUG INTERACTIONS WITH TRIKAFTA® (elexacaftor/tezacaftor/
ivacaftor and ivacaftor)

IN THIS SECTION: ALSO IN THIS SECTION:
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Drug-drug interactions tool

Previously the Drug Interaction Tool for TRIKAFTA located on this website classified clofazimine as a weak CYP3A4 inhibitor and stated that no dosage adjustment for TRIKAFTA was required. There are insufficient data available to classify the degree of CYP3A inhibition produced by clofazimine.

Please see the table below and refer to the US Prescribing Information for recommended dosage of TRIKAFTA and recommended dose adjustments for use with CYP3A inducers and inhibitors.


For more information about this and other drug interactions, please contact Vertex Medical Information at +1-877-634-8789 or medicalinfo@vrtx.com.

The Drug-Drug Interactions (DDI) Tool provides the established or predicted effect of TRIKAFTA on other medicinal products or effect of other medicinal products on TRIKAFTA.1-4

 

  • 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.

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

Drug Name Potential Effect Clinical Comment

Alprazolam
(Xanax®)2
  • No effect predicted
  • No dosage adjustments recommended

Amikacin2
  • No effect predicted
  • No dosage adjustments recommended

Aripiprazole
(Abilify®)2
  • No effect predicted
  • No dosage adjustments recommended

Atorvastatin
(Lipitor®)1
  • Atorvastatin exposure may increase
  • Use with caution and appropriate monitoring

Azithromycin
(Zithromax®)2
  • No effect predicted
  • No dosage adjustments recommended

Aztreonam
(Azactam®, Cayston®)2
  • No effect predicted
  • No dosage adjustments recommended

Budesonide
(Pulmicort®(inhaled), Rhinocort®(inhaled))2
  • No effect predicted
  • No dosage adjustments recommended

Bupropion
(Forfivo®, Wellbutrin®)2
  • No effect predicted
  • No dosage adjustments recommended

Carbamazepine
(Carbatrol®, Epitol®, Equetro®, Tegretol®)1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended

Ceftazidime
(Fortaz®, Tazicef®)2
  • No effect predicted
  • No dosage adjustments recommended

Cetirizine
(Zyrtec®)2
  • No effect predicted
  • No dosage adjustments recommended

Chloramphenicol2
  • No effect predicted
  • No dosage adjustments recommended

Ciprofloxacin*
(Cipro®)1
  • No effect predicted
  • No dosage adjustments recommended
    • Interaction with tezacaftor and ivacaftor has been studied. Exposure of ivacaftor increased with concomitant use, but effect was not clinically significant.

Citalopram
(Celexa®)2
  • No effect predicted
  • No dosage adjustments recommended

Clarithromycin1
  • Increased TRIKAFTA exposure

Clonazepam
(Klonopin®)2
  • No effect predicted
  • No dosage adjustments recommended

Clozapine
(Clozaril®, Versacloz®)2
  • No effect predicted
  • No dosage adjustments recommended

Colistimethate/Colistin
(Coly-Mycin M®)2
  • No effect predicted
  • No dosage adjustments recommended

Cyclosporine
(Gengraf®, Neoral®, Sandimmune®)1
  • Cyclosporine exposure may increase
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring

Desipramine*
(Norpramin®)1
  • No effect predicted
  • No dosage adjustments recommended
    • Interaction with ivacaftor has been studied.

Desloratadine
(Clarinex®)2
  • No effect predicted
  • No dosage adjustments recommended

Dexamethasone2
  • No effect predicted
  • No dosage adjustments recommended

Diazepam
(Valium®)2
  • No effect predicted
  • No dosage adjustments recommended

Digoxin*
(Lanoxin®)1,2
  • Increased digoxin exposure
  • Drugs with a narrow therapeutic index should be used with appropriate monitoring
    • Interaction with ivacaftor or tezacaftor/ivacaftor has been studied. Co-administration increased digoxin exposure by 1.3-fold.

Diphenhydramine2
  • No effect predicted
  • No dosage adjustments recommended

Dornase alfa
(Pulmozyme®)2
  • No effect predicted
  • No dosage adjustments recommended

Duloxetine
(Cymbalta®)2
  • No effect predicted
  • No dosage adjustments recommended

Erythromycin*
(Ery-Tab®, Erythrocin®)1
  • Increased TRIKAFTA exposure
  • TRIKAFTA dosing regimen should be adjusted. For full dosing table, click here
    • Simulations suggest that co-administration with moderate CYP3A inhibitors may increase elexacaftor and tezacaftor exposure by approximately 1.9- to 2.3-fold and 2.1-fold, respectively.

Escitalopram
(Lexapro®)2
  • No effect predicted
  • No dosage adjustments recommended

Esomeprazole
(Nexium®)2
  • No effect predicted
  • No dosage adjustments recommended

Ethambutol
(Myambutol®)2
  • No effect predicted
  • No dosage adjustments recommended

Ethinyl estradiol/
Levonorgestrel*
(Afirmelle®, Altavera®, Aviane®, Ayuna®, Enpresse®, Falmina®, Kurvelo®, Lessina®, Levora®, Marlissa®, Myzilra®, Nordette®, Portia-28®, Trivora-28®, Vienva®)1,2
  • No effect predicted
  • TRIKAFTA not expected to modify efficacy of oral hormonal contraceptives
    • Interaction between ethinyl estradiol/
      levonorgestrel and elexacaftor/
      tezacaftor/
      ivacaftor has been studied. Co-administration with ethinyl estradiol/
      levonorgestrel increased ethinyl estradiol exposure (AUC) by 1.3-fold and levonorgestrel exposure by 1.2-fold. However, effects were not clinically significant.
      Hormonal contraceptives may play a role in the occurrence of rash in patients taking elexacaftor/
      tezacaftor/
      ivacaftor. For patients taking hormonal contraceptives who develop rash, consider interrupting elexacaftor/
      tezacaftor/
      ivacaftor and hormonal contraceptives. Following the resolution of rash, consider resuming elexacaftor/
      tezacaftor/
      ivacaftor without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

Ethinyl estradiol/
Norethindrone
(Loestrin®)2
  • No effect predicted
  • TRIKAFTA not expected to modify efficacy of oral hormonal contraceptives
    • Hormonal contraceptives may play a role in the occurrence of rash in patients taking elexacaftor/
      tezacaftor/
      ivacaftor. For patients taking hormonal contraceptives who develop rash, consider interrupting elexacaftor/
      tezacaftor/
      ivacaftor and hormonal contraceptives. Following the resolution of rash, consider resuming elexacaftor/
      tezacaftor/
      ivacaftor without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.

Everolimus
(Afinitor®, Zortress®)1
  • Everolimus exposure may increase
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring

Fluconazole*
(Diflucan®)1
  • Increased TRIKAFTA exposure
  • TRIKAFTA dosing regimen should be adjusted. For full dosing table, click here
    • Interaction with ivacaftor has been studied. Co-administration with fluconazole increased ivacaftor exposure (AUC) by 2.9-fold; simulations suggest elexacaftor and tezacaftor exposure may increase by approximately 1.9- to 2.3-fold and 2.1-fold, respectively.

Fluoxetine
(Prozac®)2
  • No effect predicted
  • No dosage adjustments recommended

Fluticasone
(Flonase®, Flovent®, Xhance®)2
  • No effect predicted
  • No dosage adjustments recommended

Fluvastatin
(Lescol®)1,4
  • Fluvastatin exposure may increase
  • Use with caution and appropriate monitoring

Glimepiride
(Amaryl®)1
  • Glimepiride exposure may increase
  • Use with caution and appropriate monitoring

Glipizide
(Glucotrol®)1
  • Glipizide exposure may increase
  • Use with caution and appropriate monitoring

Glyburide
(Diabeta®, Glynase®)1
  • Glyburide exposure may increase
  • Use with caution and appropriate monitoring

Ibuprofen
(Advil®)2
  • No effect predicted
  • No dosage adjustments recommended

Ipratropium
(Atrovent®)2
  • No effect predicted
  • No dosage adjustments recommended

Itraconazole*
(Sporanox®)1
  • Increased TRIKAFTA exposure
  • TRIKAFTA dosing regimen should be adjusted. For full dosing table, click here
    • Interaction with elexacaftor, tezacaftor, and ivacaftor has been studied. Co-administration with itraconazole increased elexacaftor exposure (AUC) by 2.8-fold, tezacaftor exposure by 4.0- to 4.5-fold, and ivacaftor exposure by 15.6-fold.

Ketoconazole
(Nizoral®)1
  • Increased TRIKAFTA exposure
  • TRIKAFTA dosing regimen should be adjusted. For full dosing table, click here
    • Interaction with ivacaftor has been studied. Co-administration with ketoconazole increased ivacaftor exposure (AUC) by 8.5-fold.

Lansoprazole
(Prevacid®)2
  • No effect predicted
  • No dosage adjustments recommended

Levofloxacin2
  • No effect predicted
  • No dosage adjustments recommended

Loratadine
(Claritin®)2
  • No effect predicted
  • No dosage adjustments recommended

Lovastatin1,4
  • Lovastatin exposure may increase
  • Use with caution and appropriate monitoring

Meropenem
(Merrem®)2
  • No effect predicted
  • No dosage adjustments recommended

Metformin
(Glumetza®, Riomet®)2
  • No effect predicted
  • No dosage adjustments recommended

Methylprednisolone
(Medrol®)2
  • No effect predicted
  • No dosage adjustments recommended

Midazolam*1,2
  • No effect predicted
  • No dosage adjustments recommended
    • Interaction with tezacaftor/ivacaftor has been studied.

Mirtazapine
(Remeron®)2
  • No effect predicted
  • No dosage adjustments recommended

Montelukast
(Singulair®)2
  • No effect predicted
  • No dosage adjustments recommended

Mycophenolate mofetil
(CellCept®)2
  • No effect predicted
  • No dosage adjustments recommended

Nateglinide1
  • Nateglinide exposure may increase
  • Use with caution and appropriate monitoring

Omeprazole
(Prilosec®)2
  • No effect predicted
  • No dosage adjustments recommended

Pancreatin2
  • No effect predicted
  • No dosage adjustments recommended

Pancrelipase
(Creon®, Pancreaze®, Pertzye®, Viokace®, Zenpep®)2
  • No effect predicted
  • No dosage adjustments recommended

Paroxetine
(Brisdelle®, Paxil®, Pexeva®)2
  • No effect predicted
  • No dosage adjustments recommended

Phenobarbital1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended

Phenytoin
(Dilantin®, Phenytek®)1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended

Pitavastatin
(Livalo®, Zypitamag®)1
  • Pitavastatin exposure may increase
  • Use with caution and appropriate monitoring

Posaconazole
(Noxafil)1
  • Increased TRIKAFTA exposure

Pravastatin1
  • Pravastatin exposure may increase
  • Use with caution and appropriate monitoring

Prednisolone
(Orapred®)2
  • No effect predicted
  • No dosage adjustments recommended

Prednisone2
  • No effect predicted
  • No dosage adjustments recommended

Quetiapine
(Seroquel®)2
  • No effect predicted
  • No dosage adjustments recommended

Repaglinide1
  • Repaglinide exposure may increase
  • Use with caution and appropriate monitoring

Rifabutin
(Mycobutin®)1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended

Rifampin*
(Rifadin®)1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended
    • Interaction with ivacaftor has been studied. Co-administration of ivacaftor with rifampin significantly decreased ivacaftor exposure by 89%.

Rifapentine
(Priftin®)2
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA

Risperidone
(Perseris®, Risperdal®)2
  • No effect predicted
  • No dosage adjustments recommended

Rosiglitazone*
(Avandia®)1
  • No effect predicted
  • No dosage adjustments recommended
    • Interaction with ivacaftor has been studied.

Rosuvastatin
(Crestor®, Ezallor®)1
  • Rosuvastatin exposure may increase
  • Use with caution and appropriate monitoring

Salbutamol/
Albuterol
(AccuNeb®, Proair®, Proventil®, Ventolin®, VoSpire®)2
  • No effect predicted
  • No dosage adjustments recommended

Salmeterol
(Serevent®)2
  • No effect predicted
  • No dosage adjustments recommended

Sertraline
(Zoloft®)2
  • No effect predicted
  • No dosage adjustments recommended

Simvastatin
(Zocor®, Flolipid®)1
  • Simvastatin exposure may increase
  • Use with caution and appropriate monitoring

Sirolimus
(Rapamune®)1
  • Sirolimus exposure may increase
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring

St. John’s wort
(Hypericum perforatum)1
  • Decreased TRIKAFTA exposure
  • May reduce effectiveness of TRIKAFTA, concomitant use not recommended

Sulfamethoxazole/trimethoprim
(Bactrim®, Septra®)2
  • No effect predicted
  • No dosage adjustments recommended

Tacrolimus
(Prograf®)1
  • Tacrolimus exposure may increase
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring

Telithromycin1
  • Increased TRIKAFTA exposure

Tiotropium
(Spiriva®)2
  • No effect predicted
  • No dosage adjustments recommended

Tobramycin
(Bethkis®, Kitabis®, Tobi®, Tobrex®)2
  • No effect predicted
  • No dosage adjustments recommended

Trazodone2
  • No effect predicted
  • No dosage adjustments recommended

Triazolam
(Halcion®)2
  • No effect predicted
  • No dosage adjustments recommended

Vancomycin
(Firvanq®, Vancocin®)2
  • No effect predicted
  • No dosage adjustments recommended

Venlafaxine
(Effexor XR®)2
  • No effect predicted
  • No dosage adjustments recommended

Voriconazole
(Vfend®)1
  • Increased TRIKAFTA exposure

Warfarin
(Jantoven®)1
  • Warfarin exposure may be altered
  • Monitoring of the INR is recommended
    INR, International Normalized Ratio

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

Drug interaction profiles and related dosing considerations1

Clinical considerations for TRIKAFTA are based on drug interaction studies, modeling, other clinical factors, and/or predicted interactions due to elimination pathways.
Dosage adjustments are required for concomitant use with strong and moderate CYP3A inhibitors.

Clinical considerations for TRIKAFTA are based on drug interaction studies, modeling, other clinical factors, and/or predicted interactions due to elimination pathways. Dosage adjustments are required for concomitant use with strong and moderate CYP3A inhibitors.

Clinical considerations for TRIKAFTA are based on drug interaction studies, modeling, other clinical factors, and/or predicted interactions due to elimination pathways. Dosage adjustments are required for concomitant use with strong and moderate CYP3A inhibitors.

Drug interaction profiles and dose adjustments
  Dose recommendation TRIKAFTA interaction

Strong CYP3A inducers including: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum)

CONCOMITANT USE NOT RECOMMENDED
 

Reduced exposure of TRIKAFTA expected with strong CYP3A inducers

  • The concomitant use of CYP3A inducers may reduce TRIKAFTA efficacy

Strong CYP3A inhibitors including: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

 The dosage of TRIKAFTA should be reduced when co‑administered with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here
 

Increased exposure of TRIKAFTA expected with strong or moderate CYP3A inhibitors

Moderate CYP3A inhibitors including: fluconazole, erythromycin

 The dosage of TRIKAFTA should be reduced when co‑administered with moderate CYP3A inhibitors. For full dosing table, including dose adjustments, click here

CYP2C9 substrates including: warfarin, glimepiride, glipizide 

 Caution and appropriate monitoring should be used with CYP2C9, P-gp, and OATP1B1 and OATP1B3 substrates
 

Increased exposure of substrates may occur with TRIKAFTA

  • Ivacaftor may inhibit CYP2C9
  • Ivacaftor or tezacaftor/ivacaftor increases digoxin exposure and may increase exposure of other sensitive P-gp substrates
  • Elexacaftor and M23-ELX inhibit OATP1B1 and OATP1B3 in vitro

P-glycoprotein (P-gp) substrates including: digoxin, cyclosporine, everolimus, sirolimus, tacrolimus 

OATP1B1 and OATP1B3 substrates including1,2: statins (atorvastatin, cerivastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin), glyburide, nateglinide, repaglinide
Drug interaction profiles and dose adjustments

Strong CYP3A inducers including: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum)

Dose recommendation

TRIKAFTA interaction

CONCOMITANT USE
NOT RECOMMENDED

 

Reduced exposure of TRIKAFTA expected with strong CYP3A inducers

  • The concomitant use of CYP3A inducers may reduce TRIKAFTA efficacy

Strong CYP3A inhibitors including: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

Dose recommendation

TRIKAFTA interaction

The dosage of TRIKAFTA should be reduced when co‑administered with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here
 

Increased exposure of TRIKAFTA expected with strong or moderate CYP3A inhibitors

Moderate CYP3A inhibitors including: fluconazole, erythromycin

Dose recommendation

TRIKAFTA interaction

The dosage of TRIKAFTA should be reduced when co‑administered with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here
 

Increased exposure of TRIKAFTA expected with strong or moderate CYP3A inhibitors

CYP2C9 substrates including: warfarin, glimepiride, glipizide

P-glycoprotein (P-gp) substrates including: digoxin, cyclosporine, everolimus, sirolimus, tacrolimus

OATP1B1 and OATP1B3 substrates including:1,2 statins (atorvastatin, cerivastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin), glyburide, nateglinide, repaglinide

Dose recommendation

TRIKAFTA interaction

Caution and appropriate monitoring should be used with CYP2C9, P-gp, and OATP1B1 and OATP1B3 substrates

 

Increased exposure of substrates may occur with TRIKAFTA

  • Ivacaftor may inhibit CYP2C9
  • Ivacaftor or tezacaftor/ivacaftor increases digoxin exposure and may increase exposure of other sensitive P-gp substrates
  • Elexacaftor and M23-ELX inhibit OATP1B1 and OATP1B3 in vitro
Drug interaction profiles and dose adjustments
  Dose recommendation TRIKAFTA interaction

Strong CYP3A inducers including: rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum)

CONCOMITANT USE NOT RECOMMENDED
 

Reduced exposure of TRIKAFTA expected with strong CYP3A inducers

  • The concomitant use of CYP3A inducers may reduce TRIKAFTA efficacy

Strong CYP3A inhibitors including: ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin

 The dosage of TRIKAFTA should be reduced when co‑administered with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here
 

Increased exposure of TRIKAFTA expected with strong or moderate CYP3A inhibitors

Moderate CYP3A inhibitors including: fluconazole, erythromycin

 The dosage of TRIKAFTA should be reduced when co‑administered with moderate CYP3A inhibitors. For full dosing table, including dose adjustments, click here

CYP2C9 substrates including: warfarin, glimepiride, glipizide 

 Caution and appropriate monitoring should be used with CYP2C9, P-gp, and OATP1B1 and OATP1B3 substrates
 

Increased exposure of substrates may occur with TRIKAFTA

  • Ivacaftor may inhibit CYP2C9
  • Ivacaftor or tezacaftor/ivacaftor increases digoxin exposure and may increase exposure of other sensitive P-gp substrates
  • Elexacaftor and M23-ELX inhibit OATP1B1 and OATP1B3 in vitro

P-glycoprotein (P-gp) substrates including: digoxin, cyclosporine, everolimus, sirolimus, tacrolimus 

OATP1B1 and OATP1B3 substrates including1,2: statins (atorvastatin, cerivastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin), glyburide, nateglinide, repaglinide
View dosing and administration
See the results in patients aged 12 years or older

Important Safety Information

Elevated Transaminases and Hepatic Injury

  • Liver failure leading to transplantation has been reported in a patient with cirrhosis and portal hypertension while receiving TRIKAFTA. Avoid use of TRIKAFTA in patients with pre-existing advanced liver disease (e.g., as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment
  • Isolated elevations of transaminases or bilirubin have been observed in patients with CF treated with TRIKAFTA. In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including in patients without a history of pre-existing liver disease
  • Assessments of liver function tests (ALT, AST, and bilirubin) are recommended prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter
  • In the event of significant elevations in liver function tests, e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment
  • For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered

Indications and Usage

TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Concomitant Use With CYP3A Inducers

  • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended

Concomitant Use With CYP3A Inhibitors

  • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

Pediatric Use

  • The safety and effectiveness of TRIKAFTA in patients with CF younger than 6 years of age have not been established

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0)

Most Common Adverse Reactions

  • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA (N=202) and higher than placebo (N=201) by ≥1% in the 24-week placebo-controlled, parallel-group Phase 3 trial (Trial 1) were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, and blood bilirubin increased
     
  • The safety profile for the patients with CF receiving TRIKAFTA (N=55) enrolled in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1
     
  • The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=66) was similar to that observed in trials of patients age 12 years and older

Click here to access full Prescribing Information for TRIKAFTA.

References:

1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-10551 (v2.0); 2021. 3. FDA U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed September 1, 2021. 4. Kunze A, Huwyler J, Camenisch G, Poller B. Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014;42(9):1514-1521.

Important Safety Information

Elevated Transaminases and Hepatic Injury

  • Liver failure leading to transplantation has been reported in a patient with cirrhosis and portal hypertension while receiving TRIKAFTA. Avoid use of TRIKAFTA in patients with pre-existing advanced liver disease (e.g., as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment
  • Isolated elevations of transaminases or bilirubin have been observed in patients with CF treated with TRIKAFTA. In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including in patients without a history of pre-existing liver disease
  • Assessments of liver function tests (ALT, AST, and bilirubin) are recommended prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter
  • In the event of significant elevations in liver function tests, e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment
  • For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered

Concomitant Use With CYP3A Inducers

  • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended

Concomitant Use With CYP3A Inhibitors

  • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

Pediatric Use

  • The safety and effectiveness of TRIKAFTA in patients with CF younger than 6 years of age have not been established

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0)

Most Common Adverse Reactions

  • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA (N=202) and higher than placebo (N=201) by ≥1% in the 24-week placebo-controlled, parallel-group Phase 3 trial (Trial 1) were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, and blood bilirubin increased
        
  • The safety profile for the patients with CF receiving TRIKAFTA (N=55) enrolled in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1
     
  • The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=66) was similar to that observed in trials of patients age 12 years and older

Click here to access full Prescribing Information for TRIKAFTA.

 

References:

1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-10551 (v2.0); 2021. 3. FDA U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed September 1, 2021. 4. Kunze A, Huwyler J, Camenisch G, Poller B. Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014;42(9):1514-1521.

Indications and Usage

TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Indications and Usage

Indications and Usage

TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation or a mutation that is responsive based on in vitro data.

Important Safety Information

Important Safety Information

Elevated Transaminases and Hepatic Injury

  • Liver failure leading to transplantation has been reported in a patient with cirrhosis and portal hypertension while receiving TRIKAFTA. Avoid use of TRIKAFTA in patients with pre-existing advanced liver disease (e.g., as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless the benefits are expected to outweigh the risks. If used in these patients, they should be closely monitored after the initiation of treatment
  • Isolated elevations of transaminases or bilirubin have been observed in patients with CF treated with TRIKAFTA. In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including in patients without a history of pre-existing liver disease
  • Assessments of liver function tests (ALT, AST, and bilirubin) are recommended prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter
  • In the event of significant elevations in liver function tests, e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment
  • For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered

Concomitant Use With CYP3A Inducers

  • Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended

Concomitant Use With CYP3A Inhibitors

  • Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

Pediatric Use

  • The safety and effectiveness of TRIKAFTA in patients with CF younger than 6 years of age have not been established

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0)

Most Common Adverse Reactions

  • The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA (N=202) and higher than placebo (N=201) by ≥1% in the 24-week placebo-controlled, parallel-group Phase 3 trial (Trial 1) were headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rhinorrhea, rhinitis, influenza, sinusitis, and blood bilirubin increased
        
  • The safety profile for the patients with CF receiving TRIKAFTA (N=55) enrolled in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1
     
  • The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=66) was similar to that observed in trials of patients age 12 years and older

Click here to access full Prescribing Information for TRIKAFTA.

 

References:

1. TRIKAFTA [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2021. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-10551 (v2.0); 2021. 3. FDA U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed September 1, 2021. 4. Kunze A, Huwyler J, Camenisch G, Poller B. Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014;42(9):1514-1521.