Drug Interactions

Drug Interactions

Drug-drug interactions tool

Please see the table below and refer to the US Prescribing Information for recommended dosage of ALYFTREK 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 ALYFTREK on other medicinal products or effect of other medicinal products on ALYFTREK.

  • 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.

Drug Name Potential Effect Clinical Considerations

Alprazolam
(Xanax®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Amikacin
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Aripiprazole
(Abilify®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Atorvastatin
(Lipitor®)
  • Atorvastatin exposure may increase2
  • Appropriate monitoring should be used

Azithromycin
(Zithromax®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Aztreonam
(Azactam®, Cayston®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Budesonide
(Pulmicort®(inhaled), Rhinocort®(inhaled))
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Bupropion
(Forfivo®, Wellbutrin®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Carbamazepine
(Carbatrol®, Epitol®, Equetro®, Tegretol®)
  • Decreased ALYFTREK exposure1,2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Ceftazidime
(Fortaz®, Tazicef®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Cetirizine
(Zyrtec®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Chloramphenicol
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Ciprofloxacin*
(Cipro®)
  • No clinically significant interaction predicted1,2
  • No dosage adjustments recommended
    • No clinically significant differences in tezacaftor pharmacokinetics were observed when tezacaftor/ivacaftor was used concomitantly with ciprofloxacin

Citalopram
(Celexa®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Citalopram
(Celexa®)2
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Clarithromycin
  • Increased ALYFTREK exposure2

Clonazepam
(Klonopin®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Clozapine
(Clozaril®, Versacloz®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Colistimethate/Colistin
(Coly-Mycin M®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Cyclosporine
(Gengraf®, Neoral®, Sandimmune®)
  • Cyclosporine exposure may increase2
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring4

Desloratadine
(Clarinex®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Desvenlafaxine
(Pristiq®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Dexamethasone
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Diazepam
(Valium®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Digoxin*
(Lanoxin®)
  • Increased digoxin exposure1,2
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring3
    • Interaction with tezacaftor/ivacaftor has been studied. Concomitant use increased digoxin exposure by 1.3-fold.
    • Interaction with tezacaftor/ivacaftor has been studied. Concomitant use increased digoxin exposure by
      1.3-fold.

Diphenhydramine
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Dornase alfa
(Pulmozyme®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Duloxetine
(Cymbalta®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Efavirenz
(Sustiva®)
  • Decreased ALYFTREK exposure1,2
  • Concomitant use not recommended

Erythromycin*
(Ery-Tab®, Erythrocin®)
  • Increased ALYFTREK exposure1,2
  • ALYFTREK dosing regimen should be adjusted. For full dosing table, click here
    • Simulations suggest that concomitant use with moderate CYP3A inhibitors may increase vanzacaftor, tezacaftor, and deutivacaftor exposure by approximately 2.4- to 3.9-fold, 2.1-fold, and 2.9- to 4.8-fold, respectively.

Escitalopram
(Lexapro®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Esomeprazole
(Nexium®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Ethambutol
(Myambutol®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Ethinyl estradiol/
Levonorgestrel*
(Afirmelle®, Altavera®, Aviane®, Ayuna®, Enpresse®, Falmina®, Kurvelo®, Lessina®, Levora®, Marlissa®, Myzilra®, Nordette®, Portia-28®, Trivora-28®, Vienva®)
  • No clinically significant interaction predicted2
  • ALYFTREK not expected to modify efficacy of oral hormonal contraceptives
    • Vanzacaftor/tezacaftor/deutivacaftor was not evaluated for concomitant use with oral contraceptives.
      Hormonal contraceptives may play a role in the occurrence of rash in patients taking vanzacaftor/ tezacaftor/ deutivacaftor.
      For patients taking hormonal contraceptives who develop rash, consider interrupting vanzacaftor/ tezacaftor/ deutivacaftor and hormonal contraceptives.
      Following the resolution of rash, consider resuming vanzacaftor/ tezacaftor/ deutivacaftor without the hormonal contraceptives. If rash does not recur, resumption of hormonal contraceptives can be considered.
  • ALYFTREK not
    expected to
    modify efficacy
    of oral
    hormonal
    contraceptives
    • Vanzacaftor/
      tezacaftor/
      deutivacaftor 
      was not
      evaluated for
      concomitant
      use with oral
      contraceptives.
      Hormonal
      contraceptives
      may play a role in
      the occurrence
      of rash in
      patients taking
      vanzacaftor/
      tezacaftor/
      deutivacaftor.
      For patients
      taking hormonal
      contraceptives
      who develop
      rash, consider
      interrupting
      vanzacaftor/
      tezacaftor/
      deutivacaftor
      and hormonal
      contraceptives.
      Following the
      resolution of
      rash, consider
      resuming
      vanzacaftor/
      tezacaftor/
      deutivacaftor
      without the
      hormonal
      contraceptives.
      If rash does
      not recur,
      resumption of
      hormonal
      contraceptives
      can be
      considered.

Ethinyl estradiol/
Norethindrone*
(Loestrin®)
  • No clinically significant interaction predicted1,2
  • ALYFTREK not expected to modify efficacy of oral hormonal contraceptives
    • Vanzacaftor/tezacaftor/deutivacaftor was not evaluated for concomitant use with oral contraceptives.
      Interaction between tezacaftor/ivacaftor and ivacaftor alone has been studied and were found to have no clinically relevant effect on the exposures of the oral contraceptive.
      Hormonal contraceptives may play a role in the occurrence of rash in patients taking vanzacaftor/tezacaftor/deutivacaftor.
      For patients taking hormonal contraceptives who develop rash, consider interrupting vanzacaftor/tezacaftor/deutivacaftor and hormonal contraceptives.
      Following the resolution of rash, consider resuming vanzacaftor/tezacaftor/deutivacaftor without the hormonal contraceptives.
      If rash does not recur, resumption of hormonal contraceptives can be considered.
  • ALYFTREK not
    expected to
    modify efficacy
    of oral
    hormonal
    contraceptives
    • Vanzacaftor/
      tezacaftor/
      deutivacaftor
      was not
      evaluated for
      concomitant
      use with oral
      contraceptives.
      Interaction
      between
      tezacaftor/
      ivacaftor and
      ivacaftor
      alone has been
      studied and
      were found to
      have no
      clinically
      relevant effect
      on the exposures
      of the oral
      contraceptive.
      Hormonal
      contraceptives
      may play a role
      in the occurrence
      of rash in
      patients taking
      vanzacaftor/
      tezacaftor/
      deutivacaftor.
      For patients
      taking hormonal
      contraceptives
      who develop
      rash, consider
      interrupting
      vanzacaftor/
      tezacaftor/
      deutivacaftor
      and hormonal
      contraceptives.
      Following the
      resolution of
      rash, consider
      resuming
      vanzacaftor/
      tezacaftor/
      deutivacaftor
      and without
      the hormonal
      contraceptives.
      If rash does
      not recur,
      resumption
      of hormonal
      contraceptives
      can be
      considered.

Everolimus
(Afinitor®, Zortress®)
  • Everolimus exposure may increase2
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring4

Fexofenadine
(Allegra®)
  • Fexofenadine exposure may increase2
  • Caution is recommended

Fluconazole*
(Diflucan®)
  • Increased ALYFTREK exposure1,2
  • ALYFTREK dosing regimen should be adjusted. For full dosing table, click here
    • No clinically significant differences in vanzacaftor or deutivacaftor pharmacokinetics were observed when used concomitantly with fluconazole.

Fluoxetine
(Prozac®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Fluticasone
(Flonase®, Flovent®, Xhance®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Glimepiride
(Amaryl®)
  • Glimepiride exposure may increase2
  • Use with caution

Glipizide
(Glucotrol®)
  • Glipizide exposure may increase2
  • Use with caution and appropriate monitoring

Glyburide
(Diabeta®, Glynase®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Ibuprofen
(Advil®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Ipratropium
(Atrovent®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Itraconazole*
(Sporanox®)
  • Increased ALYFTREK exposure1,2
  • ALYFTREK dosing regimen should be adjusted. For full dosing table, click here
    • Co-administration with itraconazole, a strong CYP3A inhibitor, increased vanzacaftor AUC by 10.5-fold, tezacaftor AUC by 4.0- to 4.5-fold and deutivacaftor AUC by 11.1-fold.
      AUC, area under the curve.

Ketoconazole
(Nizoral®)
  • Increased ALYFTREK exposure2

Lansoprazole
(Prevacid®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Levofloxacin
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Loratadine
(Claritin®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Meropenem
(Merrem®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Metformin
(Glumetza®, Riomet®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Methylprednisolone
(Medrol®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Midazolam*
  • No clinically significant interaction predicted1,2
  • No dosage adjustments recommended
    • Interaction with tezacaftor/ivacaftor has been studied.

Mirtazapine
(Remeron®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Montelukast
(Singulair®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Mycophenolate mofetil
(CellCept®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Nateglinide
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Omeprazole
(Prilosec®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Pancreatin
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Pancrelipase
(Creon®, Pancreaze®, Pertzye®, Viokace®, Zenpep®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Paroxetine
(Brisdelle®, Paxil®, Pexeva®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Phenobarbital
  • Decreased ALYFTREK exposure2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Phenytoin
(Dilantin®, Phenytek®)
  • Decreased ALYFTREK exposure2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Pitavastatin
(Livalo®, Zypitamag®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Posaconazole
(Noxafil)
  • Increased ALYFTREK exposure2

Pravastatin
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Prednisolone
(Orapred®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Prednisone
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Quetiapine
(Seroquel®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Repaglinide
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Rifabutin
(Mycobutin®)
  • Decreased ALYFTREK exposure2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Rifampin*
(Rifadin®)
  • Decreased ALYFTREK exposure1,2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Rifapentine
(Priftin®)
  • Decreased ALYFTREK exposure2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Risperidone
(Perseris®, Risperdal®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Rosiglitazone
(Avandia®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Rosuvastatin
(Crestor®, Ezallor®)
  • Rosuvastatin exposure may increase2
  • Appropriate monitoring should be used

Salbutamol/
Albuterol
(AccuNeb®, Proair®, Proventil®, Ventolin®, VoSpire®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Salmeterol
(Serevent®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Semaglutide
(Rybelsus®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Sertraline
(Zoloft®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Simvastatin
(Zocor®, Flolipid®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Sirolimus
(Rapamune®)
  • Sirolimus exposure may increase2
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring4

Sitagliptin
(Januvia®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

St. John’s wort
(Hypericum perforatum)
  • Decreased ALYFTREK exposure2
  • May reduce effectiveness of ALYFTREK, concomitant use not recommended

Sulfamethoxazole/trimethoprim
(Bactrim®, Septra®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Sulfasalazine
(Azulfidine®)
  • Increased exposure of sulfasalazine2
  • Caution and appropriate monitoring should be used

Tacrolimus
(Prograf®)
  • Tacrolimus exposure may increase2
  • Drugs with a narrow therapeutic index should be used with caution and appropriate monitoring4

Telithromycin
  • Increased ALYFTREK exposure2

Tiotropium
(Spiriva®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Tobramycin
(Bethkis®, Kitabis®, Tobi®, Tobrex®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Trazodone
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Triazolam
(Halcion®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Vancomycin
(Firvanq®, Vancocin®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Venlafaxine
(Effexor XR®)
  • No clinically significant interaction predicted2
  • No dosage adjustments recommended

Voriconazole
(Vfend®)
  • Increased ALYFTREK exposure2

Warfarin
(Jantoven®)
  • Warfarin exposure may be increased1
  • Use caution when ALYFTREK is used concomitantly with CYP2C9 substrates. Monitor the International Normalized Ratio (INR) more frequently with concomitant use of ALYFTREK with warfarin

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

Drug interaction profiles and related dose adjustments1,2

Clinical considerations for ALYFTREK 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.

 

Dose recommendation

ALYFTREK interaction

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

CONCOMITANT USE
NOT RECOMMENDED

 Reduced exposure of ALYFTREK expected with strong or moderate CYP3A inducers

  • The concomitant use of CYP3A inducers may reduce ALYFTREK efficacy

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

The dosage of ALYFTREK should be reduced when used concomitantly with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here

 Increased exposure of ALYFTREK expected with strong or moderate CYP3A inhibitors

  • The concomitant use of strong or moderate CYP3A inhibitors may increase the risk of ALYFTREK adverse reactions

Moderate CYP3A inhibitors including:
fluconazole, erythromycin, verapamil

The dosage of ALYFTREK should be reduced when used concomitantly 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 BCRP substrates

 Increased exposure of substrates may occur with ALYFTREKab

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

Breast cancer resistance protein (BCRP) substrates, including:
rosuvastatin, sulfasalazine

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

Dose
recommendation

ALYFTREK
interaction

CONCOMITANT
USE NOT
RECOMMENDED

 Reduced exposure of ALYFTREK expected with strong or moderate CYP3A inducers

  • The concomitant use of CYP3A inducers may reduce ALYFTREK efficacy

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

Dose
recommendation

ALYFTREK
interaction

The dosage of ALYFTREK should be reduced when used concomitantly with strong CYP3A inhibitors. For full dosing table, including dose adjustments, click here

 Increased exposure of ALYFTREK expected with strong or moderate CYP3A inhibitors

  • The concomitant use of strong or moderate CYP3A inhibitors may increase the risk of ALYFTREK adverse reactions

Moderate CYP3A inhibitors including:
fluconazole, erythromycin, verapamil

Dose
recommendation

ALYFTREK
interaction

The dosage of ALYFTREK should be reduced when used concomitantly with strong or moderate CYP3A inhibitors. For full dosing table, including dose adjustments, click here

 Increased exposure of ALYFTREK expected with strong or moderate CYP3A inhibitors

  • The concomitant use of strong or moderate CYP3A inhibitors may increase the risk of ALYFTREK adverse reactions

CYP2C9 substrates including:
warfarin, glimepiride, glipizide

 

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

 

Breast cancer resistance protein (BCRP)
substrates, including:
rosuvastatin, sulfasalazine

Dose
recommendation

ALYFTREK
interaction

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

 Increased exposure of substrates may occur with ALYFTREKab

aIncreased exposure to CYP2C9 and BCRP substrates has not been studied clinically.
bIncreased exposure of P-gp substrates may increase the risk of adverse reactions related to these substrates.

aIncreased exposure to CYP2C9 and BCRP substrates has not been studied clinically.
bIncreased exposure of P-gp substrates may increase the risk of adverse reactions related to these substrates.

See dosing and administration
Trials 1 & 2

See the results in patients aged 12 years and older

Indications and Usage

Indications and Usage

ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in patients 6 years of age and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in patients 6 years of age and older who have at least one F508del mutation or another responsive 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 confirm the presence of at least one indicated mutation.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.

Important Safety Information

WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE 

Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor.

Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests (LFTs) at baseline.

Interrupt ALYFTREK for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming ALYFTREK.

ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely.

Warnings and Precautions

Drug-Induced Liver Injury and Liver Failure

  • Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported in patients with and without a history of liver disease taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of ELX/TEZ/IVA
  • Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported in patients with and without a history of liver disease taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of ELX/TEZ/IVA
  • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring in patients with a history of liver disease, elevated LFTs at baseline, or a history of elevated LFTs with drugs containing ELX, TEZ, and/or IVA
  • Interrupt ALYFTREK in the event of signs or symptoms of liver injury, which may include:
    • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
    • Clinical signs or symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
  • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved and if benefit is expected to outweigh risk, resume ALYFTREK with close monitoring
  • ALYFTREK should not be used in patients with severe hepatic impairment. ALYFTREK is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely

Hypersensitivity Reactions, Including Anaphylaxis

  • Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the postmarketing setting of drugs containing ELX, TEZ, and/or IVA (same or similar active ingredients in ALYFTREK). If signs or symptoms of serious hypersensitivity reactions develop during ALYFTREK treatment, discontinue ALYFTREK and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume ALYFTREK

Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions

  • There are no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with drugs containing ELX/TEZ/IVA due to adverse reactions. Consider the benefits and risks before using ALYFTREK in these patients. If ALYFTREK is used in these patients, closely monitor for adverse reactions as clinically appropriate

Reduced Effectiveness with Concomitant Use With CYP3A Inducers

  • Following concomitant use of strong or moderate CYP3A inducers with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were decreased, which may reduce ALYFTREK effectiveness. Concomitant use with strong or moderate CYP3A inducers is not recommended

Adverse Reactions with Concomitant Use With CYP3A Inhibitors

  • Following concomitant use of strong or moderate CYP3A inhibitors with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were increased, which may increase the risk of adverse reactions associated with ALYFTREK. Reduce the ALYFTREK dosage with concomitant use of strong or moderate CYP3A inhibitors

Cataracts

  • Non-congenital lens opacities have been reported in pediatric patients treated with drugs containing ivacaftor (similar to an active ingredient in ALYFTREK). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients treated with ALYFTREK

Adverse Reactions

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently with ALYFTREK than with ELX/TEZ/IVA in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%)

Most Common Adverse Reactions

  • The most common adverse reactions to ALYFTREK (≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1%) were cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT, rash, increased AST, and sinus congestion

Use in Specific Populations

Pediatric Use

  • The safety and effectiveness of ALYFTREK in patients <6 years of age have not been established

Please see full Prescribing Information, including Boxed WARNING, for ALYFTREK.

 

References:
1. ALYFTREK [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-27245 (v2.0); 2024. 3. Buxton ILO. Pharmacokinetics and pharmacodynamics: The dynamics of drug absorption, distribution, action, and elimination. In: Brunton LL, Lazo JS, Parker KL (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill; 2006:1-20. 4. Nelson J, Alvey N, Bowman L, et al. Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation. Pharmacotherapy. 2022;42:599-633.

Indication and Important Safety Information, including Boxed WARNING

Indication and Important Safety Information, including Boxed WARNING

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COLLAPSE

Important Safety Information

WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor.

Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests (LFTs) at baseline.

Interrupt ALYFTREK for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming ALYFTREK.

ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely.

WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor.

Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, then every 3 months for the next 12 months, and annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests (LFTs) at baseline.

Interrupt ALYFTREK for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming ALYFTREK.

ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely.

Indications and Usage

ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in patients 6 years of age and older who have at least one F508del mutation or another responsive 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 confirm the presence of at least one indicated mutation.

Indications and Usage

ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in patients 6 years of age and older who have at least one F508del mutation or another responsive 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 confirm the presence of at least one indicated mutation.

Important Safety Information

WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE

Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor.

Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests (LFTs) at baseline.

Interrupt ALYFTREK for significant elevations in LFTs or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved, resume treatment only if benefit is expected to outweigh risk. Closer monitoring is advised after resuming ALYFTREK.

ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely.

Warnings and Precautions

Drug-Induced Liver Injury and Liver Failure

  • Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported in patients with and without a history of liver disease taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of ELX/TEZ/IVA
  • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring in patients with a history of liver disease, elevated LFTs at baseline, or a history of elevated LFTs with drugs containing ELX, TEZ, and/or IVA
  • Interrupt ALYFTREK in the event of signs or symptoms of liver injury, which may include:
    • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
    • Clinical signs or symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
  • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved and if benefit is expected to outweigh risk, resume ALYFTREK with close monitoring
  • ALYFTREK should not be used in patients with severe hepatic impairment. ALYFTREK is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely

Hypersensitivity Reactions, Including Anaphylaxis

  • Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the postmarketing setting of drugs containing ELX, TEZ, and/or IVA (same or similar active ingredients in ALYFTREK). If signs or symptoms of serious hypersensitivity reactions develop during ALYFTREK treatment, discontinue ALYFTREK and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume ALYFTREK

Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions

  • There are no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with drugs containing ELX/TEZ/IVA due to adverse reactions. Consider the benefits and risks before using ALYFTREK in these patients. If ALYFTREK is used in these patients, closely monitor for adverse reactions as clinically appropriate

Reduced Effectiveness with Concomitant Use With CYP3A Inducers

  • Following concomitant use of strong or moderate CYP3A inducers with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were decreased, which may reduce ALYFTREK effectiveness. Concomitant use with strong or moderate CYP3A inducers is not recommended

Adverse Reactions with Concomitant Use With CYP3A Inhibitors

  • Following concomitant use of strong or moderate CYP3A inhibitors with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were increased, which may increase the risk of adverse reactions associated with ALYFTREK. Reduce the ALYFTREK dosage with concomitant use of strong or moderate CYP3A inhibitors

Cataracts

  • Non-congenital lens opacities have been reported in pediatric patients treated with drugs containing ivacaftor (similar to an active ingredient in ALYFTREK). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients treated with ALYFTREK

Adverse Reactions

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently with ALYFTREK than with ELX/TEZ/IVA in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%)

Most Common Adverse Reactions

  • The most common adverse reactions to ALYFTREK (≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1%) were cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT, rash, increased AST, and sinus congestion

Use in Specific Populations

Pediatric Use

  • The safety and effectiveness of ALYFTREK in patients <6 years of age have not been established

Please see full Prescribing Information, including Boxed WARNING, for ALYFTREK.

 

References:
1. ALYFTREK [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-27245 (v2.0); 2024. 3. Buxton ILO. Pharmacokinetics and pharmacodynamics: The dynamics of drug absorption, distribution, action, and elimination. In: Brunton LL, Lazo JS, Parker KL (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill; 2006:1-20. 4. Nelson J, Alvey N, Bowman L, et al. Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation. Pharmacotherapy. 2022;42:599-633.

Warnings and Precautions

Drug-Induced Liver Injury and Liver Failure

  • Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure have been reported in patients with and without a history of liver disease taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA), which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of ELX/TEZ/IVA
  • Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. Consider more frequent monitoring in patients with a history of liver disease, elevated LFTs at baseline, or a history of elevated LFTs with drugs containing ELX, TEZ, and/or IVA
  • Interrupt ALYFTREK in the event of signs or symptoms of liver injury, which may include:
    • Significant elevations in LFTs (e.g., ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN)
    • Clinical signs or symptoms suggestive of liver injury (e.g., jaundice, right upper quadrant pain, nausea, vomiting, altered mental status, ascites)
  • Consider referral to a hepatologist and follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If resolved and if benefit is expected to outweigh risk, resume ALYFTREK with close monitoring
  • ALYFTREK should not be used in patients with severe hepatic impairment. ALYFTREK is not recommended in patients with moderate hepatic impairment and should only be considered when there is a clear medical need and benefit outweighs risk. If used, monitor patients closely

Hypersensitivity Reactions, Including Anaphylaxis

  • Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the postmarketing setting of drugs containing ELX, TEZ, and/or IVA (same or similar active ingredients in ALYFTREK). If signs or symptoms of serious hypersensitivity reactions develop during ALYFTREK treatment, discontinue ALYFTREK and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume ALYFTREK

Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions

  • There are no available safety data for ALYFTREK in patients who previously discontinued or interrupted treatment with drugs containing ELX/TEZ/IVA due to adverse reactions. Consider the benefits and risks before using ALYFTREK in these patients. If ALYFTREK is used in these patients, closely monitor for adverse reactions as clinically appropriate

Reduced Effectiveness with Concomitant Use With CYP3A Inducers

  • Following concomitant use of strong or moderate CYP3A inducers with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were decreased, which may reduce ALYFTREK effectiveness. Concomitant use with strong or moderate CYP3A inducers is not recommended

Adverse Reactions with Concomitant Use With CYP3A Inhibitors

  • Following concomitant use of strong or moderate CYP3A inhibitors with ALYFTREK, exposures of vanzacaftor, tezacaftor, and deutivacaftor were increased, which may increase the risk of adverse reactions associated with ALYFTREK. Reduce the ALYFTREK dosage with concomitant use of strong or moderate CYP3A inhibitors

Cataracts

  • Non-congenital lens opacities have been reported in pediatric patients treated with drugs containing ivacaftor (similar to an active ingredient in ALYFTREK). Baseline and follow-up ophthalmological examinations are recommended in pediatric patients treated with ALYFTREK

Adverse Reactions

Serious Adverse Reactions

  • Serious adverse reactions that occurred more frequently with ALYFTREK than with ELX/TEZ/IVA in 2 or more patients (≥0.4%) were influenza (1.5%), increased AST (0.4%), increased GGT (0.4%), depression (0.4%), and syncope (0.4%)

Most Common Adverse Reactions

  • The most common adverse reactions to ALYFTREK (≥5% of patients and at a frequency higher than ELX/TEZ/IVA by ≥1%) were cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT, rash, increased AST, and sinus congestion

Use in Specific Populations

Pediatric Use

  • The safety and effectiveness of ALYFTREK in patients <6 years of age have not been established

Please see full Prescribing Information, including Boxed WARNING, for ALYFTREK.

 

References:
1. ALYFTREK [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2024. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-27245 (v2.0); 2024. 3. Buxton ILO. Pharmacokinetics and pharmacodynamics: The dynamics of drug absorption, distribution, action, and elimination. In: Brunton LL, Lazo JS, Parker KL (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill; 2006:1-20. 4. Nelson J, Alvey N, Bowman L, et al. Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation. Pharmacotherapy. 2022;42:599-633.