Dosing & Administration

DOSING INFORMATION

Recommended dosing for patients aged 6 years and older1,2

  • Prior to initiating and during treatment with ALYFTREK, assess liver function via laboratory tests. Please see the Dosage and Administration section of the full Prescribing Information
  • ALYFTREK offers convenient once-daily dosing, requiring one fat-containing meal a day
    • ALYFTREK should be taken consistently at approximately the same time each day. Patients can decide, in partnership with their care team, what time of day works best
    • ALYFTREK should be taken with fat-containing meals or snacks. Examples include food prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, meats, or peanut butter
  • The initial dose of ALYFTREK can be taken the next day approximately 12 hours or more after the final dose of ETI2
  • Food or drink containing grapefruit should be avoided during treatment with ALYFTREK

Aged 12+ Years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

2 OBLONG tablets of:
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Tablets are purple and debossed with “V10” on one side and plain on the other

Aged 6 to <12 years | <40 kg (<88 lb)

3 ROUND tablets of:
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

Tablets are purple and debossed with "V4" on one side and plain on the other

MISSED DOSE

Recommendations for a missed dose1

6-hours or less

If 6 hours or less have passed, take the missed dose as soon as possible. Continue as scheduled the following day

more than 6-hours

If more than 6 hours have passed, do not take the missed dose. Take the next dose as scheduled the following day

DOSING ADJUSTMENTS

Recommended dosage for hepatic impairment1

In patients with mild hepatic impairment (Child-Pugh Class A)

NO DOSE ADJUSTMENT

  • Liver function tests should be closely monitored

In patients with moderate hepatic impairment
(Child-Pugh Class B)

TREATMENT IS NOT RECOMMENDED

USE SHOULD ONLY BE CONSIDERED WHEN THERE IS A CLEAR MEDICAL NEED AND THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISKS

If used, no dose adjustment is recommended.

  • Liver function tests should be closely monitored

In patients with severe hepatic impairment (Child-Pugh Class C)

SHOULD NOT BE USED

  • ALYFTREK has not been studied in patients with severe hepatic impairment

Dosing adjustments for renal impairment1

  • No dose adjustment is recommended in patients with mild (eGFR 60 to <90 mL/min/1.73 m2) or moderate (eGFR 30 to <60 mL/min/1.73 m2) renal impairment. ALYFTREK has not been studied in patients with severe renal impairment or end-stage renal disease and should be used only if the benefits are expected to outweigh the risks

Recommended dose adjustments for concomitant use with CYP3A inducers or inhibitors1,2

 

Drug Interaction Profile

Weight

Dosing Considerations

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

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

CONCOMITANT USE
NOT RECOMMENDED

Aged 6 to <12 years | <40 kg (<88 lb)

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

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

ONCE WEEKLY 

1 OBLONG tablet of: 
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

ONCE WEEKLY 

2 ROUND tablets of: 
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

Moderate CYP3A inhibitors including: fluconazole, erythromycin, verapamil

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

EVERY OTHER DAY

1 OBLONG tablet of:
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

EVERY OTHER DAY

2 ROUND tablets of:
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

 

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

Weight

Dosing Considerations

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

CONCOMITANT
USE NOT
RECOMMENDED

Aged 6 to <12 years | <40 kg (<88 lb)

 

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

Weight

Dosing Considerations

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

ONCE WEEKLY 

1 OBLONG tablet of: 
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

ONCE WEEKLY 

2 ROUND tablets of: 
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

 

Moderate CYP3A inhibitors including:
fluconazole, erythromycin, verapamil

Weight

Dosing Considerations

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

EVERY OTHER DAY

1 OBLONG tablet of: 
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

EVERY OTHER DAY

2 ROUND tablets of:
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

 

Drug Interaction Profile

Weight

Dosing Considerations

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

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

CONCOMITANT USE
NOT RECOMMENDED

Aged 6 to <12 years | <40 kg (<88 lb)

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

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

ONCE WEEKLY 

1 OBLONG tablet of: 
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

ONCE WEEKLY 

2 ROUND tablets of: 
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

Moderate CYP3A inhibitors including: fluconazole, erythromycin, verapamil

Aged 12+ years | Any Weight
Aged 6 to <12 years | ≥40 kg (≥88 lb)

EVERY OTHER DAY

1 OBLONG tablet of:
vanzacaftor 10 mg/
tezacaftor 50 mg/
deutivacaftor 125 mg

Aged 6 to <12 years | <40 kg (<88 lb)

EVERY OTHER DAY

2 ROUND tablets of:
vanzacaftor 4 mg/
tezacaftor 20 mg/
deutivacaftor 50 mg

For more information about specific drug interactions and adjustment recommendations, see the Drug-Drug Interactions Tool

eGFR, estimated glomerular filtration rate; lb, pounds.

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-27244 (v1.0); 2024.