ALYFTREK

ALYFTREK is an FDA-registered drug product whose active ingredient is VANZACAFTOR, TEZACAFTOR, AND DEUTIVACAFTOR. It is labelled by Vertex Pharmaceuticals Incorporated taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 51167-121, application NDA218730, label effective 20260826. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing VANZACAFTOR, TEZACAFTOR, AND DEUTIVACAFTOR are most often described in connection with: least one, cftr gene, either responsive, based clinical, vitro data, results production, cystic fibrosis, pediatric patients. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients 6 years of age and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive based on clinical and/or in vitro data (see Table 5 ) or results in production of CFTR protein [see Clinical Pharmacology (12.1) ]. If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. ALYFTREK is a combination of deutivacaftor, a CFTR potentiator, tezacaftor, and vanzacaftor indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients aged 6 years and older who have a clinical diagnosis of CF and who have at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. ( 1 , 12.1 ) If the patient's genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein. ( 1 )

2 DOSAGE AND ADMINISTRATION Prior to initiating ALYFTREK obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months during the next 12 months, then at least annually thereafter. ( 2.1 , 5.1 ) Recommended Dosage for Adult and Pediatric Patients Aged 6 Years and Older (with fat-containing food) ( 2.2 ) Age Weight Once Daily Oral Dosage 6 to less than 12 years old Less than 40 kg Three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg Greater than or equal to 40 kg Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg 12 years and older Any Weight Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg Should not be used in patients with severe hepatic impairment. Use not recommended in patients with moderate hepatic impairment unless the benefit outweighs the risk. If used, no dose adjustment is recommended. Liver function tests should be closely monitored. ( 2.4 , 5.1 , 6.1 , 8.7 ) See full prescribing information for dosage modifications for concomitant use of ALYFTREK with strong or moderate CYP3A inhibitors. ( 2.3 , 5.7 , 7.1 ) 2.1 Recommended Laboratory Testing Prior to ALYFTREK Initiation and During Treatment Prior to initiating ALYFTREK, obtain liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) for all patients. Monitor liver function tests every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease, elevated liver function tests at baseline, or a history of elevated liver function tests with drugs containing elexacaftor, tezacaftor, and/or ivacaftor [see Warnings and Precautions (5.1) and Use in Specific Populations (8.7) ]. 2.2 Recommended Dosage The recommended ALYFTREK dosage in adult and pediatric patients aged 6 years and older is provided in Table 1. Administer ALYFTREK orally (swallow the tablets whole) with fat-containing food, once daily, at approximately the same time each day [see Clinical Pharmacology (12.3) ]. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, peanut butter, cheeses, nuts, whole milk, or meats. Table 1: Recommended Dosage of ALYFTREK in Adult and Pediatric Patients Aged 6 Years and Older Age Weight Once Daily Oral Dosage 6 to less than 12 years old Less than 40 kg Three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg (total dose of vanzacaftor 12 mg/tezacaftor 60 mg/ deutivacaftor 150 mg) Greater than or equal to 40 kg Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg (total dose of vanzacaftor 20 mg/tezacaftor 100 mg/ deutivacaftor 250 mg) 12 years and older Any weight Two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg (total dose of vanzacaftor 20 mg/tezacaftor 100 mg/ deutivacaftor 250 mg) 2.3 Dosage Modification for Strong or Moderate CYP3A Inhibitors Table 2 describes the recommended dosage modification for ALYFTREK when used concomitantly with strong or moderate CYP3A inhibitors [see Warnings and Precautions (5.7) ] . Administer ALYFTREK orally (swallow the tablets whole) with fat-containing food, once daily, at approximately the same time each day [see Clinical Pharmacology (12.3) ]. Table 2: Dosage Modification for Concomitant Use of ALYFTREK with Strong or Moderate CYP3A Inhibitors in Adult and Pediatric Patients Aged 6 Years and Older Age Weight Moderate CYP3A Inhibitors Strong CYP3A Inhibitors 6 to less than 12 years old Less than 40 kg Two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg every other day (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg) Two tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg once a week (total dose of vanzacaftor 8 mg/tezacaftor 40 mg/deutivacaftor 100 mg) Greater than or equal to 40 kg One tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day One tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week 12 years and older Any weight One tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg every other day One tablet of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg once a week 2.4 Recommended Dosage for Patients with Hepatic Impairment Severe Hepatic Impairment (Child-Pugh Class C) : ALYFTREK should not be used in patients with severe hepatic impairment (HI) (Child-Pugh Class C). Moderate Hepatic Impairment (Child-Pugh Class B) : The use of ALYFTREK in patients with moderate HI (Child-Pugh Class B) is not recommended. Use of ALYFTREK should only be considered in patients with moderate HI when there is a clear medical need, and the benefit outweighs the risk. If used, the recommended dosage in patients with moderate HI is the same as for patients with normal hepatic function. Liver function tests should be closely monitored [see Dosage and Administration (2.1 , 2.2) ] . Mild Hepatic Impairment (Child-Pugh Class A) : The recommended dosage of ALYFTREK in patients with mild HI (Child-Pugh Class A) is the same as in patients with normal hepatic function. Liver function tests should be closely monitored [see Dosage and Administration (2.1 , 2.2) ] . 2.5 Recommendations Regarding Missed Dose(s) If 6 hours or less have passed since the missed dose, take the missed dose as soon as possible and continue on the original schedule. If more than 6 hours have passed since the missed dose, skip the missed dose, and continue on the original schedule the next day.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Drug-Induced Liver Injury and Liver Failure [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.2) ] Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions [see Warnings and Precautions (5.3) ] Intracranial Hypertension [see Warnings and Precautions (5.4) ] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.5) ] Cataracts [see Warnings and Precautions (5.8) ] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The adverse reactions data below are from clinical trials of ALYFTREK in patients 6 years of age and older with CF with at least one responsive CFTR variant who were able to tolerate ELX/TEZ/IVA. Adverse reactions data in patients who previously discontinued or interrupted ELX/TEZ/IVA due to adverse reactions are not available . Adverse Reactions in Patients Aged 12 Years and Older with CF The safety of ALYFTREK is based on 480 patients with CF aged 12 years and older who have at least one F508del variant or another responsive variant in the CFTR gene in two, 52-week, active-controlled trials (Trials 1 and 2) [see Clinical Studies (14) ]. In both trials, patients received a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor (ELX/TEZ/IVA) in a 4-week run-in period and then were subsequently randomized to continue ELX/TEZ/IVA (elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg in the morning and ivacaftor 150 mg in the evening) or receive ALYFTREK (vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg) once daily. Patients with a history of prior intolerance to ELX/TEZ/IVA (i.e., patients who discontinued or interrupted treatment due to adverse reactions) were excluded. Trials 1 and 2 were not designed to evaluate meaningful comparisons of the incidence of adverse reactions between the ALYFTREK and ELX/TEZ/IVA treatment groups. For additional information regarding ELX/TEZ/IVA adverse reactions, refer to ELX/TEZ/IVA Prescribing Information. In Trial 1 and Trial 2 combined, the proportion of patients who discontinued treatment prematurely due to adverse reactions were 3.8% and 3.7% in ALYFTREK and ELX/TEZ/IVA treatment groups, respectively. Serious adverse reactions that occurred more frequently with ALYFTREK treatment than with ELX/TEZ/IVA treatment that occurred 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%). Table 3: Adverse Reactions Occurring in ≥5% of ALYFTREK-Treated Patients and ≥1% Higher than ELX/TEZ/IVA-Treated Patients Aged 12 Years and Older with CF Who Had at Least One F508del Variant or Responsive Variant in the CFTR Gene (Trials 1 and 2) Adverse Reactions ALYFTREK N=480 ELX/TEZ/IVA N=491 Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ELX, elexacaftor; IVA, ivacaftor; TEZ, tezacaftor Cough Cough is composed of several similar terms including productive cough. 120 (25%) 116 (24%) Nasopharyngitis 102 (21%) 95 (19%) Upper respiratory tract infection Upper respiratory tract infection is composed of several similar terms including viral upper respiratory tract infection. 101 (21%) 97 (20%) Headache 76 (16%) 63 (13%) Oropharyngeal pain 69 (14%) 60 (12%) Influenza 52 (11%) 26 (5%) Fatigue 51 (11%) 46 (9%) ALT increased 38 (8%) 29 (6%) Rash 37 (8%) 22 (4%) AST increased 33 (7%) 27 (5%) Sinus congestion 32 (7%) 15 (3%) Adverse events that occurred in ≥5% of ELX/TEZ/IVA-treated patients at a similar or higher incidence than the ALYFTREK-treated patients included: infective pulmonary exacerbation of CF, COVID-19, diarrhea, abdominal pain, pyrexia, nasal congestion, increased sputum, increased blood creatinine phosphokinase, rhinorrhea, hemoptysis, nausea, back pain, arthralgia, constipation, sinusitis, dyspnea, and vomiting. Liver Function Test Elevations The incidence of adverse reactions of transaminase elevations was 9% in ALYFTREK-treated patients and 7.1% in ELX/TEZ/IVA-treated patients in Trials 1 and 2. In these trials, 1.5% of ALYFTREK-treated patients and 0.6% of ELX/TEZ/IVA-treated patients discontinued treatment for elevated transaminases. Table 4 shows the incidence of maximum transaminase (ALT or AST) elevations in Trials 1 and 2. Table 4: Number and Incidence of Maximum Transaminase Elevation in Patients Aged 12 Years and Older with CF Who Had at Least One F508del Variant or Responsive Variant in the CFTR Gene (Trials 1 and 2) Maximum ALT or AST Elevation ALYFTREK N=480 ELX/TEZ/IVA Trials 1 and 2 were not designed to evaluate meaningful comparisons of safety between the ALYFTREK and ELX/TEZ/IVA treatment groups. For additional information regarding ELX/TEZ/IVA transaminase elevations, refer to ELX/TEZ/IVA Prescribing Information. N=491 Abbreviations: ALT: alanine aminotransferase; AST, aspartate aminotransferase; ELX, elexacaftor; IVA, ivacaftor; TEZ, tezacaftor. >3× ULN 29 (6%) 15 (3.1%) >5× ULN 12 (2.5%) 6 (1.2%) >8× ULN 6 (1.3%) 1 (0.2%) Rash In Trials 1 and 2, the incidence of rash (e.g., rash, rash pruritic) was 11% in ALYFTREK-treated patients and 7.7% in ELX/TEZ/IVA-treated patients. The rashes were generally mild to moderate in severity. The incidence of rash was 9.4% in males and 13% in females with ALYFTREK treatment and 7.6% in males and 7.9% in females with ELX/TEZ/IVA treatment. A role of hormonal contraceptives in the occurrence of rash cannot be excluded [see Drug Interactions (7.3) ] . Increased Creatine Phosphokinase In Trials 1 and 2, the incidence of maximum creatine phosphokinase >5× the ULN was 7.9% with ALYFTREK treatment and 6.5% with ELX/TEZ/IVA treatment. Discontinuation due to increased creatinine phosphokinase was 0.2% for ALYFTREK-treated patients and 0.2% for ELX/TEZ/IVA-treated patients. Cases of rhabdomyolysis without renal involvement have been reported in patients who had recently exercised taking a fixed-dose combination drug containing ELX/TEZ/IVA (the same or similar active ingredients as ALYFTREK). Increased Blood Pressure Elevations in mean systolic and diastolic blood pressure have been reported in patients taking a fixed-dose combination drug containing ELX/TEZ/IVA (the same or similar active ingredients as ALYFTREK). The proportion of patients who had systolic blood pressure >140 mmHg and >10 mmHg increase from baseline on at least two occasions was 3.5% in ALYFTREK-treated patients and 3.3% in ELX/TEZ/IVA-treated patients. The proportion of patients who had diastolic blood pressure >90 mmHg and >5 mmHg increase from baseline on at least two occasions was 1.7% in ALYFTREK-treated patients and 1.8% in ELX/TEZ/IVA-treated patients. The mean systolic and diastolic blood pressures remained in the normal range from both ALYFTREK and ELX/TEZ/IVA treatment arms. Adverse Reactions in Pediatric Patients Aged 6 to Less Than 12 Years with CF A 24-week, open-label trial of ALYFTREK was conducted in 78 patients with CF aged 6 to less than 12 years with at least one variant responsive to ELX/TEZ/IVA (Trial 3). In Trial 3, patients who weighed less than 40 kg received ALYFTREK (vanzacaftor 12 mg/tezacaftor 60 mg/deutivacaftor 150 mg once daily) and patients who weighed 40 kg or more received ALYFTREK (vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg once daily). Adverse reactions for these patients were generally similar to those reported in Trial 1 and Trial 2. In Trial 3, the incidence of maximum transaminase (ALT or AST) >3×, >5×, and >8× ULN were 3.8%, 1.3%, and 0%, respectively. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ALYFTREK or drugs containing the same or similar active ingredients as ALYFTREK. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Nervous System Disorders : intracranial hypertension Psychiatric Disorders : anxiety, depression, suicidal ideation and behavior, insomnia

What is ALYFTREK used for?
1 INDICATIONS AND USAGE ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients 6 years of age and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is either responsive based on clinical and/or in vitro data (see Table 5 ) or results in production of …

Who makes ALYFTREK?
Vertex Pharmaceuticals Incorporated is the labeler of record for ALYFTREK.

What form does ALYFTREK come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is ALYFTREK prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has ALYFTREK been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.