Tezacaftor

Tezacaftor facilitates the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.

• SYMDEKO is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence [see Clinical Pharmacology (12.1) and Clinical Studies (14) ] . If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.

• None. None.contraindicated

Pediatric patients aged 6 to less than 12 years weighing less than 30 kg: one tablet (containing tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one tablet (containing ivacaftor 75 mg) in the evening, approximately 12 hours apart. SYMDEKO should be taken with fat-containing food. ( 2.1 , 2.2 , 12.3 ) Adults and pediatric patients aged 12 years and older or pediatric patients aged 6 to less than 12 years weighing 30 kg or more: one tablet (containing tezacaftor 100 mg/ivacaftor 150 mg) in the morning and one tablet (containing ivacaftor 150 mg) in the evening, approximately 12 hours apart. SYMDEKO should be taken with fat-containing food. ( 2.1 , 2.2 , 12.3 ) Reduce dosage in patients with moderate and severe hepatic impairment. ( 2.3 , 8.6 , 12.3 ) See full prescribing information for dosage modifications due to drug interactions with SYMDEKO. ( 2.4 , 7.2 , 12.3 ) 2.1 General Dosage Information Swallow the tablets whole. SYMDEKO should be taken with fat-containing food, such as food recommended in standard nutritional guidelines. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, or meats, etc. [see Clinical Pharmacology (12.3) ] . 2.2 Recommended Dosage in Adults, Adolescents, and Children Aged 6 Years and Older Adults, adolescents, and children aged 6 years and older should be dosed according to Table 1. The morning and the evening doses should be taken approximately 12 hours apart.

Elevated transaminases (ALT or AST): Transaminases (ALT and AST) should be assessed prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. In patients with a history of transaminase elevations, more frequent monitoring should be considered. Dosing should be interrupted in patients with significant elevations of transaminases, e.g., patients with ALT or AST >5 × upper limit of normal (ULN), or ALT or AST >3 × ULN with bilirubin >2 × ULN. Following resolution of transaminase elevations, consider the benefits and risks of resuming treatment. ( 5.1 , 6 ) Hypersensitivity reactions: Anaphylaxis has been reported with SYMDEKO in the postmarketing setting. Initiate appropriate therapy in the event of a hypersensitivity reaction. ( 5.2 ) Intracranial hypertension : Intracranial hypertension (IH) has been reported in the postmarketing setting with the use of drugs containing the same or similar active ingredients as SYMDEKO. If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt SYMDEKO and refer for prompt medical evaluation. ( 5.3 ) Neuropsychiatric events, including suicidal thoughts and behaviors : Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting for SYMDEKO or drugs containing the same or similar active ingredients. Monitor patients closely for new or worsening symptoms.

The following adverse reactions are discussed in greater detail in other sections of the label: Transaminase Elevations [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.2) ] Intracranial Hypertension [see Warnings and Precautions (5.3) ] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.4) ] Cataracts [see Warnings and Precautions (5.6) ] The most common adverse drug reactions to SYMDEKO (occurring in ≥3% of patients) were headache, nausea, sinus congestion, and dizziness. ( 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 overall safety profile of SYMDEKO is based on data from 1001 patients in three double-blind, placebo-controlled, clinical trials: two parallel-group trials of 12 and 24-week duration and one cross-over design trial of 8 weeks duration. Eligible patients were also able to participate in an open-label extension safety study (up to 96 weeks of SYMDEKO). In the three placebo-controlled trials (Trials 1, 2, and 3), a total of 496 patients with CF aged 12 years and older received at least one dose of SYMDEKO.

8.1 Pregnancy Risk Summary There are limited and incomplete human data from clinical trials and postmarketing reports on the use of SYMDEKO or its individual components, tezacaftor and ivacaftor, in pregnant women to inform a drug-associated risk. Although there are no animal reproduction studies with the concomitant administration of tezacaftor and ivacaftor, separate reproductive and developmental studies were conducted with tezacaftor and ivacaftor in pregnant rats and rabbits. In animal reproduction studies, oral administration of tezacaftor to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse developmental effects at doses that produced maternal exposures up to approximately 3 times the exposure at the maximum recommended human dose (MRHD) in rats and 0.2 times the MRHD in rabbits (based on summed AUCs for tezacaftor and M1 metabolite). Oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse developmental effects at doses that produced maternal exposures up to approximately 6 and 16 times the exposure at the MRHD, respectively.

Metabolism

The pharmacokinetics of tezacaftor and ivacaftor are similar between healthy adult volunteers and patients with CF. Following once-daily dosing of tezacaftor and twice-daily dosing of ivacaftor in patients with CF, plasma concentrations of tezacaftor and ivacaftor reach steady-state within 8 days and within 3 to 5 days, respectively, after starting treatment.

No specific antidote is available for overdose with SYMDEKO. Treatment of overdosage consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

• Feb 12, 2018NDANDA210491Vertex Pharms Inc
• Oct 21, 2019NDANDA212273Vertex Pharms Inc
• Apr 26, 2023NDANDA217660Vertex Pharms Inc
• Dec 20, 2024NDANDA218730Vertex Pharms Inc

1. 1Infective Pulmonary Exacerbation Of Cystic Fibrosis1,98911%
2. 2Headache1,0025.6%
3. 3Hospitalisation9065.1%
4. 4Cough7794.4%
5. 5Cystic Fibrosis7694.3%
6. 6Infection6883.9%
7. 7Pneumonia6703.8%
8. 8Anxiety6673.7%
9. 9Fatigue6413.6%
10. 10Rash6273.5%
11. 11Productive Cough5843.3%
12. 12Abdominal Pain Upper5633.2%
13. 13Weight Increased5333.0%
14. 14Depression4962.8%
15. 15Nausea4792.7%

The 10 most recently updated of 109 ClinicalTrials.gov registrations naming Tezacaftor as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pharmacokinetics of Antibiotics in Patients With Cystic Fibrosis Trated With Elexacaftor/Tezacaftor/Ivacaftor (ETI)
  Recruiting · Observational · 30 enrolled · Fondation Ildys
  NCT07629986updated 2026-06-05
• Evaluation of Long-term Safety and Efficacy of ELX/TEZ/IVA in Cystic Fibrosis Participants 12 Months of Age and Older
  Active not recruiting · Phase 3 · Interventional · 50 enrolled · Vertex Pharmaceuticals Incorporated
  NCT06460506updated 2026-06-05
• Ensuring Access to Optimal Therapy in CF: The ENACT Study
  Recruiting · Phase 4 · Interventional · 100 enrolled · Arkansas Children's Hospital Research Institute
  NCT07148739updated 2026-06-02
• Glucose Metabolism in Cystic Fibrosis Related Diabetes (CFRD)
  Recruiting · Observational · 30 enrolled · University of Alabama at Birmingham
  NCT07102043updated 2026-06-01
• Study to Evaluate Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) Long-term Safety and Efficacy in Subjects Without F508del
  Active not recruiting · Phase 3 · Interventional · 297 enrolled · Vertex Pharmaceuticals Incorporated
  NCT05331183updated 2026-05-29
• Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age
  Active not recruiting · Phase 3 · Interventional · 210 enrolled · Vertex Pharmaceuticals Incorporated
  NCT05422222updated 2026-05-28
• Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis
  Active not recruiting · Phase 1 · Interventional · 165 enrolled · Vertex Pharmaceuticals Incorporated
  NCT06154447updated 2026-05-26
• Trikafta Exercise Study in Cystic Fibrosis
  Recruiting · Observational · 20 enrolled · University of British Columbia
  NCT05279040updated 2026-05-18
• Sinus Disease in Young Children With Cystic Fibrosis
  Recruiting · Observational · 80 enrolled · University of California, Los Angeles
  NCT06191640updated 2026-05-11
• A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy
  Active not recruiting · Phase 3 · Interventional · 822 enrolled · Vertex Pharmaceuticals Incorporated
  NCT05444257updated 2026-05-05

Frequently asked questions

How does Tezacaftor work?

Tezacaftor facilitates the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of mature CFTR protein delivered to the cell surface. Ivacaftor is a CFTR potentiator that facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein at the cell surface.

What is Tezacaftor used for?

According to FDA labeling, Tezacaftor carries indications including: SYMDEKO is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence [see Clinical Pharmacology (12.1) and Clinical Studies (14) ] . If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the brand names for Tezacaftor?

Tezacaftor is marketed under brand names including Alyftrek.

What are the contraindications for Tezacaftor?

Tezacaftor labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.