Trikafta
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani
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Overview
Trikafta is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator that is FDA approved for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on clinical and/or 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 responsive mutation.. Common adverse reactions include 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, Blood bilirubin increased.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Adults and Pediatric Patients Aged 6 Years and Older:
Morning Dose: Two tablets (each containing elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg) taken orally.
Evening Dose: One tablet (containing ivacaftor 150 mg) taken orally.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Trikafta in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Trikafta in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Pediatric Patients Aged 2 to Less Than 6 Years:
Weight ≥14 kg: Morning Dose: Two tablets (each containing elexacaftor 50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg) taken orally. Evening Dose: One tablet (containing ivacaftor 75 mg) taken orally.
Weight <14 kg: Morning Dose: Two tablets (each containing elexacaftor 25 mg, tezacaftor 12.5 mg, and ivacaftor 18.75 mg) taken orally. Evening Dose: One tablet (containing ivacaftor 37.5 mg) taken orally.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Trikafta in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Trikafta in pediatric patients.
Contraindications
Trikafta is contraindicated in patients with a history of hypersensitivity to elexacaftor, tezacaftor, ivacaftor, or any of the excipients in the formulation.
Warnings
Elevated Liver Transaminases: Elevations of liver transaminases (ALT and AST) have been observed in patients treated with Trikafta. It is recommended to assess ALT, AST, and bilirubin levels prior to initiating treatment, every 3 months during the first year, and annually thereafter. In patients with significant elevations, consider discontinuing Trikafta.
Adverse Reactions
Clinical Trials Experience
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, Blood bilirubin increased.
Postmarketing Experience
There is limited information regarding Trikafta Postmarketing Experience in the drug label.
Drug Interactions
CYP3A Inducers:
Co-administration with strong CYP3A inducers (e.g., rifampin, St. John's wort) may significantly decrease elexacaftor, tezacaftor, and ivacaftor exposure, reducing Trikafta's effectiveness. Concomitant use is not recommended.
CYP3A Inhibitors:
Co-administration with strong CYP3A inhibitors (e.g., ketoconazole) increases ivacaftor exposure. Adjust Trikafta dosage when co-administered with strong CYP3A inhibitors.
Potential for Trikafta to Affect Other Drugs:
Ivacaftor may inhibit CYP3A and P-glycoprotein (P-gp). Monitor for adverse reactions when co-administering Trikafta with sensitive CYP3A or P-gp substrates (e.g., digoxin, cyclosporine).
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Trikafta in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Trikafta in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Trikafta during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Trikafta in women who are nursing.
Pediatric Use
The safety and efficacy of Trikafta have been established in pediatric patients aged 2 years and older. The use of Trikafta in this age group is supported by evidence from adequate and well-controlled studies in adults and pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Trikafta in geriatric settings.
Gender
There is no FDA guidance on the use of Trikafta with respect to specific gender populations.
Race
There is no FDA guidance on the use of Trikafta with respect to specific racial populations.
Renal Impairment
No dose adjustment is recommended for patients with mild to moderate renal impairment. Caution is advised when administering Trikafta to patients with severe renal impairment or end-stage renal disease.
Hepatic Impairment
No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh Class A). For patients with moderate hepatic impairment (Child-Pugh Class B), the recommended dose is two tablets in the morning and one tablet in the evening, taken with fat-containing food. Trikafta is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C).
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Trikafta in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Trikafta in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Trikafta Administration in the drug label.
Monitoring
There is limited information regarding Trikafta Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Trikafta and IV administrations.
Overdosage
There is limited information regarding Trikafta overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Trikafta Pharmacology in the drug label.
Mechanism of Action
Elexacaftor and Tezacaftor: Both are CFTR correctors that facilitate the cellular processing and trafficking of normal or mutant CFTR (F508del) protein, increasing the quantity of functional CFTR at the cell surface.
Ivacaftor: A CFTR potentiator that enhances the channel-open probability (gating) of the CFTR protein at the cell surface, improving chloride transport.
The combined effect of these three components leads to an increase in CFTR activity, as measured by chloride transport.
Structure
There is limited information regarding Trikafta Structure in the drug label.
Pharmacodynamics
Sweat Chloride: In clinical studies, Trikafta significantly reduced sweat chloride concentrations, indicating improved CFTR function.
Pulmonary Function: Patients demonstrated substantial improvements in percent predicted forced expiratory volume in one second (ppFEV1), reflecting enhanced lung function.
Respiratory Symptoms: Improvements were observed in the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score, indicating better respiratory-related quality of life.
Pharmacokinetics
Absorption: Maximum plasma concentrations (C_max) of elexacaftor, tezacaftor, and ivacaftor are typically reached within 4 hours after dosing.
Distribution: The mean apparent volume of distribution is approximately 53.1 L for elexacaftor, 96.0 L for tezacaftor, and 353.0 L for ivacaftor, indicating extensive tissue distribution.
Metabolism: All three components are extensively metabolized, primarily via CYP3A4 and CYP3A5 enzymes.
Elimination: The majority of each drug and their metabolites are excreted in the feces, with minimal urinary excretion. The mean elimination half-life is approximately 24.7 hours for elexacaftor, 20.2 hours for tezacaftor, and 12.4 hours for ivacaftor.
Nonclinical Toxicology
There is limited information regarding Trikafta Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Trikafta Clinical Studies in the drug label.
How Supplied
Tablets:
For patients aged 6 years and older:
Morning Dose: Each tablet contains elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg.
Evening Dose: Each tablet contains ivacaftor 150 mg.
Oral Granules:
For patients aged 2 to less than 6 years:
Weight less than 14 kg:
Morning Dose: Each packet contains elexacaftor 80 mg, tezacaftor 40 mg, and ivacaftor 60 mg.
Evening Dose: Each packet contains ivacaftor 59.5 mg.
Weight 14 kg or greater:
Morning Dose: Each packet contains elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg.
Evening Dose: Each packet contains ivacaftor 75 mg.
Storage
Tablets:
Store at room temperature between 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).
Oral Granules:
Store at room temperature between 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).
After mixing with soft food or liquid, administer the dose within one hour.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Trikafta Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Trikafta interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
In the United States, the combination of elexacaftor, tezacaftor, and ivacaftor is marketed under the brand name Trikafta.
In the European Union and other regions, the same combination is marketed under the brand name Kaftrio.
Look-Alike Drug Names
There is limited information regarding Trikafta Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.