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IMPORTANT SAFETY INFORMATION
WARNING: DRUG-INDUCED LIVER INJURY AND LIVER FAILURE
- TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Cases of liver failure leading to transplantation and death have been reported in patients with and without a history of liver disease taking TRIKAFTA, in both clinical trials and the postmarketing setting. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA.
- Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then 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 liver function test (LFT) elevations at baseline.
- Interrupt TRIKAFTA 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 TRIKAFTA.
- TRIKAFTA should not be used in patients with severe hepatic impairment (Child-Pugh Class C). TRIKAFTA is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B). If used, use with caution at a reduced dosage and monitor patients closely.
INDICATIONS AND USAGE
TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (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 indicated mutation.
WARNINGS AND PRECAUTIONS
Drug-Induced Liver Injury and Liver Failure
- TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Liver failure leading to transplantation and death has been reported in patients with and without a history of liver disease taking TRIKAFTA. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA
- Assess LFTs (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating TRIKAFTA, then 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 LFT elevations at baseline
- Interrupt TRIKAFTA 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 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 TRIKAFTA with close monitoring
- TRIKAFTA should not be used in patients with severe hepatic impairment. TRIKAFTA 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, use with caution at a reduced dosage and monitor patients closely
Hypersensitivity Reactions, Including Anaphylaxis
- Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the postmarketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue TRIKAFTA and institute appropriate therapy. Consider benefits and risks for the individual patient to determine whether to resume treatment with TRIKAFTA
Concomitant Use With CYP3A Inducers
- Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by concomitant use of strong CYP3A inducers, which may reduce therapeutic effectiveness of TRIKAFTA. Concomitant use with strong CYP3A inducers is not recommended
Concomitant Use With CYP3A Inhibitors
- Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors
Cataracts
- Non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow‑up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA
ADVERSE REACTIONS
Serious Adverse Reactions
- Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0%)
Most Common Adverse Reactions
- The most common adverse reactions occurring in ≥5% of patients treated with TRIKAFTA and higher than placebo by ≥1% were 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 and constipation
USE IN SPECIFIC POPULATIONS
Pediatric Use
- The safety and effectiveness of TRIKAFTA in patients with CF younger than 2 years of age have not been established
Please see full Prescribing Information, including Boxed WARNING.