Elexacaftor, Tezacaftor, And Ivacaftor

1 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 (see Table 6 ) [see Clinical Pharmacology (12.1) ] . 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 [see Clinical Pharmacology (12.1) ] .

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) ] Intracranial Hypertension [see Warnings and Precautions (5.3) ] Cataracts [see Warnings and Precautions (5.6) ] The most common adverse drug reactions to TRIKAFTA (≥5% of patients and at a frequency 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, blo...

8.1 Pregnancy Risk Summary There are limited and incomplete human data from clinical trials on the use of TRIKAFTA or its individual components, elexacaftor, tezacaftor and ivacaftor, in pregnant women to inform a drug-associated risk. Although there are no animal reproduction studies with the concomitant administration of elexacaftor, tezacaftor and ivacaftor, separate reproductive and developmental studies were conducted with each active component of TRIKAFTA in pregnant rats and rabbits.

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 [see Adverse Reactions (6) ]. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of TRIKAFTA . 5 WARNINGS AND PRECAUTIONS Drug-induced liver injury and liver failure : TRIKAFTA can cause serious and potentially fatal drug-induced liver injury. Assess liver function tests (ALT, AST, alkaline phosphatase, bilirubin) in all patients prior to initiating and throughout treatment with TRIKAFTA. Interrupt TRIKAFTA in the event of significant elevations in liver function tests or signs or symptoms of liver injury. 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). ( 2.1 , 2.3 , 5.1 , 6 , 8.7 , 12.3 ) Hypersensitivity reactions : Angioedema and anaphylaxis have been reported with TRIKAFTA in the postmarketing setting. 4 CONTRAINDICATIONS None. None. ( 4 )