Trikafta

About Trikafta (Elexacaftor, Tezacaftor, and Ivacaftor tablets; Ivacaftor Tablets)

• On April 26, 2023, Vertex Pharmaceuticals announced the US FDA approval for Trikafta. 
• Marketed as Elexacaftor/tezacaftor/ivacaftor, it is available under the brand names Trikafta in the US and Kaftrio in the EU. 
• Trikafta is a combination medication comprising ivacaftor, a CFTR potentiator, along with tezacaftor and elexacaftor. It is designated for the treatment of cystic fibrosis (CF) in patients aged 6 years and above, specifically those with at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data. 
• In cases where the patient’s genotype is unknown, confirmation of the presence of at least one F508del mutation or a responsive mutation based on in vitro data should be conducted using an FDA-cleared CF mutation test.
• Elexacaftor/tezacaftor/ivacaftor consists of ivacaftor, a chloride channel opener, and elexacaftor and tezacaftor, which are CFTR modulators. 
• The approval covers its use in the United States for individuals aged six and older with cystic fibrosis possessing a F508del mutation or other mutations in the CFTR gene. 
• Additionally, it is approved for use in Canada, the European Union, and Australia. 
• This tridrug treatment collaboratively enhances chloride and sodium ion transport while correcting dysregulated fluid shifts characteristic of cystic fibrosis.

Strength

Tablets containing Elexacaftor 100 mg, Tezacaftor 50 mg, and ivacaftor 75 mg in a fixed dosage combination. The above contents are combined with Ivacaftor 150 mg tablets.

Recommended Dosage

Ingest the tablets whole. Trikafta should be consumed alongside meals rich in fat. Examples of suitable fat-containing foods include those prepared with butter or oils, as well as those featuring eggs, cheeses, nuts, whole milk, or meats. 

• The recommended dosage for adults and pediatric patients aged 6 years and older involves taking the morning and evening doses approximately 12 hours apart. Trikafta is designed for oral administration. 
• For patients aged 6 to less than 12 years weighing less than 30 kgs, the recommended dosage includes two tablets, each containing elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg, along with one tablet of ivacaftor 75 mg. 
• For those aged 6 to less than 12 years weighing 30 kgs or more, the dosage comprises two tablets, each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg, plus one tablet of ivacaftor 150 mg. 
• Patients aged 12 years and older should take two tablets, each containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg, and one tablet of ivacaftor 150 mg.

Important

If a Trikafta dose is missed and it’s been less than 6 hours, take it promptly and continue the schedule. If more than 6 hours have passed, for a missed morning dose, take it promptly, skip the evening dose, and resume the next morning. For a missed evening dose, do not take it, and the next morning dose should be taken as scheduled. Avoid simultaneous morning and evening doses. In case of adverse reactions, consult the treating doctor promptly.

Warnings & Precautions

• Before starting the medicine Trikafta, it is necessary to evaluate liver function tests, every 3 months, and yearly (Elevated liver function tests (ALT, AST, or bilirubin). Consider regular monitoring for hepatobiliary illness or elevated tests. Dosing discontinues in patients with ALT or AST levels above 5 times the upper limit of normal, and consider restarting medication when transaminase levels resolve.
• Co-administration of CYP3A inducers with TRIKAFTA may reduce Ivacaftor dosage and Elexacaftor and Tezacaftor exposure.
• Pediatric patients with Ivacaftor-containing regimens may develop non-congenital lens opacities (Cataracts).

Common Trikafta Side Effects

• Headache
• Upper respiratory tract infection
• Abdominal pain
• Diarrhea
• Rash
• Increased alanine aminotransferase
• Nasal congestion
• Increased blood creatine phosphokinase
• Increased aspartate aminotransferase
• Rhinorrhea
• Rhinitis
• Influenza
• Sinusitis 
• Increased blood bilirubin

Use in Specific population

• There is currently no available information regarding the presence of elexacaftor, tezacaftor, or ivacaftor in human breast milk, their impact on the breastfed infant, or their effects on milk production. 
• The safety and efficacy of Trikafta, indicated for the treatment of cystic fibrosis (CF) in patients aged 6 to less than 18 years with at least one F508del mutation in the CFTR gene or a mutation responsive based on in vitro data, have been established.
• However, the safety and effectiveness of Trikafta in patients with CF below the age of 6 years have not been conclusively determined. 
• Trikafta has not undergone studies in individuals with severe renal impairment or end-stage renal disease. While no dosage adjustment is recommended for patients with mild or moderate renal impairment, caution is advised in those with severe renal impairment or end-stage renal disease.
• For patients with mild hepatic impairment, no dose modification is necessary. On the other hand, Trikafta treatment is not recommended for individuals with moderate hepatic impairment.

Storage and Handling

To protect them from light, store the medicines at 25ºC. Excursions are permitted between 15ºC to 30ºC.