Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor)

What is Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) for?

Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) is a combination of ivacaftor, tezacaftor, and elexacaftor indicated for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is available in co-packaged fixed-dose combination tablets containing elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg, and tablets containing ivacaftor 150 mg. ¹

How does Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) work?

Trikafta is a combination of three drugs (ivacaftor, tezacaftor, and elexacaftor) that target the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein. It helps the protein made by the CFTR gene mutation function more effectively. ²

Where has Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) been approved?

Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) was approved for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene by:

• The Food and Drug Administration (FDA), USA, on October 21, 2019. ¹
• The European Medicines Agency (EMA), Europe, on August 21, 2020, under the brand-name Kaftrio (ivacaftor/tezacaftor/elexacaftor).³

Please note that this medication may have also been approved in other regions than the ones we’ve listed. If you have a question about its approval in a specific country feel free to contact our support team for assistance.

We have supported patients from various countries access Trikafta. The majority of our patients who have requested access to this medicine come from:

• United Kingdom (UK)
• Netherlands
• India
• Belgium
• France
• Argentina

How is Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) taken?

Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) should be taken orally, together with fat-containing food. The recommended dose is:

• Two tablets (each containing elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg) taken in the morning and one ivacaftor tablet (containing ivacaftor 150 mg) taken in the evening, approximately 12 hours apart. ¹

Reduction in dose may be required based on symptoms and experienced side effects. Complete information about Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) dosage and administration can be found in the official prescribing information listed in our references section ¹.

Note: Please consult with your treating doctor for personalised dosing and potential drug interactions.

Are there any known side effects or adverse reactions of Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor)?

Common adverse reactions¹

The most common adverse reactions listed in the prescribing information include:

• headaches 
• upper respiratory tract 
• infections 
• abdominal pains 
• diarrhea rashes.

Serious adverse reactions¹

The serious adverse reactions listed in the prescribing information include:

• high liver enzymes in the blood 
• abnormality of the eye lens (cataract) 
• rash 
• influenza (flu) events.

Use in specific populations

Pediatric Use

The safety and effectiveness of Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) in patients with cystic fibrosis (CF) younger than 12 years of age have not been established. ¹

In some children and adolescents treated with Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor), abnormality of the eye lens (cataract) have been observed. Eye examinations before and during treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) are therefore recommended in pediatric patients. ¹

Elevated liver function tests

Elevated liver function tests (transaminases and bilirubin) have been observed in patients treated with Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor). Therefore, assessments of liver function tests (ALT, AST, and bilirubin) are recommended for all patients prior to initiating Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor). For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered. Depending on the results of the liver function tests, dosing should be interrupted. ¹

Hepatic Impairment

Patients with severe hepatic impairment (Child-Pugh Class C) should not be treated with Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor). Use of Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) unless the benefit exceeds the risk. If used in patients with moderate hepatic impairment, Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) should be used with caution and at a reduced dose. Liver function tests should be closely monitored. No dose modification is recommended for patients with mild hepatic impairment (Child-Pugh Class A). ¹

Use with CYP3A inducers

Co-administration with strong CYP3A inducers (e.g., rifampin, St. John’s wort) may reduce Trikafta (elexacaftor/tezacaftor/ivacaftor; ivacaftor) efficacy. Therefore, co-administration is not recommended. ¹

For a comprehensive list of side effects and adverse reactions please refer to the official prescribing information ¹.

References

1. Full prescribing information [FDA]: Trikafta (elexacaftor/ivacaftor/tezacaftor) [PDF], Vertex Pharmaceuticals Incorporated, Oct.2019.

2. U.S. Food and Drug Administration. FDA approves new breakthrough therapy for cystic fibrosis. 21/10/2019 (last update: 21/10/2019), cited on 10/01/2020.

3. Kaftrio product page. European Medicines Agency, last checked on Sept 2, 2020.