Elexacaftor/tezacaftor/ivacaftor

Elexacaftor/tezacaftor/ivacaftor is a combination drug used in the treatment of cystic fibrosis (CF) in individuals aged 12 years and older who have at least one F508del mutation in the CFTR gene, which is the most common mutation causing cystic fibrosis. This combination therapy represents a significant advancement in the management of cystic fibrosis, targeting the underlying cause of the disease rather than just its symptoms.

Composition

The drug is a combination of three different molecules: elexacaftor, tezacaftor, and ivacaftor. Each component plays a unique role in enhancing the function of the defective CFTR protein found in individuals with cystic fibrosis.

• Elexacaftor works by increasing the amount of CFTR protein on the cell surface.
• Tezacaftor facilitates the movement of the CFTR protein to the cell surface.
• Ivacaftor increases the activity of the CFTR protein once it is on the cell surface.

Mechanism of Action

The CFTR protein is essential for regulating salt and water transport across cell membranes, which is crucial for the production of mucus, sweat, saliva, tears, and digestive enzymes. Mutations in the CFTR gene lead to the production of a defective CFTR protein, resulting in the thick, sticky mucus characteristic of cystic fibrosis. The combination of elexacaftor, tezacaftor, and ivacaftor addresses the defective CFTR protein's function by improving its quantity and activity on the cell surface, thereby alleviating the symptoms of cystic fibrosis.

Clinical Use

This combination therapy is indicated for the treatment of cystic fibrosis in patients with specific genetic mutations. It has shown significant improvements in lung function, nutritional status, and overall quality of life in individuals with cystic fibrosis. However, it is important to note that this therapy is not a cure for cystic fibrosis but a treatment that manages the condition.

Side Effects

Common side effects include headache, upper respiratory tract infection, abdominal pain, diarrhea, rash, and flu-like symptoms. Liver function tests should be monitored regularly during treatment, as the therapy can affect liver enzymes.

Approval

The combination of elexacaftor/tezacaftor/ivacaftor was approved by the Food and Drug Administration (FDA) in the United States and by the European Medicines Agency (EMA) in the European Union. Its approval marked a significant milestone in the treatment of cystic fibrosis, offering hope to many patients and families affected by this challenging condition.

See Also

• Cystic Fibrosis
• CFTR gene
• Orkambi
• Symdeko
• Kalydeco

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