Kaftrio (Tezacaftor, Elexacaftor, Ivacaftor)

Kaftrio is a CFTR modulator used in the management of cystic fibrosis, a genetic disorder affecting chloride transport.

• Cystic fibrosis (homozygous F508del): Improves lung function, reduces pulmonary exacerbations, and supports nutritional status.
• Cystic fibrosis (heterozygous F508del with a minimal‑function mutation): Provides similar respiratory and nutritional benefits.
• Cystic fibrosis (≥12 years, at least one F508del allele): Enhances overall disease control and quality of life.

• Kaftrio combines three agents that act on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Tezacaftor and elexacaftor act as correctors, improving folding, processing, and trafficking of the F508del‑mutated CFTR to the cell surface. Ivacaftor functions as a potentiator, increasing the open probability of the CFTR channel once it reaches the membrane, thereby enhancing chloride ion transport across epithelial cells.

Kaftrio may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Headache: mild to moderate intensity.
• Diarrhea: usually transient.
• Nausea: may occur after dosing.
• Abdominal pain: occasional.
• Rash: skin irritation or erythema.
• Elevated liver enzymes: mild increases in ALT/AST.

Serious or Rare Side Effects

• Significant liver injury: marked elevation of hepatic enzymes or bilirubin.
• Pulmonary exacerbation worsening: rare cases of rapid lung function decline.
• Cataracts: infrequent ocular changes reported.
• Severe allergic reaction (anaphylaxis): rare but potentially life‑threatening.

When prescribing Kaftrio, clinicians should consider several safety measures.

• Monitor liver function: obtain baseline tests and repeat periodically.
• Assess drug interactions: review concomitant CYP3A4 modulators and adjust therapy as needed.
• Pregnancy and breastfeeding: discuss potential risks with the patient and consider alternative treatments if appropriate.
• Adherence: advise taking tablets with a fat‑containing meal to maximize absorption.
• Avoid use in severe hepatic impairment: contraindicated in patients with advanced liver disease.
• Store at ambient temperature below 25°C: keep in the original pack, protect from moisture.

Kaftrio interacts with several medicines that affect its metabolism or efficacy.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin): may markedly reduce Kaftrio exposure.
• Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase drug levels and risk of toxicity.

Moderate Interactions (Monitor Closely)

• Azole antifungals (e.g., itraconazole): may require dose adjustment of Kaftrio.
• HMG‑CoA reductase inhibitors (e.g., simvastatin): increased risk of myopathy; monitor muscle symptoms.
• Oral contraceptives: possible reduction in hormonal efficacy; consider additional contraceptive methods.