Kaftrio (Tezacaftor, Elexacaftor, Ivacaftor)

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

• Cystic fibrosis (≥12 years) with at least one F508del mutation: improves lung function and reduces pulmonary exacerbations.
• Cystic fibrosis (≥12 years) homozygous F508del: enhances CFTR protein processing and chloride transport.
• Cystic fibrosis (≥12 years) heterozygous F508del plus a second mutation: provides clinical benefit by increasing CFTR activity.

• Kaftrio combines two CFTR correctors (elexacaftor and tezacaftor) that improve folding and trafficking of the F508del CFTR protein to the cell surface, with a CFTR potentiator (ivacaftor) that increases the channel’s opening probability. Together they enhance chloride ion transport across epithelial cells, restoring more normal fluid balance in the lungs and other organs.

Kaftrio may cause a range of adverse reactions. Patients should be aware of both common and less frequent events.

Common Side Effects

• Headache: mild to moderate intensity.
• Diarrhea: may be watery or loose.
• Nausea: often transient.
• Abdominal pain: cramp-like discomfort.
• Rash: skin erythema or pruritus.
• Elevated liver enzymes: mild transaminase increase.

Serious or Rare Side Effects

• Hepatic injury: significant transaminase elevation or jaundice.
• Cataracts: lens opacity reported in some patients.
• Respiratory distress: worsening of pulmonary symptoms.
• Severe rash or hypersensitivity: including Stevens‑Johnson syndrome.

Before initiating Kaftrio, clinicians should consider several safety measures.

• Monitor liver function: obtain baseline tests and repeat periodically.
• Assess drug interactions: review concomitant CYP3A4 modulators and other CFTR modulators.
• Pregnancy and lactation: use only if potential benefit justifies potential risk.
• Take with fat-containing food: enhances absorption of ivacaftor.
• Contraindication in severe hepatic impairment: avoid in patients with Child‑Pugh class C disease.
• Store at ambient temperature: keep below 25 °C, retain original packaging, protect from moisture.

Kaftrio interacts with several medicines through CYP3A4 and transport pathways.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may markedly reduce exposure.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): can increase drug levels and toxicity.
• BCRP inhibitors (e.g., elacridar): may raise ivacaftor concentrations.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole): may require dose adjustment.
• Oral contraceptives: reduced efficacy, consider alternative contraception.
• Statins metabolized by CYP3A4 (e.g., simvastatin): monitor for myopathy.
• Antacids containing aluminum or magnesium: may affect absorption if taken simultaneously.