Kalydeco (Ivacaftor)

Kalydeco acts on the cystic fibrosis transmembrane conductance regulator (CFTR) pathway to treat patients with specific genetic variants.

• Cystic fibrosis with G551D mutation: improves lung function and reduces pulmonary exacerbations.
• Cystic fibrosis with R117H mutation: enhances chloride transport and stabilises disease progression.
• Cystic fibrosis with other responsive gating mutations: provides measurable clinical benefit in lung function and symptom control.

• Ivacaftor binds to the CFTR protein at the cell surface and increases the probability that the chloride channel remains open. By potentiating the defective CFTR gating caused by specific mutations, it restores chloride ion flow across epithelial membranes, improving hydration of airway surfaces and reducing mucus viscosity in patients with cystic fibrosis.

Adverse reactions have been reported with ivacaftor therapy.

Common Side Effects

• Headache: mild to moderate intensity.
• Diarrhoea: usually transient.
• Upper respiratory tract infection: nasopharyngitis or sinusitis.
• Nausea: occasional, may lessen over time.
• Abdominal pain: mild discomfort.
• Rash: skin irritation or erythema.

Serious or Rare Side Effects

• Elevated liver enzymes: monitor hepatic function.
• Cataracts: periodic ophthalmologic assessment recommended.
• Severe allergic reaction: anaphylaxis or angioedema.
• Cardiac arrhythmia: QT prolongation in susceptible individuals.
• Pulmonary haemorrhage: rare but potentially life‑threatening.

Patients should be evaluated for safety considerations before initiating therapy.

• Liver function monitoring: assess baseline transaminases and repeat periodically.
• Vision assessment: schedule regular eye examinations for cataract detection.
• Cardiac evaluation: review QT interval and electrolyte status in patients with arrhythmia risk.
• Drug interaction review: check concomitant medications that affect CYP3A metabolism.
• Hypersensitivity: discontinue if signs of severe allergic reaction appear.
• Store at ambient temperature: keep tablets in the original container, protect from moisture and heat.

Ivacaftor is metabolised primarily by CYP3A enzymes, making it susceptible to pharmacokinetic interactions.

Major Interactions (Avoid)

• Strong CYP3A inducers (e.g., rifampin, carbamazepine): may markedly reduce ivacaftor exposure.
• Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole): can increase ivacaftor plasma levels and risk toxicity.
• Antacids containing aluminium or magnesium: may decrease absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Azole antifungals (e.g., fluconazole): may modestly raise ivacaftor concentrations.
• Macrolide antibiotics (e.g., erythromycin): require periodic liver function testing.
• Warfarin: monitor INR as ivacaftor may affect anticoagulant effect.