Orkambi (Lumacaftor, Ivacaftor)

Lumacaftor/Ivacaftor, the active ingredient in Orkambi, is a combination product presented as a fixed‑dose oral tablet for oral use. It treats cystic fibrosis in patients who have two copies of the F508del mutation.

GNH USA supplies Orkambi as a licensed, GDP‑compliant international pharmaceutical supplier serving hospitals, pharmacies and clinics worldwide.

Orkambi is a CFTR modulator indicated for cystic fibrosis patients with the F508del homozygous genotype. It improves lung function and reduces pulmonary exacerbations.

- Cystic fibrosis (12 years and older, F508del homozygous): Improves lung function and decreases exacerbation frequency. - Cystic fibrosis (adolescents 12–17 years, F508del homozygous): Enhances pulmonary outcomes and quality of life. - Cystic fibrosis (adults ≥18 years, F508del homozygous): Slows decline in respiratory function and supports nutritional status.

Common Side Effects: - Respiratory tract infection: mild to moderate upper respiratory symptoms. - Headache: transient, often resolves without intervention. - Diarrhea: usually self‑limiting. - Nausea: may occur after dosing. - Elevated liver enzymes: asymptomatic increase in ALT/AST. - Rash: mild skin irritation.

Serious or Rare Side Effects: - Severe liver injury: jaundice, hepatic failure requiring monitoring. - Pulmonary hemorrhage: coughing up blood, requires urgent care. - Anaphylaxis: rapid onset of allergic reaction, may be life‑threatening. - Vision changes: blurred vision or cataract formation. - Elevated serum creatinine: indicates possible renal impact. - Cardiac arrhythmias: rare but reported in post‑marketing data.

Before initiating therapy, patients should be evaluated for liver function and potential drug interactions. - Liver function monitoring: check ALT/AST before treatment and periodically during therapy. - Drug interaction review: assess concomitant CYP3A4 substrates and inhibitors. - Pregnancy risk assessment: use only if benefits outweigh potential fetal risks. - Adherence with meals: take tablets with a high‑fat meal to improve absorption. - Storage at ambient temperature: keep below 25 °C in the original pack, protect from moisture.

Orkambi may interact with several medications that affect CYP3A4 metabolism.

Major Interactions (Avoid): - Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may markedly reduce lumacaftor/ivacaftor exposure. - Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase drug levels and risk of toxicity.

Moderate Interactions (Monitor Closely):\n- Azole antifungals (e.g., fluconazole): may modestly raise ivacaftor concentrations. - Macrolide antibiotics (e.g., clarithromycin): can increase exposure to both components. - HIV protease inhibitors (e.g., ritonavir): may elevate ivacaftor levels. - St. John’s wort: may lower drug concentrations. - Oral contraceptives: potential reduced efficacy, consider alternative contraception.