Products
Lumacaftor is commercially available in a fixed combination with the CFTR potentiator ivacaftor in the form of film-coated tablets (Orkambi). The drug was approved in the EU and US in 2015 and in many countries in 2016.
Structure and properties
Lumacaftor (C24H18F2N2O5, Mr = 452.4 g/mol) exists as a white powder that is practically insoluble in water.
Effects
Lumacaftor (ATC R07AX30) enhances the conformational stability of F508del-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), resulting in increased transport of the chloride transporter to the cell surface. This increases the concentration of the protein in the cell membrane. Lumacaftor has a half-life of approximately 26 hours.
Indications
For the treatment of patients with cystic fibrosis with the F508del mutation in the -gene (homozygous carriers).
Dosage
According to the SmPC. Tablets are taken in the morning and evening (every 12 hours) with a fat-containing meal.
Contraindications
For complete precautions, see the drug label.
Interactions
Lumacaftor is a potent CYP3A inducer as well as an inhibitor or inducer of P-glycoprotein and thus may affect the metabolism of other drugs.
Adverse effects
The most common potential adverse effects of the fixed combination include:
- Respiratory disorders (dyspnea), nasopharyngitis, upper respiratory tract infections.
- Nausea, diarrhea, flatulence.
- Fatigue
- Skin rash
