Drug desensitization to lumacaftor/ivacaftor: A fast lane to drug tolerance

J Cyst Fibros. 2023 Sep;22(5):941-943. doi: 10.1016/j.jcf.2023.03.015. Epub 2023 Apr 10.

Abstract

We present the case of a girl (now 11 years and 9 months old) with cystic fibrosis (F508del homozygote), who developed pruritic rash and urticaria six days after the first dose of the CFTR modulators lumacaftor/ivacaftor. The treatment was paused and had to be interrupted due to an immediate recurrence of the urticarial rash after rechallenge. We developed a drug desensitization protocol, aligned to protocols used for desensitization against oral antibiotics. In contrast to other published protocols, it was performed by rapidly increasing the dose of lumacaftor/ivacaftor granulate at 15 min intervals. The medication was continued without interruption, the rash did not reappear during follow-up of two years. This drug desensitization protocol provides a potential new therapeutic option for patients with drug hypersensitivity reactions to CFTR modulators, especially when there are no alternative treatments. Lumacaftor/ivacaftor is available as granulate, doses can be titrated during desensitization and used for long-term treatment.

Publication types

  • Case Reports

MeSH terms

  • Aminophenols / therapeutic use
  • Aminopyridines / therapeutic use
  • Benzodioxoles / therapeutic use
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / therapeutic use
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Drug Combinations
  • Drug Tolerance
  • Exanthema* / chemically induced
  • Exanthema* / drug therapy
  • Female
  • Forced Expiratory Volume
  • Humans
  • Infant
  • Mutation

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor
  • lumacaftor
  • Drug Combinations
  • Aminophenols
  • Aminopyridines
  • Benzodioxoles