Cystic Fibrosis: Drug Therapy

Therapy goals

• Improvement of the symptomatology
• Stabilization of lung function

Therapy recommendations

Note: Cystic fibrosis therapy is based on the three pillars of nutritional medicine (see below. , sports medicine, and physiotherapy (see “Other Therapy” below), as well as pharmacotherapy. Pharmacotherapy

• Pharmacotherapy of cystic fibrosis (CF).
  • Secretolytic therapy (liquefaction of secretions:
    • Use of oral expectorants (e.g., N-acetylcysteine) and secretolysis by recombinant human DNAse (DNAse dornase alfa: this can depolymerize DNA in vitro, thereby liquefying CF sputum and improving its viscoelastic properties).
    • Inhalation of hypertonic saline solutions; mannitol (→ water influx and thus reduces viscosity).
    • Inhaled secretolytic therapies can be combined (e.g., hypertonic saline and dornase alpha).
  • Anticholinergics or betamimetics (short-acting) to dilate the bronchi.
  • Glucocorticoids (inhaled steroids (ICS)) for chronic bronchitis [low evidence].
  • Antibiosis (antibiotic therapy; if needed); in addition, monitoring of bronchopulmonary bacterial colonization by sputum examinations or throat swabs so that early therapy of pseudomonas infection is ensured.
  • To keep lung function stable, respiratory training with the flutter valve should be performed several times a day.
  • For upper respiratory tract therapy, nasal irrigation cortisone-containing nasal sprays are used.
• Pharmacotherapy of exocrine pancreatic insufficiency:
  • Pancreatic enzyme substitution (approximately 3,000 I.U. lipase/g fat).
  • High-calorie, high-fat diet (see below nutritional medicine).
  • Supply of fat-soluble vitamins (A, D, E, K) and the water-soluble vitamin B12.
  • Electrolyte balance – especially table salt, calcium and iron supplements.
  • Enemas for acute intestinal obstruction (“intestinal blockage”).
• Pharmacotherapy of endocrine pancreatic insufficiency:
  • Insulin therapy
• Personalized therapy (mutation-specific therapies); these complement but do not replace symptomatic therapy (see above ):
  • Ivacaftor – designed to enhance chloride transport of CFTR in the cell membrane, i.e., to reliquefy mucus; effective only in G551D mutation (approximately 3% of cases).
  • Lumacaftor, which enhances trafficking of the Phe508 deleted CFTR protein to the cell membrane; acts specifically against delta F508 mutation (40-50% of cases) Note: Since lumacaftor is a strong CYP3A inducer, this leads, among other things, to an attenuation of the effect of hormonal contraceptives (hormonal contraception).
  • Combination of CFTR corrector lumacaftor and CFTR potentiator ivacaftor: first causal therapy for cystic fibrosis patients with homozygous delta F508 mutation.
  • The European Commission has approved the extension of the marketing authorization for lumacaftor/ivacaftor for use in children with cystic fibrosis aged 6 to 11 years who have two copies of the F508del mutation (as of January 2018).
  • Kaftrio (combination of ivacaftor, tezacaftor, and elexacaftor); Indication: patients whose cystic fibrosis is due to the F508del mutation inherited from one or both parents. If they inherited this mutation from only one parent, they should also have another mutation called a “minimal function mutation” from the other parent. This situation applies to approximately 60% of all cystic fibrosis patients in Germany (approval by the European Medicines Agency (EMA) was granted on August 21, 2020). See the results of a phase III study of 403 cystic fibrosis (CF) patients who were heterozygous for the Phe508del mutation and had a different mutation: elexacaftor–tezacaftor-ivacaftor was effective in CF patients with Phe508del minimal function genotypes in whom previous CFTR modulator regimens were ineffective.
• Agents (see below) in complications depending on the specific indication.
• See also under “Further therapy”.

Further notes

• The genes of a multidrug-resistant variant of Mycobacterium abscessus (atypical nontuberculous mycobacteria) are increasingly complicating the treatment of cystic fibrosis patients.
• A 15-year-old female patient with cystic fibrosis survived a severe infection with Mycobacterium absessus thanks to therapy with bacteriophages, some of which were genetically modified.Note: Bacteriophages (singular phage, the; ancient Greek βακτήριον; baktérion “rod” and φαγεῖν phageín “to eat”) – also known briefly as phages – are various groups of viruses that specialize in bacteria and archaea as host cells. Phages can be used therapeutically to treat bacterial infections that do not respond to conventional antibiotics.

Active ingredients (main indication)

Inhalations

In case of complications