What are the pharmacologic treatments for Cystic Fibrosis (CF)?

From the Guidelines

Pharmacologic treatment of cystic fibrosis should focus on a multi-faceted approach, including CFTR modulators, airway clearance medications, infection control antibiotics, nutritional support, and anti-inflammatory treatments, to improve lung function, reduce exacerbations, and enhance quality of life. The treatment regimen may include CFTR modulators such as ivacaftor (Kalydeco), lumacaftor/ivacaftor (Orkambi), tezacaftor/ivacaftor (Symdeko), and elexacaftor/tezacaftor/ivacaftor (Trikafta), with selection based on specific genetic mutations 1. Airway clearance is supported with inhaled medications including:

• dornase alfa (Pulmozyme) at 2.5mg once daily to break down DNA in mucus
• hypertonic saline (3-7%) to improve hydration of secretions
• bronchodilators like albuterol to open airways Infection control involves antibiotics tailored to cultured pathogens, with options including:
• inhaled tobramycin (300mg twice daily in alternating months)
• azithromycin (500mg three times weekly) for anti-inflammatory effects
• aggressive IV antibiotic courses for exacerbations 1 Nutritional support includes:
• pancreatic enzyme replacement therapy (PERT) dosed at 500-4,000 lipase units/kg/meal
• fat-soluble vitamin supplements (A, D, E, K)
• high-calorie diets Anti-inflammatory treatments may include ibuprofen at high doses in select patients. This approach is supported by recent guidelines and evidence reviews, including the 2013 cystic fibrosis pulmonary guidelines, which provide up-to-date evidence of safety and efficacy of chronic treatments of CF lung disease 1. The use of chronic medications for CF lung disease has led to significant improvement in survival, and a multidisciplinary committee of experts in CF pulmonary care has established recommendations for the use of these medications 1. Overall, the goal of pharmacologic treatment in cystic fibrosis is to improve lung function, reduce exacerbations, and enhance quality of life, and a multi-faceted approach is necessary to achieve this goal.

From the FDA Drug Label

1 INDICATIONS AND USAGE TRIKAFTA is indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on clinical and/or in vitro data 2 DOSAGE AND ADMINISTRATION 2.2 Recommended Dosage in Adults and Pediatric Patients Aged 2 Years and Older Recommended dosage for adult and pediatric patients aged 2 years and older is provided in Table 1.

The pharmacologic treatment of cystic fibrosis includes:

• Tezacaftor (PO): for patients aged 2 years and older with at least one F508del mutation in the CFTR gene or a responsive mutation, with a recommended dosage provided in Table 1 2
• Tobramycin (INH): for patients with cystic fibrosis, with a dosage of 4 times 28 mg capsules twice-daily 3 3 Key points:
• Tezacaftor is administered orally with fat-containing food, in the morning and in the evening approximately 12 hours apart
• Tobramycin is administered via inhalation, with a treatment cycle of 28 days on-treatment and 28 days off-treatment

From the Research

Pharmacologic Treatment of Cystic Fibrosis

The pharmacologic treatment of cystic fibrosis involves several approaches, including:

• Mucolytics, such as dornase alfa, to decrease sputum viscosity and increase mucociliary clearance 4, 5
• Anti-inflammatories, such as azithromycin, to reduce inflammation in the lungs 4
• Antibiotics, such as tobramycin, to treat pulmonary infections 4, 5
• CFTR modulators, such as ivacaftor and elexacaftor-tezacaftor-ivacaftor, to facilitate CFTR production and/or function 4, 6, 7

CFTR Modulators

CFTR modulators are a class of drugs that target the underlying cause of cystic fibrosis, which is the defective CFTR protein. These drugs work by:

• Correcting the processing and transport of the CFTR protein to the cell surface, such as lumacaftor 6, 7
• Increasing the open probability and transport of chloride through the CFTR channel, such as ivacaftor 6, 7
• Improving lung function and reducing the rate of pulmonary exacerbations 4, 6, 7

Other Therapies

Other pharmacologic therapies that are being explored for the treatment of cystic fibrosis include:

• Gene therapy to directly target the genetic defect 5, 8
• Nano-compounds to enhance drug delivery and target epithelial cells and biofilms 8
• Leukoprotease inhibitors to decrease the acute inflammatory reaction in the lung 5