What medications are used to treat cystic fibrosis?

Medications Used in Cystic Fibrosis

The cornerstone medications for CF include CFTR modulators (particularly elexacaftor-tezacaftor-ivacaftor for eligible patients), inhaled antibiotics (tobramycin or aztreonam for Pseudomonas aeruginosa), mucolytics (dornase alfa), and inhaled hypertonic saline, with treatment selection based on specific CFTR mutations, disease severity, and infectious organisms present. 1, 2

CFTR Modulator Therapy (Disease-Modifying Treatment)

First-Line CFTR Modulators

• Elexacaftor-tezacaftor-ivacaftor is the most effective CFTR modulator combination, improving lung function by 13.8% (95% CI: 12.1%-15.4%) and reducing pulmonary exacerbations by 63% (rate ratio 0.37; 95% CI: 0.25-0.55) in patients with at least one F508del mutation 2
• This triple combination is now eligible for approximately 90% of CF patients aged 2 years or older, covering 177 different CFTR variants 2, 3
• Ivacaftor alone (150 mg twice daily) should be used for patients with gating mutations (G551D and others), producing a 10.4% improvement in FEV1 and 55% reduction in pulmonary exacerbations 1

Mutation-Specific Recommendations

• For patients with R117H mutation: ivacaftor is conditionally recommended for adults ≥18 years and children 6-17 years with FEV1 <90% predicted 4
• For patients with two F508del copies: lumacaftor-ivacaftor is strongly recommended for those ≥12 years with FEV1 <90% predicted 4
• Patients with nonsense mutations (W1282X, G542X, R553X) are not currently eligible for standard CFTR modulators and require mutation-specific experimental approaches 5, 6

Inhaled Antibiotics for Pseudomonas Aeruginosa

Strongly Recommended Agents

• Inhaled tobramycin (300 mg twice daily via nebulizer or 4×28 mg capsules twice daily via Podhaler) is the gold standard for patients ≥6 years with moderate-to-severe disease and persistent P. aeruginosa, providing substantial improvements in lung function, quality of life, and exacerbation reduction 1, 7
• Tobramycin should be administered in 28-day on/28-day off cycles 7
• Inhaled aztreonam (75 mg three times daily) is an alternative, producing 6.3-10.3% absolute improvement in FEV1 after 28 days and prolonging time to exacerbation (92 vs 71 days; P=0.002) 1

Administration Sequence

• When multiple inhaled therapies are used, the recommended order is: bronchodilator → hypertonic saline → dornase alfa → airway clearance → inhaled antibiotic 1

Mucolytic Agents

Dornase Alfa (Recombinant Human DNase)

• Strongly recommended for patients ≥6 years with moderate-to-severe disease (Grade A recommendation), improving lung function, quality of life, and reducing exacerbations with high certainty of substantial net benefit 1
• Also recommended for mild disease or asymptomatic patients ≥6 years (Grade B recommendation) to improve lung function and reduce exacerbations 1

Hypertonic Saline

• Inhaled hypertonic saline (7% solution twice daily) is recommended for patients ≥6 years (Grade B recommendation), improving lung function and quality of life while reducing exacerbations by 56% compared to normal saline 1
• Patients should be pretreated with an inhaled bronchodilator to minimize cough and bronchospasm 1

Anti-Inflammatory Therapy

Azithromycin

• Chronic azithromycin (250-500 mg once daily or three times weekly) is recommended for patients ≥6 years with persistent P. aeruginosa (Grade B recommendation), improving lung function and reducing exacerbations with high certainty of moderate benefit 1

Corticosteroids - NOT Recommended

• Inhaled corticosteroids are recommended AGAINST for routine use in CF patients ≥6 years without asthma or ABPA (Grade D recommendation), showing zero net benefit 1
• Oral corticosteroids are recommended AGAINST for chronic use (Grade D recommendation) due to negative net benefit including growth suppression and bone density loss 1

Treatment of Non-Tuberculous Mycobacteria

MAC (Mycobacterium avium Complex)

• Clarithromycin-sensitive MAC requires daily oral triple therapy: azithromycin (preferred over clarithromycin) + rifampin + ethambutol 1
• Add initial intravenous amikacin for: (1) AFB smear-positive samples, (2) cavitation or severe radiological disease, or (3) systemic illness 1
• Never use macrolide monotherapy due to rapid resistance development 1

M. abscessus Complex

• Initial intensive phase: oral macrolide (azithromycin preferred) + IV amikacin + 1-2 additional IV antibiotics (tigecycline, imipenem, cefoxitin) for 3-12 weeks 1
• Continuation phase: oral macrolide + inhaled amikacin + 2-3 oral agents (minocycline, clofazimine, moxifloxacin, linezolid) 1
• Linezolid dosing should be 600 mg once daily (rather than twice daily) to reduce hematological and neurological toxicity 1

Medications to AVOID

Prophylactic Antibiotics

• Oral antistaphylococcal antibiotics for prophylaxis are recommended AGAINST (Grade D recommendation) due to increased risk of P. aeruginosa acquisition and negative net benefit 1

Insufficient Evidence

• Other inhaled antibiotics (carbenicillin, ceftazidime, colistin, gentamicin) have insufficient evidence for routine chronic use 1
• Leukotriene modifiers, N-acetylcysteine, and inhaled glutathione have insufficient evidence for recommendation 1

Critical Monitoring Considerations

• Tobramycin requires monitoring for ototoxicity and nephrotoxicity, particularly with concomitant use of other aminoglycosides, loop diuretics, or nephrotoxic agents 7
• CFTR modulators require monitoring for drug interactions via CYP3A4 system 1
• Baseline and interval testing for drug toxicity is essential for all NTM treatment regimens 1