What medications are used to treat cystic fibrosis?

Medications for Cystic Fibrosis

For patients with cystic fibrosis and at least one F508del or gating mutation, initiate CFTR modulator therapy with elexacaftor-tezacaftor-ivacaftor (or ivacaftor alone for gating mutations), as this represents the most transformative treatment available, improving lung function by 13.8% and reducing pulmonary exacerbations by 63%. 1, 2

CFTR Modulator Therapy (First-Line for Eligible Patients)

For patients with gating mutations (G551D and others):

• Ivacaftor 150 mg twice daily produces a 10.4% improvement in FEV1 and 55% reduction in pulmonary exacerbations 3, 1
• This therapy fundamentally corrects the underlying CFTR protein dysfunction at the cell surface 4

For patients with F508del variants (85.5% of US patients):

• Triple therapy with elexacaftor-tezacaftor-ivacaftor is the standard of care, producing 13.8% improvement in lung function (95% CI: 12.1%-15.4%) and reducing annualized exacerbation rates from 0.98 to 0.37 (rate ratio 0.37; 95% CI: 0.25-0.55) 2
• Benefits persist for at least 144 weeks in postapproval studies 2
• An additional 177 variants are eligible for this combination therapy 2
• This treatment has fundamentally changed disease trajectory, increasing life expectancy and decreasing mortality and lung transplantation rates 4

Critical monitoring for CFTR modulators:

• Monitor for drug interactions via CYP3A4 system 1
• These medications represent a paradigm shift from symptomatic management to addressing the underlying protein defect 5

Inhaled Antibiotics for Pseudomonas Aeruginosa

For patients ≥6 years with moderate-to-severe disease and persistent P. aeruginosa:

• Inhaled tobramycin is strongly recommended: 300 mg twice daily via nebulizer OR 4×28 mg capsules twice daily via Podhaler 3, 1
• This provides substantial improvements in lung function, quality of life, and exacerbation reduction with high certainty of benefit (Grade A recommendation) 3
• Treatment cycles consist of 28 days on-treatment followed by 28 days off-treatment 6

For patients ≥6 years with mild disease and persistent P. aeruginosa:

• Inhaled tobramycin is recommended to reduce exacerbations (Grade B recommendation) 3

Alternative inhaled antibiotic:

• Inhaled aztreonam 75 mg three times daily produces 6.3-10.3% absolute improvement in lung function after 28 days and prolongs time to exacerbation (92 vs 71 days; P=0.002) 1

Mucolytic Agents

For patients ≥6 years with moderate-to-severe disease:

• Dornase alfa is strongly recommended, improving lung function, quality of life, and reducing exacerbations with high certainty of substantial net benefit (Grade A recommendation) 3, 1

For patients ≥6 years with asymptomatic or mild disease:

• Dornase alfa is recommended to improve lung function and reduce exacerbations (Grade B recommendation) 3

Hypertonic saline (7% solution twice daily):

• Recommended for patients ≥6 years, improving lung function and quality of life while reducing exacerbations by 56% compared to normal saline 3, 1
• Pretreat with inhaled bronchodilator to minimize cough or bronchospasm 3
• Level of evidence: fair; net benefit: moderate; Grade B recommendation 3

Anti-Inflammatory Therapy

For patients ≥6 years with persistent P. aeruginosa:

• Azithromycin 250-500 mg once daily or three times weekly is recommended, improving lung function by 3.6-6.2% and reducing exacerbations with high certainty of moderate benefit (Grade B recommendation) 3, 1, 7
• Screen for non-tuberculous mycobacteria before initiating and reevaluate every 6-12 months 7
• Monitor for adverse effects including nausea, diarrhea (occurring in <5% of patients), hearing loss, and cardiac arrhythmias (1.1 cases per 1000 person-years) 7

For patients ≥6 years with FEV1 >60% predicted:

• Oral ibuprofen at high doses (achieving therapeutic serum levels) is recommended to slow loss of lung function 3
• Pharmacokinetic studies must be performed on each individual to ensure appropriate serum levels, as subtherapeutic doses may exacerbate inflammation 3
• Monitor renal function due to concerns about long-term adverse effects 3
• Level of evidence: fair; net benefit: moderate; Grade B recommendation 3

Medications to AVOID

Oral antistaphylococcal antibiotics for prophylaxis:

• Recommended AGAINST due to increased risk of P. aeruginosa acquisition and negative net benefit (Grade D recommendation) 3, 1

Inhaled corticosteroids (without asthma or ABPA):

• Recommended AGAINST for routine use, as seven trials involving 388 patients showed no statistically significant improvement in lung function or exacerbations 3
• Zero net clinical benefit; Grade D recommendation 3

Oral corticosteroids (without asthma or ABPA):

• Strongly recommended AGAINST for chronic use in patients 6-18 years due to adverse effects including growth retardation, cataracts, glucose abnormalities, and increased P. aeruginosa colonization 3
• Level of evidence: good; net benefit: negative; Grade D recommendation 3

Leukotriene modifiers:

• Insufficient evidence to recommend for or against routine use (Grade I recommendation) 3

Cromolyn:

• Insufficient evidence to recommend for or against routine use, with poor quality evidence and virtually no demonstrated benefit (Grade I recommendation) 3

Treatment Sequencing for Multiple Inhaled Therapies

When patients require multiple inhaled medications and chest physiotherapy, administer TOBI Podhaler (or other inhaled tobramycin) LAST 6. This sequencing optimizes drug delivery after airway clearance.

Common Pitfalls to Avoid

• Do not use subtherapeutic doses of ibuprofen, as this may worsen inflammation rather than reduce it 3
• Do not initiate azithromycin without screening for non-tuberculous mycobacteria, as monotherapy can lead to resistance 7
• Do not prescribe CFTR modulators without confirming eligible mutations, as approximately 10% of patients remain ineligible for current modulator therapies 4
• Do not overlook the need for bronchodilator pretreatment before hypertonic saline, as this prevents bronchospasm 3