Which medications are known to cause a dry non‑productive cough?

Medications That Cause Dry Non-Productive Cough

ACE inhibitors are the most important and common pharmaceutical cause of chronic dry cough, occurring in approximately 10-29% of patients, and should be the first medication class considered when evaluating drug-induced cough. 1

Primary Culprits: ACE Inhibitors

Key Characteristics

• All ACE inhibitors cause cough as a class effect with no significant difference between individual agents (captopril, enalapril, lisinopril, ramipril, cilazipril, quinapril) 1, 2, 3
• The cough is characteristically dry, tickling, non-productive, and persistent 1, 2, 3
• Onset is variable: can occur within hours of the first dose or be delayed for weeks to months (even up to a year) after starting therapy 1
• Not dose-related: reducing the dose will not eliminate the cough 1, 3

High-Risk Populations

• Females have significantly higher incidence (37.9% vs 15.5% in males) 4
• Non-smokers are more susceptible than smokers 5
• East Asian/Chinese ethnicity shows increased risk 1, 5
• Patients with heart failure experience higher rates than those treated for hypertension alone 5

Management Algorithm

1. Discontinue the ACE inhibitor immediately - this is the only uniformly effective treatment 1, 5
2. Do not try alternative ACE inhibitors - cough will recur with any agent in this class 1, 3
3. Switch to an angiotensin receptor blocker (ARB) such as valsartan or losartan 5
4. Expect resolution within 1-4 weeks, though it may take up to 3 months in some patients (median 26 days) 1

Mechanism

• ACE inhibitors suppress kininase II activity, leading to accumulation of bradykinin, substance P, and prostaglandins in the upper airway 1, 6, 3
• This causes sensitization of airway sensory C-fibers and increased cough reflex sensitivity 1, 7

Other Medications Causing Dry Cough

Beta-Blockers

• Can cause dry cough with or without bronchospasm 1
• Mechanism involves airway reactivity rather than bradykinin accumulation 1

Inhaled Medications

• Various inhaled therapies can trigger chronic dry cough in the absence of chest imaging abnormalities 1

Immunosuppressants

• Mycophenolate mofetil causes dry cough without radiographic changes 1

Antibiotics

• Nitrofurantoin produces chronic dry cough 1
• Other antibiotics (amphotericin, erythromycin, sulfonamides, aminoglycosides) may cause cough with bronchospasm 1

Anesthetic Agents

• Propofol can cause dry cough 1

Anti-Inflammatory Drugs

• Aspirin and NSAIDs cause bronchospasm with or without cough 1
• Mesalamine (used for inflammatory bowel disease) is a known cause of pulmonary toxicity and cough 1

Other Agents

• Interferon alpha (rare complication in chronic viral gastroenteritis) 1
• Antiretroviral therapy (case reports in HIV-positive patients) 1

Critical Clinical Pitfalls

Common Mistakes to Avoid

• Do not assume timing excludes ACE inhibitors - cough can develop months or even a year after starting therapy 1
• Do not reduce ACE inhibitor dose - the effect is not dose-dependent 1, 5
• Do not switch to another ACE inhibitor - this is futile as it's a class effect 1, 3
• Remember ACE inhibitors sensitize the cough reflex and may potentiate cough from other causes 1

Diagnostic Approach

• Always obtain a complete medication history when evaluating chronic cough 1
• Consider therapeutic withdrawal of suspected medications to confirm diagnosis 1
• Resolution of cough after drug cessation confirms the diagnosis 1

Special Consideration: Indomethacin

• Some evidence suggests indomethacin 50 mg twice daily may reduce ACE inhibitor-induced cough in patients who must continue therapy, though discontinuation remains the definitive treatment 1, 4