What to do about rhinorrhea and cough associated with lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Management of Lisinopril-Induced Rhinorrhea and Cough

If the cough is persistent and troublesome, discontinue lisinopril immediately and switch to an angiotensin receptor blocker (ARB), as this is the only uniformly effective treatment and represents the guideline-recommended first-line alternative with equivalent cardiovascular benefits. 1, 2

Diagnostic Confirmation

Before attributing symptoms to lisinopril, you must systematically exclude other causes:

• Rule out pulmonary edema and other respiratory causes first - the cough should only be attributed to lisinopril after excluding pulmonary congestion, respiratory infections, and other lung pathology 1
• Confirm ACE inhibitor causation by demonstrating that cough resolves within 1-4 weeks after discontinuation (though resolution may take up to 3 months in some patients) and recurs with rechallenge 1
• Recognize the characteristic pattern: dry, non-productive cough with a persistent "tickle" in the back of the throat, typically appearing within the first months of therapy 1

Important caveat: In approximately 30% of patients with confirmed ACE inhibitor-induced cough, the symptom does not recur with rechallenge, suggesting it may have been coincidental 1, 3

Initial Management Decision Algorithm

If Cough is Mild and Tolerable:

• Continue lisinopril - encourage the patient to persist with therapy given the substantial mortality and morbidity benefits of ACE inhibitors in appropriate indications 1
• The cough does not represent serious pathology and many patients can tolerate it when informed of the drug's life-saving benefits 1

If Cough is Persistent and Troublesome (Interfering with Sleep or Quality of Life):

Discontinue lisinopril immediately - this is the only uniformly effective treatment 1, 2

First-Line Alternative: Switch to an ARB

Start an ARB as the definitive replacement therapy:

• Losartan 25-50 mg once daily (initial dose), titrating to 50-100 mg once daily 1, 3
• Candesartan 4-8 mg once daily (initial dose), titrating to 32 mg once daily 1, 3
• Valsartan 20-40 mg twice daily (initial dose), titrating to 160 mg twice daily 1, 3

Rationale: ARBs provide equivalent cardiovascular benefits without inhibiting ACE, thus avoiding bradykinin accumulation (the mechanism responsible for cough), with cough incidence similar to placebo (2-3%) versus 7.9% with ACE inhibitors 2, 3, 4, 5

ARB Implementation Protocol:

1. Check baseline labs: renal function (creatinine) and potassium before starting 2
2. Start with low dose and titrate every 2-4 weeks if blood pressure remains ≥140/90 mmHg and medication is well-tolerated 2
3. Monitor within 1-2 weeks: blood pressure, renal function, and potassium 2, 3
4. Accept intermediate doses if target doses not tolerated - some ARB therapy is better than none 2
5. Expect cough resolution within 1-4 weeks after switching, though may take up to 3 months 3, 6

Critical Safety Warning with ARBs:

Although rare (<1%), angioedema can occur with ARBs in patients who previously experienced angioedema with ACE inhibitors - use extreme caution during initial ARB treatment as cross-reactivity has been reported 1, 2, 3

Alternative Strategy: Pharmacologic Cough Suppression (If ACE Inhibitor Cannot Be Stopped)

If there is a compelling reason to continue lisinopril and the patient refuses to switch:

• Amlodipine 5 mg once daily - demonstrated 61% significant cough reduction in randomized controlled trials 3, 6
• Nifedipine 30 mg daily - showed cough elimination or significant reduction in 51% of patients 3
• Sodium cromoglycate 20 mg capsules 4 times daily - showed reduction in 9/10 patients 1, 3
• Indomethacin 50 mg twice daily for 14 days - eliminated cough in 27% and significantly reduced in 69% of patients 3, 7

However, these suppressive therapies have only fair quality evidence with intermediate benefit and should be considered second-line to ARB substitution 1, 3

Monitoring Parameters After ARB Switch:

• Acceptable creatinine increase: up to 50% above baseline or 266 μmol/L (3 mg/dL), whichever is smaller 2
• Acceptable potassium: up to 5.5 mmol/L 2
• If potassium >5.5 mmol/L: halve ARB dose and recheck within 1-2 weeks 2
• Seek specialist advice if: potassium exceeds 6.0 mmol/L or creatinine increases by >100% 2
• Asymptomatic hypotension: does not require dose adjustment 2

Common Pitfalls to Avoid:

• Do not assume all cough is ACE inhibitor-related without excluding pulmonary edema and respiratory causes 1, 2
• Do not combine ARBs with both ACE inhibitors and aldosterone antagonists - this increases hyperkalemia and renal dysfunction risk 2
• Do not abruptly withdraw renin-angiotensin system inhibition without replacement therapy - clinical deterioration is likely; seek specialist advice before discontinuation 1, 2
• Do not stop concomitant nephrotoxic drugs (NSAIDs) or potassium supplements without first assessing for signs of congestion 1, 2

Special Population Considerations:

Women and certain ethnic groups have higher cough incidence: females experience cough in 37.9% versus 15.5% in males, and Chinese patients have rates approaching 50% versus 5-10% in white patients of European descent 1, 7, 8