What is the appropriate treatment for a male patient with hypertension, taking Amlodipine (amlodipine) and Hydrochlorothiazide (hydrochlorothiazide), who presents with a two-month history of persistent cough, wheezing, and shortness of breath?

ACE Inhibitor-Induced Cough, Not Antibiotics

This patient's two-month history of persistent cough and wheezing is most likely caused by the ACE inhibitor component of their antihypertensive regimen (if they are on one), not an infection requiring antibiotics. The appropriate treatment is to discontinue the ACE inhibitor and switch to an angiotensin receptor blocker (ARB). 1

Diagnostic Confirmation

• ACE inhibitor-induced cough occurs in 10-20% of patients and typically presents as a dry, persistent cough that can begin within days to weeks after starting the medication. 1
• The diagnosis is confirmed by resolution of cough within 1-4 weeks after discontinuation of the ACE inhibitor, though it may take up to 3 months in some cases. 1, 2
• Antibiotics have no role in treating ACE inhibitor-induced cough, as this is a medication side effect, not an infectious process. 1

Primary Treatment: Switch to an ARB

• Discontinuing the ACE inhibitor is the only uniformly effective treatment, with cough resolution expected within 1-4 weeks. 1, 2
• Switching to an ARB is the Grade A recommendation as first-line alternative therapy, since ARBs do not affect bradykinin metabolism (the cause of ACE inhibitor cough) and have cough rates similar to placebo (2-3% vs 7.9% with ACE inhibitors). 1, 2, 3
• Losartan 25 mg once daily is the most studied ARB for patients with ACE inhibitor-induced cough, with titration to 50 mg daily if needed for blood pressure control. 2
• Alternative ARBs include valsartan or candesartan, with all ARBs having equivalent cough profiles. 2, 3

Alternative Approach: Continue ACE Inhibitor with Cough Suppression

If the ACE inhibitor cannot be discontinued due to compelling indications (such as heart failure or post-MI):

• Amlodipine 5 mg once daily has demonstrated the ability to attenuate ACE inhibitor-induced cough in randomized controlled trials, with 61% of patients showing significant cough reduction. 1, 2
• This patient is already on amlodipine, which may be providing some protective effect but is clearly insufficient. 1
• Hydrochlorothiazide may reduce ACE inhibitor-induced cough in a dose-dependent manner, and this patient is already on this medication. 4

Blood Pressure Management Considerations

• The patient's current regimen of amlodipine and hydrochlorothiazide provides a solid foundation for blood pressure control. 5, 6, 7
• When switching to an ARB, start with losartan 25 mg once daily and monitor blood pressure, renal function, and potassium within 1-2 weeks. 2
• If blood pressure is inadequately controlled on the ARB plus current medications, the dose can be titrated upward. 2
• Triple therapy with an ARB, calcium channel blocker (amlodipine), and thiazide diuretic (hydrochlorothiazide) is a logical and evidence-based approach for patients requiring multiple agents. 6, 7

Monitoring and Follow-up

• Monitor for cough resolution within 1-4 weeks after switching from ACE inhibitor to ARB. 1, 2
• Check blood pressure, renal function, and potassium levels within 1-2 weeks of initiating ARB therapy. 2
• Pay particular attention to postural blood pressure changes in elderly patients. 2
• Although rare, angioedema can occur with ARBs in patients who previously experienced it with ACE inhibitors; use caution during initial treatment. 2

Important Caveats

• Do not use sympathomimetic decongestants for symptomatic cough relief, as these can elevate blood pressure. 8
• If cough persists after 3 months following ACE inhibitor discontinuation, consider alternative diagnoses such as asthma, COPD, or gastroesophageal reflux disease. 1
• Approximately 30% of patients with confirmed ACE inhibitor-induced cough may tolerate a rechallenge after cough resolution, suggesting a repeat trial may be attempted if there are compelling indications. 2