Perindopril Can Cause Dry Cough, Not Typically Productive Cough

Perindopril, like other ACE inhibitors, commonly causes cough, but this cough is typically dry rather than productive. 1, 2

Characteristics of ACE Inhibitor-Induced Cough

ACE inhibitor-induced cough is a well-documented class effect that occurs in approximately 5-35% of patients taking these medications 1
The cough is typically dry and is associated with a tickling or scratching sensation in the throat 1, 2
Cough is the most common adverse event leading to discontinuation of perindopril therapy 2, 3
The cough is not dose-dependent and can occur regardless of the dose being administered 1

Women are more likely to experience ACE inhibitor-induced cough than men 1, 4
Nonsmokers have a higher incidence of cough compared to smokers 1
Persons of Chinese origin have increased susceptibility 1
Patients treated for congestive heart failure cough more frequently than those treated for hypertension 1

The cough is believed to be caused by the accumulation of bradykinin and substance P in the upper airway or lung when ACE is inhibited 1, 2
These substances are normally degraded by ACE, and their accumulation may lead to sensitization of airway sensory nerves 1
Prostaglandins, which may be stimulated by bradykinin, may also play a role in the development of cough 1

Cough may occur within hours of the first dose or be delayed for weeks to months after starting therapy 1
The cough typically resolves within 1-4 weeks after discontinuation of the ACE inhibitor 1
In some patients, cough may persist for up to 3 months after stopping the medication 1

If a patient on perindopril presents with cough, the medication should be considered as a potential cause regardless of when the cough started relative to medication initiation 1
The diagnosis is confirmed by resolution of cough after discontinuation of the ACE inhibitor 1
It's important to rule out other causes of cough, especially if the cough is productive rather than dry 1

The only uniformly effective treatment for ACE inhibitor-induced cough is discontinuation of the medication 1
Switching to an angiotensin receptor blocker (ARB) is recommended, as ARBs do not cause cough 1, 5, 6
Some pharmacologic agents have shown limited ability to attenuate ACE inhibitor-induced cough in small studies, including inhaled sodium cromoglycate, theophylline, and certain calcium-channel antagonists 1
In approximately 30% of patients who have experienced ACE inhibitor-induced cough, the cough may not recur if rechallenged with the same medication after a period of discontinuation 1

Cough is the most common clinical adverse event reported with perindopril 3
Less than 2% of perindopril-treated patients discontinue therapy specifically because of cough 3
Some studies suggest that perindopril may have a lower incidence of cough compared to certain other ACE inhibitors like enalapril and captopril 4

If a patient presents with productive cough while on perindopril, other causes should be investigated, as ACE inhibitor-induced cough is typically dry 1
In rare cases, ACE inhibitors including perindopril have been associated with more serious pulmonary adverse effects such as diffuse pneumonitis 7
Treatment with ACE inhibitors may sensitize the cough reflex, potentially exacerbating cough from other causes 1