From the Guidelines
Long-term use of perindopril can cause several potential negative effects, including hypotension, kidney function deterioration, hyperkalemia, and rare but serious side effects like angioedema and blood disorders. The most common side effects of perindopril, an ACE inhibitor, are related to its mechanism of action and include hypotension, which can occur especially when treatment is initiated or the dosage is increased 1. Kidney function can deteriorate with long-term use, particularly in patients with pre-existing renal artery stenosis or those taking NSAIDs or diuretics concurrently 1. Hyperkalemia (elevated potassium levels) is another concern, especially in patients with kidney disease or those taking potassium supplements or potassium-sparing diuretics 1. Some patients may experience taste disturbances, headaches, dizziness, and fatigue. Regular monitoring of blood pressure, kidney function, and electrolyte levels is essential during long-term perindopril therapy to detect and manage these potential adverse effects early 1. It is also important to note that ACE inhibitors like perindopril can cause a persistent dry cough in some patients, although this is not the most common side effect associated with perindopril specifically 1. Overall, while perindopril is an effective medication for managing hypertension and heart failure, its potential negative effects must be carefully considered and monitored to ensure the best possible outcomes for patients. Key considerations for minimizing adverse effects include:
- Starting with low doses and titrating upward as needed and tolerated
- Monitoring renal function and electrolyte levels regularly
- Avoiding concurrent use with other medications that may increase the risk of adverse effects, such as NSAIDs or potassium-sparing diuretics
- Being aware of the potential for hypotension, especially in patients with low systemic blood pressure or those who are volume-depleted
- Educating patients about the signs and symptoms of angioedema and the importance of seeking immediate medical attention if they occur.
From the FDA Drug Label
Adverse events that occurred in 1% or greater of the patients and that were more common for perindopril than placebo by at least 1% (regardless of whether they were felt to be related to study drug) are shown in the first two columns below. The most common medical reasons for discontinuation that were more frequent on perindopril than placebo were cough, drug intolerance and hypotension. Body as a Whole: malaise, pain, cold/hot sensation, chills, fluid retention, orthostatic symptoms, anaphylactic reaction, facial edema, angioedema (0. 1%). Gastrointestinal: constipation, dry mouth, dry mucous membrane, appetite increased, gastroenteritis. Respiratory: posterior nasal drip, bronchitis, rhinorrhea, throat disorder, dyspnea, sneezing, epistaxis, hoarseness, pulmonary fibrosis (<0. 1%). Urogenital: vaginitis, kidney stone, flank pain, urinary frequency, urinary retention. Cardiovascular: hypotension, ventricular extrasystole, myocardial infarction, vasodilation, syncope, abnormal conduction, heart murmur, orthostatic hypotension. Potential Adverse Effects Reported with ACE Inhibitors: Other medically important adverse effects reported with other available ACE inhibitors include: cardiac arrest, eosinophilic pneumonitis, neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia, acute renal failure, nephritis, hepatic failure, jaundice (hepatocellular or cholestatic), symptomatic hyponatremia, bullous pemphigoid, pemphigus, acute pancreatitis, falls, psoriasis, exfoliative dermatitis and a syndrome which may include: arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations, a positive ANA, leukocytosis, eosinophilia or an elevated ESR.
The potential negative effects of long-term use of perindopril include:
- Respiratory issues: cough, bronchitis, rhinorrhea, dyspnea
- Cardiovascular problems: hypotension, ventricular extrasystole, myocardial infarction
- Gastrointestinal issues: constipation, dry mouth, gastroenteritis
- Urogenital problems: vaginitis, kidney stone, flank pain, urinary frequency
- Other issues: malaise, pain, fluid retention, orthostatic symptoms, anaphylactic reaction These adverse effects are based on data from U.S. placebo-controlled trials and a double-blind, placebo-controlled study in 12,218 patients with stable coronary artery disease 2 2.
From the Research
Potential Negative Effects of Long-Term Perindopril Use
The potential negative effects of long-term perindopril use can be understood by examining the available evidence from various studies.
- Cough is a common side effect associated with ACE inhibitors, including perindopril, although it is reported that less than 2% of perindopril-treated patients discontinue therapy due to cough 3.
- Other adverse events such as first-dose hypotension and hyperkalemia appear to occur less often with perindopril compared to other ACE inhibitors 3.
- The most frequent complaints reported in long-term trials include cough, headache, asthenia, mood and/or sleep disturbance, and dizziness 4.
- In patients with impaired renal function, perindopril has been found to be safe, with no significant changes in plasma creatinine, creatinine clearance, or kalemia 5.
- Perindopril has been shown to have a favorable safety profile, with no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus 3.
Specific Adverse Effects
Some specific adverse effects associated with long-term perindopril use include:
- Cough (reported in 7.0% of patients) 4
- Headache (reported in 5.6% of patients) 4
- Asthenia (reported in 5.1% of patients) 4
- Mood and/or sleep disturbance (reported in 5.1% of patients) 4
- Dizziness (reported in 3.2% of patients) 4
Patient Populations
The safety and tolerability of perindopril have been evaluated in various patient populations, including: