Perindopril is an oral ACE inhibitor used to treat high blood pressure and heart failure. It works by relaxing blood vessels, lowering blood pressure, and reducing strain on the heart. It is a prodrug converted in the liver to its active form, perindoprilat. Perindopril helps prevent heart attacks and strokes in patients with cardiovascular diseases risk. Perindopril is approved by major regulatory agencies like the FDA and EMA for treating hypertension, heart failure, and preventing cardiovascular events. It is available as both brand-name and generic forms worldwide after demonstrating safety and efficacy through clinical trials. Post-approval, ongoing monitoring ensures patient safety.
BRAND NAMES
Coversyl: Coversyl (Perindopril) is used for hypertension and heart failure, typically started at 4 mg once daily, with a maximum dose of 8 mg.
Aceon: Aceon (Perindopril) treats high blood pressure and heart disease, starting at 4 mg once daily, up to 8 mg max, with dose adjustments for kidney issues.
MECHANISM OF ACTION
Perindopril is a prodrug that is converted into its active form, perindoprilat, which inhibits the angiotensin-converting enzyme (ACE). Normally, ACE converts angiotensin I into angiotensin II, a powerful vasoconstrictor that tightens blood vessels and raises blood pressure. By blocking this process, perindopril lowers angiotensin II levels, leading to the relaxation and widening of blood vessels, thereby reducing blood pressure. It also lowers aldosterone secretion, which decreases sodium and water retention, reducing blood volume and further lowering blood pressure. Together, these effects lessen the heart’s workload and enhance blood flow, making perindopril effective for treating hypertension, heart failure, and preventing cardiovascular complications.
PHARMACOKINETICS
Absorption: Perindopril is well absorbed from the gastrointestinal tract after oral administration, with an absolute bioavailability of about 20–30%. Food does not significantly affect its absorption.
Distribution: Perindopril is moderately bound to plasma proteins (about 20%) and distributes widely into body tissues.
Metabolism: Perindopril itself is metabolized in the liver to perindopril; no other significant metabolites are formed.
Elimination Half-Life: The half-life of perindopril at ranges from about 3 to 10 hours, allowing for once-daily dosing. Approximately 50% of the administered dose is excreted unchanged in the urine, with the remainder eliminated as metabolites.
DOSAGE AND ADMINISTRATION
Perindopril is typically initiated at 4 mg once daily, with the dose adjusted between 4 to 8 mg daily based on patient response and tolerance; it is taken orally, with or without food, preferably in the morning, and requires careful dose adjustments and monitoring in elderly patients, those with kidney impairment, or patients at risk of low blood pressure.
DRUG INTERACTIONS
- Potassium-sparing diuretics and potassium supplements: increase risk of hyperkalemia (high potassium).
- Diuretics (especially loop and thiazide): may cause excessive blood pressure lowering or low sodium.
- NSAIDs (e.g., ibuprofen): can reduce the blood pressure-lowering effect and may worsen kidney function.
- Other antihypertensives: additive blood pressure lowering effects.
- Lithium: risk of lithium toxicity increases.
- Aliskiren (direct renin inhibitor): increased risk of kidney problems and hyperkalemia, especially in diabetic patients.
- Potassium-sparing diuretics (spironolactone, eplerenone): increased risk of hyperkalemia.
CONTRAINDICATIONS
- History of angioedema related to previous ACE inhibitor therapy
- Hypersensitivity to perindopril or any ACE inhibitor
- Hereditary or idiopathic angioedema
- Pregnancy (especially second and third trimesters)
- Severe renal impairment or patients with bilateral renal artery stenosis
- Use with aliskiren in patients with diabetes or renal impairment
SIDE EFFETCS
Common Side Effects:
- Cough – dry, persistent (due to bradykinin accumulation)
- Dizziness – especially on standing (postural hypotension)
- Headache
- Fatigue
- Nausea or gastrointestinal discomfort
- Taste disturbances (metallic or reduced taste)
- Skin rash or itching
Serious Side Effects:
- Angioedema – swelling of face, lips, throat (medical emergency)
- Hyperkalemia – high potassium levels (may cause heart issues)
- Hypotension – especially after the first dose
- Kidney dysfunction – increased serum creatinine or acute renal failure
- Liver enzyme elevations or hepatitis (rare)
- Neutropenia or agranulocytosis (very rare, especially in patients with autoimmune disease)
TOXICITY
- Symptoms of Overdose:
- Severe hypotension
- Dizziness, fainting
- Bradycardia or tachycardia
- Electrolyte disturbances (especially hyperkalemia)
- Renal failure
- Circulatory shock (in severe cases)
- Toxic Dose:
Exact toxic dose is not well-defined, but large overdoses can cause life-threatening hypotension and renal impairment.
- Management:
- Supportive care (monitor BP, electrolytes, renal function)
- IV fluids to treat hypotension
- Vasopressors if needed
- Hemodialysis is not effective in removing perindoprilat, but may help in managing renal failure or electrolyte imbalance
- Monitor for angioedema, especially airway compromise
