perindopril
ACE inhibitor· Brands: Coversyl, Aceon, PrexumPO
Mechanism of action
Perindopril is a prodrug that is hydrolysed to the active metabolite perindoprilat, which inhibits angiotensin-converting enzyme (ACE). This reduces the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and decreases aldosterone secretion. The result is vasodilation, reduced peripheral resistance, and lowered blood pressure, without reflex tachycardia. It also reduces degradation of bradykinin, which contributes to vasodilation but is also responsible for the common dry cough.
Pharmacokinetics
Perindopril is administered orally and is well absorbed, with a bioavailability of about 65% for the parent compound. It undergoes extensive first-pass hepatic metabolism to form the active metabolite perindoprilat, with a bioavailability of approximately 25%. Peak plasma concentrations of perindoprilat occur 3 to 7 hours after dosing. The effective half-life of perindoprilat is about 30 hours, allowing once-daily dosing. Elimination is predominantly renal, with approximately 75% of a dose excreted in urine as perindoprilat. Renal impairment prolongs the half-life and necessitates dose adjustment.
Indications & dosing
Hypertension
Titrate according to response. Reduce dose in renal impairment.
- adult · PO: 4–8 mg once daily · Titrate according to response. Reduce dose in renal impairment.
Heart failure
Initiate at low dose and titrate as tolerated.
- adult · PO: 2–8 mg once daily · Initiate at low dose and titrate as tolerated.
Stable coronary artery disease
For prevention of cardiovascular events.
- adult · PO: 4–8 mg once daily · For prevention of cardiovascular events.
Contraindications & precautions
- Pregnancy · ACE inhibitors can cause fetal renal damage and death. Discontinue before conception or as soon as pregnancy is detected.
- History of angioedema · Risk of recurrence of angioedema with ACE inhibitor therapy.
- Bilateral renal artery stenosis · Increased risk of renal failure; use with extreme caution.
- Hyperkalaemia · ACE inhibitors reduce aldosterone and can worsen hyperkalaemia.
- Symptomatic hypotension or aortic stenosis · May exacerbate hypotension and reduce coronary perfusion.
- Monitor blood pressure, renal function and serum potassium before and during treatment, especially in patients with renal impairment or on diuretics.
- Avoid in pregnancy; use effective contraception.
- Use with caution in patients with renal artery stenosis, or those with volume depletion, as hypotension may occur.
- Consider starting at a low dose in the elderly or in those with impaired renal function.
- If angioedema occurs, stop immediately and treat appropriately.
- Do not give with potassium-sparing diuretics or potassium supplements unless necessary.
Adverse effects
- Persistent dry cough
- Dizziness/vertigo
- Hypotension, especially first doseserious
- Hyperkalaemiaserious
- Angioedemaserious
- Renal impairment (rise in creatinine)serious
- Headache
- Fatigue
Interactions
- spironolactonemajorUse with caution. Monitor serum potassium and creatinine within 1 to 2 weeks of starting or changing the combination, and regularly thereafter. Avoid in patients with severe renal impairment (eGFR < 30 mL/min) or baseline potassium > 5.0 mmol/L. If combined, use lower doses and consider stopping if potassium rises above 5.5 mmol/L.
- diclofenacmajorAvoid the combination if possible; consider paracetamol or a non-NSAID analgesic. If diclofenac is necessary, use the lowest effective dose for the shortest duration, and monitor blood pressure, serum creatinine, and potassium within a few days of starting, and periodically thereafter.
- ibuprofenmajorAvoid concomitant use where possible. If an NSAID is required, use the lowest effective dose for the shortest duration, and consider paracetamol or alternative analgesia. Monitor blood pressure, serum creatinine, and potassium at baseline and within 1 to 2 weeks after starting or stopping the NSAID, then periodically. Ensure adequate hydration, and exercise caution in elderly patients and those with renal impairment. If hypertension worsens or renal function deteriorates, adjust therapy accordingly.
Renal & hepatic adjustment
- eGFR 60+: No adjustment required; usual dose.
- eGFR 30–59: Initiate at 2.5 mg once daily; maximum 5 mg once daily.
- eGFR 15–29: 2.5 mg once daily on alternate days.
- eGFR 0–15: Avoid; use alternative agent with specialist advice. (avoid)
- Hepatic impairment (severe): No dose adjustment required; use caution as severe hepatic impairment may increase risk of hypotension. Monitor blood pressure and renal function.
Monitoring, pregnancy & toxicity
- Blood pressure · Within 2 weeks of starting or dose change, then regularly
- Serum creatinine and eGFR · Within 1-2 weeks of starting or dose change, then periodically
- Serum potassium · Within 1-2 weeks of starting or dose change, then periodically
- Symptoms of angioedema (facial swelling, difficulty breathing) · Advise patient to report immediately
- Cough (persistent dry cough) · Assess at review
- Pregnancy: Contraindicated during pregnancy, especially in the 2nd and 3rd trimesters. Discontinue if pregnancy is confirmed; use an alternative antihypertensive such as nifedipine or beta-blocker as appropriate.
- Toxicity: Hypotension · IV fluids, vasopressors if needed, monitor blood pressure.
- Toxicity: Hyperkalemia · Stop drug, treat with IV calcium, insulin/glucose, potassium binders; monitor ECG.
- Toxicity: Angioedema · Emergency treatment: airway support, consider epinephrine, antihistamines, corticosteroids; observe for airway compromise.
- Toxicity: Renal dysfunction · Supportive care, maintain renal perfusion, monitor creatinine and potassium.
Clinical notes
Perindopril is indicated for hypertension, heart failure, and to reduce the risk of cardiovascular events in patients with stable coronary artery disease. The usual dose for hypertension is 4 mg once daily, titrated up to 8 mg if needed; an initial dose of 2.5 mg is recommended for the elderly or those with renal impairment. For heart failure, it is typically initiated at 2 mg once daily. Monitor serum potassium, creatinine, and renal function at baseline and periodically, especially in patients with renal impairment. Avoid use in pregnancy and in patients with a history of angioedema. Hyperkalaemia may occur, particularly with concurrent potassium-sparing diuretics or potassium supplements. Common adverse effects include dry cough, dizziness, and headache. Caution with NSAIDs, as they can blunt the antihypertensive effect and increase the risk of renal impairment.
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BNF; local formulary; manufacturer's summary of product characteristics