 | |
 Above: molecular structure of perindopril
Below: 3D representation of a perindopril molecule | |
| Clinical data | |
|---|---|
| Trade names | Coversyl, Coversum, Aceon |
| AHFS/Drugs.com | Perindopril Monograph[1] |
| MedlinePlus | Perindopril |
| License data |
|
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 24% |
| Protein binding | 20% |
| Metabolism | Kidney |
| Elimination half-life | 1–17 hours for perindoprilat (active metabolite) |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.120.843 |
| Chemical and physical data | |
| Formula | C19H32N2O5 |
| Molar mass | 368.474 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.[3][4][5]
As a long-acting ACE inhibitor, perindopril works by inhibiting production of the vasoconstriction hormone, angiotensin, thereby relaxing blood vessels, increasing urine output, and decreasing blood volume, leading to a reduction of blood pressure. It also increases blood renin activity and decreases aldosterone secretion, causing increased urine production and excretion of sodium.[3]
As a prodrug, perindopril is hydrolyzed in the liver to its active metabolite, perindoprilat. It was patented in 1980 and approved for medical use in 1988.[3][6] Perindopril is taken in the form of perindopril arginine/amlodipine or perindopril erbumine.[1] Both forms are therapeutically equivalent and interchangeable.[1][3] The combination perindopril/amlodipine/indapamide is on the World Health Organization's List of Essential Medicines.[7]
Perindopril should not be used during pregnancy, as it may harm the fetus.[1] Some people may have allergic reactions to perindopril, while common side-effects may include cough, headache, dizziness, diarrhea, or upset stomach.[1]
In Australia during 2023-24, it was the fourth-most prescribed drug.[8]
Medical uses
Perindopril shares the indications of ACE inhibitors as a class, including essential hypertension, stable coronary artery disease (reduction of risk of cardiac events in patients with a history of myocardial infarction or revascularization), treatment of symptomatic coronary artery disease or heart failure, and diabetic nephropathy.[1][3][9]
Combination therapy
With indapamide
In combination with indapamide, perindopril has been shown to significantly reduce the progression of chronic kidney disease and renal complications in patients with type 2 diabetes.[10][11] In addition, the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) found that whilst perindopril monotherapy demonstrated no significant benefit in reducing recurrent strokes when compared to placebo, the addition of low dose indapamide to perindopril therapy was associated with larger reductions in both blood pressure lowering and recurrent stroke risk in patients with pre-existing cerebrovascular disease, irrespective of their blood pressure.[12][13] There is evidence to support the use of perindopril and indapamide combination over perindopril monotherapy to prevent strokes and improve mortality in patients with a history of stroke, transient ischaemic attack or other cardiovascular disease.[12][14]
With amlodipine
The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BLA) was a 2005 landmark trial that compared the effects of the established therapy of the combination of atenolol and bendroflumethiazide to the new drug combination of amlodipine and perindopril (trade names Viacoram, AceryCal).[15] The study of more than 19,000 patients worldwide was terminated earlier than anticipated because it clearly demonstrated a statistically significant improvement in mortality and cardiovascular outcomes with the newer treatment. The combination of amlodipine and perindopril remains in the current treatment guidelines for hypertension.[1][16]
Warning and adverse effects
Perindopril may cause death or birth defects of a fetus if taken by the mother during pregnancy.[1][3] It is poisonous in children and is not prescribed for them.[4]
It may cause allergic reactions, and may have adverse effects in people with heart, liver or kidney problems.[1]
Precautions
- Assess kidney function before and during treatment where appropriate.[1]
- Renovascular hypertension
- Surgery/anesthesia
- An analysis on the PROGRESS trial showed that perindopril has key benefits in reducing cardiovascular events by 30% in patients with chronic kidney disease defined as a CrCl <60ml/min.[17] A 2016 and 2017 meta-analysis review looking at ACE inhibitors demonstrated a reduction in cardiovascular events but also slowed the decline of renal failure by 39% when compared to placebo.[18][19] These studies included patients with moderate to severe kidney disease and those on dialysis.
- Its renoprotective benefits of decreasing blood pressure and removing filtration pressure is highlighted in a 2016 review.[18] ACE inhibitor can result in an initial increase of serum creatinine, but mostly returns to baseline in a few weeks in majority of patients.[20] It has been suggested that increased monitoring, especially in advanced kidney failure, will minimise any related risk and improve long-term benefits.[21]
- Use cautiously in patients with sodium or volume depletion due to potential excessive hypotensive effects of renin-angiotensin blockade causing symptomatic hypotension.[9] Careful monitoring or short-term dose reduction of diuretics prior to commencing perindopril is recommended to prevent this potential effect.[9] A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended in combination with perindopril due to the risk of hyperkalaemia.[9]
- Combination with neuroleptics or imipramine-type drugs may increase the blood pressure lowering effect. Serum lithium concentrations may rise during lithium therapy.
Side effects
Usually mild at the start of treatment, side effects may include cough, fatigue, headache, nausea, or upset stomach, among other minor effects.[1][4]
Composition
Each tablet contains 2, 4, or 8 mg of the tert-butylamine salt of perindopril.[1] Perindopril is also available under the trade name Coversyl Plus, containing 4 mg of perindopril combined with 1.25 mg indapamide, a thiazide-like diuretic.[1]
In Australia, each tablet contains 2.5, 5, or 10 mg of perindopril arginine. Perindopril is also available under the trade name Coversyl Plus, containing 5 mg of perindopril arginine combined with 1.25 mg indapamide and Coversyl Plus LD, containing 2.5 mg of perindopril arginine combined with 0.625 mg indapamide.
The efficacy and tolerability of a fixed-dose combination of 4 mg perindopril and 5 mg amlodipine, a calcium channel antagonist, is used.[1][4]
Society and culture
Brand names
Perindopril is available under the following brand names among others:[1][4]
- Aceon (with erbumine (tert-Butylamine))
- Acertil
- Actiprex
- Armix
- Idaprex
- Coverene
- Coverex
- Coversum (with arginine)
- Coversyl (with arginine)
- Covinace
- Indapril
- Perindo
- Perineva
- Prenessa
- Prestalia
- Prestarium
- Preterax
- Prexanil
- Prexum
- Procaptan
- Provinace
- Pericard
- Percarnil
- Perindal
- Repres
- Relika
Marketing
In July 2014, the European Commission imposed fines of €427,700,000 on Laboratoires Servier and five companies which produce generics due to Servier's abuse of their dominant market position, in breach of European Union Competition law. Servier's strategy included acquiring the principal source of generic production of perindopril and entering into several pay-for-delay agreements with potential generic competitors.[22]
References
- ^ a b c d e f g h i j k l m n o "Perindopril". Drugs.com. 24 February 2025. Retrieved 28 March 2025.
- ^ "Regulatory Decision Summary for APO-Perindopril Arginine". Health Canada. 23 October 2014.
- ^ a b c d e f "Perindopril erbumine tablet". DailyMed, US National Library of Medicine. 13 March 2024. Retrieved 28 March 2025.
- ^ a b c d e "Perindopril". MedlinePlus, US National Library of Medicine, US National Institutes of Health. 20 July 2024. Retrieved 28 March 2025.
- ^ "Consumer Medicine Information, GenRx Perindopril" (PDF). Clinical Resources, Medicine information for health professionals. Royal Australian College of General Practitioners. Archived from the original (PDF) on 1 September 2007.
- ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 467. ISBN 978-3-527-60749-5.
- ^ The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. 2025. doi:10.2471/B09474. hdl:10665/382243.
- ^ "Top 10 drugs 2023-24 (Australia)". Australian Prescriber. 47 (6): 194. December 2024. doi:10.18773/austprescr.2024.048. PMC 11703566. PMID 39777038.
- ^ a b c d "Australian Medicines Handbook". amhonline.amh.net.au. Retrieved 10 May 2020.
- ^ Netchessova TA, Shepelkevich AP, Gorbat TV, et al. (NIKA Study Group) (March 2014). "Efficacy of single-pill perindopril/indapamide in patients with hypertension and type 2 diabetes". High Blood Pressure & Cardiovascular Prevention. 21 (1): 63–69. doi:10.1007/s40292-013-0036-x. PMID 24357222. S2CID 20819715.
- ^ Patel A, MacMahon S, Chalmers J, et al. (September 2007). "Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial". Lancet. 370 (9590): 829–840. doi:10.1016/s0140-6736(07)61303-8. PMID 17765963. S2CID 21153924.
- ^ a b PROGRESS Collaborative Group (September 2001). "Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack". Lancet. 358 (9287): 1033–1041. doi:10.1016/s0140-6736(01)06178-5. PMID 11589932. S2CID 10053225.
- ^ PATS Collaborating Group (September 1995). "Post-stroke antihypertensive treatment study. A preliminary result". Chinese Medical Journal. 108 (9): 710–717. PMID 8575241.
- ^ Beckett NS, Peters R, Fletcher AE, et al. (May 2008). "Treatment of hypertension in patients 80 years of age or older". The New England Journal of Medicine. 358 (18): 1887–1898. doi:10.1056/NEJMoa0801369. PMID 18378519.
- ^ Dahlöf B, Sever PS, Poulter NR, et al. (September 2005). "Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial". Lancet. 366 (9489): 895–906. doi:10.1016/S0140-6736(05)67185-1. PMID 16154016. S2CID 26084146.
- ^ "Hypertension clinical information and guidelines". The Heart Foundation. Australia. Archived from the original on 14 May 2020. Retrieved 10 May 2020.
- ^ Perkovic V, Ninomiya T, Arima H, et al. (October 2007). "Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study". Journal of the American Society of Nephrology. 18 (10): 2766–2772. doi:10.1681/ASN.2007020256. PMID 17804673.
- ^ a b Xie X, Liu Y, Perkovic V, et al. (May 2016). "Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials". American Journal of Kidney Diseases. 67 (5): 728–741. doi:10.1053/j.ajkd.2015.10.011. PMID 26597926.
- ^ Liu Y, Ma X, Zheng J, et al. (June 2017). "Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials". BMC Nephrology. 18 (1) 206. doi:10.1186/s12882-017-0605-7. PMC 5493067. PMID 28666408.
- ^ Garlo KG, Bates DW, Seger DL, et al. (November 2018). "Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease". JAMA Network Open. 1 (7): e183874. doi:10.1001/jamanetworkopen.2018.3874. PMC 6324397. PMID 30646338.
- ^ Ohkuma T, Jun M, Rodgers A, et al. (January 2019). "Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus". Hypertension. 73 (1): 84–91. doi:10.1161/HYPERTENSIONAHA.118.12060. hdl:10044/1/66141. PMID 30571562. S2CID 58547523.
- ^ "Antitrust: Commission fines Servier and five generic companies for curbing entry of cheaper versions of cardiovascular medicine". European Commission. 9 July 2014.
Further reading
- Wang JG, Pimenta E, Chwallek F (2014). "Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril". Vascular Health and Risk Management. 10: 189–200. doi:10.2147/VHRM.S59429. PMC 3983078. PMID 24741317.
- Shirley M, McCormack PL (October 2015). "Perindopril/amlodipine (Prestalia(®)): a review in hypertension". American Journal of Cardiovascular Drugs. 15 (5): 363–370. doi:10.1007/s40256-015-0144-1. PMID 26341621. S2CID 40807688.
- Bertrand ME, Vlachopoulos C, Mourad JJ (August 2016). "Triple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine". American Journal of Cardiovascular Drugs. 16 (4): 241–253. doi:10.1007/s40256-016-0175-2. PMID 27256435. S2CID 13318472.
- Ancion A, Tridetti J, Nguyen Trung ML, et al. (December 2019). "A Review of the Role of Bradykinin and Nitric Oxide in the Cardioprotective Action of Angiotensin-Converting Enzyme Inhibitors: Focus on Perindopril". Cardiology and Therapy. 8 (2): 179–191. doi:10.1007/s40119-019-00150-w. PMC 6828891. PMID 31578675.
External links
Media related to Perindopril at Wikimedia Commons
