Perindopril

Overview

Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.[1][2][3] WP

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.[1] WP

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. Perindopril is taken in the form of perindopril arginine/amlodipine or perindopril erbumine. Both forms are therapeutically equivalent and interchangeable. The combination drug of perindopril, amlodipine, and indapamide is on the World Health Organization's List of Essential Medicines.[1][4][5][6] WP

Perindopril should not be used during pregnancy, as it may harm the fetus. Some people may have allergic reactions to perindopril, while common side-effects may include cough, headache, dizziness, diarrhea, or upset stomach.[5] WP

In Australia during 2023-24, it was the fourth-most prescribed drug.[7] WP

Uses, dosage and effects

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][5][8] WP

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. 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. 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.[9–13] WP

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). 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.[5][14][15] WP

Risks and side effects

Precautions

• Assess kidney function before and during treatment where appropriate.[5] WP
• Renovascular hypertension WP
• Surgery/anesthesia WP
• 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. 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. These studies included patients with moderate to severe kidney disease and those on dialysis.[16][17][18] WP
• Its renoprotective benefits of decreasing blood pressure and removing filtration pressure is highlighted in a 2016 review. ACE inhibitor can result in an initial increase of serum creatinine, but mostly returns to baseline in a few weeks in majority of patients. It has been suggested that increased monitoring, especially in advanced kidney failure, will minimise any related risk and improve long-term benefits.[17][19][20] WP
• Use cautiously in patients with sodium or volume depletion due to potential excessive hypotensive effects of renin-angiotensin blockade causing symptomatic hypotension. Careful monitoring or short-term dose reduction of diuretics prior to commencing perindopril is recommended to prevent this potential effect. 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.[8] WP
• Combination with neuroleptics or imipramine-type drugs may increase the blood pressure lowering effect. Serum lithium concentrations may rise during lithium therapy. WP

Side effects

Usually mild at the start of treatment, side effects may include cough, fatigue, headache, nausea, or upset stomach, among other minor effects.[2][5] WP

Legal status

Brand names

Perindopril is available under the following brand names among others:[2][5] WP

• Aceon (with erbumine (tert-Butylamine))[2][5] WP
• Acertil[2][5] WP
• Actiprex[2][5] WP
• Armix[2][5] WP
• Idaprex[2][5] WP
• Coverene[2][5] WP
• Coverex[2][5] WP
• Coversum (with arginine)[2][5] WP
• Coversyl (with arginine)[2][5] WP
• Covinace[2][5] WP
• Indapril[2][5] WP
• Perindo[2][5] WP
• Perineva[2][5] WP
• Prenessa[2][5] WP
• Prestalia[2][5] WP
• Prestarium[2][5] WP
• Preterax[2][5] WP
• Prexanil[2][5] WP
• Prexum[2][5] WP
• Procaptan[2][5] WP
• Provinace[2][5] WP
• Pericard[2][5] WP
• Percarnil[2][5] WP
• Perindal[2][5] WP
• Repres[2][5] WP
• Relika[2][5] WP

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.[21] WP

Chemistry

Formula

C19H32N2O5 PC

CAS number

82834-16-0 PC

Molar mass (g/mol)

368.5 PC

IUPAC name (computed by PubChem)

(2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid PC

SMILES

CCC[C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O PC

InChIKey

IPVQLZZIHOAWMC-QXKUPLGCSA-N PC

PubChem CID

107807

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Perindopril erbumine tablet. 13 March 2024
2. Journal / agency Perindopril. 20 July 2024
3. Other Consumer Medicine Information, GenRx Perindopril
4. Other Fischer J, Ganellin CR. Analogue-based Drug Discovery. 2006
5. Other Perindopril. 24 February 2025
6. Journal / agency The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. 2025. doi:10.2471/B09474
7. Journal / agency Top 10 drugs 2023-24 (Australia). Australian Prescriber. December 2024. doi:10.18773/austprescr.2024.048 · PMID 39777038 · PMC11703566
8. Other Australian Medicines Handbook
9. Journal / agency Netchessova TA, Shepelkevich AP, Gorbat TV. Efficacy of single-pill perindopril/indapamide in patients with hypertension and type 2 diabetes. High Blood Pressure & Cardiovascular Prevention. March 2014. doi:10.1007/s40292-013-0036-x · PMID 24357222
10. Journal / agency Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. 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. September 2007. doi:10.1016/s0140-6736(07)61303-8 · PMID 17765963
11. Journal / agency PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. September 2001. doi:10.1016/s0140-6736(01)06178-5 · PMID 11589932
12. Journal / agency PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chinese Medical Journal. September 1995. PMID 8575241
13. Journal / agency Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ. Treatment of hypertension in patients 80 years of age or older. The New England Journal of Medicine. May 2008. doi:10.1056/NEJMoa0801369 · PMID 18378519
14. Journal / agency Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. 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. September 2005. doi:10.1016/S0140-6736(05)67185-1 · PMID 16154016
15. Other Hypertension clinical information and guidelines
16. Journal / agency Perkovic V, Ninomiya T, Arima H, Gallagher M, Jardine M, Cass A, Neal B, Macmahon S, Chalmers J. 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. October 2007. doi:10.1681/ASN.2007020256 · PMID 17804673
17. Journal / agency Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, Zhao N, Liu L, Lv J, Zhang H, Wang H. 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. May 2016. doi:10.1053/j.ajkd.2015.10.011 · PMID 26597926
18. Journal / agency Liu Y, Ma X, Zheng J, Jia J, Yan T. 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. June 2017. doi:10.1186/s12882-017-0605-7 · PMID 28666408 · PMC5493067
19. Journal / agency Garlo KG, Bates DW, Seger DL, Fiskio JM, Charytan DM. 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. November 2018. doi:10.1001/jamanetworkopen.2018.3874 · PMID 30646338 · PMC6324397
20. Journal / agency Ohkuma T, Jun M, Rodgers A, Cooper ME, Glasziou P, Hamet P, Harrap S, Mancia G, Marre M, Neal B, Perkovic V, Poulter N, Williams B, Zoungas S, Chalmers J, Woodward M. 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. January 2019. doi:10.1161/HYPERTENSIONAHA.118.12060 · PMID 30571562
21. Other Antitrust: Commission fines Servier and five generic companies for curbing entry of cheaper versions of cardiovascular medicine. 9 July 2014

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