Perindopril

Perindopril
Systematic (IUPAC) name
(2S,3aS,7aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxopentan-2-yl]amino}propanoyl]-octahydro-1H-indole-2-carboxylic acid
Clinical data
Trade names Coversyl, Coversum, Preterax, Aceon
AHFS/Drugs.com monograph
MedlinePlus a602017
Pregnancy
category
  • US: D (Evidence of risk)
Routes of
administration		 Oral
Legal status
Legal status
Pharmacokinetic data
Bioavailability 24%
Protein binding 20%
Metabolism Renal
Biological half-life 1–17 hours for perindoprilat (active metabolite)
Identifiers
CAS Number 82834-16-0 N
ATC code C09AA04 (WHO)
C09BA04 (WHO) (with diuretics)
C09BB04 (WHO) (with amlodipine)
PubChem CID 107807
IUPHAR/BPS 6367
DrugBank DB00790 YesY
ChemSpider 96956 YesY
UNII 1964X464OJ N
KEGG D03753 YesY
ChEBI CHEBI:8024 YesY
ChEMBL CHEMBL1581 YesY
Chemical data
Formula C19H32N2O5
Molar mass 368.468 g/mol
 NYesY (what is this?)  (verify)

Perindopril is a long-acting ACE inhibitor used to treat high blood pressure, heart failure, or stable coronary artery disease[1] in form of perindopril arginine (trade names include Coversyl, Coversum) or perindopril erbumine (Aceon). According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Aging by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect.[2] However, the dose prescribed to achieve the same effect differs due to different molecular weights for the two forms.

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 and/or revascularization) and treatment of symptomatic heart disease or failure. In addition, the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) found that perindopril reduces the risk of stroke in both hypertensive and nonhypertensive individuals with a history of stroke or transient ischemic attack.[3]

Dosage and administration

For perindopril as treatment for hypertension, the initial dose is 5 mg perindopril arginine (or 4 mg perindopril erbumine) once daily, then the dose may be increased to 10 mg perindopril arginine (or 8 mg perindopril erbumine) after one month of treatment to improve blood pressure control or in case of concomitant stable coronary artery disease.

The Anglo-Scandinavian Cardiac Outcomes Trial showed the benefits of taking the two drugs perindopril and amlodipine together. About 9000 British patients aged 40 to 79 were involved in the five-year trial. Half were given the new drug combination; the rest were given traditional drugs. Perindopril and amlodipine were found to be so effective, the trial was stopped early so all patients could receive the combination.[4][5]

For stable coronary artery disease

A starting dose of 4 mg for two weeks is recommended, then uptitration to 8 mg once daily, depending on acceptability.

For congestive heart disease

Coversyl (perindopril) should be started under close medical supervision at a starting dose of 2 mg. This may be increased to 4 mg once blood pressure acceptability has been demonstrated.

Elderly patients should start treatment at 2 mg daily (2.5 mg daily of perindopril arginine in Australia).

For secondary prevention of stroke

The PROGRESS study recommends a dose of 4 mg daily, optionally supplemented by 2.5 mg-daily indapamide. The reduction of stroke risk seems to be stronger with a combination of the two drugs.[3]

Contraindications

Precautions

Side effects

Side effects are mild, usually at the start of treatment; they include:

Less often

Reversible increases in blood urea and creatinine may be observed. Proteinuria has occurred in some patients. Rarely, angioneurotic edema and decreases in hemoglobin, red cells, and platelets have been reported.

Composition

Each tablet contains 2, 4, or 8 mg of the tert-butylamine salt of perindopril. Perindopril is also available under the trade name Coversyl Plus, containing 4 mg of perindopril combined with 1.25 mg indapamide.

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, has been confirmed in a prospective, observational multicenter trial of 1,250 hypertensive patients.[6] A preparation of the two drugs is available commercially as Coveram.

Also, it is available under the brand names:

References

  1. ↑ Royal Australian College of General Practitioners. "Consumer Medicine Information, GenRx Perindopril" (PDF). Clinical Resources, Medicine information for health professionals.
  2. ↑ Australian Government Department of Health and Ageing (2008). "PBS For Health Professionals". Pharmaceutical Benefits Scheme. Retrieved 2008-09-04.
  3. 1 2 PROGRESS Collaborative Group. "Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack". The Lancet. 2001 Sep 29; 358 (9287): 1033–1041. doi:10.1016/s0140-6736(01)06178-5. PMID 11589932.
  4. ↑ Charlotte Harding (2005). "What you need to know about the new wonder drug cocktail for high blood pressure...". JADN Repository. Retrieved 2007-07-01.
  5. ↑ Linda Brookes (2003). "ASCOT: Anglo-Scandinavian Cardiac Outcomes Trial -- Results From The Lipid-Lowering Arm". Medscape Today. Retrieved 2007-07-01.
  6. ↑ Bahl VK, Jadhav UM, Thacker HP. Management of Hypertension with the Fixed Combination of Perindopril and Amlodipine in Daily Clinical Practice: Results from the STRONG Prospective, Observational, Multicenter Study. American Journal of Cardiovascular Drugs May 22, 2009; 9 (3): 135-42 Link text

Further reading

External links

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