Perindopril is a long-acting ACE inhibitor used to treat high blood pressure, heart failure, or stable coronary artery disease in form of perindopril arginine or perindopril erbumine. According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Ageing by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect. However, the dose prescribed to achieve the same effect differs due to different molecular weights for the two forms. A prodrug, perindopril is hydrolyzed to its active metabolite, perindoprilat, in the liver. It was patented in 1980 and approved for medical use in 1988.
Medical uses
Perindopril shares the indications of ACE inhibitors as a class, including essential hypertension, stable coronary artery disease treatment of symptomatic heart disease or heart failure, and diabetic nephropathy. 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 found that perindopril and indapamide combination reduces the risk of stroke in both hypertensive and normotensive individuals with a history of stroke or transient ischemic attack. There is evidence to support the use of perindopril and indapamide combination over ACEI monotherapy to prevent strokes and improve mortality in patients with cardiovascular risk. The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm 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. The study of more than 19 000 patients world-wide 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 and the outcomes of the ASCOT trial paved the way for further research into combination therapy and newer agents.
Contraindications
Children
Pregnancy
Lactation
Situations where a patient has a history of hypersensitivity
Kidney failure
Precautions
Assess kidney function before and during treatment where appropriate.
Renovascular hypertension
Surgery/anesthesia
There is evidence to support that perindopril has key benefits in kidney failure. 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.
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.
Combination with neuroleptics or imipramine-type drugs may increase the blood pressure lowering effect. Serum lithium concentrations may rise during lithium therapy.
Side effects
Side effects are mild, usually at the start of treatment; they include:
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, a thiazide-like diuretic. 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. A preparation of the two drugs is available commercially as Coveram.
Society and culture
Trade names
Also, it is available under the brand names:
Marketing
On 9 July 2014, the European Commission imposed fines of €427,700,000 on Laboratoires Servier and 5 companies which produce generics due to Servier's abuse of their dominant market position, in breach of European UnionCompetition law. Servier's strategy had included acquiring the principal source of generic production of Perindopril and entering into several pay-for-delay agreements with potential generic competitors.
