Brands, Medical Use, Clinical Data
- Angiotensin-Converting Enzyme Inhibitors
- Antihypertensive Agents
Brands / Synonyms
Used in patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction.
Perindopril is indicated in patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction. It can be used with conventional treatment for management of coronary artery disease, such as antiplatelet, antihypertensive or lipid-lowering therapy. It is also indicated for the treatment of patients with essential hypertension. Perindopril belongs to a group of medicines called ACE inhibitors which block the action of a chemical in the body called angiotensin converting enzyme (ACE). Normally ACE produces another chemical, angiotensin. Thus perindopril reduces the amount of angiotensin in the blood. Angiotensin has two actions. Firstly it acts on blood vessels to make them narrow and secondly it acts on the kidney to produce less urine. As perindopril stops the production of angiotensin, these actions are reversed. Therefore more urine is produced by the kidneys, which results in less fluid in the blood vessels. The blood vessels also widen. The overall effect of this is a drop in blood pressure and a decrease in the workload of the heart.
Mechanism of Action
The mechanism through which perindoprilat lowers blood pressure is believed to be primarily inhibition of angiotensin converting enzyme (ACE) activity. ACE is a peptidyl dipeptidase that catalyzes conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion. The latter results in diuresis and natriuresis and may be associated with a small increase of serum potassium.
Biotrnasformation / Drug Metabolism
Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine.
ACEONÒ (perindopril erbumine) Tablets is contraindicated in patients known to be
hypersensitive to this product or to any other ACE inhibitor. ACEONÒ Tablets is also
contraindicated in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
Diuretics: Patients on diuretics, and especially those started recently, may occasionally experience
an excessive reduction of blood pressure after initiation of ACEONÒ Tablets therapy.
The possibility of hypotensive effects can be minimized by either discontinuing the diuretic or increasing the salt
intake prior to initiation of treatment with perindopril. If diuretics cannot be interrupted, close medical
supervision should be provided with the first dose of ACEONÒ Tablets, for at least
two hours and until blood pressure has stabilized for another hour.
The rate and extent of perindopril absorption and elimination are not affected by concomitant diuretics. The
bioavailability of perindoprilat was reduced by diuretics, however, and this was associated with a decrease in plasma
Potassium Supplements and Potassium-Sparing Diuretics: ACEONÒ
Tablets may increase serum potassium because of its potential to decrease aldosterone production. Use of
potassium-sparing diuretics (spironolactone, amiloride, triamterene and others), potassium supplements or other drugs
capable of increasing serum potassium (indomethacin, heparin, cyclosporine and others) can increase the risk of
hyperkalemia. Therefore, if concomitant use of such agents is indicated, they should be given with caution and the
patient's serum potassium should be monitored frequently.
Lithium: Increased serum lithium and symptoms of lithium toxicity have been reported in patients
receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and
frequent monitoring of serum lithium concentration is recommended. Use of a diuretic may further increase the risk of
Digoxin: A controlled pharmacokinetic study has shown no effect on plasma digoxin concentrations
when coadministered with ACEONÒ Tablets, but an effect of digoxin on the plasma
concentration of perindopril/perindoprilat has not been excluded.
Gentamicin: Animal data have suggested the possibility of interaction between perindopril and
gentamicin. However, this has not been investigated in human studies. Coadministration of both drugs should proceed
Food Interaction: Oral administration of ACEONÒ Tablets with food
does not significantly lower the rate or extent of perindopril absorption relative to the fasted state. However, the
extent of biotransformation of perindopril to the active metabolite, perindoprilat, is reduced approximately 43%,
resulting in a reduction in the plasma ACE inhibition curve of approximately 20%, probably clinically insignificant.
In clinical trials, perindopril was generally administered in a non-fasting state.