Active ingredient: Perindopril Erbumine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents

Dosage Forms

• Tablet

Brands / Synonyms

Aceon; Perindopril

Indications

Used in patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction.

Pharmacology

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.

Absorption

Rapid

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine.

Contraindications

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.

Drug Interactions

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 ACE inhibition.

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 lithium toxicity.

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 with caution.

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.