Angiotensin-converting enzyme or kininase is an exopeptidase allowing the conversion of angiotensin I into angiotensin II, a vasoconstrictor and the breakdown of bradykinin, a vasodilator, into an inactive heptapeptide.

Perindopril acts via its active metabolite, perindoprilat, while the other metabolites are inactive.

Essential Hypertension: The usual effective dose in mild-to-moderate hypertension is 4 mg/day administered as a single dose. The antihypertensive efficacy is maintained throughout the whole 24-hr period. The peak antihypertensive effect is reached within 4-6 hrs after a single dose of perindopril and this efficacy is maintained till the end of the dosage interval. A fall in blood pressure is rapidly obtained; in responding patients, blood pressure control is achieved within 1 month and is maintained without escape. Discontinuation of treatment is not accompanied by a rebound effect. The vasodilator properties and restoration of the elastic qualities of large arterial trunks have been confirmed in man together with a reduction in left ventricular hypertrophy. The addition of a diuretic potentiates the antihypertensive effect.

In animals as in man, perindopril restores large artery elasticity and corrects structural alterations in small arteries.

Coversyl restores normal endothelium-dependent vasodilation in coronary arteries of hypertensive patients.

Congestive Heart Failure: In experimental heart failure induced by coronary artery ligation, perindopril corrects myocardial hypertrophy, corrects the excess subendocardial collagen, restores the isoenzymatic profile of myosin, and decreases the frequency of reperfusion arrhythmias. Perindopril decreases cardiac work (decreased preload and afterload).

Hemodynamic studies in heart failure patients have demonstrated: A decrease in left and right ventricular filling pressures; a decrease in systemic peripheral resistance; a moderate decrease in heart rate; an increase in cardiac output and certain regional blood flows, particularly muscular.

During treatment, a significant improvement is observed in the clinical signs of heart failure, together with increased exercise tolerance, measured either by bicycle ergometer or treadmill.

No significant alteration of blood pressure is observed at the recommended doses both after acute and long-term administration. The maximal variation in systolic and diastolic blood pressure after the 1st dose of perindopril is not significantly different from that observed with placebo.

Similarly, long-term treatment with perindopril does not alter renal function or serum potassium.

Indication Essential hypertension, congestive heart failure.

Dosage In hypertension, the usual therapeutic dose is 4 mg daily in a single oral dose in the morning. It may be increased to a single 8-mg dose, if necessary, after 1 month of treatment.

In congestive heart failure, treatment should begin at a single oral dose of 2 mg in the morning and this may be increased to a single 4-mg dose after 15 days.

Combination with a Diuretic: Stop diuretic therapy at least 3 days before starting treatment with perindopril and re-prescribe it at a later date if necessary; start treatment with perindopril at a dose of 2 mg.

In elderly patients, treatment should be instituted with a dose of 2 mg; and this may be increased to 4 mg if necessary after 1 month of treatment.

In case of renal failure, the dose depends on the creatinine clearance:Between 30 and 60 mL/min: 2 mg daily; between 15 and 30 mL/min: 2 mg every other day; <15 mL/min: 2 mg on dialysis day.

Perindopril should be taken before meal as absorption of food decreases conversion to perindoprilat.

Contraindication Patients with history of hypersensitivity to perindopril. This drug must not be used in children nor during pregnancy and breastfeeding.

Special Precaution Evaluation of patients should include assessment of renal function both prior to initiation of perindopril therapy and during treatment where appropriate.

Renovascular Hypertension: Perindopril can be used when surgery is not indicated or prior to surgery. Treatment should be started with a dose of 2 mg. Renal function of patients with renovascular hypertension should be closely monitored.

Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, perindopril blocks angiotensin II formation, secondary to compensatory renin release. This may lead to hypotension which can be corrected by volume expansion.

Hemodialysis: Anaphylactic-like reactions (edema of the tongue and lips with dyspnea and fall in blood pressure) have been observed during hemodialysis using highly permeable membranes (polyacrylonitrile) in patients treated by ACE inhibitors. This combination should be avoided.

Adverse Reaction The effects reported have been rare and mild. They are usually observed at the start of treatment when blood pressure is still poorly controlled: Headaches, mood and/or sleep disorders, asthenia. Gastrointestinal disorders are fairly nonspecific; disorders of taste, dizziness and cramps have been reported. Localized skin rashes have been observed in a few cases.

As with other ACE inhibitors, angioneurotic edema has been reported, though rarely.

Dry cough is sometimes reported but is not usually troublesome.

With regard to the laboratory parameters, there may be slight fall in hemoglobin, red blood cells and platelets at the start of treatment.

Drug Interaction Drug combinations to be avoided: There is a risk of hyperkalemia if perindopril is given in conjunction with potassium salts or potassium-sparing diuretics, especially in patients with impaired renal function.

If such a combination is absolutely necessary, it should be prescribed with caution and blood potassium must be frequently monitored.

Drug combinations that require special precautions: In some patients who are already receiving diuretic therapy, especially if this treatment has been recently instituted, there may be an excessive fall in blood pressure at the start of treatment with perindopril (see Dosage & Administration).

Drug combinations that may give problems: As for all antihypertensives, concurrent administration of a neuroleptic or imipramine-like antidepressant increases the risk of postural hypotension. Serum lithium concentration may rise during lithium therapy.

Presentation & Packing Tab 2 mg x 30's. 4 mg x 30's.

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