Covinace

Covinace

perindopril

Manufacturer:

Pharmaniaga Manufacturing Berhad

Distributor:

Pharmaniaga Logistics
Full Prescribing Info
Contents
Perindopril tert-butylamine.
Description
Each tablet contains Perindopril tert-butylamine 8 mg.
Action
Pharmacology: Perindopril is a converting enzyme inhibitor (CEI) of angiotensin I into angiotensin II.
Perindopril acts through its active metabolite perindoprilat and the other metabolites are inactive.
Hypertension: The usual effective dose in mild to moderate hypertension is 4 mg per day given in a single dose. Efficacy is maintained throughout the 24-hour cycle and the peak antihypertensive effect is reached 4 to 6 hours after a single dose of perindopril.
Fall in blood pressure is rapidly obtained and, in responding patients, normal values are reached within 1 month and are maintained without therapeutic escape.
There is no rebound effect on withdrawal of treatment.
In man, perindopril has vasodilator properties, it restores the elastic qualities of the large arteries and reduces left ventricular hypertrophy.
Combination with a diuretic potentiates the antihypertensive effect.
Congestive heart failure: In congestive heart failure, the reduced renal blood flow stimulates the renin-angiotensin system, which at the same time causes: the increased levels of angiotensin II, a very potent vasopressor agent, which impedes cardiac work by increasing peripheral resistance.
increased aldosterone secretion which leads to volume overload due to salt-and-water retention, and results in the same effect.
This causes increased impedance (resistance) to left ventricular ejection flow (afterload), and increased preload (blood volume to be ejected). Heart failure 1 is made worse by the activation of the renin-angiotensin system. By inhibiting the converting enzyme, Perindopril prevents the vicious circle being established, and improves haemodynamic efficiency. But the structural properties of Perindopril on the myocardium itself are essential, since they suggest that early treatment could confer great benefit with regard to protection of myocardial function.
Pharmacokinetics: Perindopril is rapidly and considerably absorbed after oral dosing; peak levels are reached in one hour and the bioavailability is from 65% to 70%. Perindopril is transformed into its active metabolite perindoprilat. The plasma half-life of perindopril is one hour. The degree of biotransformation into perindoprilat is about 20% and peak plasma perindoprilat levels are reached in 3 to 4 hours.
Apart from active perindoprilat, perindopril gives rise to 5 inactive metabolites. Perindoprilat is eliminated in the urine and the half-life of its free fraction is about 3 to 5 hours. The dissociation of the perindoprilat-angiotensin-converting enzyme complex gives an "effective" elimination half-life of 25 hours. Perindoprilat elimination is delayed in elderly subjects and in patients with cardiac and renal failure. The dosage must be adjusted according to the reduction in creatinine clearance.
The dialysis clearance of perindopril is 70 mL/min.
Indications/Uses
Hypertension. Congestive heart failure.
Dosage/Direction for Use
Hypertension: The recommended dosage is 4 mg in a single oral dose in the morning. This may be increased to a single 8 mg dose, if necessary, after 1 month of treatment.
In the elderly patient, treatment should be instituted with a single oral dose of 2 mg in the morning and this maybe increased to 4 mg if necessary after 1 month of treatment.
Congestive heart failure: Treatment should begin at a single oral dose of 2 mg in the morning and this maybe increased to a single 4 mg dose after 15 days.
Overdosage
No cases of overdosage have so far been reported, though the expected signs and symptoms are those related to hypotension.
Apart from gastric lavage, a venous line should rapidly be inserted for infusion with isotonic saline. Perindopril is dialysable (70 mL/min).
Contraindications
Use in Pregnancy: Perindopril is contraindicated in pregnant mothers. When used during the second and third trimesters of pregnancy, perindopril can cause injury and even death to the developing foetus. When pregnancy is detected, perindopril should be discontinued as soon as possible.
INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL MORBIDITY AND DEATH WHEN USED THROUGHOUT PREGNANCY.
Use in lactation: There is little passage into maternal milk in the experimental animal. No data are available in humans.
Use in Children: As no paediatric studies have been carried out, perindopril is contraindicated in the child.
Warnings
INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL MORBIDITY AND DEATH WHEN USED THROUGHOUT PREGNANCY.
Risk of arterial hypotension and/or renal failure: considerable water and sodium depletion (strict sodium-free diet and/or diuretic treatment) or stenosis of the renal arteries causing a stimulation of the renin-angiotensin system. The blocking of this system by a converting enzyme inhibitor may then induce, in particular after the first dose and during the first two weeks of treatment, a precipitous fall in blood pressure and/or although more rarely and after a variable time, sometimes acute functional renal failure.
On institution of treatment in these specific situations, the following recommendations must be respected: In hypertension previously treated with a diuretic: The diuretic should be withdrawn at least 3 days before institution of perindopril and reinstituted later if necessary; If this is impossible, therapy should be instituted at an initial dose of 2 mg.
In renovascular hypertension, a low initial dose of 2 mg should be used (see Precautions).
Plasma creatinine should be assayed before treatment and during the month following institution of treatment.
Special Precautions
Renal failure: In the renal failure, the dosage of perindopril must be adjusted according to the degree of renal insufficiency.
In these patients, normal medical practice involves periodic testing of blood potassium and creatinine.
The recommended dosages are as follows: (See table.)

Click on icon to see table/diagram/image

Renovascular hypertension: The correct treatment for renovascular hypertension is revascularization.
Nevertheless, perindopril may be use in patients presenting renovascular hypertension and awaiting corrective surgery or when surgery is impossible. Treatment must then be instituted with care (see Warnings) and renal function must be continually monitored.
Therapy during anaesthesia: In cases of anaesthesia for major surgery, or during anaesthesia achieved with potentially hypotensive agents, perindopril may induce hypotension which must be corrected by increasing blood volume.
Use in Elderly: Treatment should be instituted at the dosage of 2 mg per day in a single dose and renal function must be evaluated before starting treatment.
Use In Pregnancy & Lactation
Pregnancy: Perindopril is contraindicated in pregnant mothers. When used during the second and third trimesters of pregnancy, perindopril can cause injury and even death to the developing foetus. When pregnancy is detected, Perindopril should be discontinued as soon as possible.
INCREASED RISK OF BIRTH DEFECTS, FOETAL AND NEONATAL MORBIDITY AND DEATH WHEN USED THROUGHOUT PREGNANCY.
Breast-feeding: There is little passage into maternal milk in the experimental animal. No data are available in humans.
Adverse Reactions
Reported side effects are rare and benign. The most frequent complaints were often reported at the start of treatment, when blood pressure was poorly controlled: headaches, mood and/or sleep disturbances, asthenia.
Non-specific gastrointestinal disorders, such as taste disturbances, dizziness and cramps have been reported. Several localised skin rashes were also noted. A non-productive, irritating, dry cough were sometimes observed, though this caused little discomfort. Several other relatively non-specific side effects were often reported during multiple-agent therapy: sexual disorders, dryness of the mouth.
As far as the laboratory findings are concerned, a very slight reduction in haemoglobin was sometimes observed at the start of treatment. A slight increase in blood potassium levels, which returned to normal on combination with a hypokalemia diuretic, has been reported. Elevated blood urea and creatinine, reversible on interruption of treatment, was also observed.
Drug Interactions
Inadvisable combinations: The combination of perindopril with potassium supplements or potassium-sparing diuretics may induced hyperkalemia in particular in renal failure. Converting enzyme inhibitors must not be combined with hyperkalemia drugs except in the case of hypokalemia.
If this combination is nevertheless required, it must be prescribed with care and in particular with frequent monitoring of the blood potassium levels.
Combinations justifying a warning: In certain patients already receiving a diuretic drug, and in particular if this treatment was instituted recently, there may be a severe initial fall in blood pressure at the start of perindopril treatment.
The risk of symptomatic hypotension may be reduced by withdrawing the diuretic several days before institution of perindopril therapy.
Combinations to be taken into account: As with all antihypertensive drugs, combination with a neuroleptic or a tricyclic antidepressant increases the risk of orthostatic hypotension.
Storage
Store below 30°C.
Protect from light.
MIMS Class
ACE Inhibitors/Direct Renin Inhibitors
ATC Classification
C09AA04 - perindopril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.
Presentation/Packing
Tab 4 mg (white to off-white, oblong) x 3 x 10's. 8 mg (white to off white, round biconvex with intersected breakline on one side and plain on the other) x 3 x 10's.
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