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Logo COVERSYL® 4 mg

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

COVERSYL® 4 mg

COMPOSITION:
Each COVERSYL 4 mg tablet contains 4 mg
perindopril, terbutylamine salt.

PHARMACOLOGICAL CLASSIFICATION:
A 7.1.3 Vascular medicines - other hypotensives.

PHARMACOLOGICAL ACTION:
COVERSYL (perindopril) is a specific, non-sulphydryl competitive angiotensin-1 converting enzyme (ACE) inhibitor.
Perindopril acts through its active metabolite, perindoprilat, the other metabolites being pharmacologically inactive.
Following oral administration the absorption of perindopril is rapid (peak concentration within 1 hour), and relatively complete (plasma-availability above 75%). The peak concentration of perindoprilat, the active metabolite, is reached within 3 to 4 hours and peak pharmacological activity is obtained within 4 to 6 hours.
In terms of trough versus peak blood pressure effect, the trough effect ranges between 75 - 100% of peak effect.
Perindopril and perindoprilat both have a low volume of distribution and plasma protein binding is weak. Perindoprilat binds to angiotensin converting enzyme at both plasma and tissue levels.
Apart from active perindoprilat, perindopril gives rise to 5 metabolites all of which are inactive. Perindopril is eliminated in the urine and the half-life of its free fraction is approximately one hour. Breakdown of the bond between perindoprilat and the angiotensin converting enzyme leads to a pharmacodynamic half-life of about 25 hours. Elimination of perindoprilat is slower in the elderly, as well as in patients with cardiac failure or renal failure. In such patients dosage adjustments should be applied in relation to the degree of reduction in creatinine clearance.
Reduction in blood pressure in patients treated with perindopril was accompanied by a reduction in peripheral resistance with no significant changes in heart rate or glomerular filtration rate. An increase in the compliance of large arteries was also observed, suggesting a direct effect on arterial smooth muscle, consistent with the results of animal studies.

INDICATIONS:
COVERSYL is indicated in: Mild to moderate hypertension.
Congestive heart failure not adequately controlled by conventional therapy with diuretics and digitalis and in whom vasodilatation is indicated.

CONTRA-INDICATIONS:
Pregnancy:
The safety during pregnancy has not been established.
Children:
The safety in children has not been established.
Lactation:
The safety of COVERSYL during lactation has not been established.
Hypersensitivity to the product or any of its components.

WARNINGS:
Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and switched to a different medicine.
Should a woman contemplate pregnancy, the doctor should consider alternative medication.
ACE- inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios as well as hypotension, oliguria and anuria in newborns have been reported after administration of ACE-inhibitors in the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur.

DOSAGE AND DIRECTIONS FOR USE:
Mild to moderate hypertension:
The recommended dosage is 4 mg orally taken in the morning before breakfast which can be increased to a single dose of 8 mg if necessary after one month of treatment. The tablets should be taken before meals.
In elderly patients and in cardiac failure substantially lower dosage should be used because of impaired clearance.
Insulin and non-insulin dependent diabetics can be treated with the usual doses.
Congestive heart failure
The treatment should be initiated under close medical supervision. Initial dose of 2 mg orally as a single dose in the morning which may, in most instances, be increased to 4 mg (once blood pressure acceptability has been demonstrated).
Concomitant diuretic therapy in hypertension
Caution is recommended in patients who are currently being treated with diuretics. As the effects of ACE inhibitors may be potentiated in a situation where hypovolemia may occur, the diuretic therapy should be discontinued prior to initiation of therapy with COVERSYL. In the case of combination with a diuretic it is not advisable to prescribe a potassium salt or a potassium sparing agent before assay of blood potassium, and attention should be paid to possible overdosage of the diuretic.
Renal insufficiency
In patients with renal insufficiency, the dosage of perindopril must be adjusted in relation to the severity of the insufficiency. The following dosages may be recommended:
        Creatinine clearance         Recommended dosage
        Between 30 and 60 mL/min         2 mg per day
        Between 15 and 30 mL/min         2 mg every other day
        <15 mL/min         2 mg on day of dialysis
Perindopril is dialysable (70 mL/min).

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The following adverse reactions may occur: headaches, mood and/or sleep disturbances, asthenia, unspecific digestive disorders, dizziness, muscular cramps, localised skin rash, cough, sexual disorders, dry mouth, nausea, diarrhoea, orthostatic effects (including hypotension) and palpitation.
Angioneurotic oedema of the face, extremities, lips, tongue and glottis or larynx has been reported with angiotensin converting enzyme-inhibitors. In such cases COVERSYL should be discontinued and appropriate medical measures taken immediately.
Congestive Heart Failure
Hypotension has been reported in patients commencing treatment with ACE-inhibitors. This usually occurs in patients on multiple or high-dose diuretics with hypovolaemia, hyponatraemia, pre-existing hypotension, patients with unstable cardiac failure, renal impairment, those on highvasodilator therapy, patients aged 70 years and over, dietary salt restriction, dialysis, diarrhoea and vomiting. If hypotension occurs, the patient should be placed in the supine position and if necessary, given an intravenous infusion of normal saline.
Chemical Laboratory Test Findings
A fall in haemoglobin may occur at the start of treatment. A rise in plasma potassium has been reported.
Interactions
The combination of COVERSYL with other antihypertensive agents may increase the antihypertensive effect, especially combined with a diuretic: the effects of ACE inhibitors may be potentiated in a situation where hypovolemia may occur. If this is the case, vascular filling by perfusion of isotonic saline solution should be carried out.
Special populations
Dosage should be adjusted in the elderly and in patients with renal insufficiency. (See DOSAGE AND DIRECTION FOR USE).
Surgery/Anaesthesia
In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, perindopril blocks angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Expected symptoms and signs would be linked to hypotension. Apart from gastric washout, the setting up of an intravenous line for the infusion of isotonic saline solution is recommended. Perindopril is dialysable (70 mL/min). Further treatment is symptomatic and supportive.

IDENTIFICATION:
COVERSYL 4 mg: white barrel-shaped tablets scored on both sides.

PRESENTATION:
In blister packs of 30 and 600 tablets with desiccant.
For State Use: Blister packs of 28 tablets with desiccant.

STORAGE INSTRUCTIONS:
Store below 25°C in a dry place. Keep out of reach of children.

REGISTRATION NUMBER:
X/7.1.3/314

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SERVIER LABORATORIES SOUTH AFRICA (PTY) LTD.
6 Rivonia Gate,
381 Rivonia Boulevard, Rivonia, 2128.

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
May 1999

                840
                01/2002
                CTP
Updated on this site: October 2001
Current: September 2004
Source: Community Pharmacy

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