Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE).

• Hypertension: Treatment of arterial hypertension
• Heart failure: Treatment of congestive heart failure
• Reduction of risk of cardiovascular events in patients with stable coronary artery disease, in addition to other preventive medications.
• Combination with indapamide for prevention of stroke recurrence in patients with previous stroke or transient ischaemic attack (secondary stroke prevention).

Posology and method of administration
It is recommended that COVRIX tablet is taken once daily in the orning before a meal.

Hypertension
COVRIX tablet may be used in monotherapy or in combination with other classes of antihypertensive therapy.

The recommended starting dose is 4 mg given once daily in the morning.

Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt and/or volume depletion, cardiac decompensation or severe hypertension) may experience an excessive drop in blood pressure following theinitial dose. A starting dose of 2 mg is recommended in such patients and the initiation of
treatment should take place under medical supervision. The dose may be increased to 8 mg once daily after one month of treatment.

Symptomatic hypotension may occur following initiation of therapy with COVRIX tablet; this is more likely in patients who are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume and/or salt depleted.

If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with COVRIX tablet.

In hypertensive patients in whom the diuretic cannot be discontinued, therapy with COVRIX tablet should be initiated with a 2 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of COVRIX tablet should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed.
In elderly patients treatment should be initiated at a dose of 2 mg which may be progressively increased to 4 mg after one month then to 8 mg if necessary depending on renal function.

Symptomatic heart failure
It is recommended that COVRIX 2 mg tablet, generally associated with a non-potassiumsparing diuretic and/or digoxin and/or a beta blocker, be introduced under close medical supervision with a recommended starting dose of COVRIX 2 mg tablet taken in the morning. This dose may be increased by increments of 2 mg at intervals of no less than 2
weeks to 4 mg once daily if tolerated. The dose adjustment should be based on the clinical response of the individual patient.

In severe heart failure and in other patients considered to be at high risk (patients with impaired renal function and a tendency to have electrolyte disturbances, patients receiving simultaneous treatment with diuretics and/or treatments with vasodilating agents), treatment should be initiated under careful supervision

Patients at high risk of symptomatic hypotension e.g. patients with salt depletion with or without hyponatraemia, patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy should have these conditions corrected, if possible, prior to therapy with COVRIX tablets. Blood pressure, renal function and serum potassium should be monitored closely, both before and during treatment with COVRIX tablet.

For prevention of stroke recurrence: In patients with a history of cerebrovascular disease, COVRIX should be introduced at a dose of 2 mg daily for two weeks, then increased to 4 mg daily for a further 2 weeks, before introducing indapamide. Treatment can be initiated at any time from 2 weeks up to several years after the initial stroke episode.

For reduction of risk of cardiovascular events:In patients with stable coronary artery disease, COVRIX should be introduced at a dose of 4 mg once daily for two weeks in addition to other preventive medications, then increased to 8 mg once daily, depending on renal function.
Elderly patients should receive COVRIX 2 mg once daily for one week, then 4 mg once daily the next week, before increasing the dose up to 8 mg once daily depending on renal function.

Dosage adjustment in renal impairment
Dosage in patient with renal impairment should be based on creatine clearance as outlined
in table 1 below:
Table 1 : dosage adjustment in renal impairment
Creatine clearance (ml/min) Recommended dose
ClCR > 60 4 mg per day
30 < ClCR < 60 2 mg per day
15 < ClCR < 30 2 mg every other day
Haemodialysed patients *, ClCR < 15 2 mg on the day of dialysis
* Dialysis clearance of perindoprilate is 70 ml/min. For patients on haemodialysis, the
dose should be taken after dialysis.

Paediatric use
Use in children is not recommended.

Contraindications

• Unilateral and bilateral renal artery stenosis;
• Hypersensitivity to perindopril, to any of the excipients or to any other ACE inhibitor;
• History of angioedema associated with previous ACE inhibitor therapy;
• Hereditary or idiopathic angioedema;
• Second and third trimesters of pregnancy

Special warning and precautions for use
Anaphylactic reactions can occur. Angioedema can occur (potentially affecting the airway,presenting with abdominal pain). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume depleted patients).
Dry coughing may arise, so immediately tell your doctor to assess whether treatment should be interrupted. Allergic reactions and oedemas may appear in the face. In case of patients under haemodialysis: tell your doctor. As this medicine contains lactose, it should not be administered in case of galactosemia, glucose malabsorption syndrome or lactase deficiency (rare metabolic disorders).

Tell your doctor in case of:

• renal or heart failure, diabetes, altherosclerosis,
• hypotension or salt-free diets.

In case of surgery, tell your anaesthetist.

Driving and using machines
Take special care if driving or using machines because vertigo sensations may appear.

Possible side effects

• cough, pharyngitis, sinusitis, rhinitis, insomnia, depression, muscular pain, joint pain,arthritis, upper extremity pain, lower extremity pain, headache, fatigue, vertigo,digestive disorders, taste disorders;
• Biological test alterations:
  - weak reduction of haemoglobin, agranulocytosis;
  - weak increase in potassium plasma levels;
  - increases in blood urea, plasma creatinine and triglycerides.
  In case of persistent disturbance, ask your doctor.
• Stop taking this medicinal product and immediately ask your doctor in any of the following situations : swollen face, lips, tongue or larynx leading to difficulties in breathing or swallowing.

Storage condition : Store below 25° C

Manufacturer: Laboratorios Liconsa, S.A.Guadalajara, SPAIN
Imported by : Sinensix Pharma (Thailand) Co., Ltd. Bangkok, Thailand