This combination is indicated as substitution therapy for the treatment of hypertension and/or stable coronary artery disease in patients who are already controlled on separate doses of perindopril and amlodipine administered concurrently at the same dose level. Treatment should not be initiated with this fixed combination.

Perindopril is a prodrug that is converted in the body to its active metabolite perindoprilat, which inhibits angiotensin-converting enzyme (ACE). ACE catalyzes the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Angiotensin II also stimulates aldosterone secretion from the adrenal cortex and regulates renin release through negative feedback. ACE inhibition reduces angiotensin II levels, leading to decreased vasoconstriction, increased plasma renin activity, and reduced aldosterone secretion. This results in increased sodium and water excretion (natriuresis and diuresis) and may cause a rise in serum potassium.

Amlodipine is a dihydropyridine calcium channel blocker that inhibits calcium ion entry through L-type calcium channels in vascular smooth muscle and cardiac muscle. Calcium influx is essential for muscle contraction; therefore, blocking these channels leads to relaxation of vascular smooth muscle.Amlodipine has a greater effect on vascular smooth muscle than on cardiac muscle. Although mild negative inotropic effects may be observed in vitro, they are not seen at therapeutic doses in vivo.

perindopril arginine & amlodipine is as substitution therapy for patients already controlled with separate doses of perindopril (5 or 10 mg) and amlodipine (5 or 10 mg), given concurrently at the dose level. Treatment should not be initiated with this combination.

Food intake may reduce hepatic biotransformation of perindopril to perindoprilat. Recommended treatment is one tablet per day as a single dose, preferably to be taken in the morning and before a meal. As perindopril and amlodipine may be used for different clinical indications, dose adjustments should be based on clinical judgment and the individual patient profile.

Adjustments can be made by decreasing or increasing the dose of either perindopril and/or amlodipine using separate perindopril and/or amlodipine products within the recommended dose range until clinical stability is re-established. Consult the Product Information of the individual perindopril and/or amlodipine products being used when adjusting the dose.

In the event that down-titration is required, adjustments using amlodipine 2.5 mg or a dose of perindopril equivalent to perindopril arginine 2.5 mg, as separate products should be considered until clinical stability is re-established.

Baclofen may enhance the antihypertensive effect of this combination. Blood pressure and renal function should be monitored, and dose adjustment may be required. Concomitant use may increase the hypotensive effects of perindopril and amlodipine. Co-administration with nitroglycerin, other nitrates, or other vasodilators may further lower blood pressure and should therefore be used with caution.

This combination is contraindicated

• in patients with a history of hypersensitivity to perindopril, amlodipine, other ACE inhibitors, dihydropyridines, or any excipients in the formulation.
• It is also contraindicated during pregnancy and lactation.

Common adverse effects include oedema, drowsiness, dizziness, headache (especially at the start of therapy), taste disturbance, paraesthesia, visual disturbances (including double vision), tinnitus, vertigo, palpitations, flushing, hypotension, dyspnoea, cough, abdominal pain, nausea, vomiting, dyspepsia, changes in bowel habits, diarrhoea, constipation, itching, rash, joint swelling (especially ankle swelling), muscle cramps, fatigue, and weakness.

This combination should not be initiated during pregnancy or lactation. Patients planning pregnancy should be switched to alternative antihypertensive medicines with established safety profiles in pregnancy. If pregnancy is confirmed, this treatment should be discontinued immediately and alternative therapy started if necessary.

This medicine contains lactose monohydrate; therefore, patients with rare hereditary problems such as galactose intolerance, glucose-galactose malabsorption, or lactase deficiency should avoid it.

ACE inhibitors may increase serum potassium due to reduced aldosterone production. Therefore, regular monitoring of serum electrolytes (sodium, potassium, and urea) is recommended, especially when used with diuretics.

Paediatric use: This combination is not recommended for children as safety and efficacy data are not established.

Combined antihypertensive preparations

Store in a dry place below 25°C. Keep the container tightly closed and protect from light.