Coveram 4 mg+5 mg

INDICATIONS

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

PHARMACOLOGY

Perindopril, a pro-drug, is hydrolyzed to perindoprilat, which inhibits ACE in humans and in animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion. The latter results in diuresis and natriuresis and may be associated with an increase in serum potassium Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses.

DOSAGE & ADMINISTRATION

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.

INTERACTION

Baclofen may increase the antihypertensive effect of this combination. Monitor blood pressure and renal function, and adjust the dose of this combination if necessary. Combined use of these medicines may increase the hypotensive effects of perindopril and amlodipine. Combined use with nitroglycerine and other nitrates or other vasodilators, may further reduce blood pressure and therefore should be considered with caution.

SIDE EFFECTS

The most commonly reported adverse reactions with perindopril and amlodipine given separately are: oedema, somnolence, dizziness, headache (especially at the beginning of the treatment), dysgeusia, paraesthesia, visual impairment (including diplopia), tinnitus, vertigo, palpitations, flushing, hypotension (and effects related to hypotension), dyspnoea, cough, abdominal pain, nausea, vomiting, dyspepsia, change of bowel habit, diarrhoea, constipation, pruritus, rash, exanthema, joint swelling (ankle swelling), muscle spasms, fatigue, asthenia.

PREGNANCY & LACTATION

This combination should not be initiated during pregnancy and lactation. Patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with this combination should be stopped immediately, and, if appropriate, alternative treatment should be started.

PRECAUTIONS & WARNINGS

As this combination contains lactose monohydrate, patients with rare hereditary problems of galactose intolerance, glucose galactose malabsorption, or total lactase deficiency should not take This combination.Since ACE inhibitors reduce angiotensin II formation resulting in decreased production of aldosterone, increases in serum potassium have been observed in some patients treated with ACE inhibitors including perindopril. Serum electrolytes (including sodium potassium and urea) should be measured from time to time when ACE inhibitors are given especially in combination with diuretics.

USE IN SPECIAL POPULATIONS

Paediatric use: Use of this combination in children is not recommended as no data establishing safety or effectiveness in children are available.

THERAPEUTIC CLASS

Combined antihypertensive preparations

STORAGE CONDITIONS

Store in a dry place below 25⁰C. Keep the container tightly closed and protect from light.