Coveram

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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.

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This combination is contraindicated: In patients with a history of previous hypersensitivity to either of the active ingredients; perindopril or amlodipine, ACE inhibitors, dihydropyridines or excipient ingredients present in this combination. During pregnancy and for lactating women.

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.

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.

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.

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.

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.

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