Protace-H

Protace-H tablet is indicated for the treatment of mild to moderate hypertension in patients (in whom combination therapy is appropriate) who have been stabilised on the individual components given in the same proportion.

Ramipril is an angiotensin converting enzyme (ACE) inhibitor, which after hydrolysis to ramiprilat, blocks the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. So, inhibition of ACE by ramipril results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and decreased aldosterone secretion. Thus ramipril exerts its antihypertensive activity. It is also effective in the management of heart failure and reduction of the risk of stroke, myocardial infarction and death from cardiovascular events. It is long acting and well tolerated; so, can be used in long term therapy. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of anangiotensin converting enzyme (ACE) inhibitor tends to reverse the potassium loss associated with these diuretics.

A patient whose blood pressure is not adequately controlled with Ramipril (or another ACE inhibitor) alone or with Hydrochlorothiazide (or another thiazide diuretic) alone may be switched to this combination therapy. The usual starting dose is one tablet once daily. If necessary, the dose may be increased to two tablets once daily.

Ramipril : Concomitant administration with diuretics may lead to serious hypotension and in addition dangerous hyperkalemia with potassium sparing diuretics. Concomitant therapy with lithium may increase the serum lithium concentration. NSAIDs may reduce the antihypertensive effect of Ramipril and cause deterioration of renal function. Hydrochlorothiazide : When administered concurrently, the following drugs may interact with thiazide diuretics: alcohol, barbiturates, or narcotics. Antidiabetic drugs (oral agents and insulin)- dosage adjustment of the antidiabetic drug may be required. Other antihypertensive drugadditive effect or potentiation

This preparation must not be used in patients with hypersensitivity to ramipril, hydrochlorothiazide or other thiazide diuretics. History of hereditary angioneurotic oedema. Severe impairment of renal function. Haemodynamically relevant unilateral or bilateral renal artery stenosis, mitral stenosis, aortic stenosis, and in patients with low blood pressure (hypotensive patients) or in patients with an unstable circulatory situation (haemodynamically unstable patients) where there might be a risk of life-threatening fall in blood pressure and renal failure. Clinically relevant electrolyte disturbances e.g. hypokalemia, hyponatremia or hypercalcemia which may worsen following treatment.

Ramipril can cause profound hypotension and renal impairment and a persistent dry cough. It may also cause angioedema (onset may be delayed), rash (which may be associated with pouritus and urticaria), pancreatitis and upper respiratory-tract symptoms such as sinusitis, and rhinitis. Gastro-intestinal effects reported with ACE inhibitors include nausea, vomiting. dyspepsia, diarrhoea and constipation. Altered liver function tests, cholestatic jaundice and hepatitis have been reported.Blood disorders including thronbocytopenia, leucopenia, neutropenia and haemolytic anaemia have also been reported. Other reported side-effects include headache, dizziness, fatigue, taste disturbance, bronchospasm, fever, and photosensitivity. Hydrochlorothiazide can cause tachycardia, serum sickness, weight loss, maculopapular rash, photosensitivity, flushing and acidosis.

Pregnancy should be excluded before start of treatment with ramipril and avoided during treatment; exposure of the mother to ACE inhibitors in mid or late pregnancy has been associated with oligohydramnios and neonatal hypotension with anuria or renal failure. From animal experiments it is know that use of ramipril may cause a decreased utero-placental perfusion. There is also a potential risk of fetal or postnatal effect as ACE inhibitors also influence the local renin-angiotensin system. In peri-post natal studies increased renal pelvic dilatation was observed in the first generation offspring. However, ramipril was not fetotoxic in studies althoug ACE inhibitors have shown fetotoxicity in some species. Ramipril should not be used during lactation.

This should be used with caution in patients with impaired renal function, hyperkalemia, hypotension, surgery/ anesthesia and impaired hepatic function.

Ramipril: Limited data on human overdosage are available. The most likely clinical manifestations would be symptoms attributable to hypotension. Because the hypotensive effect of Ramipril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat Ramipril overdosage by infusion of normal saline solution. Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia, may accentuate cardiac arrhythmias. The degree to which Hydrochlorothiazide is removed by hemodialysis has not been established.

Store in a cool and dry place, protected from light.