Generic
Olmesartan Medoxomil + Hydrochlorothiazide
Indications
Olmesartan Medoxomil & Hydrochlorothiazide combination is indicated for the treatment of hypertension.
Pharmacology
Angiotensin-II formed from angiotensin-I in a reaction catalyzed by angiotensin-converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Olmesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin-II by selectively blocking the binding of angiotensin-II to the AT 1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland). In-vitro-binding studies indicate that Olmesartan is a reversible & competitive inhibitor of AT 1 receptor. Olmesartan does not inhibit ACE (kinase-I, the enzyme that converts angiotensin-I to angiotensin-II and degrades bradykinin). Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing the 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 Aldosterone secretion & urinary Potassium loss and decreases serum Potassium. The renin-aldosterone link is mediated by angiotensin-II. So, co-administration of an angiotensin-II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
Dosage Administration
Hypertension: The usual starting dose is 20/12.5 mg one tablet once daily. Dosing should be individualized. Depending on the blood pressure response, the dose may be titrated at intervals of 2-4 weeks to two tablets 40/25 once daily.
Contraindications
Safety and effectiveness in nursing mother & pregnancy have not been established. The drug should be discontinued during these conditions.
Side Effects
Periodic determination of serum electrolytes should be performed at appropriate intervals to detect possible electrolyte imbalance like hypokalemia, hyponatremia and hypochloremic alkalosis. Hyperuricemia may occur in certain patients receiving thiazide therapy. Impaired renal function.
Pregnancy And Lactation
Renal Impairment Patients: The usual regimens of therapy with this may be followed provided the patient's creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides. So, this preparation is not recommended. Hepatic Impairment Patients: No dosage adjustment is necessary with hepatic impairment. Paediatric use: Safety and effectiveness in paediatric patients have not been established. Geriatric use: Clinical studies of Olmesartan and Hydrochlorothiazide combination did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious.
Therapeutic
Olmesartan: Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia. Supportive treatment should be instituted. 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.
Storage Conditions
Olmesartan: Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia. Supportive treatment should be instituted. 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.
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