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 AT1 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 AT1 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 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.
Each film coated tablet contains Olmesartan Medoxomil 20 mg and Hydrochlorothiazide 12.5 mg.
Hypertension- The usual starting dose of Sevitan-HTZ 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. Patients with Renal Impairment- The usual regimens of therapy with Sevitan-HTZ may be followed provided the patients creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides. So, Sevitan-HTZ is not recommended. Patients with Hepatic Impairment- No dosage adjustment is necessary with hepatic impairment.
The common side-effects are nausea, headache, dizziness, hyperuricemia, upper respiratory tract infection and urinary tract infection. Other adverse effects are chest pain, back pain, peripheral edema, abdominal pain, dyspepsia, gastroenteritis, and diarrhea.
The combination of Olmesartan and Hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product. Because of the Hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
The drug should be discontinued during these conditions.
No significant drug interactions were reported in studies in which Olmesartan Medoxomil was co-administered with hydrochlorothiazide, digoxin or warfarin in healthy volunteers. Olmesartan Medoxomil is not metabolized by the cytochrome P450 system and has no effects on P450 enzymes; thus, interactions with drugs that inhibit, induce or are metabolized by those enzymes are not expected.
When administered concurrently, the following drugs may interact with Thiazide diuretics:
• Alcohol, Barbiturates or Narcotics - Potentiation of orthostatic hypotension may occur
• Antidiabetic drugs (oral agents and Insulin) - Dosage adjustment of the antidiabetic drug may be required
• Other antihypertensive drugs - Additive effect
• Corticosteroids, ACTH
Limited data are available in regard to over dosage in humans. The most likely manifestation of over dosage would be hypotension and tachycardia. Supportive treatment should be instituted.
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
Store in a cool and dry place, protect from light and moisture.
Keep out of the reach of children.
Each box contains 6 Alu-Alu blister packs of 7 film coated tablets.