Olmesan Plus 20 mg+12.5 mg Tablet

Olmesartan Medoxomil & Hydrochlorothiazide combination is indicated for the treatment of hypertension.

Combined antihypertensive preparations

Hydrochlorothiazide inhibits the reabsorption of Na in the distal tubules causing increased excretion of Na and water including K and hydrogen ions.Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Its action is therefore independent of the pathways for angiotensin II synthesis.An AT2 receptor is also found in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Olmesartan has more than a 12,500-fold greater affinity for the AT1 receptor than for the AT2 receptor.​Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is a mechanism of many drugs used to treat hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because olmesartan medoxomil does not inhibit ACE, it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II levels do not overcome the effect of olmesartan on blood pressure.

The usual recommended starting dose of Olmesartan Medoxomil is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose may be increased to 40 mg. No initial dosage adjustment is recommended for elderly patients, for patients with moderate to marked renal impairment (creatinine clearance<40 ml/min) or with moderate to marked hepatic dysfunction.Hydrochlorothiazide is effective in doses between 12.5 mg and 50 mg once daily.Replacement Therapy: Olmesartan & Hydrochlorothiazide may be substituted for its titrated components.Dose Titration by Clinical Effect: The dose of Olmesartan & Hydrochlorothiazide tablet is one tablet once daily. More than one tablet daily is not recommended. Olmesartan & Hydrochlorothiazide tablet may be administered with other antihypertensive agents. A patient whose blood pressure is inadequately controlled by Olmesartan or Hydrochlorothiazide alone may be switched to once daily Olmesartan & Hydrochlorothiazide tablet. Dosing should be individualized. Depending on the blood pressure response, the dose may be titrated at intervals of 2-4 weeks. If blood pressure is not controlled by Olmesartan alone, Hydrochlorothiazide may be added starting with a dose of 12.5 mg and later titrated to 25 mg once daily. If a patient is taking Hydrochlorothiazide, Olmesartan may be added starting with a dose of 20 mg once daily and titrated to 40 mg, for inadequate blood pressure control. If large doses of hydrochlorothiazide have been used as monotherapy and volume depletion or hyponatremia is present, caution should be used when adding Olmesartan or switching to Olmesartan & Hydrochlorothiazide tablet, as marked decreases in blood pressure may occur. Consideration should be given to reducing the dose of Hydrochlorothiazide to 12.5 mg before adding Olmesartan. The antihypertensive effect of Olmesartan & Hydrochlorothiazide is related to the dose of both components over the range of 10 mg/12.5 mg to 40 mg/25 mg

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.

Olmesartan: 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.Hydrochlorothiazide: 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. Lithium.

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 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, diarrhea.

Pregnancy Categories C (first trimester) and D (second and third trimesters). This combination drug should not be used during pregnancy.Lactation: It is not known whether Olmesartan is excreted in human milk, but Olmesartan is secreted at low concentration in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

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.

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.

Store in a cool and dry place, protect from light and moisture. Keep out of the reach of children.

Renal impairment: The usual regimens of therapy with Olmesartan & Hydrochlorothiazide tablet may be followed provided the patient's creatinine clearance>30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so this combination tablet is not recommended.Patients with Hepatic Impairment: No dosage adjustment is necessary with hepatic impairment.Paediatric population: The safety and efficacy of Olmesartan & Hydrochlorothiazide in children and adolescents below 18 years has not been established. No data are available.

Combined antihypertensive preparations

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.

Safety and effectiveness in nursing mother & pregnancy have not been established. The drug should be discontinued during these conditions.

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.