Generic
Losartan Potassium + Hydrochlorothiazide
Indications
This is indicated for the treatment of hypertension. It is also indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.
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. Losartan and its principal active metabolite block 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 losartan is a reversible, competitive inhibitor of the AT1 receptor. Neither Losartan nor its active metabolite inhibits ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. 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 an angiotensin II receptor antagonist tends to reverse the Potassium loss associated with these diuretics.
Dosage Administration
Hypertension- The usual starting dose of 50/12.5 is one tablet once daily. For patients who do not respond adequately to one tablet the dosage may be increased to 100/25 once daily. A patient whose blood pressure is not adequately controlled with Losartan 100 mg monotherapy may be switched to this combination 100/12.5 once daily. In hypertensive patients with left ventricular hypertrophy initial dose is 50/12.5, if additional blood pressure reduction is needed, 100/12.5 may be given, followed by 100/25 if required. The maximum dose is 100/25 once daily. In general, the antihypertensive effect is attained within three weeks after initiation of therapy. No initial dosage adjustment of 50/12.5 is necessary for elderly patients. But maximum dose of 100/25 once daily dose should not be used as initial therapy in elderly patients. Severe Hypertension: The starting dose for initial treatment of severe hypertension is one tablet of 50/12.5 once daily. For patients who do not respond adequately to this dose after 2 to 4 weeks of therapy, the dosage may be increased to 100/25 once daily. The maximum dose is one tablet of 100/25 once daily.
Side Effects
Losartan Potassium: No significant drug-drug pharmacokinetic interactions have been found in interaction studies with Hydrochlorothiazide, Digoxin, Warfarin, Cimetidine and Phenobarbital. As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g. Spironolactone, Triamterene, Amiloride), potassium supplements, or salt substitutes containing potassium may lead to increase in serum potassium. As with other antihypertensive agents, the antihypertensive effect of Losartan may be blunted by the non-steroidal anti-inflammatory drug Indomethacin. 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 or potentiation. Cholestyramine and colestipol resins: absorption of Hydrochlorothiazide is impaired in the presence of anionic exchange resins
Pregnancy And Lactation
The combination of Losartan 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.
Therapeutic
Angiotensin-II receptor antagonists should be avoided in pregnancy unless essential. They may adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohy dramnios have also been reported. Information on the use of angiotensin-II receptor antagonists in breastfeeding is limited. They are not recommended in breastfeeding and alternative treatment options, with better-established safety information during breastfeeding, are available.
Storage Conditions
Hypersensitivity: Angiooedema Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals Hypokalemia may rarely develop, especially with brisk diuresis, when severe cirrhosis is present, or after prolonged therapy Impaired renal function and Symptomatic hypotension
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