Generic

Losartan Potassium + Hydrochlorothiazide

Indications

Hypertension

Losacor® (Loasartan) and Losacor® plus (Losartan & Hydrochlorothiazide) are indicated for the treatment of hypertension. Losacor® may be used alone or in combination with other antihypertensive agents. Type 2 Diabetic Patients with Proteinuria and Hypertension Losacor ® is also indicated to delay the progression of renal disease, end stage renal disease, and to reduce proteinuria. Hypertensive Patients with Left Venticular Hypertrophy Losacor ® plus is indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.

Pharmacology

Angiotensin II is formed by angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE). It is an effective vasoconstrictor and the main vasoactive hormone of the renin-angiotensin system. It is also the pathology of hypertension. An important part of physiology. It also stimulates the adrenal cortex to secrete aldosterone. Losartan and its main active metabolite block the vasoconstriction and aldosterone secretion of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptors in many tissues (such as vascular smooth muscle, adrenal glands). In vitro binding studies have shown that Losartan is a reversible competitive inhibitor of AT1 receptor. Neither losartan nor its active metabolite inhibits ACE (kinase II, an enzyme that converts angiotensin I to angiotensin II and breaks down bradykinin); nor does it bind or block other known cardiovascular regulation Very important hormone receptors or ion channels.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the mechanism of renal tubular electrolyte reabsorption and directly increase the excretion of approximately the same amount of sodium and chlorine. Indirectly, the diuretic effect of hydrochlorothiazide reduces plasma volume, leading to increased plasma renin activity, increased aldosterone secretion, increased urinary potassium loss, and decreased serum potassium. Renal aldosterone binding is mediated by angiotensin II, so co-administration of angiotensin II receptor antagonists tends to reverse the potassium loss associated with these diuretics.

Dosage & Administration

Hypertension

The usual starting dose of losartan is 50 mg once daily, with 25 mg recommended for patients with intravascular volume depletion (e.g. patients treated with diuretic) and patients with hepatic impairment. Losartan can be administered at a total daily dose of 25 to 100 mg.

Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily and can be given at doses of 12.5 mg as Losacor ® plus. To minimize the dose dependent side effects, it is usually appropriate to begin thecombination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Hypertensive Patients with Left Venticular Hypertrophy Treatment should be initiated with losartan 50 mg once daily. Hydrochlorothiazide 12.5 mg should be added if blood pressure reduction is inadequate. For further blood pressure reduction other antihypertensives should be added.

Interaction

No clinically significant pharmacokinetic interactions were observed when losartan was coadministered with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite. Ketoconazole did not affect the conversion of losartan to the active metabolite.

Contraindications

Losacor ® and Losacor ® plus are 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.

Side Effects

In general, treatment with losartan and losartan potassium hydrochlorothiazide is well tolerated. For the most part, adverse experiences have generally been mild and transient in nature and have not required discontinuation of therapy. The overall incidence of adverse experiences with losartan and hydrochlorothiazide was comparable to placebo. Some adverse reactions such as dizziness, fatigue, coughing, diarrhea etc may be observed.

Pregnancy & Lactation

Due to the mechanism of action of angiotensin II antagonists, a risk for the fetus cannot be excluded. As for any drug that also acts directly on the renin-angiotensin-aldosterone system, losartan should not be used during pregnancy. If pregnancy is detected during therapy, it should be discontinued as soon as possible. It is not known whether losartan is excreted in human milk. Losartan and its active metabolites were shown to be present in rat milk. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue the drug taking into account the importance of the drug to the mother.

Precautions & Warnings

Renal Insufficiency

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with losartan. These changes in renal function were reversible upon discontinuation of therapy. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin-converting enzymes inhibitors has been associated with oliguria and/or progressive azotemia and rarely with acute renal failure. Similar outcome have been reported with losartan. Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Hepatic Insufficiency

Based on pharmacokinetic data it was found that there is significantly increased plasma concentrations of losartan and its active metabolite in cirrhotic patients. A lower dose should be considered for patients with hepatic impairment, or a history of hepatic impairment.

Therapeutic Class

Combined antihypertensive preparations

Storage Conditions

Store in a cool and dry place below 30°C. Protect from light.

Pharmaceutical Name

Healthcare Pharmaceuticals Ltd.