ALSARTAN Tablet

For the treatment of hypertension. It is used alone or in combination with other antihypertensive agents.

Dosage and Administration

The usual starting dose of Losartan potassium is 50mg once daily, with 25mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) and patients with a history of hepatic impairment. Losartan potassium can be administered once or twice daily with total daily dose ranging from25mg to 100mg.

If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.

If blood pressure is not controlled by Losartan potassium alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect.

No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis.

Losartan potassium may be administered with other antihypertensive agents.

Losartan may be administered with or without food.

Contraindicated in pregnancy and in patients who are hypersensitive to any component of this product.

Side effects have usually been mild and transient in nature and have not required discontinuation of therapy. The overall incidence of side effects reported with Losartan was comparable to placebo.

In controlled clinical trials for essential hypertension, dizziness was the only side effect reported as drug related that occurred with an incidence greater than placebo in 1% or more of patients treated with Losartan. In addition, dose-related orthostatic effects were seen in less than 1% of patients.

The following adverse reaction have been reported in post marketing experience:

Hypersensitivity: Angioedema including swelling of the larynx and glottis causing airway obstruction (and/or swelling of the face, lips, pharynx and/or tongue) has been reported rarely in patients treated with Losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors.

Gastro-intestinal: Hepatitis (reported rarely), diarrhoea, liver function abnormalities.

Haematologic: Anaemia.

Musculoskeletal: Myalgia.

Nervous System / Psychiatric: Migraine

Skin: Urticaria, pruritus, rash.

In clinical pharmacokinetic trials, no drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, ketoconazole and phenobarbital (phenobarbitone).

As with other drugs that block angiotensinⅡor its effects, concomitant use of other drugs which retain potassium or may increase potassium levels (e.g. potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium) may lead to increases in serum potassium. Co-medication is not advisable.

Contraindicated in pregnancy and in patients who are hypersensitive to any component of this product.

(See the package insert about the details.)

Hypersensitivity: Angioedema.

Hypotension and electrolyte/fluid imbalance: In patients who are intravascularly volume depleted (e.g. those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of Losartan or a lower starting dose should be used.

The use of Losartan in patients with haemodynamically significant obstructive valvular disease or cardiomyopathy has not been adequately studied.

Liver function impairment: Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of Losartan in cirrhotic patients, a lower dose should be considered for patients with a history of hepatic impairment.

Renal function impairment: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported (in particular, in patients whose renal function is dependent on the renin-angiotensin-aldosterone system such as those with severe cardiac insufficiency or pre-existing renal dysfunction).

As with other drugs that affect the renin-angiotensin-aldosterone system, increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy.

Pediatric Use: Safety and effectiveness in paediatric patients have not been established.

Use in the elderly: No overall difference in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Angiotensin Ⅱ [formed from angiotensinⅠin a reaction catalyzed by angiotensin converting enzyme (ACE<, kininase Ⅱ)], 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 angiotensinⅡto the AT, receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Both Losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor.

In vitro binding studies indicate that Losartan is a reversible, competitive inhibitor of the AT1 receptor. The active metabolite is 10 -40 times more potent by weight than Losartan and appear to be a reversible, non-competitive inhibitor of the AT1 receptor.

Neither Losartan nor its active metabolite inhibits ACE (kininase Ⅱ, the enzyme that converts angiotensin Ⅰ to angiotensinⅡand degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.