ANGILOCK Tablet

In the treatment of all grades of hypertension.

Dosage and Administration

The usual starting and maintenance dose is 50mg once daily for most patients.

The maximal antihypertensive effect is attained 3-6 weeks after initiation of therapy. Some patients may receive an additional benefit by increasing the dose to 100mg once daily. In patients who are salt depleted corrective measures should be used before starting Angilock and the initial dose should be reduced to 25mg. No dosage adjustment is necessary for patients upto 75 years of age. There is limited clinical experience in older patients and a lower starting dose of 25mg once daily is recommended.

No initial dosage adjustment is necessary in patients with mild renal impairment (i.e. creatinine clearance 20-50mL/min). For patients with moderated to severe renal impairment (i.e. creatinine clearance <20m/min) or patients on dialysis, a lower starting dose of 25mg is recommended.

Angilock may be administered with other antihypertensive agents.

Angilock may be administered with or without food.

Use in Elderly

Patients upto 75 years: No initial dosage adjustment is necessary for this group of patients.

Patients over 75 years: A lower starting dose of 25mg once daily is recommended.

It is also contraindicated to patients who are hypersensitive to any component of this product.

In patients who are intravenously volume depleted (e.g. those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administer Losartan or a lower starting dose (usually 25mg) should be used.

A lower dose should be considered for patients with a history of hepatic and renal impairment. Losartan should not be used with potassium-sparing diuretics.

In controlled clinical trials in patients with essential hypertension, dizziness was the only side effect reported that occurred with an incidence greater than placebo in 1% or more of patients treated with Losartan. Rarely, rash was reported although the incidence in controlled clinical trials was less than placebo.

Angioedema, involving swelling of the face, lips and /or tongue has been reported rarely in patients treated with Losartan. Serious hypotension (particularly on initiating treatment in salt-depleted patients) or renal failure (mainly in patients with renal artery stenosis) may be encountered during Losartan treatment.

No drug interaction of clinical significance has been identified. Compounds which have been studied in clinical pharmacokinetic trials include hydrochlorothiazide, digoxin, warfarin, cimetidine, ketoconazole and phenobarbital.

Although there is no experience with the use of Losartan in pregnant women, animal studies with Losartan potassium have demonstrated fetal and neonatal injury and death, the mechanism of which is believed to be pharmacologically mediated through effects on the renin-angiotensin aldosterone system. Losartan should not be used in pregnancy and if pregnancy is detected Losartan should be discontinued as soon as possible.

It is not known whether Losartan is excreted in human breast milk. However, significant level of Losartan found in rat milk which suggests that the drug should not be used in lactating mother.

Losartan is an oral, specific angiotensin-Ⅱreceptor (type AT1) antagonist. AngiotensinⅡbinds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys, and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone. AngiotensinⅡalso stimulates smooth-muscle proliferation. Based on binding and pharmacological bioassays, it binds selectively to the AT1 receptor. In vitro and in vivo, both losartan and its pharmacologically active carboxylic acid metabolite block all physiologically relevant actions of angiotensinⅡ, regardless of the source or route of synthesis.

During losartan administration, removal of angiotensin-Ⅱnegative feedback on renin secretion leads to increased plasma renin activity. Increases in plasma renin activity lead to increases in angiotensinⅡin plasma. Even with these increases, antihypertensive activity and suppression of plasma aldosterone concentration are maintained. indicating effective angiotensin-Ⅱreceptor blockade.

Losartan has been shown to block responses to angiotensinⅠand angiotensinⅡwithout affecting responses to bradykinin, a finding which is consistent with the specific mechanism of action of losartan. In contrast, ACE inhibitors have been shown to block responses to angiotensinⅠand enhance responses to bradykinin without altering the response to angiotensinⅡ, thus providing a pharmacodynamic distinction between losartan and ACE inhibitors.