Angioedema: Patients with a history of angioedema should be closely monitored. Hypotension and intravascular volume depletion: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corected before the administration of losartan/HCTZ tablets.

Electrolyte Imbalances: common in patients with renal impairment, with or without diabetes, and should be addressed. Therefore, the plasma concentrations of potassium and creatinine clearance values should be closely monitored; especially patients with heart failure and creatnine clearance between 30-50mL/min should be closely monitored. The concomitant use of potassium sparing diuretics, potassium supplements and potassium containing salt substitues with losartan/ hydrochlorothiazide is not recommended.

Liver function impairment: Losartan/HCTZ should be used with caution in patients with a history of mild to moderate hepatic impairment. There is no therapeutic experience with losartan in patients with severe hepatic impairment. Therefore Losartan/HCTZ is contraindicated in patients with severe hepatic impairment.

Renal function impairment: As a consenquence of inhibiting the renin-angiotensin-aldosterone system (RAAS), changes in renal function, including renal fialure, 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 preexisting 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. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Renal Transplantation: There is no experience in patients with recent kidney transplantation.

Primary hyperaldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, the use of losartan/HCTZ tablets is not recommended.

Coronary heart disease and cerebrovascluar disease: As with any antihypertensive agents, excessive blood pressure decrease in patients with ischaemic cardiovascular and cerebrovascular disease could result in a myocardial infarction or stroke.

Heart failure: In patients with heart failure, with or without renal impairment, there is – as with other drugs acting on the renin-angiotensin system – a risk of severe arterial hypotension, and (often acute) renal impairment.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyophathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

Ethnic differences: As observed for angiotensin converting enzyme inhibitors, losartan and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.

Hypotension and electrolyte/fluid imbalance: As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid or electrolyte imbalance, e.g. volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia which may occur during intercurrent diarrhoea or vomiting. Periodic determination of serum electrolytes should be performed at appropriate intervals in such patients. Dilutional hyponatremia may occur in oedematous patients in hot weather.

Metabolic and endocrine effects: Thiazide therapy may imapir glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required. Latent diabetes mellitus may become manifest during thiazide therapy. Thiazides may decrease urinary calcium excertion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. Thiazide therapy may precipitate hyperuricaemia and/or gout in certain patients. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.

Hepatic impairment: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, as it may cause intrahepatic cholestasis, and since minor alterations of fluid and electrolyte balance may precipitate hepatic comma. Losartan/HCTZ is contraindicated for patients with severe hepatic impairment. In patients receiving thiazides, hypersensitivity reactions may occur with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.