LOSARTAN POTASSIUM/HYDROCHLOROTHIAZIDE

Posology Hypertension Losartan and hydrochlorothiazide is not for use as initial therapy, but in patients whose blood pressure is not adequately controlled by losartan potassium or hydrochlorothiazide alone. Dose titration with the individual components (losartan and hydrochlorothiazide) is recommended.

When clinically appropriate direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled. 5 mg) once daily. 5 mg, the dosage may be increased to one tablet of Losartan potassium/hydrochlorothiazide 100 mg/25 mg (losartan 100 mg/ HCTZ 25 mg) once daily.

The maximum dose is one tablet of Losartan potassium/hydrochlorothiazide 100 mg/25 mg once daily. In general, the antihypertensive effect is attained within three to four weeks after initiation of therapy. e. creatinine clearance 30-50 ml/min).

Losartan and hydrochlorothiazide tablets are not recommended for haemodialysis patients. e. 3). Intravascular volume depletion Volume and/or sodium depletion should be corrected prior to administration of Losartan/HCTZ tablets. 3). Elderly Dosage adjustment is not usually necessary for the elderly.

Paediatric population There is no experience in children and adolescents. The safety and efficacy of Losartan potassium/hydrochlorothiazide in children and adolescents (<18 years) has not yet been established. No data is available. Therefore, losartan/hydrochlorothiazide should not be administered to children and adolescents.

1). Losartan potassium/hydrochlorothiazide tablets should be swallowed with a glass of water. Losartan potassium/hydrochlorothiazide may be administered with or without food.

Losartan has been evaluated in clinical studies as follows: • In a controlled clinical trial in > 3,000 adult patients 18 years of age and older for essential hypertension. 1) In these clinical trials, the most common adverse event was dizziness.

The frequency of adverse events listed below is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

In controlled clinical trials for essential hypertension, hypertensive patients with left ventricular hypertrophy, chronic heart failure as well as for hypertension and type 2 diabetes mellitus with renal disease, the most common adverse event was dizziness.

Hypertension In controlled clinical trials for essential hypertension with losartan the following adverse events were reported: Nervous system disorders Common: dizziness Uncommon: somnolence, headache, sleep disorders Ear and labyrinth disorders Common: vertigo Cardiac disorder Uncommon: palpitations, angina pectoris Vascular disorders Uncommon: (orthostatic) hypotension (dose-related orthostatic effects) ║, Skin and subcutaneous tissue disorders Uncommon: rash Gastrointestinal disorders Uncommon: abdominal pain, obstipation Rare: Intestinal angioedema.

General disorders and administration site conditions Uncommon: asthenia, fatigue, oedema Investigations Common: hyperkalaemia Rare: increased alanine aminotransferase (ALT) § Hypertensive patients with left ventricular hypertrophy In a controlled clinical trial in hypertensive patients with left ventricular hypertrophy the following adverse events were reported: Nervous system disorders Common: dizziness Ear and labyrinth disorders common: vertigo General disorders and administration site conditions Common: asthenia,fatigue Chronic heart failure In a controlled clinical trial in patients with cardiac insufficiency the following adverse events were reported: Blood and lymphatic system disorders Common: anaemia Nervous system disorders Common: dizziness Uncommon: headache Rare: paraesthesia Cardiac disorders Rare: syncope, artrial fibrillation, cerebrovascular accident Vascular disorders Common: (orthostatic) hypotension (including dose- related orthostatic effects) ║ Respiratory, thoracic and mediastinal disorders Uncommon: dyspnoea, cough Gastrointestinal disorders Uncommon: diarrhoea, nausea, vomiting Rare: Intestinal angioedema.

Hypersensitivity Angiooedema. 8). Hypotension and Electrolyte/Fluid Imbalance Symptomatic hypotension, especially after the first dose and after increasing of the dose, may occur in patients who are volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting.

2). This also applies to children 6 to 18 years of age. Electrolyte imbalances Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. 8, 'Hypertension and type 2 diabetes with renal disease - Investigations’ and ‘Post- marketing experience - Investigations’ Therefore, the plasma concentrations of potassium as well as creatinine clearance values should be closely monitored, especially patients with heart failure and a Creatinine Clearance between 30-50 ml/min should be closely monitored.

5). Hepatic 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.

There is no therapeutic experience with losartan in patients with severe hepatic impairment. 2). 2). Renal Impairment As a consequence of inhibiting the renin-angiotensin 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.

Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. 2). Renal function should be regularly monitored during treatment with losartan as it may deteriorate.

e. 1).