LOSARTAN HYDROCHLOROTHIAZIDE

Posology Hypertension Losartan potassium 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 potassium 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. 5mg once daily. 5mg, the dosage may be increased to one tablet of Losartan potassium/ Hydrochlorothiazide 100mg/25mg daily.

The maximum dose is one tablet of Losartan potassium/ Hydrochlorothiazide 100mg/25mg once daily. In general, the antihypertensive effect is attained within three to four weeks after initiation of therapy. 5mg is available for those patients titrated to 100mg of Losartan potassium/ Hydrochlorothiazide who require additional blood pressure control.

e. creatinine clearance 30-50 ml/min). Losartan potassium and Hydrochlorothiazide tablets are not recommended for haemodialysis patients. e. 3). Use in patients with intravascular volume depletion Volume and/or sodium depletion should be corrected prior to administration of Losartan potassium/Hydrochlorothiazide tablets.

).

Use in the elderly Patients over 75 years:

Dosage adjustment is not usually necessary for the elderly. Use in children and adolescents (< 18 years) There is no experience in children and adolescents. Therefore, Losartan potassium/ 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 tablets may be administered with or without food.

The adverse reactions below are classified where appropriate by system organ class and frequency according to the following convention: Very common (≥1/10); Common (≥1/100, < 1/10); Uncommon (≥1/1,000, ≤1/100); Rare (≥1/10,000, ≤1/1,000); Very rare (≤1/10,000); Not known (cannot be estimated from the available data).

In clinical trials with losartan potassium salt and hydrochlorothiazide, no adverse reactions peculiar to this combination of substances were observed. The adverse reactions were restricted to those which were formerly observed with losartan potassium salt and/or hydrochlorothiazide.

In controlled clinical trials for essential hypertension, dizziness was the only adverse reaction reported as substance-related that occurred with an incidence greater than placebo in 1% or more of patients treated with losartan potassium and hydrochlorothiazide.

Next to these effects, there are further adverse reactions reported after the introduction of the product to the market as follows: System organ class Adverse reaction Frequency Hepato-biliary disorders Hepatitis Rare Investigations Hyperkalaemia, elevation of ALT Rare The adverse reactions that have been seen with one of the individual components and may be potential adverse reactions with Losartan potassium/Hydrochlorothiazide are the following: Losartan potassium The following adverse reactions have been reported for losartan in clinical studies and in post-marketing experience: System organ class Adverse reaction Frequency Anaemia, Henoch- Schönlein purpura, ecchymosis, haemolysis UncommonBlood and lymphatic system disorders Thrombocytopenia Not known System organ class Adverse reaction Frequency Cardiac disorders Hypotension, orthostatic hypotension, sternalgia, angina pectoris, grade II-AV block, cerebrovascular event, myocardial infarction, palpitation, arrhythmias (atrial fibrillations, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation) Uncommon Ear and labyrinth disorders Vertigo, tinnitus Uncommon Eye disorders Blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity Uncommon Abdominal pain, nausea, diarrhoea, dyspepsia Common Constipation, dental pain, dry mouth, flatulence, gastritis, vomiting, obstipation Uncommon Pancreatitis Not known Gastrointestinal disorders Intestinal angioedema Rare Asthenia, fatigue, chest pain Common Fever, facial oedema, oedema Uncommon General disorders and administration site conditions Flu-like symptoms, malaise Not known Hepato-biliary disorders Liver function abnormalities Not known Immune system disorders Hypersensitivity: anaphylactic reactions, angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx, and /or tongue; in some of these patients angioedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors.

8). 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.

3). Electrolyte imbalances Electrolyte imbalances are 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 a creatinine clearance between 30-50 ml/ min should be closely monitored.

5). Liver function impairment Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of losartan potassium in cirrhotic patients, Losartan potassium/ Hydrochlorothiazide should be used with caution in patients with a history of mild to moderate hepatic impairment.

There is no therapeutic experience with losartan potassium in patients with severe hepatic impairment. 2). 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.

Losartan potassium 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.

e. 1).