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. 5mg) once daily. 5mg, the dosage may be increased to one tablet of Losartan potassium/Hydrochlorothiazide 100mg/25mg (losartan 100mg/ HCTZ 25mg) once 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 who require additional blood pressure control.

e. creatinine clearance 30-50ml/min). Losartan 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/HCTZ tablets.

). Use in the elderly Dosage adjustment is not usually necessary for the elderly. Paediatric population Use in children and adolescents (< 18 years) There is no experience in children and adolescents. Therefore, losartan/hydrochlorothiazide should not be administered to children and adolescents.

1). 5mg Film-coated Tablets should be swallowed whole with a glass of water. 5mg Film-coated Tablets may be administered with or without food.

The adverse events below are classified where appropriate by system organ class and frequency according to 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 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 and hydrochlorothiazide.

Next to these effects, there are further adverse reactions reported after the introduction of the product to the market as follows: Hepato-biliary disorders Rare: Hepatitis Investigations Rare: Hyperkalaemia, elevation of ALT Additional 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 Blood and lymphatic system disorders Uncommon: Anaemia, Henoch-Schönlein purpura, ecchymosis, haemolysis Not known: Thrombocytopenia Immune system disorders Rare: hypersensitivity: anaphylactic reactions, angiooedema 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 angiooedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors Metabolism and nutrition disorders Uncommon: Anorexia, gout Psychiatric disorders Common: Insomnia Uncommon: Anxiety, anxiety disorder, panic disorder, confusion, depression, abnormal dreams, sleep disorder, somnolence, memory impairment Nervous system disorders Common: Headache, dizziness Uncommon: Nervousness, paraesthesia, peripheral neuropathy, tremor, migraine, syncope Not known: Dysgeusia Eye disorders Uncommon: Blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity Ear and labyrinth disorders Uncommon: Vertigo, tinnitus Cardiac disorders Uncommon: 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) Vascular disorders Uncommon: Vasculitis Not known: dose-related orthostatic effects Respiratory, thoracic and mediastinal disorders Common: Cough, upper respiratory infection, nasal congestion, sinusitis, sinus disorder Uncommon: Pharyngeal discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, rhinitis, respiratory congestion Gastrointestinal disorders Common: Abdominal pain, nausea, diarrhoea, dyspepsia Uncommon: Constipation, dental pain, dry mouth, flatulence, gastritis, vomiting, obstipation Rare: Intestinal angioedema Not known: Pancreatitis Hepato-biliary disorders Not known: Liver function abnormalities Skin and subcutaneous tissue disorders Uncommon: Alopecia, dermatitis, dry skin, erythema, flushing, photosensitivity, pruritus, rash, urticaria, sweating Musculoskeletal and connective tissue disorders Common: Muscle cramp, back pain, leg pain, myalgia Uncommon: Arm pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness Not known: Rhabdomyolysis Renal and urinary disorders Common: Renal failure and renal impairment Uncommon: Nocturia, urinary frequency, urinary tract infection Reproductive system and breast disorders Uncommon: Decreased libido, erectile dysfunction /impotence General disorders and administration site conditions Common: Asthenia, fatigue, chest pain Uncommon: Facial oedema, oedema, fever Not known: Flu-like symptoms and malaise Investigations Common: Hyperkalaemia, mild reduction of haematocrit and haemoglobin, hypoglycaemia Uncommon: Mild increase in urea and creatinine serum levels Very rare: Increase in hepatic enzymes and bilirubin.

8). 8). These patients presented with abdominal pain, nausea, vomiting and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, losartan should be discontinued and appropriate monitoring should be initiated until complete resolution of symptoms has occurred.

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). 5mg Film-coated Tablets 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. 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 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.

1. e. 1).