LOSARTAN/HYDROCHLOROTHIAZIDE

Posology Hypertension 2 /3 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/Hydrochlorothiazide 100 mg/25 mg (losartan 100 mg/ HCTZ 25 mg) once daily.

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

For dosages, which cannot be achieved with Losartan/Hydrochlorothiazide 100 mg/12,5 mg film-coated tablets other strengths of Losartan/Hydrochlorothiazide medicinal products are available. e. creatinine clearance 30-50 ml/min). Losartan potassium and hydrochlorothiazide is 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. 3).

Use in the elderly:

Dosage adjustment is not usually necessary for the elderly. Paediatric population 3 /3 There is no experience in children and adolescents. Therefore, losartan/hydrochlorothiazide should not be administered to children and adolescents.

g. one glass of water). Losartan potassium/Hydrochlorothiazide 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: ≥1/1 00, <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 events peculiar to this combination of substances were observed. The adverse events 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 reactions 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 13 /3 Investigation 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 The following adverse reactions have been reported for losartan in clinical studies and in post- marketing experience: Blood and lymphatic system disorders Uncommon: Anaemia, Henoch-Schönlein purpura, ecchymosis, haemolysis Not known: thrombocytopaenia 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) Ear and labyrinth disorders Uncommon: Vertigo, tinnitus Eye disorders Uncommon: Blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity Gastrointestinal disorders Common: Abdominal pain, nausea, diarrhoea, dyspepsia Uncommon: Constipation, dental pain, dry mouth, flatulence, gastritis, vomiting, obstipation Rare: Intestinal angioedema Not known: pancreatitis General disorders and administration site conditions Common: Asthenia, fatigue, chest pain Uncommon: Facial oedema, oedema, fever Not known: flu-like symptoms, malaise 14 /3 Hepatobiliary disorders Not known: Liver function abnormalities Immune system disorders Rare: 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 Metabolism and nutrition disorders Uncommon: Anorexia, gout 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: Rhabdomyolisis Nervous system disorders Common: Headache, dizziness Uncommon: Nervousness, paraesthesia, peripheral neuropathy, tremor, migraine, syncope Not known: dysgeusia Psychiatric disorders Common: Insomnia Uncommon: Anxiety, anxiety disorder, panic disorder, confusion, depression, abnormal dreams, sleep disorder, somnolence, memory impairment Renal and urinary disorders Common: renal impairment, renal failure Uncommon: Nocturia, urinary frequency, urinary tract infection Reproductive system and breast disorders Uncommon: Decreased libido, erectile dysfunction/impotence Respiratory, thoracic and mediastinal disorders 15 /3 Common: Cough, upper respiratory infection, nasal congestion, sinusitis, sinus disorder Uncommon: Pharyngeal discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, rhinitis, respiratory congestion Skin and subcutaneous tissue disorders Uncommon: Alopecia, dermatitis, dry skin, erythema, flushing, photosensitivity, pruritus, rash, urticaria, sweating Vascular disorders Uncommon: Vasculitis Not known: dose-related orthostatic effects 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.

Not known:

Hyponatraemia Hydrochlorothiazide Blood and lymphatic system disorders Uncommon: Agranulocytosis, aplastic anaemia, haemolytic anaemia, leukopenia, purpura, thrombocytopenia Immune system disorders Rare: Anaphylactic reaction Metabolism and nutrition disorders Uncommon: Anorexia, hyperglycaemia, hyperuricaemia, hypokalaemia, hyponatraemia Psychiatric disorders Uncommon: Insomnia Nervous system disorders Common: Cephalalgia Eye disorders Uncommon: Transient blurred vision, xanthopsia Vascular disorders 16 /3 Uncommon: Necrotizing angiitis (vasculitis, cutaneous vasculitis) Respiratory, thoracic and mediastinal disorders Uncommon: Respiratory distress including pneumonitis and pulmonary oedema Gastrointestinal disorders Uncommon: Sialoadenitis, spasms, stomach irritation, nausea, vomiting, diarrhoea, constipation Hepatobiliary disorders Uncommon: Icterus (intrahepatic cholestatis), pancreatitis Skin and subcutaneous tissue disorders Uncommon: Photosensitivity, urticaria, toxic epidermal necrolysis Not known: cutaneous lupus erythematosus Eye disorders Not known: choroidal effusion Musculoskeletal and connective tissue disorders Uncommon: Muscle cramps Neoplasms benign, malignant and unspecified (incl cysts and polyps) Not known’: Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma) Renal and urinary disorders Uncommon: Glycosuria, interstitial nephritis, renal dysfunction, renal failure General disorders and administration site conditions Uncommon: Fever, dizziness Description of selected adverse […]

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.

2. ). 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 in cirrhotic patients, Losartan potassium and Hydrochlorothiazide 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.

Therefore, the use of Losartan potassium and Hydrochlorothiazide tablets is not recommended.

Coronary heart disease and cerebrovascular 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 5 /3 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 patients than in non- blacks, possibly because of higher prevalence or low-renin states in the black hypertensive population.

Pregnancy AIIRAs should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti- hypertensive treatments which have an established safety profile for use in pregnancy.

6). Dual blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure).

1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. 8). These patients presented with abdominal pain, nausea, vomiting and diarrhoea.

Symptoms resolved after discontinuation of angiotensin II receptor antagonist. If intestinal angioedema is diagnosed, losartan should be discontinued and appropriate monitoring should be initiated until complete resolution of symptoms has occurred.

Hydrochlorothiazide 6 /3 Hypotension and electrolyte/fluid imbalance As with all antihypertensive therapy, symptomatic hypotension may occur in some patients. , volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia […]

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