Losartan + Hydrochlorothiazide Tab 50mg/12.5mg (EKOSART PLUS SANDOZ)-30
Losartan/HCTZ is indicated for the treatment of essential hypertension in patients whose blood pressure is not adequately controlled on losartan or hydrochlorothiazide alone.
Dosage and Administration:
Losartan/HCTZ may be administered with other antihypertensive agents. Losartan/HCTZ tablets should be allowed with a glass of water. Losartan/HCTZ may be administered with or without food. Hypertension: Losartan and hydrochlorothiazide is not for use as initial therapy, but in patients whose blood pressure is not adequately controlled by losartan postassium or hydrochlorothiazide alone. Dose titration with the individual components (losartan and hydrochlorothiazide) si recommended. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled. The usual maintenance dose is one tablet of losartan 50mg/HCTZ 12.5mg, the dosage may be increased to maximum 2 tablets daily of losartan 50mg/HCTZ 12.5mg or one tablet of losartan 100mg/HCTZ 12mg once daily. The maximum dose is one tablet of losartan 100mg/ HCTZ 25mg once daily. In general, the antihypertensive effect is attained within three to four weeks after initiation of therapy. Use in patients with renal impairment and haemodialysis patients: No initial dosage adjustment is necessary in patients with moderate renal impairment (i.e. creatinine clearance 30-50mL/ min). Losartan and hydrochlorothiazide tablets must not be used in patients with severe renal impairment (i.e. creatinine clearance < 30mL/ min).
Use in patients with introvascular volume depletion: Volume and/or sodium depletion should be corrected prior administration of Losartan/HCTZ tablets.
Use in the elderly: Dosage adjustment is not usually necessary for the elderly.
Use in children and adolescents (< 18 years): There is no experience in children and adolesents.
Therefore, losartan/hydrochlorothiazide should not be administered to children and adolescents.
– Hypersensitivity to losartan, sulphonamide-derived substances (as hydrochlorothiazide) or to any of the excipients – Therapy resistant hypokalaemia or hypercalacaemia – Severe hepatic impairment, cholestasis and biliary obstructive disorders – Refractory hyponatraemia – Symptomatic hyperuricaemia/ gout – Pregnancy – Severe renal impairment – Anuria
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.
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: Hyperkalemia, 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: Anemia, Henoch-Schonlein purpura, ecchymosis, haemolysis.
Immune system disorders
Rare: Anaphylactic reactions, angioedema, urticaria Metabolism and nutrition disorders
Uncommon: Anorexia, gout
Uncommon: Anxiety, anxiety disorder, panic disorder, confusion, depression, abnormal dreams, sleep disorder, somnolence, memory impairment
Nervous system disorders
Common: Headache, dizziness
Uncommon: Nervousness, paresthesia, peripheral neuropathy, tremor, migraine, syncope
Uncommon: Vertigo, tinnitus
Uncommon: Hypotension, orthostatic hypotension, sternalgia, angina, pectoris, grade II-AV block, cerebrovascular event, myocardial infarction, paliptation, arrhythmias (atrial fibrllations, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation)
Uncommon: Vasculitis Respiratory,
Thoracic and mediastinal disorders
Common: Cough, upper respiratory infection, nasal congestion, sinusitis, sinus disorder
Uncommon: Pharyngeal discomfort, pharyngitis, laryngitis, dyspnea, bronchitis, epistaxis, rhinitis, respiratory congestion
Common: Abdominal pain, nausea, diarrhea, dyspepsia
Uncommon: Constipation, dental pain, dry mouth, flactulence, gastritis, vomiting
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 tissure 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
Uncommon: Nocturia, urinary frequency, urinary tract infection
Reproductive system and breast disorders
Uncommon: Decreased libido, impotence
General disorders and administration site conditions
Common: Asthenia, fatigue, chest pain
Uncommon: Facial edema, fever
Common: Hyperkalemia, mild reductionof hematocrit and hemoglobin
Uncommon: Mild increase in urea and creatinine serum levels
Very rare: Increase in hepatic enzymes and bilrubin
Hydrochlorothiazide Blood and lymphatic system disorders
Uncommon: Agranulocytosis, aplastic anemia, haemolytic anaemia, leukopenia, purpura, thrombocytopenia Immune system disorders Rare: Anaphylactic reaction
Metabolism and nutrition disorders
Uncommon: Anorexia, hyperglycemia, hyperuicemia, hypokalemia, hyponatremia
Nervous system disorders
Common: Cephalalgia Eye disorders
Uncommon: Transient blurred vision, xanthopsia
Vascular disorders Uncommon: Necrotising angiitis (vasculitis, cutaneous vasculitis)
Respiratory thoractic and mediastinal disorders
Uncommon: Sialoadenitis, spasms, stmoach irritation, nausea, vomiting, diarrhoea, constipation
Uncommon: Icterus (intrahepatic cholestasis), pancreatitis
Skin and subcutaneous tissue disorders
Uncommon: Photosensitivity, urticaria, toxic epidermal necrolysis
Musculoskeletal and connective tissue disorders
Uncommon: Muscle cramps
Renal and urinary disorders
Uncommon: Glycosuria, interstitial nephiritis, renal dysfunction, renal failure
Genral disorders and administration site conditions
Uncommon: Fever, dizziness
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