Composition:
Each film-coated tablet contains
Losartan potassium USP …………………….. 25/50 mg
Additional ingredients:
Microcrystalline cellulose, Croscarmellose sodium, Magnesium Stearate, Colloidal anhydrous silica, Purified water
Tablet coating:
Opadry O3B 52014 yellow

Indications: Treatment of essential hypertension in adults and in children and adolescents 6-18 years of age
Treatment of renal disease in adult patients with hypertension and type 2 diabetes mellitus with proteinuria 0.5 g/day as part of an antihypertensive treatment.
Treatment of chronic heart failure (in patients 60 years), when treatment with Angiotensin converting enzyme (ACE) inhibitors is not considered suitable due to incompatibility, especially cough, or contraindication. Patients with heart failure who have been stabilised with an ACE inhibitor should not be switched to losartan. The patients should have a left ventricular ejection fraction 40% and should be clinically stable and on an established treatment regimen for chronic heart failure.
Reduction in the risk of stroke in adult hypertensive patients with left ventricular hypertrophy documented by ECG.
Administration and Dosage:
Losartan tablets should be swallowed with a glass of water. KSART may be administered with or without food.
Hypertension
The usual starting and maintenance dose is 50 mg once daily for most patients. The maximal antihypertensive effect is attained 36 weeks after initiation of therapy. Some patients may receive an additional benefit by increasing the dose to 100 mg once daily (in the morning).
Losartan may be administered with other antihypertensive agents, especially with diuretics (e.g. hydrochlorothiazide).
Hypertensive type II diabetic patients with proteinuria 0.5 g/day
The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response from one month onwards after initiation of therapy. Losartan may be administered with other antihypertensive agents (e.g. diuretics, calcium channel blockers, alpha- or beta- blockers and centrally acting agents) as well as with insulin and other commonly used hypoglycemic agents (e.g. sulfonylureas, glitazones and glucosidase inhibitors).
Heart failure
The usual initial dose of losartan in patients with heart failure is 12.5 mg once daily. The dose should generally be titrated at weekly intervals (i.e. 12.5 mg daily, 25 mg daily and 50 mg daily) to the usual maintenance dose of 50 mg once daily, as tolerated by the patient.
Reduction in the risk of stroke in hypertensive patients with left ventricular hypertrophy documented by ECG
The usual starting dose is 50 mg of losartan once daily. A low dose of hydrochlorothiazide should be added and/ or the dose of losartan should be increased to 100 mg once daily based on blood pressure response.

Side effects:
Losartan has been evaluated in clinical studies as follows:
In controlled clinical trials in approximately 3300 adult patients 18 years of age and older for essential hypertension, in a controlled clinical trial in 9193 hypertensive patients 55 to 80 years of age with left ventricular hypertrophy
in a controlled clinical trial in approximately 3900 patients 20 years of age and older with chronic heart failure; in a controlled clinical trial in 1513 type 2 diabetic patients 31 years of age and older with proteinuria
in a controlled clinical trial in 177 hypertensive paediatric patients 6 to 16 years of age
In these clinical trials, the most common adverse reaction was dizziness.
The frequency of adverse reactions 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).
Nervous system disorders:
Common:
DIZZINESS, vertigo
Uncommon:
somnolence, headache, sleep disorders
Cardiac disorder:
Uncommon:
palpitations, angina pectoris
Vascular disorders:
Uncommon:
symptomatic hypotension (especially in patients with intravascular volume depletion, e.g. patients with severe heart failure or under treatment with high dose diuretics), dose related orthostatic effects, rash.
Gastro-intestinal disorders:
Uncommon:
abdominal pain, obstipation
General disorders and administration site conditions:
Uncommon:
asthenia, fatigue, oedema
Investigations:
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan tablets. Elevations of ALT occurred rarely and usually resolved upon discontinuation of therapy. Hyperkalaemia (serum potassium>5.5 mmol/l) occurred in 1.5% of patients in hypertension clinical trials.
Hypertensive patients with left ventricular hypertrophy
In a controlled clinical trial in 9193 hypertensive patients 55 to 80 years of age, with left ventricular hypertrophy, the following adverse reactions 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 approximately 3900 patients 20 years of age and older, with cardiac insufficiency, the following adverse reactions were reported:
Nervous system disorders:
Uncommon:
Dizziness, headache
Rare:
Paraesthesia
Drug interactions:
Other antihypertensive agents may increase the hypotensive action of losartan. Concomitant use with other substances which may induce hypotension as an adverse reaction (like tricyclic antidepressants, antipsychotics, baclofen and amifostine) may increase the risk of hypotension.
Losartan is predominantly metabolised by cytochrome P450 (CYP) 2C9 to the active carboxyacid metabolite. In a clinical trial it was found that fluconazole (inhibitor of CYP2C9) decreases the exposure to the active metabolite by approximately 50%. It was found that concomitant treatment of losartan with rifampicin (inducer of metabolism enzymes) gave a 40% reduction in plasma concentration of the active metabolite. The clinical relevance of this effect is unknown. No difference in exposure was found with concomitant treatment with fluvastatin (weak inhibitor of CYP2C9). As with other medicinal products that block angiotensin II or its effects, concomitant use of other medicinal products which retain potassium (e.g. potassium sparing diuretics: amiloride, triamterene, spironolactone) or may increase potassium levels (e.g. heparin), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. Co-medication is not advisable.
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Very rare cases have also been reported with angiotensin II receptor antagonists. Co-administration of lithium and losartan should be undertaken with caution. If this combination proves essential, serum lithium level monitoring is recommended during concomitant use.
When angiotensin II antagonists are administered simultaneously with NSAIDs (i.e. selective COX2 inhibitors, acetylsalicylic acid at anti-inflammatory doses and nonselective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of angiotensin II antagonists or diuretics and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor preexisting renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.

Precautions in usage:
Hypersensitivity
Angio-oedema. Patients with a history of angio-oedema (swelling of the face, lips, throat, and/ or tongue) should be closely monitored.
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 and diarrhoea or vomiting. These conditions should be corrected prior to administration of losartan, or a lower starting dose should be used. 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. In a clinical study conducted in type 2 diabetic patients with nephropathy, the incidence of hyperkalemia was higher in the group treated with losartan as compared to the placebo group .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 3050 ml/ min should be closely monitored.
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. Therefore losartan must not be administered in patients with severe hepatic impairment.
Losartan is not recommended in children with hepatic impairment.
Renal impairment
As a consequence of inhibiting the rennin-angiotensin system, changes in renal function including renal failure has 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 medicinal products 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.
Use in paediatric patients with renal impairment
Losartan is not recommended in children with glomerular filtration rate < 30 ml/ min/ 1.73 m2 as no data are available.
Renal function should be regularly monitored during treatment with losartan as it may deteriorate. This applies particularly when losartan is given in the presence of other conditions (fever, dehydration) likely to impair renal function.
Pregnancy
Losartan should not be initiated during pregnancy. Unless continued losartan therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with losartan should be stopped immediately, and, if appropriate, alternative therapy should be started.

Overdosage:
Symptoms of intoxication
No case of overdose has been reported. The most likely symptoms, depending on the extent of overdose, are hypotension, tachycardia, possibly bradycardia.
Treatment of intoxication
Measures are depending on the time of medicinal product intake and kind and severity of symptoms. Stabilisation of the cardiovascular system should be given priority. After oral intake, the administration of a sufficient dose of activated charcoal is indicated. Afterwards, close monitoring of the vital parameters should be performed. Vital parameters should be corrected if necessary.
Neither losartan nor the active metabolite can be removed by haemodialysis.
Contraindications:
Hypersensitivity to the active substance or to any of the Excipients, 2nd and 3rd trimester of pregnancy Severe Severe hepatic impairment.

Pharmaceutical Form: Film-coated tablet.
Pharmacotherapeutic group:
Anti Hypertensive, Angiotensin II receptor antagonists. АТС
C09CA01.
Pharmacologic properties:
Pharmacodynamics:
Losartan is a synthetic oral angiotensin II receptor (type AT1) antagonist. Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin/angiotensin system and an important determinant of the pathophysiology of hypertension. Angiotensin II binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone. Angiotensin II also stimulates smooth muscle cell proliferation.
Losartan selectively blocks the AT1 receptor. In vitro and in vivo losartan and its pharmacologically active carboxylic acid metabolite E3174 block all physiologically relevant actions of angiotensin II, regardless of the source or route of its synthesis.
Losartan does not have an agonist effect nor does it block other hormone receptors or ion channels important in cardiovascular regulation. Furthermore losartan does not inhibit ACE (kininase II), the enzyme that degrades bradykinin.
During administration of losartan, removal of the angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA). Increase in the PRA leads to an increase in angiotensin II in plasma. Despite these increases, antihypertensive activity and suppression of plasma aldosterone concentration are maintained, indicating effective angiotensin II receptor blockade. After discontinuation of losartan, PRA and angiotensin II values fell within three days to the baseline values.
Both losartan and its principal active metabolite have a far greater affinity for the AT1receptor than for the AT2receptor. The active metabolite is 10 to 40 times more active than losartan on a weight for weight basis.
Hypertension studies
In controlled clinical studies, once daily administration of losartan to patients with mild to moderate essential hypertension produced statistically significant reductions in systolic and diastolic blood pressure. Measurements of blood pressure 24 hours post dose relative to 5 – 6 hours post dose demonstrated blood pressure reduction over 24 hours; the natural diurnal rhythm was retained. Blood pressure reduction at the end of the dosing interval was 70 – 80 % of the effect seen 56 hours post dose.
LIFE study
The Losartan Intervention for Endpoint Reduction in Hypertension [LIFE] study was a randomised, triple blind, active controlled study in 9193 hypertensive patients aged 55 to 80 years with ECG documented left ventricular hypertrophy. Patients were randomised to once daily losartan 50 mg or once daily atenolol 50 mg. If goal blood pressure (< 140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. Other antihypertensives, with the exception of ACE inhibitors, angiotensin II antagonists or betablockers were added if necessary to reach the goal blood pressure.
Paediatric hypertension
The antihypertensive effect of losartan was established in a clinical study involving 177 hypertensive paediatric patients 6 to 16 years of age with a body weight> 20 kg and a glomerular filtration rate> 30 ml/ min/ 1.73 m2. Patients who weighed > 20 kg to < 50 kg received 2.5, 25 or 50 mg of losartan daily and patients who weighed > 50 kg received either 5, 50 or 100 mg of losartan daily. At the end of three weeks, losartan administration once daily lowered trough blood pressure in a dose-dependent manner.
Overall, there was a dose response. The dose response relationship became very obvious in the low dose group compared to the middle dose group (period I: 6.2 mmHg vs. 11.65 mmHg), but was attenuated when comparing the middle dose group with the high dose group (period I: 11.65 mmHg vs. 12.21 mmHg). The lowest doses studied, 2.5 mg and 5 mg, corresponding to an average daily dose of 0.07 mg/ kg, did not appear to offer consistent antihypertensive efficacy.
Pharmacokinetics: Absorption
Following oral administration, losartan is well absorbed and undergoes first pass metabolism, forming an active carboxylic acid metabolite and other inactive metabolites. The systemic bioavailability of losartan tablets is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 34 hours, respectively.
Distribution
Both losartan and its active metabolite are 99% bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 litres.
Biotransformation
About 14% of an intravenously or orally administered dose of losartan is converted to its active metabolite. Following oral and intravenous administration of 14C-labelled losartan potassium, circulating plasma radioactivity primarily is attributed to losartan and its active metabolite. Minimal conversion of losartan to its active metabolite was seen in about 1% of individuals studied.
In addition to the active metabolite, inactive metabolites are formed.
Elimination
Plasma clearance of losartan and its active metabolite is about 600 ml/min and 50 ml/min, respectively. Renal clearance of losartan and its active metabolite is about 74 ml/min and 26 ml/min, respectively. When losartan is administered orally, about 4% of the dose is excreted unchanged in the urine, and about 6% of the dose is excreted in the urine as active metabolite. The pharmacokinetics of losartan and its active metabolite are linear with oral losartan potassium doses up to 200 mg.
Following oral administration, plasma concentrations of losartan and its active metabolite decline poly-exponentially, with a terminal half-life of about 2 hours and 69 hours, respectively. During once daily dosing with 100 mg, neither losartan nor its active metabolite accumulates significantly in plasma.
Both biliary and urinary excretions contribute to the elimination of losartan and its metabolites. Following an oral dose/intravenous administration of 14Clabelled losartan in man, about 35% / 43% of radioactivity is recovered in the urine and 58%/ 50% in the faeces.

Storage condition: Store below 30°C.
Keep all medicines out of reach of children.
Adverse Drug reaction*:
“Inform doctors about unexpected reactions after using drugs”
Shelf-life:
36 months
Package:
Clear PVC/PVDC blister with aluminum foil.
Each blister contains 14 tablets. 2 or 10 such blisters are packed in a carton along with pack insert.
Manufacturer:
Kusum Healthcare Pvt. Ltd.
Address: SP 289 (A), RIICO INDL. AREA, CHOPANKI, BHIWADI (RAJ.), (INDIA).