Full Prescribing Info
Losartan potassium.
Each tablet contains Losartan potassium 50 mg.
Losartan potassium, the first of a new class of agents for the treatment of hypertension, is an angiotensin II receptor (type AT1) antagonist.
Losartan potassium also provides a reduction in the combined risk of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy and renal protection for type 2 diabetic patients with proteinuria.
Pharmacology: Pharmacodynamics: Losartan potassium, the first of a new class of agents for the treatment of hypertension is an angiotensin II receptor (type AT1) antagonist.
Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin-angiotensin system, and a major 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 vasocontriction and the release of aldosterone. Angiotensin II also stimulates smooth muscle cell proliferation. A second angiotensin II receptor has been identified as the AT2 receptor subtype, but it plays no known role in cardiovascular homeostasis.
Losartan is a potent, synthetic, orally active compound. Based on binding and pharmacological bioassays, it binds selectively to the AT1 receptor. In vitro and in vivo, both losartan and its pharmacologically active carboxylic acid metabolite (E-3174) block all physiologically relevant actions of angiotensin II, regardless of the source or route of synthesis. In contrast to some peptide antagonists of angiotensin II, losartan has no agonist effects.
Losartan binds selectively to the AT1 receptor and does not bind to or block other hormone receptors or ion channels important in cardiovascular regulation. Furthermore, losartan does not inhibit ACE (kininase II), the enzyme that degrades bradykinin.
Consequently, effects not directly related to blocking the AT1 receptor, such as the potentiation of bradykinin-mediated effects or the generation of oedema, are not associated with losartan.
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 3-4 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. Studies in rats indicate that losartan crosses the blood-brain barrier poorly, if at all.
Metabolism: About 14% of an intravenously- or orally-administered dose of losartan is converted to its active metabolite.
In addition to the active metabolite, inactive metabolites are formed, including two major metabolites formed by hydroxylation of the butyl side chain and a minor metabolite, an N-2 tetrazole glucuronide.
Elimination: Plasma clearance of losartan and its active metabolite is about 600mL/min and 50mL/min, respectively. Renal clearance of losartan and its active metabolite is about 74mL/min and 26mL/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 polyexponentially with a terminal half-life of about 2 hours and 6-9 hours, respectively. During once-daily dosing with 100 mg, neither losartan nor its active metabolite accumulates significantly in plasma.
Both biliary and urinary excretion contribute to the elimination of losartan and its metabolites.
Hypertension: Zosaar is indicated for the treatment of hypertension.
Reduction in the Risk of Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy: Indicated to reduce the risk of cardiovascular morbidity and mortality as measured by the combined incidence of cardiovascular death, stroke and myocardial infarction in hypertension patients with left ventricular hypertrophy.
Renal Protection in Type 2 Diabetic Patients with Proteinuria: Indicated to delay the progression of renal disease as measured by a reduction in the combined incidence of doubling of serum creatinine, end stage renal disease (need for dialysis or renal transplantation), or death; and to reduce proteinuria.
Dosage/Direction for Use
Zosaar 50mg Tablet 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 3-6 weeks after initiation of therapy. Some patients may receive an additional benefit by increasing the dose to 100mg once daily.
For patients with intravascular volume-depletion (e.g., those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered (see PRECAUTIONS).
No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis. A lower dose should be considered for patients with a history of hepatic impairment (see PRECAUTIONS).
Reduction in the Risk of Cardiovascular Morbidity and Mortality in Hypertensive Patients with Left Ventricular Hypertrophy: The usual starting dose is 50 mg of Zosaar once daily. A low dose of hydrochlorothiazide should be added and/or the dose of Zosaar should be increased to 100 mg once daily based on blood pressure response.
Renal Protection in Type 2 Diabetic Patients with Proteinuria: The usual starting dose is 50 mg once daily. The dose may be increased to 100 mg once daily based on blood pressure response.
Zosaar 50mg Tablet may be administered with other anti-hypertensive agents (e.g., diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting agents) as well as insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones and glucosidase inhibitors).
Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.
Neither losartan nor the active metabolite can be removed by haemodialysis.
Zosaar 50mg Tablet is contraindicated in patients who are hypersensitive to any component of this product.
Special Precautions
Hypersensitivity: Angioedema. (See Side Effects.)
Hypotension and Electrolyte/Fluid Imbalance: In patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of Zosaar 50mg Tablet, or a lower starting dose should be used (see Dosage & Administration).
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 proteinuria, the incidence of hyperkalaemia was higher in the group treated with Zosaar 50mg Tablet as compared to the placebo group; however, few patients discontinued therapy due to hyperkalaemia (see Laboratory Test Findings under Side Effects).
Liver Function 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 (see Dosage & Administration).
Renal Function Impairment: As a consequence of inhibiting the renin-angiotensin system, changes in renal function including renal failure have been reported in susceptible individuals; these changes in renal function may be reversible upon discontinuation of therapy.
Other medicines that affect the renin-angiotensin system may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Similar effects have been reported with Zosaar 50mg Tablet; these changes in renal function may be reversible upon discontinuation of therapy.
Use in Children: Safety and effectiveness in children have not been established.
Use in Elderly: There is no age-related difference in the efficacy or safety profile of losartan.
Use In Pregnancy & Lactation
Pregnancy: When used in pregnancy during the second and third trimesters, medicines that act directly on the renin-angiotensin system can cause injury and even death in the developing fetus. When pregnancy is detected, Zosaar 50mg Tablet should be discontinued as soon as possible.
Although there is no experience with the use of Zosaar 50mg Tablet in pregnant women, animal studies with losartan potassium have demonstrated foetal and neonatal injury and death, the mechanism of which is believed to be pharmacologically mediated through effects on the renin-angiotensin system. In humans, foetal renal perfusion, which is dependent upon the development of the renin angiotensin system, begins in the second trimester; thus risk to the foetus increased if Zosaar 50mg Tablet is administered during the second or third trimesters of pregnancy.
Nursing Mothers: It is not known whether losartan is excreted in human milk. Because many medicines are excreted in human milk and because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the medicine, taking into account the importance of the medicine to the mother.
Side Effects
Losartan potassium has been found to be generally well tolerated in hypertension; side effects have usually been mild and transient in nature and have not required discontinuation of therapy.
The most common drug-related side effects are asthenia/fatigue, dizziness, hypotension and hyperkalaemia (see Hypotension and Electrolyte/Fluid Imbalance under Precautions).
Hypersensitivity have been reported in post-marketing experience. Anaphylactic reactions, angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other medicines including ACE inhibitors.
Vasculitis, including Henoch-Schoenlein purpura, has been reported rarely.
Gastrointestinal: Hepatitis (reported rarely), liver function abnormalities, vomiting.
Haematologic: Anaemia.
Musculoskeletal: Myalgia.
Nervous System/Psychiatric: Migraine.
Respiratory: Cough.
Skin: Urticaria, pruritus.
Drug Interactions
No interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital and ketoconazole and erythromycin. Rifampicin and fluconazole have been reported to reduce levels of active metabolite. The clinical consequences of these interactions have been evaluated. As with other medicines that block angiotensin II or its effect, concomitant use of potassium sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.
As with other antihypertensive agents, the antihypertensive effect of losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin.
Store below 30°C. Protect from light and moisture.
ATC Classification
C09CA01 - losartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
FC tab 50 mg (an oval-shaped, biconvex, white; on one side engraved with E117, and with breakline on the other) x 3 x 10's. 2 x 14's
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