Pharmacology: Pharmacodynamics: Losartan potassium represents the 1st of a new class of antihypertensives, is a specific angiotensin-II receptor (type AT1) antagonist. Angiotensin II is a potent vasoconstrictor and the primary active hormone of the renin-angiotensin-aldosterone system, playing a major part in the pathophysiology of
hypertension. The cardiovascular homeostatic effects of angiotensin II are elicited through the AT1 receptor. Losartan is a potent, synthetic orally active compound, which binds selectively to the AT1 receptor. In vitro and In vivo, both losartan and its pharmacologically active metabolite, E-3174 block all physiologically relevant actions of angiotensin II including vasoconstriction, sodium and water retention and sympathetic stimulation. This leads to reduction in the blood pressure. Losartan does not have agonist effects and does not bind or block other hormone receptors or ion channels important in cardiovascular regulation.
Pharmacokinetics: Following oral administration, losartan potassium is well absorbed and undergoes substantial first-pass metabolism; the systemic bioavailability is approximately 33%. It undergoes first-pass metabolism to form an active carboxylic acid metabolite E-3174 (EXP-317), which has greater pharmacological activity than losartan and E-3174 occur about 1 hr and 3-4 hrs, respectively, after an oral dose. Both losartan and E-3174 are >98% bound to plasma proteins. Losartan is excreted in the urine, and in the feces via bile, as unchanged drug and metabolites. Following oral dosing about 35% of the dose is excreted in the urine and about 60% in the feces. The terminal elimination half-lives (t½) of losartan and E-3174 are about 1.5-2.5 hrs and 3-9 hrs, respectively.
Management of hypertension.
Starting and Maintenance Dose: 25 or 50 mg once daily for most patients with or without food. The maximal antihypertensive effect is attained 3-6 weeks after initiation of therapy. Some patients may receive an additional benefit by increasing the dose up to 100 mg once daily, in 1 or 2 divided doses.
Intravascular Volume Depletion: In patients who are intravascularly volume depleted (eg, those treated with high-dose diuretics), symptomatic hypotension may occur. Such a condition should be corrected prior to administration of losartan or a lower starting dose should be used.
Elderly Up to 75 years: No initial dosage adjustment is necessary for this group of patients, or as prescribed by the physician. >75 years: At present there is limited clinical experience in this group; a lower starting dose of 25 mg once daily is recommended.
Renal Impairment: No initial dosage adjustment is necessary in patients with mild renal impairment ie, creatinine clearance (CrCl) 20-50 mL/min. For patients with moderate to severe renal impairment ie, CrCl <20 mL/min or patients on dialysis, lower starting dose of 25 mg once daily is recommended.
Hypersensitivity to losartan potassium or to any of the components of Besartan.
Use in pregnancy: Although there is no experience with the use of losartan in pregnant women, animal studies with losartan have demonstrated foetal and neonatal injury and death, the mechanism of which is believed to be its effects on the renin-angiotensin-aldosterone system. In humans, foetal renal perfusion, which is dependent upon the development of the renin-angiotensin-aldosterone system, begins in the 2nd trimester.
When used in pregnancy during the second trimesters, drugs that act directly on the renin-angiotensin-aldosterone system, begins can cause injury and even death in the developing foetus. Losartan is contraindicated in pregnancy, and if pregnancy is detected, losartan should be discontinued immediately.
Use in lactation: It is not known whether Losartan is excreted in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.
Intravascular Volume Depletion: In patients who are intravascularly volume depleted (eg, those treated with high-dose diuretics), symptomatic hypotension may occur. Such a condition should be corrected prior to administration of Losartan, or a lower starting dose should be used.
Hepatic Impairment: Based on pharmacokinetic data, which demonstrate significantly increased plasma concentrations of losartan, or a lower starting dose should be considered for patients with history of hepatic impairment.
Renal Artery Stenosis: Other drugs that affect the renin-angiotensin-aldosterone system may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. While not confirmed, this potentially may occur with angiotensin-II receptor antagonists.
Use in children: Safety and efficacy in children have not been established.
Use in pregnancy:
Although there is no experience with the use of losartan in pregnant
women, animal studies with losartan have demonstrated foetal and
neonatal injury and death, the mechanism of which is believed to be its
effects on the renin-angiotensin-aldosterone system. In humans, foetal
renal perfusion, which is dependent upon the development of the
renin-angiotensin-aldosterone system, begins in the 2nd trimester.
When used in pregnancy during the second trimesters, drugs that act
directly on the renin-angiotensin-aldosterone system, begins can cause
injury and even death in the developing foetus. Losartan is
contraindicated in pregnancy, and if pregnancy is detected, losartan
should be discontinued immediately.
Use in lactation: It is not known whether Losartan is
excreted in human milk. Because of the potential for adverse effects on
the nursing infant, a decision should be made whether to discontinue
breast-feeding or discontinue the drug, taking into account the
importance of the drug to the mother.
Adverse effects with losartan have usually been mild and transient in nature and have not required discontinuation of therapy. The overall incidence of adverse effects reported with losartan was comparable to placebo.
In controlled clinical trials of essential hypertension, dizziness was the only drug-related adverse effect that occurred with an incidence greater than placebo in ≥1% of patients treated with losartan. In addition, dose-related orthostatic effects were seen in <1% of patients. Rarely, rash was reported, although the incidence in controlled clinical trials was less than placebo. In contrast to ACE inhibitors, losartan is not found to cause accumulation of bradykinin and so incidence of cough observed with losartan is significantly less as compared to ACE inhibitors and is not more than that observed with placebo in several clinical trials.
No drug interactions of clinical significance have been identified with losartan. Compounds which have been studied in clinical pharmacokinetic trials include hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbitone.
Store at temperatures not exceeding 30°C.
Shelf-Life: 24 months.
C09CA01 - losartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Besartan FC tab 50 mg
100's (P1,450/box)
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