Category:
Antihypertensive, angiotensin II receptor antagonist.                                                                       (USP DI 2004)
Composition:
Each film-coated tablet contains 25 or 50 mg of Losartan potassium.
Chemistry:
Losartan potassium a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-[ p-(o -1 H - tetrazol-5-ylphenyl)-benzyl] imidazole-5-methanol monopotassium salt. Its empirical formula is C22H22ClKN6O, and its structural formula is:

Molecular weight: 461.01                                               (PDR 2005)
Mechanism of Action:
Angiotensin II, is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone- secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland).                                                      (PDR 2005)       
Pharmacokinetics:
- Absorption: Well-absorbed. Bioavailability approximately 33%
- Protein binding: 98.7% (Carboxylic acid metabolite: 99.8%)
- Biotransformation: By Cytp450
- Half-life: (elimination): Losartan 2h, carboxylic acid: 6-9h
- Elimination: Renal (35%), fecal (60%)                                                                                              (USP DI 2004)
Indications:
Lozar is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.                                                                                                                                 (USP DI 2004)
Contraindications:
Lozar is contraindicated in patients who are hypersensitive to any component of this product.               (PDR 2005)
Warnings:
Fetal / Neonatal Morbidity and Mortality
Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected Lozar should be discontinued as soon as possible.
The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death.
Hypotension-Volume-Depleted Patients:
In patients who are intravascularly volume-depleted (e.g those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with Lozar. These conditions should be corrected prior to administration of Lozar or a lower starting dose should be used.                                                                              (PDR 2005)
Precautions:
Impaired Hepatic Function: Based on pharmacokinetic data which demonstrate significantly increased plasma concentrations of Lozar in cirrhotic patients, a lower dose should be considered for patients with impaired liver function.
Hypersensitivity: Angioedema
Impaired Renal Function: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with Lozar; in some patients, these changes in renal function were reversible upon discontinuation of therapy.
In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and /or progressive azotemia and (rarely) with acute renal failure and/ or death. Similar outcomes have been reported with Lozar. In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases, in serum creatinine or BUN have been reported. Similar effects have been reported with Lozar; in some patients, these effects were reversible upon discontinuation of therapy.
(PDR 2005)       
Usage in Pregnancy:
Pregnancy Categories C (first trimester) and D (second and third trimesters).                                             (PDR 2005)
Nursing Mothers: It is not known whether Lozar is excreted in human milk but significant levels of Lozar and its active metabolite were shown to be present in rat milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.                                                                                    (PDR 2005)
Pediatric Use:
Safety and effectiveness in pediatric patients have not been established.                                               (PDR 2005)
Drug Interactions:
No significant drug-drug pharmacokinetics interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.
As with other drugs that block angiotensin II or its effects, 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.                                                                                      (PDR 2005)
Adverse Reactions:
In general treatment with Lozar is well-tolerated. The overall incidence of adverse experiences reported with Lozar was similar to placebo. Some adverse reactions which occur in at least 1% of patients treated with Losartan and occur more frequent on Losartan than placebo are: diarrhea, muscle cramps, pain in back and leg, dizziness, insomnia, nasal congestion.                                                                                            (PDR 2005)
Dosage and Administration:
The usual starting dose of Lozar is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) and patients with a history of hepatic impairment. Lozar can be administered once or twice daily with total daily doses ranging from 25 mg to 100 mg.
If the antihypertensive effect measured at through using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response.
If blood pressure is not controlled by Lozar alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect.
No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis.
Lozar may be administered with other antihypertensive agents. Lozar may be administered with or without food.                                                                                                                                                  (PDR 2005)
Storage:
Store below 40°C, preferably between15 and 30°C, in a tightly closed container. Protect from light.   (USP DI 2004)
How Supplied:
Lozar 25 mg is available as blue, scored, oblong film-coated tablet. There are blisters of 10’s, boxes of 30’s.
Lozar 50 mg is available as light violet, scored, oblong film-coated tablet. There are blisters of 10’s, boxes of 30’s.
References:
• (USP DI 2004)              • (PDR 2005)