Trade Names:Cozaar- Tablets 25 mg- Tablets 50 mg- Tablets 100 mg
Blocks vasoconstriction and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the angiotensin II receptor (AT 1 receptor) in vascular smooth muscle and the adrenal gland.
Well absorbed. Food decreases absorption but has only minor effects on losartan AUC or AUC of active metabolite. Systemic bioavailability is about 33%. T max is 1 h (losartan) and 3 to 4 h (metabolite). While C max of drug and active metabolite are equal, metabolite AUC is 4 times greater than that of losartan.
Linear pharmacokinetics. Vd is 34 L (losartan) and 12 L (metabolite). Losartan and active metabolite are highly bound to plasma proteins, primarily albumin. Neither losartan or metabolite accumulates in plasma upon repeated daily dosing.
Undergoes substantial first-pass metabolism by CYP-450 2C9 and 3A4 enzymes. Fourteen percent of an oral dose is converted to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonist activity.
The t ½ is 2 h (losartan) and 6 to 9 h (metabolite). Renal Cl is 75 mL/min (losartan) and 25 mL/min (metabolite). Total plasma Cl is 600 mL/min (losartan) and 50 mL/min (metabolite). Biliary excretion contributes to the elimination of losartan and metabolite. About 4% is excreted unchanged in the urine and 6% excreted as active metabolite in urine.
Plasma concentrations and AUC of losartan and its active metabolite are increased 50% to 90% and renal Cl reduced 55% to 85% in patients with mild (CrCl 50 to 74 mL/min) and moderate (CrCl 30 to 49 mL/min) renal function impairment. Make dose adjustments as needed unless the patient is volume depleted.Hepatic Function Impairment
Plasma concentrations of losartan are increased 5 times and active metabolite increased 1.7 times in patients with mild to moderate alcoholic cirrhosis. Total plasma Cl of losartan is reduced about 50% and oral bioavailability is increased 2 times. A lower starting dose is recommended.Gender
Plasma losartan concentrations are twice as high in hypertensive women as hypertensive men, but plasma concentrations of active metabolite are similar. No dosage adjustment is necessary.
Treatment of hypertension; nephropathy in type 2 diabetic patients; reduce risk of stroke in patients with hypertension and left ventricular hypertrophy.
PO 50 mg/day; 25 mg/day if volume depleted or history of hepatic impairment.Maintenance dose
PO 25 to 100 mg/day.Children 6 yr of age and older Initial dose
PO 0.7 mg/kg (max, 50 mg) once daily.Maintenance dose
PO 0.7 to 1.4 mg/kg/day (max, 100 mg).Nephropathy in Type 2 DiabetesAdults Initial dose
PO 50 mg/day; the dose may be increased to 100 mg/day based on BP response.Hypertension in Patients with Left Ventricular HypertrophyAdults
PO 50 mg/day; add hydrochlorothiazide 12.5 mg/day and/or increase the dose of losartan to 100 mg/day followed by an increase in hydrochlorothiazide to 25 mg/day based on BP response.
Store tablets at controlled room temperature (59° to 86°F). Protect from light. Store suspension in refrigerator (36° to 46°F) for up to 4 wk. Discard any unused suspension after 4 wk.
Losartan plasma levels may be elevated, increasing the antihypertensive and adverse effects.Grapefruit juice
Rate and magnitude of losartan metabolism to its active metabolite may be decreased, possibly reducing the efficacy; however, based on available data, a clinically important interaction is unlikely.Indomethacin
The antihypertensive effect of losartan may be blunted.Lithium
Plasma concentrations may be increased by losartan, resulting in an increase in the pharmacologic and adverse effects of lithium.Potassium supplement
Concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.Rifamycins (eg, rifampin)
Losartan plasma levels may be reduced, decreasing the antihypertensive effects.
None well documented.
Hypotension (7%); orthostatic hypotension (4%).
Asthenia/fatigue (14%); hypesthesia (5%); dizziness (3%).
Cataract (7%); nasal congestion (2%).
Diarrhea (15%); gastritis (5%); dyspepsia (4%).
Anaphylactic reactions, angioedema (including swelling of the larynx and glottis, swelling of the face, lips, pharynx, and tongue), vasculitis (including Henoch-Schönlein purpura) (postmarketing).
Minor increases in BUN or serum creatinine, small decreases in Hgb and Hct, occasional elevations in liver enzymes and serum bilirubin (postmarketing).
Hypoglycemia (14%); hyperkalemia (7%); weight gain (4%); hyponatremia (postmarketing).
Back pain (12%); muscular weakness (7%); knee pain, leg pain (5%); muscle cramp (1%); rhabdomyolysis (postmarketing).
Cough (11%); bronchitis (10%); upper respiratory tract infection (8%); sinusitis (6%); dry cough (postmarketing).
Chest pain (12%); diabetic vascular disease, influenzaî“¸like symptoms (10%); infection (5%); diabetic neuropathy, fever, trauma (4%).
When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.
Category D (second and third trimester); Category C (first trimester).
Safety and efficacy not established in hypertensive patients younger than 6 yr of age or in children with GFR less than 30 mL/min/1.73 m 2 .
Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and tongue have been reported rarely.
Use caution in treating patients whose renal function may depend on the renin-angiotension-aldosterone system (eg, patients with severe CHF).
A lower starting dose is recommended for patients with hepatic impairment.
May not be as effective in black hypertensive patients, especially those with left ventricular hypertrophy.
Symptomatic hypotension may occur after initiation of losartan in patients who are volume depleted (eg, those treated with diuretics). Correct these conditions prior to administration of losartan or use a lower starting dose.
Bradycardia, hypotension, tachycardia.
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