Losartan Potassium

 Losartan

Absorption

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.

Distribution

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.

Metabolism

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.

Elimination

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.

Special Populations

Renal Function Impairment
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.

Indications and Usage

Treatment of hypertension; nephropathy in type 2 diabetic patients; reduce risk of stroke in patients with hypertension and left ventricular hypertrophy.

Contraindications

Standard considerations.

Dosage and Administration

Hypertension
Adults Initial dose 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 Diabetes
Adults 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 Hypertrophy
Adults 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.

General Advice

• May use alone or in combination with other antihypertensive agents.
• Administer without regard to meals. Administer with food if GI upset occurs.
• Preparation of 2.5 mg/mL suspension for pediatric use: Add 10 mL purified water to an 8 oz (240 mL) amber polyethylene terephthalate (PET) bottle containing ten 50 mg losartan tablets; immediately shake for 2 min; let stand for 1 h then shake for 1 min to disperse tablet contents; add 190 mL of 50/50 mixture of Ora-Plus and Ora-Sweet SF and shake for 1 min to disperse ingredients.
• Shake suspension well before measuring and administering prescribed dose. Use dosing syringe, dosing spoon, or dosing cup to measure and administer dose. Return suspension to refrigerator immediately after measuring dose.

Storage/Stability

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.