Pronunciation:

(loe SAR tan)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

>10%:

Cardiovascular: Chest pain (12% diabetic nephropathy)

Central nervous system: Fatigue (14% diabetic nephropathy)

Endocrine: Hypoglycemia (14% diabetic nephropathy)

Gastrointestinal: Diarrhea (2% hypertension to 15% diabetic nephropathy)

Genitourinary: Urinary tract infection (13% diabetic nephropathy)

Hematologic: Anemia (14% diabetic nephropathy)

Neuromuscular & skeletal: Weakness (14% diabetic nephropathy), back pain (2% hypertension to 12% diabetic nephropathy)

Respiratory: Cough (11% diabetic nephropathy; 17% to 29% hypertension but similar to that associated with hydrochlorothiazide or placebo therapy)

1% to 10%:

Cardiovascular: Hypotension (7% diabetic nephropathy), orthostatic hypotension (4% hypertension to 4% diabetic nephropathy), first-dose hypotension (dose related: <1% with 50 mg, 2% with 100 mg)

Central nervous system: Dizziness (4%), hypoesthesia (5% diabetic nephropathy), fever (4% diabetic nephropathy), insomnia (1%)

Dermatology: Cellulitis (7% diabetic nephropathy)

Endocrine: Hyperkalemia (<1% hypertension to 7% diabetic nephropathy)

Gastrointestinal: Gastritis (5% diabetic nephropathy), weight gain (4% diabetic nephropathy), dyspepsia (1% to 4%), abdominal pain (2%), nausea (2%)

Neuromuscular & skeletal: Muscular weakness (7% diabetic nephropathy), knee pain (5% diabetic nephropathy), leg pain (1% to 5%), muscle cramps (1%), myalgia (1%)

Respiratory: Bronchitis (10% diabetic nephropathy), upper respiratory infection (8%), nasal congestion (2%), sinusitis (1% hypertension to 6% diabetic nephropathy)

Miscellaneous: Infection (5% diabetic nephropathy), flu-like syndrome (10% diabetic nephropathy)

>1% but frequency placebo: Edema, abdominal pain, nausea, headache, pharyngitis

<1% (Limited to important or life-threatening): Allergic reaction, alopecia, anaphylactic reactions, anemia, angina, angioedema, anorexia, anxiety, arm pain, arrhythmia, arthralgia, arthritis, ataxia, AV block (second degree), bilirubin increased, blurred vision, bradycardia, bronchitis, BUN increased, confusion, conjunctivitis, constipation, CVA, dental pain, depression, dermatitis, diaphoresis, dry skin, dyspnea, ecchymosis, epistaxis, erythema, facial edema, fever, flatulence, flushing, gastritis, gout, hematocrit decreased, hemoglobin decreased, hepatitis, hip pain, hyperkalemia, hyponatremia, hypotension, impotence, joint swelling, libido decreased, memory impairment, MI, migraine, muscle weakness, nervousness, nocturia, orthostatic effects, palpitation, paresthesia, peripheral neuropathy, pharyngitis, photosensitivity, pruritus, rash, rhinitis, serum creatinine increased, sleep disorder, somnolence, syncope, tachycardia, taste perversion, tinnitus, transaminases increased, tremor, urinary frequency, urticaria, ventricular arrhythmia, vertigo, visual acuity decreased, vomiting, xerostomia

Postmarketing and/or case reports: Acute psychosis with paranoid delusions, ageusia, anemia, dysgeusia, Henoch-Sch&ouml;nlein purpura, pancreatitis, maculopapular rash, vasculitis; rhabdomyolysis has been reported (rarely) with angiotensin-receptor antagonists

Overdosage/Toxicology:

Drug Interactions:

CYP2C8/9 inducers: May decrease the levels/effects of losartan. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.

CYP2C8/9 substrates: Losartan may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of losartan. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

Fluconazole: Increases plasma levels of losartan via 2C8/9 inhibition (decreases the plasma levels of the active metabolite). Monitor for increased losartan efficacy.

Lithium: Risk of toxicity may be increased by losartan; monitor lithium levels.

NSAIDs: May decrease angiotensin II antagonist efficacy; effect has been seen with losartan, but may occur with other medications in this class; monitor blood pressure

Potassium-sparing diuretics (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Rifampin may reduce antihypertensive efficacy of losartan.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Ethanol/Nutrition/Herb Interactions:

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: 6 hours

Distribution: Vd: Losartan: 34 L; E-3174: 12 L; does not cross blood brain barrier

Protein binding, plasma: High

Metabolism: Hepatic (14%) via CYP2C9 and 3A4 to active metabolite, E-3174 (40 times more potent than losartan); extensive first-pass effect

Bioavailability: 25% to 33%; AUC of E-3174 is four times greater than that of losartan

Half-life elimination: Losartan: 1.5-2 hours; E-3174: 6-9 hours

Time to peak, serum: Losartan: 1 hour; E-3174: 3-4 hours

Excretion: Urine (4% as unchanged drug, 6% as active metabolite)

Clearance: Plasma: Losartan: 600 mL/minute; Active metabolite: 50 mL/minute

Dosage:

Hypertension:

Children 6-16 years: 0.7 mg/kg once daily (maximum: 50 mg/day); adjust dose based on response; doses >1.4 mg/kg (maximum: 100 mg) have not been studied

Adults: Usual starting dose: 50 mg once daily; can be administered once or twice daily with total daily doses ranging from 25-100 mg

Patients receiving diuretics or with intravascular volume depletion: Usual initial dose: 25 mg

Nephropathy in patients with type 2 diabetes and hypertension: Adults: Initial: 50 mg once daily; can be increased to 100 mg once daily based on blood pressure response

Stroke reduction (HTN with LVH): Adults: 50 mg once daily (maximum daily dose: 100 mg); may be used in combination with a thiazide diuretic

Dosing adjustment in renal impairment:

Children: Use is not recommended if Clcr<30 mL/minute.

Adults: No adjustment necessary.

Dosing adjustment in hepatic impairment: Reduce the initial dose to 25 mg/day; divide dosage intervals into two.

Administration:

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Nursing Implications:

Anesthesia and Critical Care Concerns/Other Considerations:

Congestive Heart Failure: Currently, the use of angiotensin II receptor blockers (ARBs) should not supersede angiotensin converting enzyme inhibitors (ACEIs) in the treatment of congestive heart failure. One may be considered, however, when an ACEI cannot be tolerated. Because they are angiotensin II blockers rather than inhibitors of ACE, ARBs do not cause increases in bradykinin levels. Angiotensin II receptor blockers are less likely to be associated with nonrenin-angiotensin effects such as cough and, presumably, angioedema. However, reports exist describing patients who previously experienced ACE inhibitor-related angioedema also experienced angioedema when administered ARBs. Whether this is a true cross-reactivity or circumstantial is currently unknown; therefore, until more information is available, ARBs should be used cautiously, if at all, in patients with a history of ACEI associated angioedema. ARBs have been known to cause hyperkalemia and renal dysfunction.

Cardiovascular Considerations:

Congestive Heart Failure: Currently, the use of angiotensin II receptor blockers (ARBs) should not supersede angiotensin converting enzyme inhibitors (ACEIs) in the treatment of congestive heart failure. One may be considered, however, when an ACEI cannot be tolerated. Because they are angiotensin II blockers rather than inhibitors of ACE, ARBs do not cause increases in bradykinin levels. Angiotensin II receptor blockers are less likely to be associated with nonrenin-angiotensin effects such as cough and, presumably, angioedema. However, reports exist describing patients who previously experienced ACE inhibitor-related angioedema also experienced angioedema when administered ARBs. Whether this is a true cross-reactivity or circumstantial is currently unknown; therefore, until more information is available, ARBs should be used cautiously, if at all, in patients with a history of ACEI associated angioedema. ARBs have been known to cause hyperkalemia and renal dysfunction.

Since ACEIs and ARBs have different sites of action, it has been hypothesized that ACEIs and ARBs could be used in combination for an enhanced response in heart failure patients. In the VeHeft (Cohn JN, 2001), patients with heart failure (most treated with ACEIs, diuretics, and digoxin and with about one-third receiving beta-blockers), were randomized to receive valsartan or placebo. Overall, the addition of valsartan did not impact survival but it reduced morbidity. Of note, during subgroup analysis, it was observed that in patients receiving both a beta-blocker and ACEI, the addition of valsartan worsened survival and morbidity. This effect needs to be studied further; but, in the meantime, use caution when combining an ACEI with an ARB in an individual already receiving a beta-blocker.

Hypertension (HTN): Losartan is effective in the treatment of hypertension. Some conditions where an ARB may be a good component of an effective hypertension regimen include: Heart failure, diabetes, chronic kidney disease, and left ventricular hypertrophy (LVH). In patients with HTN and symptomatic ventricular dysfunction or end-stage heart disease, ACE inhibitors, beta-blockers, ARBs, or aldosterone blockers are recommended along with loop diuretics. Angiotensin II receptor blockers affect the progression of diabetic nephropathy, reduce albuminuria, and may reduce progression to macroalbuminuria. They may also slow the progression of nondiabetic kidney disease. Continuation of an ARB in a patient whose serum creatinine has increased to <35% above baseline is acceptable unless accompanied by hyperkalemia.

Losartan has been compared to atenolol in patients with HTN and LVH in a double-blind trial (Dahlof B, 2002). Patients were randomized to receive once-daily losartan (50-100 mg) or atenolol (50-100 mg) with hydrochlorothiazide (12.5-25 mg) as the second agent in both arms of the study. The main outcome measure was a composite of cardiovascular death, stroke or myocardial infarction. After a mean duration of ~5 years, patients in the losartan group had a better outcome than atenolol, primarily due to a reduction in stroke. Losartan also was better tolerated. Losartan was recently FDA-approved to reduce the risk of stroke in patients with HTN and LVH.

Concomitant indomethacin therapy may blunt the reduction in sitting and 24-hour ambulatory diastolic blood pressure; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control in this setting. In patients with heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Extemporaneously Prepared:

International Brand Names: