Losartan potassium, a nonpeptide tetrazole derivative, is an angiotensin II type 1 (AT1) receptor antagonist (also referred to as an angiotensin II receptor blocker [ARB]).1,2
Losartan is used alone or in combination with other classes of antihypertensive agents, including diuretics, in the management of hypertension.1,2 Losartan monotherapy is used to treat hypertension in adults and pediatric patients aged ≥6 years.1,60
Efficacy of losartan for the treatment of hypertension in adults was established in placebo-controlled studies of 6-12 weeks' duration in patients with hypertension (baseline diastolic blood pressure: 95-115 mm Hg).1 In these patients, losartan potassium dosages of 50-150 mg once daily were associated with mean decreases in systolic blood pressure of 5.5-10.5 mm Hg and diastolic blood pressure of 3.5-7.5 mm Hg.1 Daily dosages of 150 mg did not result in greater decreases in blood pressure compared with daily dosages of 50-100 mg.1 Larger decreases in trough blood pressures were observed with twice-daily dosing compared with once daily dosing in patients receiving daily dosages of 50-100 mg.1 Rebound hypertension following abrupt withdrawal of the drug has not been reported.1
Efficacy of losartan for the treatment of hypertension in pediatric patients was established in a double-blind dose-response study conducted in patients aged 6-16 years.1,60 In the first part of the trial, patients were stratified by weight (<50 or ≥50 kg) and randomized to receive low (2.5 or 5 mg), medium (25 or 50 mg), or high (50 or 100 mg) doses of losartan once daily.1,60 After 3 weeks, the 2 higher doses of losartan reduced diastolic blood pressure by 5-6 mm Hg more than the lowest dose; the lowest dose was not consistently found to be efficacious.1,60 In the second part of the trial, patients underwent a double-blind washout to receive placebo or continue with losartan at the same dosage from the first part of the trial for an additional 2 weeks.1,60 In the second part of the trial, patients who were switched from medium or high-dose losartan to placebo had a mean increase in diastolic blood pressure of 6 mm Hg compared to those who continued to receive active treatment; diastolic blood pressure was similar in patients who switched from low-dose losartan to placebo.1,60
Angiotensin II receptor antagonists, such as losartan, are considered one of several preferred antihypertensive drugs for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, and thiazide diuretics.1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.1200
Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as diabetes mellitus or chronic kidney disease (CKD); angiotensin II receptor antagonists also may be preferred, generally as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or following myocardial infarction (MI).1200
In patients with hypertension and compelling indications (e.g., CKD with albuminuria [urine albumin 300 mg/day or greater, or urine albumin:creatinine ratio of 300 mg/g or equivalent in the first morning void]), angiotensin II receptor antagonists are usually considered an alternative for ACE inhibitor-intolerant patients.1200,1218 However, data indicate no difference in efficacy between ACE inhibitors and angiotensin II receptor antagonists with regard to blood pressure lowering and clinical outcomes (i.e., all-cause mortality, cardiovascular mortality, MI, heart failure, stroke, and end-stage renal disease).1200,1218 Adverse events (e.g., cough, angioedema) leading to drug discontinuance occur more frequently with ACE inhibitor therapy than with angiotensin II receptor antagonist therapy.1218 Because of similar efficacy and a lower frequency of adverse effects, some experts believe that angiotensin II receptor antagonists should be used instead of an ACE inhibitor for the treatment of hypertension or hypertension with certain compelling indications.1218
Most patients with hypertension, especially Black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 Angiotensin II receptor antagonists such as losartan may produce a smaller blood pressure response in hypertensive Black patients compared with non-Black patients.1,2 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar blood pressure lowering in Black patients as in other racial groups.1200
Stroke Reduction in Left Ventricular Hypertrophy
Losartan is used alone or in combination with other antihypertensive agents (e.g., hydrochlorothiazide) to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy;1,2,53 however, there is evidence that the benefit associated with such losartan-based antihypertensive therapy does not apply to Black patients.1,53
In a randomized, double-blind, comparative study (Losartan Intervention for Endpoint [LIFE] reduction in hypertension) of approximately 4 years' duration in more than 9000 patients, losartan-based antihypertensive therapy (e.g., losartan 50-100 mg with hydrochlorothiazide 12.5-25 mg daily) reduced the risk of the primary outcome of combined cardiovascular death, stroke, and MI (relative risk reduction of about 13%, adjusted for Framingham risk score and baseline left ventricular hypertrophy) compared with atenolol-containing therapy (e.g., atenolol 50-100 mg with hydrochlorothiazide 12.5-25 mg daily) despite similar control of blood pressure with each regimen.1,53 In addition, the rate of drug-related adverse events and the incidence of new-onset diabetes mellitus was less in patients receiving losartan-based therapy.53 The study population consisted primarily of white patients, 55-80 years of age, with ECG evidence of left ventricular hypertrophy but who did not have low left-ventricular ejection fraction (40% or less) or heart failure.1,2,53 The results of the study provided no evidence that the benefits of losartan in reducing the risk of cardiovascular events in patients with hypertension and left ventricular hypertrophy apply to Black patients.1 Among Black patients in the study, the risk of experiencing the primary outcome of combined cardiovascular death, stroke, and MI was lower in patients receiving atenolol (11%) than in patients receiving losartan (17%).1,2
Subgroup analysis of the LIFE study (mean follow-up 4.7 years) suggests that aspirin therapy at baseline in patients receiving losartan reduced the risk of the primary outcome of combined cardiovascular death, stroke, and MI (relative risk reduction of about 32%, adjusted for Framingham risk score and baseline left ventricular hypertrophy) compared with aspirin therapy at baseline in patients receiving atenolol, despite similar control of blood pressure with each regimen.54 Further studies are needed to determine whether these differences are associated with a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan therapy.54
Losartan is used in the management of diabetic nephropathy manifested by elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio of 300 mg/g or greater) in patients with type 2 diabetes mellitus and hypertension.1,33
The current labeled indication for losartan in hypertensive patients with type 2 diabetes mellitus and nephropathy (indicated by an elevated serum creatinine and urinary albumin to creatinine ratio of 300 mg/g or greater) is based principally on the results of a long-term (mean duration of follow-up: 3.4 years), multicenter, placebo-controlled trial, the Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study.1,33 In the RENAAL trial, therapy with losartan potassium (50 mg daily initially and titrated to 100 mg daily) reduced the risk of the primary composite clinical end point, which was defined as a doubling of the baseline serum creatinine concentration, end-stage renal disease (i.e., need for dialysis or renal transplantation), or death by 16% compared with placebo.1,33 Additional antihypertensive agents (diuretics, calcium-channel blocking agents, α- or β-adrenergic blocking agents (β-blockers), and/or centrally acting agents) were used as needed in all treatment groups to achieve a trough blood pressure of less than 140/90 mm Hg in the sitting position; ACE inhibitors and other angiotensin II receptor antagonists could not be used.1,33 Most of the delay in time to occurrence of composite clinical events seen with losartan-containing therapy was the result of a reduction in the risk of doubling serum creatinine concentration and end-stage renal disease (25 and 28% reductions, respectively); losartan-containing therapy had no appreciable effect on overall mortality.1,33 Similar mean blood pressures were achieved with losartan or placebo plus conventional antihypertensive therapy.33
Angiotensin II receptor antagonists have also been used for the management of patients with nondiabetic CKD with moderate or severely increased albuminuria† (i.e., urinary albumin to creatinine ratio >30 mg/g) to prevent progression of CKD.1630 Once initiated, these medications should be titrated to the maximum dose that is tolerated.1630 Angiotensin II receptor antagonists can also be considered in patients with CKD and normal to mildly increased albuminuria† (i.e., urinary albumin to creatinine ratio <30 mg/g) when other compelling indications (e.g., hypertension, heart failure, or low ejection fraction) are present.1630
Guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) recommend initiation of an ACE inhibitor or angiotensin II receptor antagonist in patients who have diabetes mellitus, hypertension, and moderately to severely elevated albuminuria (i.e., urine to creatinine ratio >30 mg/g).1600,1630 Once initiated, these medications should be titrated to the maximum dose that is tolerated.1600,1630 In patients who have diabetes and albuminuria, but are normotensive†, ACE inhibitors or angiotensin II receptor antagonists may be considered.1600 Treatment with ACE inhibitors or angiotensin II receptor antagonists should be continued unless the serum creatinine rises by >30% within the first month after initiation, or following an increase in dosage.1600 Joint guidelines published by KDIGO and the American Diabetes Association provide similar recommendations for patients with hypertension.1601
Angiotensin II receptor antagonists have been used in the management of heart failure†.61,1000,1001
Several clinical trials have evaluated the use of angiotensin II receptor antagonists as add-on therapy to conventional regimens including an ACE inhibitor, as add-on therapy to conventional regimens compared with an ACE inhibitor, as combination therapy with an ACE inhibitor compared with therapy with either type of agent alone, or as an alternative therapy in patients intolerant of ACE inhibitors.17,31,61,132,133 Data from these and other long-term placebo-controlled clinical trials indicate that angiotensin II receptor antagonists produce hemodynamic and neurohormonal effects associated with their suppression of the renin-angiotensin system; reduced hospitalizations and mortality also have been demonstrated.528 However, in some studies, these drugs did not show consistent effects on cardiac symptoms or exercise tolerance.17,27
In one comparative study (Evaluation of Losartan in the Elderly [ELITE]) in geriatric patients 65 years of age and older who received losartan (up to 50 mg daily) or captopril (up to 150 mg daily) in addition to conventional therapy for 48 weeks, patients receiving losartan had a 46% lower risk of death and also experienced a lower incidence of adverse effects than those receiving captopril.17 However, after interim analysis of data, the difference in survival was no longer significant and no difference in morbidity and mortality or frequency in hospitalizations for heart failure was found between the 2 therapies.17 Results of a follow-up study (ELITE II) failed to confirm a survival benefit for losartan therapy compared with captopril.133 In this study, losartan did not provide a statistically significant difference in reduction of overall death, sudden cardiac death, and/or resuscitated cardiac arrest compared with captopril, although ELITE II was not designed to demonstrate equivalence between the 2 therapies.133
Current guidelines for the management of heart failure recommend guideline-directed medical therapy with a combination of drug therapies to reduce morbidity and mortality, including ACE inhibitors, sodium-glucose cotransporter 2 inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors (ARNIs), β-blockers, and mineralocorticoid receptor antagonists.1000 Diuretics are recommended on an as-needed basis to improve symptoms of congestion and prevent worsening of disease in patients with fluid retention.1000 Once guideline-directed medical therapy is optimized, additional therapies may be considered based on patient-specific factors, including ivabradine, vericiguat, digoxin, polyunsaturated fatty acids, and potassium binders.1000
In patients with structural heart disease who do not have any prior or current signs or symptoms of heart failure (i.e., Stage B disease) who have a left ventricular ejection fraction (LVEF) ≤40%, ACE inhibitors should be used to reduce mortality and prevent symptomatic heart failure; angiotensin II receptor antagonists may be used in such patients with a recent MI who are intolerant to ACE inhibitors.1000 In patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II to III symptoms, use of an ARNI is recommended first-line to reduce morbidity and mortality.1000,1001 Angiotensin II receptor antagonists are recommended for such patients only when an ARNI is contraindicated, inaccessible, or poorly tolerated.1001 In patients with symptomatic heart failure with mildly reduced ejection fraction (i.e., LVEF 41-49%), angiotensin II receptor antagonists may be considered (particularly in patients with a LVEF on the lower end of the range) to reduce the risk of hospitalizations for heart failure and cardiovascular mortality.1000
Mortality Reduction After Acute MI
Angiotensin II receptor antagonists have been used to improve survival in hemodynamically stable patients with acute MI† .527,1100
Guidelines recommend the use of an ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarction, heart failure, or ejection fraction ≤40% who do not have any contraindications (e.g., hypotension, shock, renal dysfunction).527,1100 In patients who are intolerant to ACE inhibitors, an angiotensin II receptor antagonist is recommended, and has been shown to have similar benefits on survival.527,1100
Dispensing and Administration Precautions
Losartan potassium is administered orally without regard to meals.1 It is available as oral tablets.1 It is also commercially available in fixed-combination tablets containing losartan potassium and hydrochlorothiazide; see the full prescribing information for administration of this combination product.2
Losartan potassium tablets should be stored at 25°C (excursions permitted between 15-30°C) and protected from light.1
For pediatric patients or patients unable to swallow tablets, losartan may be administered orally as an extemporaneously prepared suspension.1 An extemporaneous suspension containing losartan potassium 2.5 mg/mL can be prepared in the following manner.1 First, add 10 mL of purified water to a 240 mL amber polyethylene terephthalate (PET) bottle containing ten 50-mg tablets of losartan potassium.1 Shake the contents for at least 2 minutes.1 Allow the concentrated suspension to stand for 1 hour and then shake for 1 minute to disperse the contents.1 Separately, prepare a mixture containing equal parts (by volume) of syrup (Ora-Sweet SF®) and suspending vehicle (Ora-Plus®).1 To the concentrated suspension of losartan, add 190 mL of the Ora-Sweet SF® and Ora-Plus®mixture, and shake for 1 minute to disperse the ingredients.1 Refrigerate the suspension at 2-8°C.1 Shake the suspension before dispensing each dose and return promptly to refrigeration.1 The extemporaneous suspension is stable for up to 4 weeks when stored at 2-8°C.1
Available as losartan potassium; dosage expressed in terms of the salt.1,2
For the treatment of hypertension in adults, the usual starting dosage of losartan is 50 mg once daily; the dosage may be increased to 100 mg once daily if needed to control blood pressure.1
A starting dosage of 25 mg once daily is recommended for patients with possible intravascular depletion (e.g., on diuretic therapy).1
Stroke Reduction in Left Ventricular Hypertrophy
For the reduction of stroke risk in patients with left ventricular hypertrophy and hypertension, the usual starting dosage of losartan is 50 mg once daily.1 Depending on the blood pressure response, add hydrochlorothiazide 12.5 mg daily and/or increase the losartan dosage to 100 mg once daily.1
For diabetic nephropathy, the usual starting dosage of losartan is 50 mg once daily.1 The dosage may be increased to 100 mg once daily based on blood pressure response.1
In patients with prior or current symptoms of heart failure† and reduced left ventricular ejection fraction (stage C heart failure), the American College of Cardiology recommends an initial losartan dosage of 25-50 mg once daily with a target dosage of 150 mg daily.1001
For the treatment of hypertension in pediatric patients ≥6 years of age, the usual recommended starting dosage of losartan is 0.7 mg/kg once daily (up to 50 mg total) as a tablet or suspension.1 Adjust the dosage based on blood pressure response.1 Dosages above 1.4 mg/kg (or >100 mg) daily have not been studied in pediatric patients.1
In patients with mild to moderate hepatic impairment, the recommended starting dosage of losartan is 25 mg once daily.1 Use in severe hepatic impairment has not been studied.1
In adults, no dosage adjustment is necessary in patients with renal impairment unless the patient is also volume depleted.1
In pediatric patients, use is not recommended in patients with an estimated glomerular filtration rate <30 mL/minute per 1.73 m2.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Fetal/Neonatal Morbidity and Mortality
A boxed warning about the risk of fetal harm is included in the prescribing information for losartan.1 Losartan may cause fetal harm when administered to a pregnant woman.1 Use of drugs that act on the renin-angiotensin system (RAS) during the second or third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.1 Oligohydramnios caused by drugs that act on the RAS can result in fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), anuria, hypotension, renal failure, and death.1 Discontinue losartan immediately when pregnancy is detected.1 In the rare case that there is no appropriate alternative therapy, apprise the mother of the potential risk to the fetus.1 If losartan is taken during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment; if oligohydramnios is observed, discontinue losartan, unless it is considered life-saving for the mother.1 Oligohydramnios may not appear until after the fetus has sustained irreversible injury.1 Closely observe neonates who have been exposed to losartan in utero for signs of hypotension, oliguria, and hyperkalemia.1 If oliguria or hypotension occurs, support blood pressure and renal perfusion.1 Exchange transfusions or dialysis may be required.1
Other Warnings and Precautions
Hypotension in Volume- or Salt-Depleted Patients
Symptomatic hypotension may occur when losartan is initiated in patients with an activated RAS, such as volume- or salt-depleted patients (e.g., those receiving high doses of diuretics).1
Correct volume or salt depletion prior to losartan administration.1
Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the RAS and by diuretics.1 Patients whose renal function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure.1
Monitor renal function periodically.1 Consider withholding or discontinuing therapy in patients who develop a clinically important decrease in renal function.1
Monitor serum potassium periodically and treat appropriately.1 Dosage reduction or discontinuation of therapy may be required.1
Concomitant use of other drugs (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes) that may increase serum potassium may lead to hyperkalemia.1
When losartan is used in fixed combination with hydrochlorothiazide, the cautions, precautions, and contraindications associated with both drugs must be considered.2 Consult the full prescribing information for the fixed combination preparation for specific information.2
Losartan can cause fetal harm when administered to a pregnant woman.1 Use of drugs that act on the RAS during the second or third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.1 Oligohydramnios in pregnant women who use drugs affecting the RAS in the second or third trimester of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), hypotension, and death.1
Discontinue losartan immediately when pregnancy is detected.1 In the rare case that there is no appropriate alternative therapy, apprise the mother of the potential risk to the fetus.1 If losartan is taken during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment; if oligohydramnios is observed, discontinue losartan, unless it is considered life-saving for the mother.1 Oligohydramnios may not appear until after the fetus has sustained irreversible injury.1 Closely observe neonates who have been exposed to losartan in utero for signs of hypotension, oliguria, and hyperkalemia.1 If oliguria or hypotension occurs, support blood pressure and renal perfusion.1 Exchange transfusions or dialysis may be required.1
Losartan is distributed into milk in rats; it is not known whether the drug is distributed into human breast milk.1 A decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the potential risk in breastfeeding infants and the importance of the drug to the mother.1
Antihypertensive effects of losartan have been established in hypertensive pediatric patients 6-16 years of age.1
Safety and efficacy of losartan in pediatric patients <6 years of age and pediatric patients with glomerular filtration rate <30 mL/minute per 1.73 m2 have not been established.1
In controlled clinical trials evaluating losartan for hypertension, 19% of patients were ≥65 years of age and 2% were ≥75 years of age.1 In controlled clinical trials evaluating losartan for renal protection in type 2 diabetes, 33% of patients were ≥65 years of age.1 In controlled clinical trials evaluating losartan for the reduction of cardiovascular death, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 62% of patients were ≥65 years of age and 18% were ≥75 years of age.1 No overall differences in pharmacokinetics, safety, or efficacy of losartan have been observed between geriatric patients and younger adults, but increased sensitivity in some older individuals cannot be ruled out.1
Systemic exposure to losartan and its active metabolite may be increased in patients with hepatic impairment.1 Following oral administration in patients with mild-to-moderate alcoholic liver cirrhosis, plasma concentrations of losartan and its active metabolite were 5 times and 1.7 times, respectively, those in healthy volunteers.1 The total plasma clearance of losartan in patients with hepatic insufficiency was about 50% lower and the oral bioavailability was doubled compared to normal subjects.1 Losartan has not been studied in patients with severe hepatic impairment.1
Plasma concentrations and AUCs of losartan and its active metabolite increased by 50-90% and renal clearance reduced by 55-85% in patients with mild (creatinine clearance [Clcr ] 50-74 mL/minute) or moderate (Clcr30-49 mL/minute) renal insufficiency.1 Neither losartan nor its active metabolite can be removed by hemodialysis.1 No dosage adjustments are recommended in patients with renal impairment unless they are also volume depleted.1
The blood-pressure lowering effect of losartan may be somewhat less in Black patients.1 Based on results of the Losartan Intervention for Endpoint (LIFE) study, there is no evidence that the benefits of losartan on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients.1
Adverse effects occurring in at least 2% of patients with hypertension receiving losartan, and at a higher incidence than with placebo, include dizziness, upper respiratory infection, nasal congestion, and back pain.1
In vitro studies indicate that cytochrome P-450 (CYP) 2C9 and 3A4 are involved in the biotransformation of losartan to active and inactive metabolites.1
Drugs Affecting Hepatic Microsomal Enzymes
Fluconazole, a CYP2C9 inhibitor, increased the AUC of losartan by approximately 70% and decreased the AUC of the active metabolite of losartan by approximately 40%.1 The manufacturer states that the pharmacodynamic consequences of concomitant use of losartan and CYP2C9 inhibitors have not been studied.1
Ketoconazole and erythromycin, CYP3A4 inhibitors, did not impact the conversion of losartan to its active metabolite.1 Erythromycin increased losartan AUC by 30%.1
Drugs Increasing Serum Potassium
Hyperkalemia may occur with concomitant administration of losartan and other drugs that raise serum potassium levels.1 Monitor serum potassium levels if used concomitantly.1
Drugs Inhibiting the Renin-Angiotensin System
Increased risk of hypotension, hyperkalemia, and changes in renal function (e.g., renal impairment) is associated with concomitant use of other drugs that block the renin-angiotensin system (RAS) (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, aliskiren).1 The manufacturer states that most patients do not derive additional benefit from combination therapy with 2 RAS inhibitors and the combination should generally be avoided.1 Closely monitor blood pressure, renal function, and electrolytes in patients receiving multiple agents that affect the RAS.1
Concomitant use of losartan and aliskiren is contraindicated in patients with diabetes mellitus.1 In addition, concomitant use of losartan and aliskiren should be avoided in patients with renal impairment (glomerular filtration rate <60 mL/minute).1
No clinically significant drug interactions have been found in studies of losartan with cimetidine.1
No clinically significant drug interactions have been found in studies of losartan with digoxin.1
No clinically significant drug interactions have been found in studies of losartan with hydrochlorothiazide.1
Concomitant use of losartan and lithium may increase serum lithium concentrations, potentially leading to lithium toxicity.1 Serum lithium concentrations should be carefully monitored during concomitant use.1
Nonsteroidal Anti-inflammatory Agents
Attenuated hypotensive effects may be observed with concomitant use of angiotensin II receptor antagonists and nonsteroidal anti-inflammatory agents (NSAIAs), including selective cyclooxygenase-2 (COX-2) inhibitors.1
In patients who are elderly, patients who are volume-depleted (including those receiving concomitant diuretic therapy), and patients with compromised renal function, concomitant use of NSAIAs and losartan may lead to deterioration of renal function, including possible acute renal failure.1 The effects are usually reversible.1 Monitor renal function periodically in patients receiving losartan and NSAIA therapy concomitantly.1
No clinically significant drug interactions have been found in studies of losartan with phenobarbital.1
Rifampin decreases the AUCs of losartan and its active metabolite by 30 and 40%, respectively.1
No clinically significant drug interactions have been found in studies of losartan with warfarin.1
Losartan, a nonpeptide tetrazole derivative, is a reversible, non-competitive inhibitor of the angiotensin II receptor (type AT1).1 Through selective blockade of angiotensin II binding at the AT1 receptor, losartan blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.1 Neither losartan nor its metabolite inhibits angiotensin converting enzyme (ACE), the enzyme involved in the conversion of angiotensin I to angiotensin II and degradation of bradykinin.1 Losartan and its metabolite also do not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.1
Losartan is a prodrug and requires activation in the liver to exert its pharmacologic activity.1 Losartan's active carboxylic acid metabolite is 10-40 times more potent by weight than losartan and appears to be a reversible, noncompetitive inhibitor of the AT1 receptor.1
A dose of losartan 100 mg inhibits angiotensin II pressor effects by about 85% at peak, with 25-40% inhibition persisting for 24 hours.1 Effects of losartan can be observed as early as 1 week; however, maximal effects may not be observed for 3-6 weeks.1 Long-term follow-up studies demonstrate that the effect of losartan is maintained for up to a year.1 There is no apparent rebound effect after abrupt withdrawal of losartan.1 No change in average heart rate was observed in controlled trials.1
Losartan is well absorbed after oral administration and undergoes substantial first-pass metabolism.1 Its bioavailability is approximately 33%.1 Mean peak concentrations occur at 1 hour for losartan and 3-4 hours for the active metabolite.1 Administration with a meal slows absorption but does not significantly impact the AUC of losartan or its active metabolite.1 The pharmacokinetics of losartan and its active metabolite are linear with doses up to 200 mg.1 Both the parent drug and metabolite are highly protein bound, primarily to albumin, with plasma free fractions of 1.3 and 0.2%, respectively.1 Distribution across the blood-brain barrier is poor, according to animal studies.1 Substantial first-pass metabolism occurs via cytochrome P-450 (CYP) enzymes.1 Approximately 14% of an orally administered dose of losartan is converted to the active metabolite, which is responsible for most of the antagonism at the angiotensin II receptor.1 In vitro studies indicate that CYP2C9 and 3A4 are involved in the metabolism of losartan.1 The terminal half-lives of losartan and its active metabolite are 2 hours and 6-9 hours, respectively.1 After a single oral dose, about 4% of unchanged drug and 6% of the active metabolite appear in urine.1 Elimination occurs primarily via biliary excretion, with 35% present in urine and 60% in feces.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 25 mg* | Organon LLC | |
Losartan Tablets | ||||
50 mg* | Cozaar® | Organon LLC | ||
Losartan Tablets | ||||
100 mg* | Cozaar® | Organon LLC | ||
Losartan Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 50 mg with Hydrochlorothiazide 12.5 mg* | Organon LLC | |
Losartan with Hydrochlorothiazide Tablets | ||||
100 mg with Hydrochlorothiazide 12.5 mg* | Hyzaar® | Organon LLC | ||
Losartan with Hydrochlorothiazide Tablets | ||||
100 mg with Hydrochlorothiazide 25 mg* | Hyzaar® | Organon LLC | ||
Losartan with Hydrochlorothiazide Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Organon LLC. Cozaar® (losartan potassium) tablets prescribing information. Jersey City, NJ; 2021 Oct. [Web]
2. Organon LLC. Hyzaar® (losartan potassium-hydrochlorothiazide) tablets prescribing information. Jersey City, NJ; 2023 Mar. [Web]
17. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol . 1999; 83:9-38A.
27. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the management of chronic heart failure in the adult: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol . 2001. From ACC website.
31. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med . 2001; 345:1667-75. [PubMed 11759645]
33. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med . 2001; 345:861-9. [PubMed 11565518]
53. Dahlöf B, Dewvereux RB, Kjeldsen SE et al and the Life study group. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet . 2002; 359:995-1003.
54. Fossum E, Moan A, Kjeldsen SE et al and the Life study group. The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study. J Am Coll Cardiol . 2005; 46:770-5. [PubMed 16139123]
60. Shahinfar S, Cano F, Soffer BA, et al. A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens. 2005;18(2 Pt 1):183-190.
61. Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840-1848.
132. Granger CB, McMurray JJ, Yusuf S et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet . 2003; 362:772-6.
133. Pitt B, Poole-Wilson PA, Segal R et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II. Lancet . 2000; 355:1582-7.
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013; 127:e362-425.
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