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Losartan

Medically reviewed on March 25, 2018

Pronunciation

(loe SAR tan)

Index Terms

  • DuP 753
  • Losartan Potassium
  • MK594

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as potassium:

Cozaar: 25 mg, 50 mg [DSC]

Cozaar: 50 mg [scored]

Cozaar: 100 mg

Generic: 25 mg, 50 mg, 100 mg

Brand Names: U.S.

  • Cozaar

Pharmacologic Category

  • Angiotensin II Receptor Blocker
  • Antihypertensive

Pharmacology

As a selective and competitive, nonpeptide angiotensin II receptor antagonist, losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II; losartan interacts reversibly at the AT1 and AT2 receptors of many tissues and has slow dissociation kinetics; its affinity for the AT1 receptor is 1000 times greater than the AT2 receptor. Angiotensin II receptor antagonists may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, they do not affect the response to bradykinin, and are less likely to be associated with nonrenin-angiotensin effects (eg, cough and angioedema). Losartan increases urinary flow rate and in addition to being natriuretic and kaliuretic, increases excretion of chloride, magnesium, uric acid, calcium, and phosphate.

Absorption

Oral: Well absorbed; slowed with food

Distribution

Vd: Losartan: 34 L; E-3174 (active metabolite): 12 L

Metabolism

Hepatic (~14%) via CYP2C9 and 3A4 to an active metabolite E-3174 (10 to 40 times more potent than losartan); extensive first-pass effect

Excretion

Urine (35%; ~4% as unchanged drug, ~6% as E-3174 [active metabolite]); feces (~60% [oral])

Clearance: Adults:

Plasma: Losartan: 600 mL/minute; E-3174 (active metabolite): 50 mL/minute

Renal: Losartan: 75 L/minute; E-3174 (active metabolite): 25 mL/minute

Onset of Action

~6 hours

Time to Peak

Serum: Losartan: Children: 2 hours, Adults: 1 hour; E-3174 (active metabolite): Children: 4.1 hours, Adults: 3.5 hours

Half-Life Elimination

Losartan: Children 6 to 16 years: 2.3 ± 0.8 hours; Adults: 2.1 ± 0.7 hours

E-3174 (active metabolite): Children 6 to 16 years: 5.6 ± 1.2 hours; Adults: 7.4 ± 2.4 hours

Protein Binding

Plasma: High, >98%; primarily to albumin

Special Populations: Renal Function Impairment

Plasma concentrations and AUC of losartan and its active metabolite are increased 50% to 90% and renal clearance reduced 55% to 85% in patients with mild (CrCl 50 to 74 mL/minute) and moderate (CrCl 30 to 49 mL/minute) renal impairment.

Special Populations: 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 clearance of losartan is reduced ~50% and oral bioavailability is about doubled.

Special Populations: Gender

Plasma losartan concentrations are about twice as high in hypertensive women as hypertensive men, but plasma concentrations of active metabolite are similar.

Use: Labeled Indications

Diabetic nephropathy: Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension.

Hypertension: Management of hypertension in adults and children ≥6 years.

Guideline recommendations: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke). ACE inhibitors and ARBs are also acceptable for monotherapy. Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk ≥10%) (ACC/AHA [Whelton 2017]).

Hypertension with left ventricular hypertrophy: To reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (LVH). Evidence suggests that this benefit does not apply to black patients.

Off Label Uses

Acute coronary syndrome (secondary prevention of cardiovascular events)

Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) and the American College of Cardiology Foundation/American Heart Association (ACC/AHA) guidelines for the management of patients with STE-ACS, an ARB is recommended and effective in patients with NSTE-ACS or STE-ACS who have indications for but are intolerant of ACE inhibitors; this includes patients with heart failure, MI, or anterior MI who have a left ventricular ejection fraction (LVEF) ≤40%. In post-STE-ACS patients, initiate within the first 24 hours.

Heart failure, intolerant of ACE inhibitors

Data from a randomized, double-blind, dose comparison study in patients with heart failure NYHA class II to IV supports the use of losartan at higher doses to reduce the rate of death or admission for heart failure in patients with heart failure [Konstam 2009].

Based on the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Heart Failure Guidelines, losartan is one of 3 effective and recommended angiotensin receptor blockers (ARBs) (ie, candesartan, losartan, and valsartan) in patients with heart failure with reduced ejection fraction (HFrEF) who cannot tolerate ACE inhibitors to reduce morbidity and mortality. The ACC/AHA also suggests that ARBs are reasonable first-line alternatives to ACE inhibitors in patients already maintained on an ARB for other indications.

Marfan syndrome

Data from a retrospective cohort study of pediatric patients (age 1 to 16 years) with Marfan syndrome treated with angiotensin receptor blockers (ARBs) after other medications failed to prevent aortic-root enlargement suggests that losartan may be beneficial for slowing the rate of progressive aortic-root dilation [Brooke 2008]. Additional trials are necessary to further define the role of losartan in this condition.

Stable coronary artery disease

Based on the American College of Cardiology/American Heart Association guideline for the diagnosis and management of patients with stable ischemic heart disease, an ACE inhibitor or ARB should be prescribed in all patients with stable ischemic heart disease who also have hypertension, diabetes mellitus, LVEF <40%, or CKD unless contraindicated.

Contraindications

Hypersensitivity to losartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus

Documentation of allergenic cross-reactivity for angiotensin receptor blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate-to-severe renal impairment (GFR <60 mL/minute/1.73 m2)

Dosing: Adult

Hypertension: Oral: Initial: 50 mg once daily; titrate as needed based on patient response up to 100 mg daily in 1 to 2 divided doses (ACC/AHA [Whelton 2017]); maximum: 100 mg/day

Usual initial doses in patients receiving diuretics or those with intravascular volume depletion: 25 mg once daily

Diabetic nephropathy: Oral: Initial: 50 mg once daily; can be increased to 100 mg once daily based on blood pressure response

Hypertension with left ventricular hypertrophy: Oral: Initial: 50 mg once daily; can be increased to 100 mg once daily based on blood pressure response. Should be used in combination with a thiazide diuretic

Heart failure (off-label use): Initial: 25 to 50 mg once daily; titrate up as tolerated; target dose: 150 mg once daily (ACC/AHA [Yancy 2013]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hypertension: Oral: Children ≥6 years and Adolescents ≤16 years:

US labeling: Initial: 0.7 mg/kg once daily (maximum initial dose: 50 mg/day); adjust dose to blood pressure response; doses >1.4 mg/kg (>100 mg) once daily have not been studied

Canadian labeling:

≥20 kg to <50 kg: Initial: 25 mg once daily; adjust dose to blood pressure response (maximum: 50 mg/day)

≥50 kg: Initial: 50 mg once daily; adjust dose to blood pressure response (maximum: 100 mg/day)

Aortic-root dilation with Marfan’s syndrome (off-label use): Children 14 months to 16 years: Initial: 0.6 mg/kg/day; can be increased to a maximum of 1.4 mg/kg/day (not to exceed adult maximum of 100 mg daily) (Brooke, 2008)

Dosing: Renal Impairment

Adults: No dosage adjustment necessary unless the patient is volume depleted; monitor closely.

Children ≥6 years and Adolescents ≤16 years:

GFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling.

GFR <30 mL/minute/1.73 m2: Use is not recommended.

Hemodialysis: Nondialyzable (both Losartan and the active metabolite)

Dosing: Hepatic Impairment

Adults:

U.S. labeling:

Mild to moderate hepatic impairment: Initial: 25 mg once daily

Severe hepatic impairment: There are no specific dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, it may be advisable to initiate therapy at a reduced dosage.

Canadian labeling: Mild to severe hepatic impairment or a history of hepatic impairment: Initial: 25 mg once daily

Children ≥6 years and Adolescents ≤16 years:

US labeling: There are no specific dosage adjustments provided in the manufacturer's labeling; however it may be advisable to initiate therapy at a reduced dosage

Canadian labeling: Use is not recommended.

Extemporaneously Prepared

A 2.5 mg/mL losartan oral suspension may be made with tablets and a 1:1 mixture of Ora-Plus and Ora-Sweet SF. Combine 10 mL of purified water and ten losartan 50 mg tablets in a 240 mL amber polyethylene terephthalate bottle. Shake well for at least 2 minutes. Allow concentrate to stand for 1 hour, then shake for 1 minute. Separately, prepare 190 mL of a 1:1 mixture of Ora-Plus and Ora-Sweet SF; add to tablet and water mixture in the bottle and shake for 1 minute. Label "shake well" and "refrigerate". Return promptly to refrigerator after each use. Stable for 4 weeks when stored in amber polyethylene terephthalate prescription bottles and refrigerated (Cozaar prescribing information, 2015).

Cozaar prescribing information, Merck & Co, Inc, Whitehouse Station, NJ, 2015.

Administration

Oral: Administer without regard to meals; however, administer consistently with respect to food intake at about the same time every day.

Dietary Considerations

Some products may contain potassium.

Storage

Store at 25°C (77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Angiotensin II: Receptor Blockers may diminish the therapeutic effect of Angiotensin II. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Consider therapy modification

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Losartan. Applicable Isavuconazonium considerations are addressed in separate monographs. Exceptions: Isavuconazonium Sulfate. Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of Losartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the losartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Avoid combination

Canagliflozin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy

Ceritinib: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (eg, warfarin, phenytoin) should be avoided when possible. Monitor therapy

CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Drospirenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Drospirenone. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification

Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Fluconazole: May decrease the serum concentration of Losartan. Specifically, fluconazole may decrease the serum concentration of E3174, the more potent active metabolite of losartan. Monitor therapy

Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Resveratrol: May decrease serum concentrations of the active metabolite(s) of Losartan. Resveratrol may increase the serum concentration of Losartan. Monitor therapy

RifAMPin: May decrease the serum concentration of Losartan. Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

The incidence of some adverse reactions varied based on the underlying disease state. Notations are made, where applicable, for data derived from trials conducted in type 2 diabetic nephropathy and hypertensive patients, respectively.

>10%: Respiratory: Cough (hypertension: 17%; incidence is higher in patients with previous cough related to ACE inhibitor therapy)

2% to 10%:

Cardiovascular: Chest pain (type 2 diabetic nephropathy: ≥4%), hypotension (type 2 diabetic nephropathy: ≥4%), orthostatic hypotension (type 2 diabetic nephropathy: ≥4%)

Central nervous system: Myasthenia (type 2 diabetic nephropathy: ≥4%), dizziness (hypertension: 3%)

Endocrine & metabolic: Hyperkalemia (type 2 diabetic nephropathy: ≥4%), hypoglycemia (type 2 diabetic nephropathy: ≥4%)

Gastrointestinal: Diarrhea (type 2 diabetic nephropathy: ≥4%)

Genitourinary: Urinary tract infection (type 2 diabetic nephropathy: ≥4%)

Hematologic & oncologic: Anemia (type 2 diabetic nephropathy: ≥4%)

Neuromuscular & skeletal: Back pain (2% to ≥4%)

Respiratory: Upper respiratory tract infection (hypertension: 8%), nasal congestion (hypertension: 2%)

Frequency not defined:

Central nervous system: Fatigue (type 2 diabetic nephropathy)

Neuromuscular & skeletal: Weakness (type 2 diabetic nephropathy)

<2%, postmarketing, and/or case reports: Abdominal pain, abnormal hepatic function tests, anaphylaxis, angioedema, arthralgia, atrial fibrillation, cerebrovascular accident, constipation, depression, drowsiness, dysgeusia, dyspnea, edema, erectile dysfunction, erythroderma, headache, hepatitis, hyponatremia, IgA vasculitis, impotence, malaise, migraine, myalgia, myositis, nausea, palpitations, paresthesia, pruritus, rhabdomyolysis, skin photosensitivity, skin rash, sleep disorder, syncope, thrombocytopenia, tinnitus, urticaria, vasculitis, vertigo, vomiting

ALERT: U.S. Boxed Warning

Fetal toxicity:

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue losartan as soon as possible.

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Angioedema has been reported rarely with some angiotensin II receptor antagonists (ARBs) and may occur at any time during treatment (especially following first dose). It may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Patients with idiopathic or hereditary angioedema or previous angioedema associated with angiotensin-converting enzyme (ACE) inhibitor therapy may be at an increased risk. Prolonged frequent monitoring may be required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. Intramuscular (IM) administration of epinephrine may be necessary. Do not readminister to patients who have had angioedema with ARBs.

• Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.

• Hypotension: Symptomatic hypotension may occur upon initiation in patients who are salt or volume depleted (eg, those treated with high-dose diuretics); correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with losartan.

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.

Disease-related concerns:

• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.

• Ascites: Avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).

• Hepatic impairment: Use with caution in patients with hepatic impairment or a history of hepatic impairment; dose adjustment needed.

• Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Use with caution with preexisting renal insufficiency.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Black patients: When used to reduce the risk of stroke in patients with HTN and LVH, may not be effective in the black population.

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

• Surgical patients: In patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing angiotensin-receptor blockers (ARB) is reasonable in the perioperative period. If ARBs are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

Monitoring Parameters

Baseline and periodic blood pressure; electrolytes, renal function

Heart Failure:

Within 1 to 2 weeks after initiation, reassess blood pressure (including postural blood pressure changes), renal function, and serum potassium; follow closely after dose changes. Patients with systolic blood pressure <80 mm Hg, low serum sodium, diabetes mellitus, and impaired renal function should be closely monitored (ACC/AHA [Yancy 2013]).

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2017a; ADA 2017b):

Patients ≥18 to ≤65 years: Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Patients ≥18 to ≤65 years and at high risk of cardiovascular disease: Goal of therapy is SBP <130 mm Hg and DBP <80 mm Hg (if can be achieved without undue treatment burden).

Patients ≥65 years (healthy or complex/intermediate health): Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Patients ≥65 years (very complex/poor health): Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

Pregnancy Risk Factor

D

Pregnancy Considerations

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. The use of drugs which act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Use is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria (exchange transfusions or dialysis may be needed). These adverse events are generally associated with maternal use in the second and third trimesters.

Untreated chronic maternal hypertension is also associated with adverse events in the fetus, infant, and mother. The use of angiotensin II receptor blockers is not recommended to treat chronic uncomplicated hypertension in pregnant women and should generally be avoided in women of reproductive potential (ACOG, 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, cold-like symptoms, back pain, loss of strength, and energy or rhinorrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe dizziness, passing out, angina, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patients should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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