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Losartan

Medically reviewed by Drugs.com. Last updated on Oct 6, 2020.

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.

Tablet, Oral, as potassium:

Cozaar: 25 mg

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

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

Proteinuric chronic kidney disease, diabetic: 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

Off Label Uses

Heart failure with reduced ejection fraction

Data from a randomized, double-blind, dose comparison study in patients with New York Heart Association (NYHA) class II to IV heart failure support 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 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the management of heart failure, losartan is one of 3 effective and recommended angiotensin II receptor blockers (ARBs) (ie, candesartan, losartan, valsartan) in patients with heart failure with reduced ejection fraction who cannot tolerate angiotensin-converting enzyme (ACE) inhibitors to reduce morbidity and mortality. The ACCF/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 with aortic aneurysm

Based on the ACCF/AHA/American Association for Thoracic Surgery 2010 guidelines for the diagnosis and management of patients with thoracic aortic disease, use of losartan is reasonable for patients with Marfan syndrome to reduce the rate of aortic dilatation unless there are contraindications. A beta-blocker is first-line therapy to slow aortic dilatation, and losartan may be added if tolerated. Patients who do not tolerate a beta-blocker may still benefit from an ARB [Wright 2020].

Non-ST-elevation acute coronary syndrome

Based on the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, an ARB is recommended and effective in patients who have indications for but are intolerant of ACE inhibitors; this includes patients with hypertension, diabetes, stable chronic kidney disease (CKD), heart failure, or myocardial infarction who have a left ventricular ejection fraction ≤40%.

Posttransplant erythrocytosis (renal transplant recipients)

Data from a limited number of small clinical trials in renal transplant recipients with posttransplant erythrocytosis suggest that losartan may be beneficial for reducing hemoglobin concentration [Julian 1998], [Klaassen 1997], [Yildiz 2001].

Proteinuric chronic kidney disease, nondiabetic

Based on the 2012 Kidney Disease Improving Global Outcomes guidelines, the use of an ACE inhibitor or an ARB is recommended in patients with proteinuric CKD to prevent progression of CKD.

ST-elevation myocardial infarction

Based on the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infraction, an ARB is recommended and effective in patients who have indications for but are intolerant of ACE inhibitors.

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

Acute coronary syndromes:

Note: Alternative in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor (eg, due to cough) (ACC/AHA [Amsterdam 2014]; ACCF/AHA [O'Gara 2013]; Guyer 2019). In patients with prior ACE inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity), an angiotensin II receptor blocker (ARB) may still be an alternative. ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Beltrami 2011); referral to an allergist may be appropriate.

Non-ST-elevation acute coronary syndrome (alternative agent) (off-label use):

Note: Initiate in stable patients prior to hospital discharge as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (ACC/AHA [Amsterdam 2014]). Dosing is based on general dosing range in the manufacturer's labeling.

Oral: Initial: 25 to 50 mg once daily depending on initial blood pressure; increase dose as tolerated up to 100 mg/day under close monitoring to avoid hypotension.

ST-elevation myocardial infarction (alternative agent) (off-label use):

Note: In hemodynamically stable patients with large anterior ST-elevation myocardial infarction, consider starting within 24 hours of presentation as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue therapy indefinitely (ACCF/AHA [O'Gara 2013]).

Oral: Initial: 25 to 50 mg once daily depending on initial blood pressure; increase dose as tolerated up to 100 mg/day under close monitoring to avoid hypotension (Dickstein 2002).

Heart failure with reduced ejection fraction (alternative agent) (off-label use):

Note: Alternative in patients who cannot tolerate an ACE inhibitor (eg, due to cough) (ACC/AHA/HFSA [Yancy 2017]; Guyer 2019). In patients with prior ACE inhibitor or angiotensin receptor-neprilysin inhibitor (ARNI)-associated angioedema (ie, without urticaria or other signs of hypersensitivity), an ARB may still be an alternative (Meyer 2019); consultation with a heart failure specialist and/or an allergist may be appropriate. ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Beltrami 2011).

Oral: Initial: 25 to 50 mg once daily; increase dose every 1 to 2 weeks based on response and tolerability to a target dose of 150 mg once daily (ACC/AHA/HFSA [Yancy 2017]; ACCF/AHA [Yancy 2013]; Konstam 2009; Meyer 2019). In closely monitored hospitalized patients, the dose may be titrated at 1- to 2-day intervals (Meyer 2019).

Hypertension:

Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (ACC/AHA [Whelton 2018]).

Oral: Initial: 25 to 50 mg once daily; evaluate response every 4 to 6 weeks and increase dose as needed up to 100 mg/day in 1 to 2 divided doses (ACC/AHA [Whelton 2018]; Mann 2020a).

Marfan syndrome with aortic aneurysm (alternative or adjunctive agent) (off-label use):

Note: A beta-blocker is first-line therapy to slow aortic dilatation. Losartan may be added in patients with an aortic aneurysm or with a risk factor for developing an aortic aneurysm. Patients who do not tolerate a beta-blocker may still benefit from an ARB (ACCF/AHA/AATS [Hiratzka 2010]; Wright 2020).

Oral: Initial: 50 mg once daily; after 2 weeks, may increase dose based on blood pressure response and tolerability up to 100 mg/day (Groenink 2013; Milleron 2015).

Posttransplant erythrocytosis (renal transplant recipients) (off-label use):

Note: For patients with a hemoglobin concentration >17 g/dL (Brennan 2019).

Oral: Initial: 25 to 50 mg once daily; if inadequate response seen within 4 weeks, may increase to 100 mg once daily based on hemoglobin and blood pressure response; if hemoglobin remains >17 g/dL after an additional 4 weeks, consider alternative therapy (Brennan 2019; Julian 1998; Klaassen 1997; Yildiz 2001).

Proteinuric chronic kidney disease (nondiabetic [off-label use] or diabetic):

Note: Dosing is based on general dosing range in the manufacturer's labeling.

Oral: Initial: 25 to 50 mg once daily depending on blood pressure; can be increased to 100 mg once daily based on blood pressure response and tolerability. Target to an appropriate blood pressure goal and a proteinuria goal of <1 g/day (KDIGO 2013; Mann 2020b).

IgA nephropathy: In addition to an appropriate blood pressure goal, a proteinuria goal of <1 g/day is also generally recommended (KDIGO 2012). Some experts treat to a proteinuria goal of <500 mg/day. If proteinuria goal is not met with monotherapy at the maximum tolerated dose, consider adding other modalities and/or agents (Cattran 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hypertension:

Children ≥6 years and Adolescents: Oral: Initial: 0.7 mg/kg once daily; maximum initial dose: 50 mg/dose; titrate to desired effect; maximum daily dose: 1.4 mg/kg/day or 100 mg/day; may be administered once daily or divided twice daily (AAP [Flynn 2017]; NHBPEP 2004; NHLBI 2011); Note: Doses >1.4 mg/kg/day (or >100 mg/day) have not been studied (Shahinfar 2005).

Canadian labeling: Children ≥6 years and Adolescents ≤16 years: Oral: Cozaar prescribing information [Canada]:

≥20 kg to <50 kg: Initial: 25 mg once daily; titrate to desired effect; maximum dose: 50 mg/day

≥50 kg: Initial: 50 mg once daily; titrate to desired effect; maximum dose: 100 mg/day

Proteinuria reduction in children with chronic kidney disease: Limited data available: Children ≥4 years and Adolescents: Oral: Initial: 0.4 to 0.8 mg/kg/day; increase dose if no adverse effects occur and blood pressure remains >90th percentile or proteinuria does not fall <50% of baseline excretion; doses can be increased slowly up to 1 mg/kg/day (maximum: 50 mg/day); dosing based on experience from three retrospective clinical trials (Chandar 2007; Ellis 2003; Ellis 2004)

Marfan syndrome aortic-root dilation: Limited data available: Children and Adolescents 14 months to 16 years: Oral: Initial: 0.6 mg/kg/day for 3 weeks (while assessing for adverse events); then gradually increase dose to 1.4 mg/kg/day (maximum: 100 mg/day); dosing based on preliminary results of a small (n=18), nonrandomized, retrospective, clinical study (Brooke 2008)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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 2018).

Cozaar (losartan) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme; October 2018.

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 used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. 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: 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 when possible. Monitor blood pressure, renal function, and potassium if combined. Consider therapy modification

Antihepaciviral Combination Products: May increase the serum concentration of Losartan. Management: 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

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

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

CYP2C9 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Losartan. CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Losartan. 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 concomitant therapy when possible. If concomitant therapy cannot be avoided, monitor for reduced clinical effects of the CYP3A4 substrate. 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

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. 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

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

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

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

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

Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Initiate lithium at lower doses in patients receiving an angiotensin II receptor blocker (ARB). Consider lithium dose reductions in patients stable on lithium therapy who are initiating an ARB. Monitor lithium concentrations closely when combined. 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

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

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin II Receptor Blockers. 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

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

Ranolazine: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Monitor therapy

RifAMPin: May decrease the serum concentration of Losartan. 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

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

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 following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Incidences occurred with hypertensive patients unless otherwise specified.

1% to 10%:

Cardiovascular: Edema (<2%), hypotension (type 2 diabetic nephropathy: ≥4%), orthostatic hypotension (type 2 diabetic nephropathy: ≥4%), palpitations (<2%), syncope (<2%)

Dermatologic: Pruritus (<2%), skin photosensitivity (<2%), skin rash (<2%), urticaria (<2%)

Endocrine & metabolic: Hyperkalemia (type 2 diabetic nephropathy: ≥4%; incidence varies in literature and may be impacted by comorbidities) (Desai 2007; Weir 2010; Yusuf 2008), hypoglycemia (type 2 diabetic nephropathy: ≥4%)

Gastrointestinal: Abdominal pain (<2%), diarrhea (type 2 diabetic nephropathy: ≥4%), nausea (<2%), vomiting (<2%)

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

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

Nervous system: Depression (<2%), dizziness (3%), drowsiness (<2%), fatigue (type 2 diabetic nephropathy: ≥4%), paresthesia (<2%), sleep disorder (<2%), vertigo (<2%)

Neuromuscular & skeletal: Arthralgia (<2%), asthenia (type 2 diabetic nephropathy: ≥4%), back pain (hypertension and type 2 diabetic neuropathy: 2% to ≥4%), myalgia (<2%)

Otic: Tinnitus (<2%)

Respiratory: Cough (ARBs: 3%) (Matchar 2008), dyspnea (<2%), nasal congestion (2%), upper respiratory tract infection (8%)

Postmarketing:

Cardiovascular: Facial edema (van Rijnsoever 1998), lip edema (Cha 1999; Kazim 2010), vasculitis (Shalavadi 2015)

Endocrine & metabolic: Hyponatremia (Das 2015)

Gastrointestinal: Dysgeusia (Heeringa 1998; Malnick 1999)

Hematologic & oncologic: Henoch-Schonlein purpura (Bosch 1998; Brouard 2001), thrombocytopenia (Ada 2002; Patel 2013)

Hepatic: Hepatitis (Al-Halawani 2014)

Hypersensitivity: Anaphylaxis (Kazim 2010), angioedema (Cha 1999; Rivera 1999)

Respiratory: Laryngeal edema (Rivera 1999)

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: Angiotensin II receptor antagonists (ARBs) do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012). Patients with a history of angioedema due to an angiotensin-converting enzyme inhibitor must be educated that sometimes there can be recurrence within months following discontinuation (Beltrami 2011). No matter the cause of angioedema, prolonged frequent monitoring is required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. IM administration of epinephrine may be necessary. Do not readminister the ARB to patients who experience angioedema from this medication.

• 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 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.

Special populations:

• Black patients: When used to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, 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 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 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 BP, electrolytes, renal function.

Heart failure:

Within 1 to 2 weeks after initiation, reassess BP (including postural blood pressure changes), renal function, and serum potassium; follow closely after dose changes. Patients with systolic BP <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 2018]):

Confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease risk ≥10%: Target BP <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased atherosclerotic cardiovascular disease risk: Target BP <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association guidelines (ADA 2020):

Patients 18 to 65 years of age, without atherosclerotic cardiovascular disease (ASCVD), and 10-year ASCVD risk <15%: Target BP <140/90 mm Hg is recommended.

Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.

Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.

Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.

Reproductive Considerations

The use of angiotensin II receptor blockers should generally be avoided in women planning a pregnancy (ACOG 203 2019).

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. When pregnancy is detected, discontinue as soon as possible. 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. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Use during pregnancy 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.

Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension (ACOG 203 2019).

The use of angiotensin II receptor blockers is generally not recommended to treat chronic hypertension in pregnant women (ACOG 203 2019).

Patient Education

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to protect kidney function in diabetic patients who have protein loss.

• It is used to lower the chance of stroke in people with high blood pressure and some certain heart problems.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Cold-like symptoms

• Back pain

• Loss of strength and energy

• Runny nose

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in urine, change in amount of urine passed, or weight gain.

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling.

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.

• Severe dizziness

• Passing out

• Chest pain

• Swelling of arms or legs

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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

Frequently Asked Questions