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Official reprint from UpToDate

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Losartan: Drug information

Copyright 1978-2017 Lexicomp, Inc. All rights reserved.

(For additional information see "Losartan: Patient drug information" and see "Losartan:
Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)

ALERT: US 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.

Brand Names: US Cozaar

Brand Names: Canada ACT Losartan; Apo-Losartan; Auro-Losartan; Cozaar; JAMP-


Losartan; Mint-Losartan; Mylan-Losartan; PMS-Losartan; RAN-Losartan; Sandoz Losartan;
Septa Losartan; Teva-Losartan

Pharmacologic Category Angiotensin II Receptor Blocker; Antihypertensive

Dosing: Adult
Hypertension: Oral: Initial: 50 mg once daily; adjust dose to blood pressure response; can
be administered once or twice daily with total daily doses ranging from 25 to 100 mg;
(maximum: 100 mg/day); usual dosage range (ASH/ISH [Weber, 2014]): 50 to 100 mg
daily; target dose (JNC 8 [James, 2013]): 100 mg daily in 1 or 2 divided doses

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: 12.5 to 25 mg once daily; target dose: 150 mg once
daily (HFSA, 2010; Konstam, 2009). The ACCF/AHA 2013 heart failure guidelines
recommend an initial dose of 25 to 50 mg once daily; target dose: 150 mg once daily
(Yancy, 2013).

Dosing: Pediatric
(For additional information see "Losartan: Pediatric drug information")

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 Marfans 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: Geriatric Refer to adult dosing.

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 manufacturers 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.

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

Generic Equivalent Available (US) Yes

Administration Oral: Administer without regard to meals; however, administer


consistently with respect to food intake at about the same time every day.

Use
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.

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.

Guideline recommendations:

Hypertension: The 2014 guideline for the management of high blood pressure in adults
(Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic
treatment to lower blood pressure for the following patients:

Patients 60 years with systolic blood pressure (SBP) 150 mm Hg or diastolic


blood pressure (DBP) 90 mm Hg.
Patients <60 years with SBP 140 mm Hg or DBP is 90 mm Hg.

Patients 18 years with diabetes and SBP 140 mm Hg or DBP 90 mm Hg.

Patients 18 years with chronic kidney disease (CKD) and SBP 140 mm Hg or
DBP 90 mm Hg.

Coronary artery disease and hypertension: The American Heart Association,


American College of Cardiology and American Society of Hypertension
(AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in
patients with coronary artery disease (CAD) recommends the use of an ARB (or
ACE inhibitor) as part of a regimen in patients with hypertension and chronic
stable angina if there is prior MI, LV systolic dysfunction, diabetes mellitus, or
CKD. A BP target of <140/90 mm Hg is reasonable for the secondary prevention
of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate
in some individuals with CAD, previous MI, stroke or transient ischemic attack, or
CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).

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


recommend an ARB (or an ACE inhibitor) for patients with hypertension and
diabetes with albuminuria (urinary albumin-to-creatinine ratio [UACR] 30 mg/g).
For patients with hypertension and diabetes without albuminuria, any of the 4
classes of blood pressure medications (eg, ACE inhibitors, ARBs, thiazide-like
diuretics, dihydropyridine calcium channel blockers) may be used and have
shown beneficial cardiovascular outcomes (ADA 2017a).

Use: Off-Label
Acute coronary syndrome (secondary prevention of cardiovascular events); Heart failure,
intolerant of ACE inhibitors; Improve kidney outcomes in hypertensive patients with chronic
kidney disease (CKD) (diabetic and nondiabetic population); Marfan syndrome

Medication Safety Issues

Sound-alike/look-alike issues:

Cozaar may be confused with Colace, Coreg, Hyzaar, Zocor

Losartan may be confused with locaserin, valsartan

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

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 U.S. labeling): Concomitant use with
aliskiren in patients with moderate-to-severe renal impairment (GFR <60 mL/minute/1.73
m2)
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.

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).

Metabolism/Transport Effects Substrate of CYP2C9 (major), CYP3A4 (major);


Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction
potential; Inhibits CYP2C8 (moderate), CYP2C9 (moderate)

Drug Interactions

(For additional information: Launch drug interactions program)

ACE Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of
ACE Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of
ACE 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. Risk D:
Consider therapy modification

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C:
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. Risk D: 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. Risk D: Consider therapy modification

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine.


Risk X: Avoid combination

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk


C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of


Losartan. Applicable Isavuconazonium considerations are addressed in separate
monographs. Exceptions: Isavuconazonium Sulfate. Risk C: 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. Risk D: Consider therapy
modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents


may enhance the hypotensive effect of Antipsychotic Agents (Second Generation
[Atypical]). Risk C: Monitor therapy

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

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

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor
therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of


Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A
inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large
increase in serum concentrations of bosentan and is not recommended. See monograph
for details. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib


may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

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

Canagliflozin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.


Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers.
Risk C: Monitor therapy
Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of
Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased.
Risk C: Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of


Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased.
Risk C: Monitor therapy

Ceritinib: May increase the serum concentration of CYP2C9 Substrates. Management:


Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index
(e.g., warfarin, phenytoin) should be avoided when possible. Risk C: Monitor therapy

Ciprofloxacin (Systemic): Angiotensin II Receptor Blockers may enhance the


arrhythmogenic effect of Ciprofloxacin (Systemic). Risk C: Monitor therapy

CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the


hyperkalemic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of


CYP2C8 Substrates. Risk C: Monitor therapy

CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates.


Management: Consider an alternative for one of the interacting drugs. Some combinations
may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D:
Consider therapy modification

CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk
C: Monitor therapy

CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D:
Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of


CYP2C9 Substrates. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4


Substrates. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates.


Management: Consider an alternative for one of the interacting drugs. Some combinations
may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D:
Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. 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).
Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates. 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).
Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor


Blockers. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C:


Monitor therapy

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

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of


Dronabinol. Risk C: Monitor therapy

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


Drospirenone. Risk C: Monitor therapy

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

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates.


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. Risk D: Consider therapy
modification

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates.


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. Risk D: Consider therapy
modification

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


Risk C: 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. Risk C: Monitor therapy

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

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

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of


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

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the


hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of
Levodopa. Risk C: 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. Risk D: Consider therapy modification

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

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk


C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates.


Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor
closely for adverse effects, during and in the 2 weeks following mifepristone treatment.
Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management:


Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients
being treated with mitotane. Risk D: Consider therapy modification

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

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

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

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

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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of
Nitroprusside. Risk C: 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. Risk C: 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. Risk D: Consider therapy modification

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

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

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure


Lowering Agents. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor


Blockers. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the


hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

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

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

Resveratrol: May decrease serum concentrations of the active metabolite(s) of Losartan.


Resveratrol may increase the serum concentration of Losartan. Risk C: Monitor therapy

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor
therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: 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. Risk D: Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates.


Management: Consider an alternative for one of the interacting drugs. Some combinations
may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D:
Consider therapy modification

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum


concentration of Tetrahydrocannabinol. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C:


Monitor therapy

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

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


Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C:


Monitor therapy

Pregnancy Risk Factor D (show table)

Pregnancy Implications
[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).

Breast-Feeding Considerations It is not known if losartan is excreted in breast milk.


Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer
recommends a decision be made whether to discontinue breastfeeding or to discontinue the
drug, taking into account the importance of treatment to the mother.

Dietary Considerations Some products may contain potassium.

Monitoring Parameters
Baseline and periodic blood pressure, electrolytes, renal function

2013 ACCF/AHA Heart Failure guideline recommendations:

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 (ACCF/AHA [Yancy,
2013]).

Reference Range
Hypertension: The 2014 guideline for the management of high blood pressure in adults
(Eighth Joint National Committee [JNC 8]):

Patients 60 years: Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

Patients <60 years: Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Patients 18 years with diabetes: Goal of therapy is SBP <140 mm Hg and DBP <90
mm Hg.

Patients 18 years with chronic kidney disease (CKD): Goal of therapy is SBP <140
mm Hg and DBP <90 mm Hg.

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).

Patents 65 years (healthy or complex/intermediate health): Goal of therapy is SBP


<140 mm Hg and DBP <90 mm Hg.

Patents 65 years (very complex/poor health): Goal of therapy is SBP <150 mm Hg


and DBP <90 mm Hg.

Mechanism of Action 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.

Pharmacodynamics/Kinetics Note: No significant differences in pharmacokinetic


parameters have been identified across studied pediatric age groups (6 to 16 years) and adult
population.

Onset of action: ~6 hours

Absorption: Well absorbed; slowed with food

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

Protein binding, plasma: High, >98%; primarily to albumin

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

Bioavailability: ~33%; AUC of E-3174 (active metabolite) is 4 times greater than losartan;
extemporaneously prepared suspension and tablet have similar bioavailability of losartan
and E-3174

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

Time to peak, serum: Losartan: Children: 2 hours, Adults: 1 hour; E-3174 (active
metabolite): Children: 4.1 hours, Adults: 3.5 hours

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

Pricing: US
Tablets (Cozaar Oral)

25 mg (90): $299.16

50 mg (30): $133.56

100 mg (30): $182.16

Tablets (Losartan Potassium Oral)


25 mg (90): $151.43

50 mg (30): $67.88

100 mg (30): $92.46

Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single
manufacturer of the brand and/or generic product, respectively. The pricing data should be used
for benchmarking purposes only, and as such should not be used to set or adjudicate any
prices for reimbursement or purchasing functions. Pricing data is updated monthly.

International Brand Names Accord (PY); Acetensa (ID); Alsartan-50 (ET); Angioten
(ID); Angisartan (LK); Angizaar (SG); Arados (EC); ARB (KR); Bepsar (LK, PH); Bicosa (KR);
Carlos (BD); Convertal (PY, UY); Cosaar (AT, CH); Cosal (KR); Cosca (KR); Coxco (TW);
Cozaar (AE, AU, BB, BE, BH, BM, BR, BS, BZ, CL, CN, CR, CY, CZ, DK, DO, EC, EE, EG, ES,
FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, ID, IE, IS, JM, JO, KR, KW, LB, LT, LU, MT, MX, MY,
NI, NL, NO, NZ, PA, PE, PH, PK, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, TH, TR,
TT, TW, VE, VN); Cozaarex (AR); Cozatan (MT); Cozavan (AU); Czartan (LK); Doxar (PH);
Ecozar (PH); Insaar (ID); Karozaar (KR); Klosart (UA); Koinsar (ID); Lasa (TW); Lifezar (PH);
Lodial (RO); Loranta (TH); Lorista (LV); Lortaan (IT); Lorzaar (DE); Losa K (KR); Losacar (IN,
MY); Losacor (AR, HK, PE); Losagen (SG, ZW); Losaltan (KR); Losanet (QA); Losar (ZW);
Losar-Denk (TZ); Losardex (IL); Losargard (PH); Losarmax (KR); Losarpex (BD); Losart (BD);
Losartas (SG, ZW); Losartin (KR); Lotan (HR); Lotim (HR); Lowtan (TW); Lozap (BG, LV);
Lozaris (TH); Lozarsin (SG); Lozato (KR); Medzart (PH); Normoten (PH); Ocsaar (IL); Osartil
(HK); Parten-50 (PH); Presartan (ZW); Rocatan (KR); Rosa (KR); Rosatan (BD); Rotamax (KR);
Rozasaltan (KR); Santesar (ID); Sartens (LV); Sartocad (SG); Satoren (CO, CR, DO, EC, GT,
HN, NI, PA, SV); Sentor (UA); Sluxdin (TW); Sortiva (QA); Tansin (LK); Tanzaril (TH); Tosan
(TH); Tozaar (ET, IN); Tozaar-50 (ZW); Zaart (HK); Zartan (KR, ZA); Zosaar (MY); Zylovaal
(MY); Zyltan (ET)

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