When pregnancy is detected, discontinue losartan as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
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 (Ref); Note: Doses >1.4 mg/kg/day (or >100 mg/day) have not been studied (Ref).
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.
Marfan syndrome, aortic-root dilation: Limited data available, optimal place in therapy not defined: Infants ≥6 months, Children, and Adolescents: Oral: Initial: 0.3 to 0.5 mg/kg/day for 21 days, then increase as tolerated to 0.7 to 0.9 mg/kg/day for 21 days, then increase up to 1 to 1.4 mg/kg/day; maximum daily dose: 1.4 mg/kg/day or 100 mg/day (whichever is lower). Note: Dose adjustments (decreased dose and/or frequency) were considered for certain adverse drug reactions (eg, fatigue, dizziness) and lab abnormalities within the study protocol. Dosing based on a large randomized study of patients with Marfan syndrome and a dilated aortic root who were randomized to receive losartan (n=305, ages: 11 ± 6.2 years) or atenolol (n=303, ages: 11.5 ± 6.5 years). Mean losartan dose required was 1.3 ± 0.2 mg/kg/day. Both losartan and atenolol showed a decrease in aortic root z score over a 3-year period (Ref). Similar results were shown in a small, retrospective cohort study (n=18, age: 14 months to 16 years) (Ref).
Proteinuria reduction, chronic kidney disease: Limited data available: Children and Adolescents: Oral: Initial: 0.35 to 0.8 mg/kg/dose once daily; maximum initial dose: 50 mg/dose. May increase as tolerated to reduce proteinuria; maximum daily dose: 1.4 mg/kg/day up to 100 mg/day. Dosing based on multiple studies in pediatric patients with proteinuria due to kidney disease either as monotherapy or in combination with ACE inhibitor therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥6 years and Adolescents: Oral:
Altered kidney function:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary unless also volume depleted. If volume depleted, consider initiating at a lower dose.
CrCl <30 mL/minute/1.73 m2: Not recommended for use.
Hemodialysis, intermittent: Not dialyzed (losartan and active metabolite): There are no dosing adjustments in the manufacturer's labeling; based on adult data, no dosage adjustment necessary (Ref).
Peritoneal dialysis: There are no dosing adjustments in the manufacturer's labeling; based on adult data, poorly dialyzed and no dosage adjustment necessary (Ref).
Children ≥6 years and Adolescents: Oral:
Mild to moderate impairment: There are no pediatric-specific dosing recommendations provided by the manufacturer; however, based on adult recommendations, a lower initial dose is recommended.
Severe impairment: There are no dosing recommendations provided by the manufacturer (has not been studied).
(For additional information see "Losartan: Drug information")
Acute coronary syndrome:
Note: Alternative therapy in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor (eg, due to cough or angioedema) (Ref). Angiotensin II receptor blockers (ARBs) do not appear to elevate the risk of angioedema (Ref); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Ref); 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 (Ref). 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 (Ref).
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 (Ref).
Heart failure with reduced ejection fraction (alternative agent) (off-label use):
Note: Alternative therapy in patients who cannot tolerate an angiotensin II receptor-neprilysin inhibitor (ARNI) or an ACE inhibitor (eg, due to cough or angioedema); consultation with a heart failure specialist and/or an allergist may be appropriate (Ref). ARBs do not appear to elevate the risk of angioedema (Ref); however, angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Ref).
Oral: Initial: 25 to 50 mg once daily; increase dose (eg, double) every ≥1 to 2 weeks based on response and tolerability to a target dose of 150 mg once daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).
Hypertension, chronic:
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) (Ref).
Oral: Initial: 25 to 50 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling) as needed up to 100 mg/day in 1 to 2 divided doses; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).
Marfan syndrome with aortic aneurysm (off-label use):
Note: Losartan may be used in patients with an aortic aneurysm or with a risk factor for developing an aortic aneurysm; may be used as monotherapy or in combination with a beta-blocker. (Ref).
Oral: Initial: 50 mg once daily; after 2 weeks, may increase dose based on blood pressure response and tolerability up to 100 mg/day (Ref).
Posttransplant erythrocytosis (kidney transplant recipients) (off-label use):
Note: For patients with a hemoglobin concentration >17 g/dL (Ref).
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 (Ref).
Proteinuric chronic kidney disease, diabetic (labeled use) or nondiabetic (off-label use):
Oral: Initial: 25 to 50 mg once daily depending on baseline BP; titrate gradually (eg, by doubling the dose every 2 to 4 weeks) up to the maximally tolerated dose, not to exceed 100 mg once daily. If proteinuria target is not met despite optimized dosage, consider additional therapies (eg, sodium-glucose cotransporter-2 inhibitor) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (losartan and active metabolite): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Poorly dialyzed (losartan and active metabolite): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
US 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); initiate therapy at a reduced dosage and titrate as needed. Use with caution in patients with ascites due to cirrhosis (Ref).
Canadian labeling: Mild to severe hepatic impairment or a history of hepatic impairment: Initial: 25 mg once daily
May be associated with increased serum creatinine and/or acute kidney injury. Increases in serum creatinine secondary to angiotensin II receptor blockers usually stabilize within 20% to 30% from baseline and are expected; additional increases may indicate renal artery stenosis or volume depletion (Ref).
Mechanism: Related to pharmacologic action; inhibits efferent kidney arteriolar vasoconstriction, lowering glomerular filtration pressure which can lead to a modest reduction in glomerular filtration rate (GFR) (Ref).
Onset: Expected to be similar to angiotensin-converting enzyme inhibitors: Intermediate; transient increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref).
Risk factors:
• Sodium or volume depletion (Ref)
• Heart failure (Ref)
• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)
• Older patients
• Hypotension (Ref)
• Preexisting kidney impairment (Ref)
• Patients with low renal blood flow (eg, renal artery stenosis) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II (Ref)
Hyperkalemia may occur.
Mechanism: Related to pharmacologic action; blocks angiotensin II from binding to the adrenal receptor and interferes with generation of angiotensin II within the adrenal cortex, decreasing aldosterone release and impairing kidney potassium excretion (Ref).
Onset: Generally occurs within 1 week of treatment initiation (Ref).
Risk factors:
• High dietary intake of potassium (Ref)
• Baseline elevated potassium (≥5 mmol/L) (Ref)
• Older patients (Ref)
• Kidney dysfunction (Ref)
• Diabetes mellitus (Ref)
• Concurrent use of medications known to decrease renin and aldosterone (eg, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, cyclosporine, tacrolimus, beta-blockers, sulfamethoxazole/trimethoprim, azole antifungals) (Ref)
• Concurrent use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes (Ref)
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) (Ref), 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%) (Ref), dyspnea (<2%), nasal congestion (2%), upper respiratory tract infection (8%)
Postmarketing:
Cardiovascular: Facial edema (Ref), lip edema (Ref), vasculitis (Ref)
Endocrine & metabolic: Hyponatremia (Ref)
Gastrointestinal: Dysgeusia (Ref)
Hematologic & oncologic: Henoch-Schonlein purpura (Ref), thrombocytopenia (Ref)
Hepatic: Hepatitis (Ref)
Hypersensitivity: Anaphylaxis (Ref), angioedema (Ref)
Respiratory: Laryngeal edema (Ref)
Hypersensitivity to losartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m2).
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.
• 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.
Disease-related concerns:
• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.
• Ascites: Generally, 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 BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Runyon 2013]).
• Hepatic impairment: Use with caution in patients with hepatic impairment or a history of hepatic impairment; dose adjustment needed.
• Kidney impairment: Use with caution with preexisting kidney insufficiency.
Special populations:
• Race/ethnicity: In Black patients, the BP-lowering effects of ARBs may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018; manufacturer’s labeling).
• 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]).
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
Yes
Tablets (Cozaar Oral)
25 mg (per each): $3.82
50 mg (per each): $5.12
100 mg (per each): $6.98
Tablets (Losartan Potassium Oral)
25 mg (per each): $0.16 - $1.68
50 mg (per each): $0.17 - $2.27
100 mg (per each): $0.19 - $3.10
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as potassium:
Cozaar: 25 mg, 50 mg, 100 mg [contains corn starch]
Generic: 25 mg, 50 mg, 100 mg
2.5 mg/mL Oral Suspension
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).
Potassium content: 25 mg tablets: 2.12 mg (0.054 mEq); 50 mg tablets: 4.24 mg (0.108 mEq; 100 mg tablets: 8.48 mg (0.216 mEq)
Oral: May be administered with or without food.
Oral: Administer without regard to meals; however, administer consistently with respect to food intake at about the same time every day.
Store at 25°C (77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Treatment of hypertension alone or in combination with other antihypertensive agents (FDA approved in ages ≥6 years and adults); treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes mellitus and a history of hypertension (FDA approved in adults); reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy (FDA approved in adults); has also been used to reduce proteinuria in children with chronic kidney disease, either as monotherapy or in combination with ACE inhibitor therapy, and in Marfan syndrome to slow the rate of progression of aortic-root dilation.
Cozaar may be confused with Colace, Coreg, Hyzaar, Zocor
Losartan may be confused with lorcaserin, valsartan
Losartan is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with hyperkalemia or severe symptomatic aortic stenosis (O’Mahony 2023).
Substrate of CYP2C9 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
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 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. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Receptor Blockers may diminish the therapeutic effect of Angiotensin II. Risk C: 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. Risk D: 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. 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
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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
Berberine-Containing Products: May enhance the hypotensive effect of Losartan. Berberine-Containing Products may increase the serum concentration of Losartan. 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
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
CYP2C9 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Losartan. CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Losartan. Risk C: Monitor therapy
Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Finerenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: 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
Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Isocarboxazid: May enhance the antihypertensive effect of Antihypertensive Agents. Risk X: Avoid combination
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: 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. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Angiotensin II Receptor Blockers. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
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
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin II Receptor Blockers. 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
Polyethylene Glycol-Electrolyte Solution: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. 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
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. 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
Ranolazine: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Risk C: Monitor therapy
Sparsentan: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk X: Avoid combination
Tacrolimus (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. 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
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Some products may contain potassium.
Avoid use of an angiotensin II receptor blocker (ARB) in patients who may become pregnant and who are not using effective contraception (ADA 2023).
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. ARBs are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ARB is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
When an ARB is used for the treatment of proteinuric chronic kidney disease in patients who could become pregnant, discontinue use at the first positive pregnancy test (ADA 2023; Fakhouri 2023)
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin II receptor blocker (ARB) during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]).Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal kidney function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ARB use during pregnancy is also associated with anuria, hypotension, kidney failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ARB in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Discontinue ARBs as soon as possible once pregnancy is detected. Agents other than an ARB are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). Closely monitor patients exposed to an ARB during pregnancy with serial ultrasounds.
ARBs are not recommended for the treatment of proteinuric chronic kidney disease during pregnancy (Fakhouri 2023).
Baseline and periodic: Blood pressure, renal function, serum electrolytes.
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.
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
Altered kidney function: 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) kidney impairment.
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.
Sex: Plasma losartan concentrations are about twice as high in hypertensive women as hypertensive men, but plasma concentrations of active metabolite are similar.
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