(loe SAR tan)
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 of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
- Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
Chronic kidney disease (CKD) and hypertension: Regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
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]).
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)
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.
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).
Refer to adult dosing.
Hypertension: Oral: Children ≥6 years and Adolescents ≤16 years:
U.S. labeling: Initial: 0.7 mg/kg once daily (maximum initial dose: 50 mg/day); adjust dose to blood pressure response; doses >1.4 mg/kg (>100 mg) once daily have not been studied
Canadian labeling:
≥20 kg to <50 kg: Initial: 25 mg once daily; adjust dose to blood pressure response (maximum: 50 mg/day)
≥50 kg: Initial: 50 mg once daily; adjust dose to blood pressure response (maximum: 100 mg/day)
Aortic-root dilation with Marfan 's syndrome (off-label use): Children 14 months to 16 years: Initial: 0.6 mg/kg/day; can be increased to a maximum of 1.4 mg/kg/day (not to exceed adult maximum of 100 mg daily) (Brooke, 2008)
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 manufacturers labeling.
GFR <30 mL/minute/1.73 m2: Use is not recommended.
Hemodialysis: Nondialyzable (both Losartan and the active metabolite)
Adults:
U.S. labeling:
Mild to moderate hepatic impairment: Initial: 25 mg once daily
Severe hepatic impairment: There are no specific dosage adjustments provided in the manufacturer 's labeling (has not been studied); however, it may be advisable to initiate therapy at a reduced dosage.
Canadian labeling: Mild to severe hepatic impairment or a history of hepatic impairment: Initial: 25 mg once daily
Children ≥6 years and Adolescents ≤16 years:
US labeling: There are no specific dosage adjustments provided in the manufacturers labeling; however it may be advisable to initiate therapy at a reduced dosage
Canadian labeling: Use is not recommended.
Oral: Administer without regard to meals; however, administer consistently with respect to food intake at about the same time every day.
Some products may contain potassium.
Store at 25 ‚ °C (77 ‚ °F); excursions are permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light.
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
A 2.5 mg/mL losartan oral suspension may be made with tablets and a 1:1 mixture of Ora-Plus and Ora-Sweet SF. Combine 10 mL of purified water and ten losartan 50 mg tablets in a 240 mL amber polyethylene terephthalate bottle. Shake well for at least 2 minutes. Allow concentrate to stand for 1 hour, then shake for 1 minute. Separately, prepare 190 mL of a 1:1 mixture of Ora-Plus and Ora-Sweet SF; add to tablet and water mixture in the bottle and shake for 1 minute. Label shake well" and "refrigerate". Return promptly to refrigerator after each use. Stable for 4 weeks when stored in amber polyethylene terephthalate prescription bottles and refrigerated (Cozaar prescribing information, 2015).
Cozaar prescribing information, Merck & Co, Inc, Whitehouse Station, NJ, 2015.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. Consider therapy modification
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Losartan. Applicable Isavuconazonium considerations are addressed in separate monographs. Exceptions: Isavuconazonium Sulfate. Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Losartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the losartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. 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. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Canagliflozin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy
Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. 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. Monitor therapy
Ciprofloxacin (Systemic): Angiotensin II Receptor Blockers may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy
CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Monitor therapy
CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. 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. Consider therapy modification
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Consider therapy modification
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. 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. 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). 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). 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. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. 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. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates. Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification
Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy
Fluconazole: May decrease the serum concentration of Losartan. Specifically, fluconazole may decrease the serum concentration of E3174, the more potent active metabolite of losartan. Monitor therapy
Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy
Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. 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. 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. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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
Resveratrol: May decrease serum concentrations of the active metabolite(s) of Losartan. Resveratrol may increase the serum concentration of Losartan. Monitor therapy
RifAMPin: May decrease the serum concentration of Losartan. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification
St Johns 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. Consider therapy modification
Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. 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
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]).
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. Frequency not always defined.
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%), fatigue (type 2 diabetic nephropathy)
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%), weakness (type 2 diabetic nephropathy)
Respiratory: Cough (hypertension: 17%; incidence higher in patients with previous cough related to ACE inhibitor therapy), upper respiratory tract infection (hypertension: 8%), nasal congestion (hypertension: 2%)
<2% (Limited to important or life-threatening): Abdominal pain, abnormal hepatic function tests, anaphylaxis, anemia, angioedema, arthralgia, atrial fibrillation, cerebrovascular accident, depression, drowsiness, dysgeusia, dyspnea, edema, erectile dysfunction, erythroderma, hepatitis, hyponatremia, IgA vasculitis, impotence, malaise, migraine, myalgia, myositis, palpitations, paresthesia, rhabdomyolysis, sleep disorder, syncope, taste disorder, thrombocytopenia, tinnitus, vasculitis, vertigo, vomiting
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.
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.
Plasma losartan concentrations are about twice as high in hypertensive women as hypertensive men, but plasma concentrations of active metabolite are similar.
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).
D
[U.S. 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).
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.
Oral: Well absorbed; slowed with food
Vd: Losartan: 34 L; E-3174 (active metabolite): 12 L
Hepatic (~14%) via CYP2C9 and 3A4 to an active metabolite E-3174 (10 to 40 times more potent than losartan); extensive first-pass effect
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
~6 hours
Serum: Losartan: Children: 2 hours, Adults: 1 hour; E-3174 (active metabolite): Children: 4.1 hours, Adults: 3.5 hours
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
Plasma: High, >98%; primarily to albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, cold-like symptoms, back pain, loss of strength, and energy or rhinorrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe dizziness, passing out, angina, or swelling of arms or legs (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patients should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.