Hypertension: Losartan potassium tablets are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, including diuretics. Hypertensive Patients with Left Ventricular Hypertrophy: Losartan potassium tablets are indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients (see PRECAUTIONS, Race and CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects , Reduction in the Risk of Stroke , Race ).
Nephropathy in Type 2 Diabetic Patients Losartan potassium tablets are indicated for the 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. In this population, losartan potassium reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects ).
Contraindications
Losartan potassium tablets are contraindicated in patients who are hypersensitive to any component of this product. Do not co-administer aliskiren with losartan potassium tablets in patients with diabetes.
Warnings and precautions
Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.
When pregnancy is detected, discontinue losartan potassium as soon as possible. These adverse outcomes are usually associated with the use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue losartan potassium, unless it is considered life-saving for the mother.
Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to losartan potassium for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use ). Losartan potassium has been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity.
With the exception of neonatal weight gain (which was affected at doses as low as 10 mg/kg/day), doses associated with these effects exceeded 25 mg/kg/day (approximately three times the maximum recommended human dose of 100 mg on a mg/m 2 basis). These findings are attributed to drug exposure in late gestation and during lactation. Significant levels of losartan and its active metabolite were shown to be present in rat fetal plasma during late gestation and in rat milk.
Hypotension — Volume-Depleted Patients: In patients who are intravascularly volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with losartan potassium tablets. These conditions should be corrected prior to administration of losartan potassium tablets, or a lower starting dose should be used (see DOSAGE AND ADMINISTRATION ).
Interactions
Agents Increasing Serum Potassium: Risk of hyperkalemia. (7.1)
Lithium: Risk of lithium toxicity. (7.2)
NSAIDs: Increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects. (7.3)
Dual Inhibition of the Renin-Angiotensin System: Increased risk of renal impairment, hypotension, syncope, and hyperkalemia. (7.4)
of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.
7.2Lithium Increases
in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use.
7.3Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving losartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.
7.4Dual Blockade of the Renin-Angiotensin System (RAS)
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years.
Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors.
Closely monitor blood pressure, renal function, and electrolytes in patients on losartan potassium and other agents that affect the RAS. Do not coadminister aliskiren with losartan potassium in patients with diabetes. Avoid use of aliskiren with losartan potassium in patients with renal impairment (GFR <60 mL/min).
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
Losartan potassium can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
When pregnancy is detected, discontinue losartan potassium as soon as possible (see Clinical Considerations). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.
Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
In patients taking losartan potassium during pregnancy, serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue losartan potassium, unless it is considered lifesaving for the mother. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Closely observe infants with histories of in utero exposure to losartan potassium for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to losartan potassium, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data Losartan potassium was administered orally to rats during the period of late gestation through lactation (Gestation Day 15 through Lactation Day 20) at doses of 10 mg/kg/day, 25 mg/kg/day, and 100 mg/kg/day.
Losartan potassium has been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity. With the exception of neonatal weight gain (which was affected at doses as low as 10 mg/kg/day), doses associated with these effects exceeded 25 mg/kg/day (approximately three times the maximum recommended human dose of 100 mg on a mg/m 2 basis).
These findings are attributed to drug exposure in late gestation and during lactation. Significant levels of losartan and its active metabolite were shown to be present in rat fetal plasma during late gestation and in rat milk.
Adverse reactions
Hypertension: Losartan potassium tablets have been evaluated for safety in more than 3300 adult patients treated for essential hypertension and 4058 patients/subjects overall. Over 1200 patients were treated for over 6 months and more than 800 for over one year. In general, treatment with losartan potassium tablets was well-tolerated. The overall incidence of adverse experiences reported with losartan potassium tablets was similar to placebo.
In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 2.3 percent of patients treated with losartan potassium tablets and 3.7 percent of patients given placebo. The following table of adverse events is based on four 6 to 12 week, placebo-controlled trials involving over 1000 patients on various doses (10 to 150 mg) of losartan and over 300 patients given placebo.
All doses of losartan are grouped because none of the adverse events appeared to have a dose-related frequency. The adverse experiences reported in ≥1% of patients treated with losartan potassium tablets and more commonly than placebo are shown in the table below. Losartan (n=1075) Incidence % Placebo (n=334) Incidence % Musculoskeletal Cramp, muscle Pain, back Pain, leg 1 2 1 0 1 0 Nervous System/Psychiatric Dizziness 3 2 Respiratory Congestion, nasal Infection, upper respiratory Sinusitis 2 8 1 1 7 0 The following adverse events were also reported at a rate of 1% or greater in patients treated with losartan, but were as, or more frequent, in the placebo group: asthenia/fatigue, edema/swelling, abdominal pain, chest pain, nausea, headache, pharyngitis, diarrhea, dyspepsia, myalgia, insomnia, cough, sinus disorder.
Adverse events occurred at about the same rates in men and women, older and younger patients, and Black and non-Black patients. A patient with known hypersensitivity to aspirin and penicillin, when treated with losartan potassium tablets, was withdrawn from study due to swelling of the lips and eyelids and facial rash, reported as angioedema, which returned to normal 5 days after therapy was discontinued. Superficial peeling of palms and hemolysis were reported in one subject.
In addition to the adverse events above, potentially important events that occurred in at least two patients/subjects exposed to losartan or other adverse events that occurred in <1% of patients in clinical studies are listed below. It cannot be determined whether these events were causally related to losartan: Body as a Whole : Facial edema, fever, orthostatic effects, syncope Cardiovascular : Angina pectoris, second degree AV block, CVA, hypotension, myocardial infarction, arrhythmias including atrial fibrillation, palpitation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation Digestive : Anorexia, constipation, dental pain, dry mouth, flatulence, gastritis, vomiting Hematologic : Anemia Metabolic : Gout Musculoskeletal : Arm pain, hip pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, fibromyalgia, muscle weakness Nervous System/Psychiatric : Anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, decreased libido, memory impairment, migraine, nervousness, paresthesia, peripheral neuropathy, panic disorder, sleep disorder, somnolence, tremor, vertigo Respiratory : Dyspnea, bronchitis, pharyngeal discomfort, epistaxis, rhinitis, respiratory congestion Skin : Alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, rash, sweating, urticaria Special Senses : Blurred vision, burning/stinging in the eye, conjunctivitis, taste perversion, tinnitus, decrease in visual acuity Urogenital : Impotence, nocturia, urinary frequency, urinary tract infection Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy.
Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135).
The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown below. * Demographics = (89% caucasian, 64% female) † Demographics = (90% caucasian, 51% female) Study 1 * HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 † Losartan Lisinopril Cough 35% 29% 62% These studies demonstrate that the incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy.
Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience. Pediatric Patients: No relevant differences between the adverse experience profile for pediatric patients and that previously reported for adult patients were identified. Hypertensive Patients with Left Ventricular Hypertrophy: In the LIFE study, adverse events with losartan potassium tablets were similar to those reported previously for patients with hypertension.
Nephropathy in Type 2 Diabetic Patients In the RENAAL study involving 1513 patients treated with losartan potassium or placebo, the overall incidences of reported adverse experiences were similar for the two groups. Losartan potassium was generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo (19% for losartan potassium, 24% for placebo). The adverse experiences, regardless of drug relationship, reported with an incidence of ≥ 4% of patients treated with losartan potassium and occurring more commonly than placebo, on a background of conventional antihypertensive therapy, are shown in the table below.
Losartan and Conventional Antihypertensive Therapy Incidence % (n=751) Placebo and Conventional Antihypertensive Therapy Incidence % (n=762) Body as a Whole Asthenia/Fatigue 14 10 Chest Pain 12 8 Fever 4 3 Infection 5 4 Influenza-like disease 10 9 Trauma 4 3 Cardiovascular Hypotension 7 3 Orthostatic hypotension 4 1 Digestive Diarrhea 15 10 Dyspepsia 4 3 Gastritis 5 4 Endocrine Diabetic neuropathy 4 3 Diabetic vascular disease 10 9 Eyes, Ears, Nose and Throat Cataract 7 5 Sinusitis 6 5 Hemic Anemia 14 11 Metabolic and Nutrition Hyperkalemia 7 3 Hypoglycemia 14 10 Weight gain 4 3 Musculoskeletal Back pain 12 10 Leg pain 5 4 Knee pain 5 4 Muscular weakness 7 4 Nervous System Hypesthesia 5 4 Respiratory Bronchitis 10 9 Cough 11 10 Skin Cellulitis 7 6 Urogenital Urinary tract infection 16 13 Postmarketing Experience: The following additional adverse reactions have been reported in postmarketing experience: Digestive: Hepatitis (reported rarely).
General Disorders and Administration Site Conditions: Malaise. Hemic: Thrombocytopenia (reported rarely). Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors.
Vasculitis, including Henoch-Schonlein purpura, has been reported. Anaphylactic reactions have been reported. Metabolic and Nutrition: Hyperkalemia, hyponatremia have been reported with losartan. Musculoskeletal: Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers. Nervous system disorders : Dysgeusia Respiratory: Dry cough (see above). Skin : Erythroderma Laboratory Test Findings: In controlle
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
LOSARTAN POTASSIUM 25MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
