Losortan Potassium

Figure 4. Kaplan-Meier curve for the primary composite endpoint of doubling of serum creatinine, end stage renal disease (need for dialysis or transplantation) or death.

The secondary endpoints of the study were change in proteinuria, change in the rate of progression of renal disease, and the composite of morbidity and mortality from cardiovascular causes (hospitalization for heart failure, myocardial infarction, revascularization, stroke, hospitalization for unstable angina, or cardiovascular death). Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine concentration. There was no significant difference in the incidence of the composite endpoint of cardiovascular morbidity and mortality.

The favorable effects of losartan were seen in patients also taking other anti-hypertensive medications (angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors were not allowed), oral hypoglycemic agents and lipid-lowering agents.

For the primary endpoint and ESRD, the effects of losartan in patient subgroups defined by age, gender and race are shown in Table 4 below. Subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.

LOSORTAN POTASSIUM INDICATIONS AND USAGE

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).

LOSORTAN POTASSIUM CONTRAINDICATIONS

Losartan potassium tablets are contraindicated in patients who are hypersensitive to any component of this product.

WARNINGS

Fetal/Neonatal Morbidity and Mortality:

Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, losartan potassium tablets should be discontinued as soon as possible.

The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.

These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester.

Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of losartan potassium tablets as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to an angiotensin II receptor antagonist will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.

If oligohydramnios is observed, losartan potassium tablets should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.

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/m² 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).

PRECAUTIONS

General:

Hypersensitivity

Angioedema (see ADVERSE REACTIONS, Post-Marketing Experience ).

Impaired Hepatic Function:

Based on pharmacokinetic data, which demonstrate significantly increased plasma concentrations of losartan in cirrhotic patients, a lower dose should be considered for patients with impaired liver function (see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY, Pharmacokinetics ).

Impaired Renal Function:

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with losartan potassium tablets; in some patients, these changes in renal function were reversible upon discontinuation of therapy.

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with losartan potassium tablets.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. Similar effects have been reported with losartan potassium tablets; in some patients, these effects were reversible upon discontinuation of therapy.

Electrolyte Imbalance:

Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be addressed. In a clinical study conducted in type 2 diabetic patients with proteinuria, the incidence of hyperkalemia was higher in the group treated with losartan potassium as compared to the placebo group; however, few patients discontinued therapy due to hyperkalemia (see ADVERSE REACTIONS).

Information for Patients:

Pregnancy:

Female patients of childbearing age should be told about the consequences of second-and third-trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Potassium Supplements:

A patient receiving losartan potassium tablets should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician (see PRECAUTIONS, Drug Interactions).

Drug Interactions:

No significant drug-drug pharmacokinetic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Rifampin, an inducer of drug metabolism, decreased the concentrations of losartan and its active metabolite (see CLINICAL PHARMACOLOGY, Drug Interactions). In humans, two inhibitors of P450 3A4 have been studied. Ketoconazole did not affect the conversion of losartan to the active metabolite after intravenous administration of losartan, and erythromycin had no clinically significant effect after oral administration. Fluconazole, an inhibitor of P450 2C9, decreased active metabolite concentration and increased losartan concentration. The pharmacodynamic consequences of concomitant use of losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not metabolize losartan to active metabolite have been shown to have a specific, rare defect in cytochrome P450 2C9. These data suggest that the conversion of losartan to its active metabolite is mediated primarily by P450 2C9 and not P450 3A4.

As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium.

Lithium:

As with other drugs which affect the excretion of sodium, lithium excretion may be reduced. Therefore, serum lithium levels should be monitored carefully if lithium salts are to be co-administered with angiotensin II receptor antagonists.

Non-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, co-administration 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.

Dual blockade of the renin-angiotensin-aldosterone system

It has been reported in the literature that in patients with established atherosclerotic disease, heart failure, or with diabetes with end organ damage, dual blockade of the renin-angiotensin-aldosterone system is associated with a higher frequency of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) as compared to use of a single renin-angiotensin-aldosterone system agent. Dual blockade (e.g., by adding an ACE inhibitor to an angiotensin II receptor antagonist) should be limited to individually defined cases with close monitoring of renal function.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Losartan potassium was not carcinogenic when administered at maximally tolerated dosages to rats and mice for 105 and 92 weeks, respectively. Female rats given the highest dose (270 mg/kg/day) had a slightly higher incidence of pancreatic acinar adenoma. The maximally tolerated dosages (270 mg/kg/day in rats, 200 mg/kg/day in mice) provided systemic exposures for losartan and its pharmacologically active metabolite that were approximately 160- and 90-times (rats) and 30- and 15-times (mice) the exposure of a    50 kg human given 100 mg per day.

Losartan potassium was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays and in the in vitro alkaline elution and in vitro and in vivo chromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitro chromosomal aberration assays.

Fertility and reproductive performance were not affected in studies with male rats given oral doses of losartan potassium up to approximately 150 mg/kg/day. The administration of toxic dosage levels in females (300/200 mg/kg/day) was associated with a significant (p< 0.05) decrease in the number of corpora lutea/female, implants/female, and live fetuses/female at C-section. At 100 mg/kg/day only a decrease in the number of corpora lutea/female was observed. The relationship of these findings to drug-treatment is uncertain since there was no effect at these dosage levels on implants/pregnant female, percent post-implantation loss, or live animals/litter at parturition. In nonpregnant rats dosed at 135 mg/kg/day for 7 days, systemic exposure (AUCs) for losartan and its active metabolite were approximately 66 and 26 times the exposure achieved in man at the maximum recommended human daily dosage (100 mg).

Pregnancy:

Pregnancy Categories C (first trimester) and D (second and third trimesters) (see WARNINGS, Fetal/Neonatal Morbidity and Mortality).

Nursing Mothers:

It is not known whether losartan is excreted in human milk, but significant levels of losartan and its active metabolite were shown to be present in rat milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

Antihypertensive effects of losartan potassium tablets have been established in hypertensive pediatric patients aged 6 to 16 years. There are no data on the effect of losartan potassium tablets on blood pressure in pediatric patients under the age of 6 or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m² (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects, and DOSAGE AND ADMINISTRATION).

Geriatric Use:

Of the total number of patients receiving losartan potassium tablets in controlled clinical studies for hypertension, 391 patients (19%) were 65 years and over, while 37 patients (2%) were 75 years and over. In a controlled clinical study for renal protection in type 2 diabetic patients with proteinuria, 248 patients (33%) were 65 years and over. In a controlled clinical study for the reduction in the combined risk of cardiovascular death, stroke and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 2857 patients (62%) were 65 years and over, while 808 patients (18%) were 75 years and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Race:

In the LIFE study, Black patients with hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on losartan potassium tablets. Given the difficulty in interpreting subset differences in large trials, it cannot be known whether the observed difference is the result of chance. However, the LIFE study does not provide evidence that the benefits of losartan potassium tablets on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects; Reduction in the Risk of Stroke).

LOSORTAN POTASSIUM 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 (10-150 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.

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.

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 post-marketing 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.

Post-Marketing Experience:

The following additional adverse reactions have been reported in post-marketing 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 controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan potassium tablets.

Creatinine, Blood Urea Nitrogen:

Minor increases in blood urea nitrogen (BUN) or serum creatinine were observed in less than 0.1 percent of patients with essential hypertension treated with losartan potassium tablets alone (see PRECAUTIONS, Impaired Renal Function).

Hemoglobin and Hematocrit:

Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.11 grams percent and 0.09 volume percent, respectively) occurred frequently in patients treated with losartan potassium tablets alone, but were rarely of clinical importance. No patients were discontinued due to anemia.

Liver Function Tests:

Occasional elevations of liver enzymes and/or serum bilirubin have occurred. In patients with essential hypertension treated with losartan potassium tablets alone, one patient (<0.1%) was discontinued due to these laboratory adverse experiences.

OVERDOSAGE

Significant lethality was observed in mice and rats after oral administration of   1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m² basis.

Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted.

Neither losartan nor its active metabolite can be removed by hemodialysis.

LOSORTAN POTASSIUM DOSAGE AND ADMINISTRATION

Adult Hypertensive Patients:

Losartan potassium tablets may be administered with other antihypertensive agents, and with or without food.

Dosing must be individualized. The usual starting dose of losartan potassium tablets is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics) (see WARNINGS, Hypotension — Volume-Depleted Patients) and patients with a history of hepatic impairment (see PRECAUTIONS, General). Losartan potassium tablets can be administered once or twice daily with total daily doses ranging from 25 mg to 100 mg.

If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3-6 weeks (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).

If blood pressure is not controlled by losartan potassium tablets alone, a low dose of a diuretic may be added. Hydrochlorothiazide has been shown to have an additive effect (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension).

No initial dosage adjustment is necessary for elderly patients or for patients with renal impairment, including patients on dialysis.

Pediatric Hypertensive patient ≥ 6 years of age:

The usual recommended starting dose is 0.7 mg/kg once daily (up to 50 mg total) administered as a tablet or a suspension (see Preparation of Suspension). Dosage should be adjusted according to blood pressure response. Doses above 1.4 mg/kg (or in excess of 100 mg) daily have not been studied in pediatric patients (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects and WARNINGS, Hypotension — Volume-Depleted Patients,).

Losartan potassium tablets are not recommended in pediatric patients <6 years of age or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m² (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Pharmacodynamics and Clinical Effects, and PRECAUTIONS).

Preparation of Suspension (for 200 mL of a 2.5 mg/mL suspension):

Add 10 mL of Purified Water USP to an 8 ounce (240 mL) amber polyethylene terephthalate (PET) bottle containing ten 50 mg losartan potassium tablets.   Immediately shake for at least 2 minutes. Let the concentrate stand for 1 hour and then shake for 1 minute to disperse the tablet contents. Separately prepare a 50/50 volumetric mixture of Ora-Plus™^*** and Ora-Sweet SF™^***. Add 190 mL of the 50/50 Ora-Plus™ /Ora-Sweet SF™ mixture to the tablet and water slurry in the PET bottle and shake for 1 minute to disperse the ingredients. The suspension should be refrigerated at    2-8°C (36-46°F) and can be stored for up to 4 weeks. Shake the suspension prior to each use and return promptly to the refrigerator.

Hypertensive Patients with Left Ventricular Hypertrophy:

The usual starting dose is 50 mg of losartan potassium tablets once daily. Hydrochlorothiazide 12.5 mg daily should be added and/or the dose of losartan potassium tablets should be increased to 100 mg once daily followed by an increase in hydrochlorothiazide to 25 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke).

Nephropathy in Type 2 Diabetic Patients

The usual starting dose is 50 mg once daily. The dose should be increased to 100 mg once daily based on blood pressure response (see CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Nephropathy in Type 2 Diabetic Patients). Losartan potassium may be administered with insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones and glucosidase inhibitors).

HOW SUPPLIED

Losartan Potassium Tablets USP, 25 mg are white to off-white, capsule-shaped, film-coated tablets debossed with the logo of "Z" on one side and "2"on other side and are supplied as follows:

Unit dose packages of 100 (10 x 10) NDC 68084-346-01

Losartan Potassium Tablets USP, 50 mg are white to off-white, capsule-shaped, film-coated tablets debossed with the logo of "Z16" on one side and lip type breakline on other side and are supplied as follows:

Unit dose packages of 100 (10 x 10) NDC 68084-347-01

Losartan Potassium Tablets USP, 100 mg are white to off-white, capsule-shaped, film-coated tablets debossed with the logo of "Z18" on one side and plain on other side and are supplied as follows:

Unit dose packages of 100 (10 x 10) NDC 68084-348-01

Storage:

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light.

^***Trademark of Paddock Laboratories, Inc.

PACKAGING INFORMATION

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Zydus Pharmaceuticals (USA) Inc. as follows:

(25 mg / 100 UD) NDC 68084-346-01 packaged from NDC 68382-135

(50 mg / 100 UD) NDC 68084-347-01 packaged from NDC 68382-136

(100 mg / 100 UD) NDC 68084-348-01 packaged from NDC 68382-137

Packaged and Distributed by:

American Health Packaging

Columbus, OH 43217

8234601/0213

Patient Information Leaflet

Read the Patient Information that comes with losartan potassium tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition and treatment.  

What is the most important information I should know about losartan potassium tablets?

Do not take losartan potassium tablets if you are pregnant or plan to become pregnant. Losartan potassium tablets can harm your unborn baby causing injury and even death. Stop taking losartan potassium tablets if you become pregnant and call your doctor right away.  If you plan to become pregnant, talk to your doctor about other treatment options before taking losartan potassium tablets.

What is losartan potassium tablet?

Losartan potassium tablet is a prescription medicine called an angiotensin receptor blocker (ARB). It is used:  

• •alone or with other blood pressure medicines to lower high blood pressure (hypertension).   
• •to lower the chance of stroke in patients with high blood pressure and a heart problem called left ventricular hypertrophy. Losartan potassium tablets may not help Black patients with this problem.
• •to slow the worsening of diabetic kidney disease (nephropathy) in patients with type 2 diabetes who have or had high blood pressure.

Losartan potassium tablets have not been studied in children less than 6 years old or in children with certain kidney problems.

.

High Blood Pressure (hypertension). Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Losartan potassium tablets can help your blood vessels relax so your blood pressure is lower.

Left Ventricular Hypertrophy (LVH) is an enlargement of the walls of the left chamber of the heart (the heart’s main pumping chamber). LVH can happen from several things. High blood pressure is the most common cause of LVH.

Type 2 Diabetes with Nephropathy. Type 2 diabetes is a type of diabetes that happens mainly in adults. If you have diabetic nephropathy it means that your kidneys do not work properly because of damage from the diabetes.

Who should not take losartan potassium tablets?

•    Do not take losartan potassium tablets if you are allergic to any of the ingredients of losartan potassium tablets. See the end of this leaflet for a complete list of ingredients in losartan potassium tablets.

What should I tell my doctor before taking losartan potassium tablets?

Tell your doctor about all of your medical conditions including if you:

• • are pregnant or planning to become pregnant  (see "What is the most important information I should know about losartan potassium tablets?").
• • are breast-feeding. It is not known if losartan potassium passes into your breast milk. You should choose either to take losartan potassium tablets or breastfeed, but not both.
• •are vomiting a lot or having a lot of diarrhea
• •have liver problems
• •have kidney problems

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.  

Losartan potassium tablets and certain other medicines may interact with each other.  Especially tell your doctor if you are taking:

• •potassium supplements
• •salt substitutes containing potassium
• •water pills (diuretics)
• •medicines used to treat pain and arthritis, called non-steroidal anti-inflammatory drugs (NSAIDS), including COX-2 inhibitors.
• •other medicines to reduce blood pressure

How should I take losartan potassium tablets?

• •Take losartan potassium tablets exactly as prescribed by your doctor. Your doctor may change your dose if needed.  
• •Losartan potassium tablets can be taken with or without food.
• •If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Just take the next dose at your regular time.
• •If you take too much losartan potassium tablets, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away.

What are the possible side effects of losartan potassium tablets?

Losartan potassium tablets may cause the following side effects that may be serious:

• • Injury or death of unborn babies (see "What is the most important information I should know about losartan potassium tablets?").
• • Allergic reaction. Symptoms of an allergic reaction are swelling of the face, lips, throat or tongue. Get emergency medical help right away and stop taking losartan potassium tablets.
• • Low blood pressure (hypotension). Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy. Call your doctor right away.
• • For people who already have kidney problems, you may see a worsening in how well your kidneys work. Call your doctor if you get swelling in your feet, ankles, or hands, or unexplained weight gain.

The most common side effects of losartan potassium tablets in people with high blood pressure are:

• •"colds" (upper respiratory infection)  
• •dizziness  
• •stuffy nose  
• •back pain

The most common side effects of losartan potassium tablets in people with type 2 diabetes with diabetic kidney disease are:

• •diarrhea
• •tiredness
• •low blood sugar
• •chest pain
• •high blood potassium
• •low blood pressure

Tell your doctor if you get any side effect that bothers you or that won’t go away.  

This is not a complete list of side effects. For a complete list, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store losartan potassium tablets?

• •Store losartan potassium tablets at 68° to 77°F (20° to 25°C).  
• • Keep losartan potassium tablets and all medicines out of the reach of children.

General information about losartan potassium tablets

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use losartan potassium tablets for a condition for which it was not prescribed. Do not give losartan potassium tablets to other people, even if they have the same symptoms that you have. It may harm them.

This leaflet summarizes the most important information about losartan potassium tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about losartan potassium tablets that is written for health professionals.  

What are the ingredients in losartan potassium tablets?

Active ingredients: losartan potassium, USP

Inactive ingredients: colloidal silica anhydrous, hydroxypropyl cellulose (low substituted), hypromellose, lactose monohydrate, magnesium stearate, maize starch (corn starch), microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc and titanium dioxide.

Packaged and Distributed by:

American Health Packaging

Columbus, OH 43217

8234601/0213

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