LOSARTAN POTASSIUM - losartan potassium tablet, film coated
Micro Labs Limited
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When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, losartan potassium should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
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Adults given 50 mg once daily for 7 days N=12 |
Age 6 to 16 given 0.7 mg/kg once daily for 7 days N=25 |
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|
Parent |
Active Metabolite |
Parent |
Active Metabolite |
AUC0 to 24a(ng•h/mL) |
442 ± 173 |
1685 ± 452 |
368 ± 169 |
1866 ± 1076 |
CMAX (ng/mL)a |
224 ± 82 |
212 ± 73 |
141 ± 88 |
222 ± 127 |
T1/2 (h)b |
2.1 ± 0.70 |
7.4 ± 2.4 |
2.3 ± 0.8 |
5.6 ± 1.2 |
TPEAK (h)c |
0.9 |
3.5 |
2 |
4.1 |
CLREN (mL/min)a |
56 ± 23 |
20 ± 3 |
53 ± 33 |
17 ± 8 |
aMean ± standard deviation
b Harmonic mean and standard deviation
Losartan, administered for 12 days, did not affect the pharmacokinetics or pharmacodynamics of a single dose of warfarin. Losartan did not affect the pharmacokinetics of oral or intravenous digoxin. There is no pharmacokinetic interaction between losartan and hydrochlorothiazide. Coadministration of losartan and cimetidine led to an increase of about 18% in AUC of losartan but did not affect the pharmacokinetics of its active metabolite. Coadministration of losartan and phenobarbital led to a reduction of about 20% in the AUC of losartan and that of its active metabolite. A somewhat greater interaction (approximately 40% reduction in the AUC of active metabolite and approximately 30% reduction in the AUC of losartan) has been reported with rifampin. Fluconazole, an inhibitor of cytochrome P450 2C9, decreased the AUC of the active metabolite by approximately 40%, but increased the AUC of losartan by approximately 70% following multiple doses. Conversion of losartan to its active metabolite after intravenous administration is not affected by ketoconazole, an inhibitor of P450 3A4. The AUC of active metabolite following oral losartan was not affected by erythromycin, another inhibitor of P450 3A4, but the AUC of losartan was increased by 30%.
Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25 to 40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.
In a single-dose study in normal volunteers, losartan had no effects on glomerular filtration rate, renal plasma flow or filtration fraction. In multiple-dose studies in hypertensive patients, there were no notable effects on systemic or renal prostaglandin concentrations, fasting triglycerides, total cholesterol or HDL-cholesterol or fasting glucose concentrations. There was a small uricosuric effect leading to a minimal decrease in serum uric acid (mean decrease <0.4 mg/dL) during chronic oral administration.
The antihypertensive effects of Losartan potassium were demonstrated principally in 4 placebo-controlled, 6- to 12-week trials of dosages from 10 to 150 mg per day in patients with baseline diastolic blood pressures of 95 to 115. The studies allowed comparisons of two doses (50 to 100 mg/day) as once-daily or twice-daily regimens, comparisons of peak and trough effects, and comparisons of response by gender, age, and race. Three additional studies examined the antihypertensive effects of losartan and hydrochlorothiazide in combination.
The 4 studies of losartan monotherapy included a total of 1075 patients randomized to several doses of losartan and 334 to placebo. The 10 and 25 mg doses produced some effect at peak (6 hours after dosing) but small and inconsistent trough (24 hour) responses. Doses of 50, 100 and 150 mg once daily gave statistically significant systolic/diastolic mean decreases in blood pressure, compared to placebo in the range of 5.5 to 10.5/3.5 to 7.5 mmHg, with the 150 mg dose giving no greater effect than 50 to 100 mg. Twice-daily dosing at 50 to 100 mg/day gave consistently larger trough responses than once-daily dosing at the same total dose. Peak (6 hour) effects were uniformly, but moderately, larger than trough effects, with the trough-to-peak ratio for systolic and diastolic responses 50 to 95% and 60 to 90%, respectively.
Addition of a low dose of hydrochlorothiazide (12.5 mg) to losartan 50 mg once daily resulted in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg.
The antihypertensive effect of losartan was studied in one trial enrolling 177 hypertensive pediatric patients aged 6 to 16 years old. Children who weighed <50 kg received 2.5, 25 or 50 mg of losartan daily and patients who weighed ³50 kg received 5, 50 or 100 mg of losartan daily. Children in the lowest dose group were given losartan in a suspension formulation (see DOSAGE AND ADMINISTRATION, Preparation of Suspension). The majority of the children had hypertension associated with renal and urogenital disease. The sitting diastolic blood pressure (SiDBP) on entry into the study was higher than the 95th percentile level for the patient’s age, gender, and height. At the end of three weeks, losartan reduced systolic and diastolic blood pressure, measured at trough, in a dose-dependent manner. Overall, the two higher doses (25 to 50 mg in patients <50 kg; 50 to 100 mg in patients ³50 kg) reduced diastolic blood pressure by 5 to 6 mmHg more than the lowest dose used (2.5 mg in patients <50 kg; 5 mg in patients >50 kg). The lowest dose, corresponding to an average daily dose of 0.07 mg/kg, did not appear to offer consistent antihypertensive efficacy. When patients were randomized to continue losartan at the two higher doses or to placebo after 3 weeks of therapy, trough diastolic blood pressure rose in patients on placebo between 5 and 7 mmHg more than patients randomized to continuing losartan. When the low dose of losartan was randomly withdrawn, the rise in trough diastolic blood pressure was the same in patients receiving placebo and in those continuing losartan, again suggesting that the lowest dose did not have significant antihypertensive efficacy. Overall, no significant differences in the overall antihypertensive effect of losartan were detected when the patients were analyzed according to age (<, >12 years old) or gender. While blood pressure was reduced in all racial subgroups examined, too few non-White patients were enrolled to compare the dose-response of losartan in the non-White subgroup.
The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study was a multinational, double-blind study comparing losartan potassium and atenolol in 9193 hypertensive patients with ECG-documented left ventricular hypertrophy. Patients with myocardial infarction or stroke within six months prior to randomization were excluded. Patients were randomized to receive once daily losartan potassium 50 mg or atenolol 50 mg. If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan potassium or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (e.g., increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium-channel blockers, alpha-blockers, or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were added to the treatment regimen to reach the goal blood pressure.
Of the randomized patients, 4963 (54%) were female and 533 (6%) were Black. The mean age was 67 with 5704 (62%) age ³65. At baseline, 1195 (13%) had diabetes, 1326 (14%) had isolated systolic hypertension, 1469 (16%) had coronary heart disease, and 728 (8%) had cerebrovascular disease. Baseline mean blood pressure was 174/98 mmHg in both treatment groups. The mean length of follow-up was 4.8 years. At the end of study or at the last visit before a primary endpoint, 77% of the group treated with losartan potassium and 73% of the group treated with atenolol were still taking study medication. Of the patients still taking study medication, the mean doses of losartan potassium and atenolol were both about 80 mg/day, and 15% were taking atenolol or losartan as monotherapy, while 77% were also receiving hydrochlorothiazide (at a mean dose of 20 mg/day in each group). Blood pressure reduction measured at trough was similar for both treatment groups but blood pressure was not measured at any other time of the day. At the end of study or at the last visit before a primary endpoint, the mean blood pressures were 144.1/81.3 mmHg for the group treated with losartan potassium and 145.4/80.9 mmHg for the group treated with atenolol [the difference in systolic blood pressure (SBP) of 1.3 mmHg was significant (p<0.001), while the difference of 0.4 mmHg in diastolic blood pressure (DBP) was not significant (p=0.098)].
| Losartan Potassium | Atenolol | Risk Reduction† | 95% CI | p-Value |
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| N (%) | Rate*
| N (%) | Rate*
| | | |
Primary Composite Endpoint |
508 (11) |
23.8 |
588 (13) |
27.9 |
13% |
2% to 23% |
0.021 |
Components of Primary Composite Endpoint (as a first event) | |
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Stroke (nonfatal‡) | 209 (5) | | 286 (6) | | | | |
Myocardial infarction (nonfatal‡) | 174 (4) | | 168 (4) | | | | |
Cardiovascular mortality | 125 (3) | | 134 (3) | | | | |
Secondary Endpoints (any time in study) | |
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Stroke (fatal/nonfatal) | 232 (5) | 10.8 | 309 (7) | 14.5 | 25% | 11% to 37% | 0.001 |
Myocardial infarction (fatal/nonfatal) | 198 (4) | 9.2 | 188 (4) | 8.7 | -7% | -13% to 12% | 0.491 |
Cardiovascular mortality | 204 (4) | 9.2 | 234 (5) | 10.6 | 11% | -7% to 27% | 0.206 |
Due to CHD | 125 (3) | 5.6 | 124 (3) | 5.6 | -3% | -32% to 20% | 0.839 |
Due to Stroke | 40 (1) | 1.8 | 62 (1) | 2.8 | 35% | 4% to 67% | 0.032 |
Other§
| 39 (1) | 1.8 | 48 (1) | 2.2 | 16% | -28% to 45% | 0.411 |
* Rate per 1000 patient-years of follow-up
† Adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy
‡ First report of an event, in some cases the patient died subsequently to the event reported
§ Death due to heart failure, non-coronary vascular disease, pulmonary embolism, or a cardiovascular cause other than stroke or coronary heart disease.
Other clinical endpoints of the LIFE study were: total mortality, hospitalization for heart failure or angina pectoris, coronary or peripheral revascularization procedures, and resuscitated cardiac arrest. There were no significant differences in the rates of these endpoints between the losartan potassium and atenolol groups.
In the LIFE study, Black patients treated with atenolol were at lower risk of experiencing the primary composite endpoint compared with Black patients treated with losartan potassium. In the subgroup of Black patients (n=533; 6% of the LIFE study patients), there were 29 primary endpoints among 263 patients on atenolol (11%, 26 per 1000 patient-years) and 46 primary endpoints among 270 patients (17%, 42 per 1000 patient-years) on losartan potassium. This finding could not be explained on the basis of differences in the populations other than race or on any imbalances between treatment groups. In addition, blood pressure reductions in both treatment groups were consistent between Black and non-Black patients. 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 provides no evidence that the benefits of losartan potassium on reducing the risk of cardiovascular events in hypertensive patients with left ventricular hypertrophy apply to Black patients.
The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3 mg/dL in females or males ≤60 kg and 1.5 to 3 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]).
Patients were randomized to receive losartan potassium 50 mg once daily or placebo on a background of conventional antihypertensive therapy excluding ACE inhibitors and angiotensin II antagonists. After one month, investigators were instructed to titrate study drug to 100 mg once daily if the trough blood pressure goal (140/90 mmHg) was not achieved. Overall, 72% of patients received the 100 mg daily dose more than 50% of the time they were on study drug. Because the study was designed to achieve equal blood pressure control in both groups, other antihypertensive agents (diuretics, calcium-channel blockers, alpha- or beta-blockers, and centrally acting agents) could be added as needed in both groups. Patients were followed for a mean duration of 3.4 years.
The study population was diverse with regard to race (Asian 16.7%, Black 15.2%, Hispanic 18.3%, White 48.6%). Overall, 63.2% of the patients were men, and 66.4% were under the age of 65 years. Almost all of the patients (96.6%) had a history of hypertension, and the patients entered the trial with a mean serum creatinine of 1.9 mg/dL and mean proteinuria (urinary albumin/creatinine) of 1808 mg/g at baseline.
The primary endpoint of the study was the time to first occurrence of any one of the following events: doubling of serum creatinine, end-stage renal disease (ESRD) (need for dialysis or transplantation), or death. Treatment with losartan potassium resulted in a 16% risk reduction in this endpoint (see Figure 4 and Table 3). Treatment with losartan potassium also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality (see Table 3).
| Incidence | Risk Reduction | 95% C.I. | p-Value |
|
| Losartan | Placebo | | | |
Primary Composite Endpoint | 43.5% | 47.1% | 16.1% | 2.3% to 27.9% | 0.022 |
Doubling of Serum Creatinine, ESRD and Death Occurring as a First Event |
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Doubling of Serum Creatinine | 21.6% | 26% | | | |
ESRD | 8.5% | 8.5% | | | |
Death | 13.4% | 12.6% | | | |
Overall Incidence of Doubling of Serum Creatinine, ESRD and Death |
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Doubling of Serum Creatinine | 21.6% | 26% | 25.3% | 7.8% to 39.4% | 0.006 |
ESRD | 19.6% | 25.5% | 28.6% | 11.5% to 42.4% | 0.002 |
Death | 21% | 20.3% | -1.7% | -26.9% to 18.6% | 0.884 |
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 potassium 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 potassium 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.
| No. of Patients | Primary Composite Endpoint | ESRD |
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Losartan Potassium Event Rate % | Placebo Event Rate % | Hazard Ratio (95% CI) | Losartan Potassium Event Rate % | Placebo Event Rate % | Hazard Ratio (95% CI) |
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Overall Results | 1513 | 43.5 | 47.1 | 0.839 (0.721, 0.977) | 19.6 | 25.5 | 0.714 (0.576, 0.885) |
Age | | | | | | | |
<65 years | 1005 | 44.1 | 49 | 0.784 (0.653, 0.941) | 21.1 | 28.5 | 0.670 (0.521, 0.863) |
≥65 years | 508 | 42.3 | 43.5 | 0.978 (0.749, 1.277) | 16.5 | 19.6 | 0.847 (0.560, 1.281) |
Gender | | | | | | | |
Female | 557 | 47.8 | 54.1 | 0.762 (0.603, 0.962) | 22.8 | 32.8 | 0.601 (0.436, 0.828) |
Male | 956 | 40.9 | 43.3 | 0.892 (0.733, 1.085) | 17.5 | 21.5 | 0.809 (0.605, 1.081) |
Race | | | | | | | |
Asian | 252 | 41.9 | 54.8 | 0.655 (0.453, 0.947) | 18.8 | 27.4 | 0.625 (0.367, 1.066) |
Black | 230 | 40 | 39 | 0.983 (0.647, 1.495) | 17.6 | 21 | 0.831 (0.456, 1.516) |
Hispanic | 277 | 55 | 54 | 1.003 (0.728, 1.380) | 30 | 28.5 | 1.024 (0.661, 1.586) |
White | 735 | 40.5 | 43.2 | 0.809 (0.645, 1.013) | 16.2 | 23.9 | 0.596 (0.427, 0.831) |
Losartan potassium tablets USP are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, including diuretics.
Losartan potassium tablets USP 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.)
Losartan potassium tablets USP 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).
Do not co-administer aliskiren with losartan potassium in patients with diabetes.
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 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.
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 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.
In patients who are intravascularly volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with losartan potassium. These conditions should be corrected prior to administration of losartan potassium, or a lower starting dose should be used (see DOSAGE AND ADMINISTRATION).
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).
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been reported in susceptible individuals treated with losartan potassium; 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.
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; in some patients, these effects were reversible upon discontinuation of therapy.
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).
Potassium Supplements: A patient receiving losartan potassium should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician (see PRECAUTIONS, Drug Interactions).
Pregnancy Categories C (first trimester) and D (second and third trimesters).See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
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.
Antihypertensive effects of losartan potassium have been established in hypertensive pediatric patients aged 6 to 16 years. There are no data on the effect of losartan potassium 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).
Of the total number of patients receiving losartan potassium 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.
In the LIFE study, Black patients with hypertension and left ventricular hypertrophy had a lower risk of stroke on atenolol than on losartan potassium. 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 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.)
Losartan potassium has 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 was well-tolerated. The overall incidence of adverse experiences reported with losartan potassium 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 and 3.7 percent of patients given placebo.
| Losartan (n=1075) Incidence % | Placebo (n=334) Incidence % |
Musculoskeletal
| | |
Cramp, muscle | 1 | 0 |
Pain, back | 2 | 1 |
Pain, leg | 1 | 0 |
Nervous System/Psychiatric
| | |
Dizziness
| 3 | 2 |
Respiratory
| | |
Congestion, nasal
| 2 | 1 |
Infection, upper respiratory | 8 | 7 |
Sinusitis | 1 | 0 |
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.
Study 1†
| HCTZ | Losartan | Lisinopril |
Cough | 25% | 17% | 69% |
Study 2††
| Placebo | Losartan | Lisinopril |
Cough | 35% | 29% | 62% |
† Demographics = (89% caucasian, 64% female)
†† Demographics = (90% caucasian, 51% female)
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.
In the LIFE study, adverse events with losartan potassium were similar to those reported previously for patients with hypertension.
| 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 |
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-Schönlein 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.
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of losartan potassium.
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 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 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 alone, one patient (<0.1%) was discontinued due to these laboratory adverse experiences.
The usual starting dose is 50 mg of losartan potassium once daily. Hydrochlorothiazide 12.5 mg daily should be added and/or the dose of losartan potassium 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).
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).
Losartan Potassium USP 25 mg tablets are White to off-white, oval shaped, film-coated tablets with “A” engraved on one side and “25” on the other side. They are supplied as follows:
NDC 42571-110-30 unit of use bottles of 30
NDC 42571-110-90 unit of use bottles of 90
NDC 42571-110-10 unit of use bottles of 1000
Losartan Potassium USP 50 mg tablets are White to off-white, oval shaped, film-coated tablets with “A50” engraved on one side and breakline on the other side. They are supplied as follows:
NDC 42571-111-30 unit of use bottles of 30
NDC 42571-111-90 unit of use bottles of 90
NDC 42571-111-10 unit dose packages of 1000
Losartan Potassium USP 100 mg tablets are White to off-white, oval shaped, film-coated tablets with “A100” engraved on one side and plain on the other side. They are supplied as follows:
NDC 42571-112-30 unit of use bottles of 30
NDC 42571-112-90 unit of use bottles of 90
NDC 42571-112-10 unit dose packages of 1000
Storage
Losartan Potassium Tablets USP
25 mg, 50 mg, 100 mg
Rx only
Read the Patient Information that comes with losartan potassium tablets USP 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 USP?
Do not take losartan potassium tablets USP if you are pregnant or plan to become pregnant. Losartan potassium tablets USP can harm your unborn baby causing injury and even death. Stop taking losartan potassium tablets USP 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.
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 USP?
What should I tell my doctor before taking losartan potassium tablets USP?
Tell your doctor if you get any side effect that bothers you or that won’t go away.
General information about losartan potassium tablets USP
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use losartan potassium tablets USP for a condition for which it was not prescribed. Do not give losartan potassium tablets USP 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 USP. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about losartan potassium that is written for health professionals.
What are the ingredients in losartan potassium tablets USP?
Active ingredients: Losartan potassium, USP
Inactive ingredients: Microcrystalline cellulose, lactose monohydrate, pregelatinized starch, magnesium stearate, Opadry white (hydroxypropyl cellulose, hypromellose, titanium dioxide). Losartan potassium 25 mg, 50 mg and 100 mg tablets contain potassium in the following amounts: 2.12 mg (0.054 mEq), 4.24 mg (0.108 mEq) and 8.48 mg (0.216 mEq), respectively.
LOSARTAN POTASSIUM
losartan potassium tablet, film coated |
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LOSARTAN POTASSIUM
losartan potassium tablet, film coated |
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LOSARTAN POTASSIUM
losartan potassium tablet, film coated |
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Labeler - Micro Labs Limited (862174955) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Micro Labs Limited, Goa | 915793658 | MANUFACTURE(42571-110, 42571-111, 42571-112) |