LOSARTAN POTASSIUM TABLETS USP R only | Losartan Potassium
| |
Adults given 50 mg once daily for 7 days N = 12 |
Age 6-16 given 0.7 mg/kg once daily for 7 days N = 25 |
||
| |
Parent |
Active Metabolite |
Parent |
Active Metabolite |
| AUC0-24
a (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 |
2.0 |
4.1 |
| CLren (mL/min) a
|
56 ± 23 |
20 ± 3 |
53 ± 33 |
17 ± 8 |
| |
Losartan potassium tablets |
Atenolol |
Risk Reduction† |
95% CI |
p-Value |
||
| |
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) |
|
||||||
| 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) |
|
||||||
| 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 |
|||||||
| |
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 |
|||||
| Doubling of Serum Creatinine |
21.6% |
26.0% |
|
|
|
| ESRD |
8.5% |
8.5% |
|
|
|
| Death |
13.4% |
12.6% |
|
|
|
| Overall Incidence of Doubling of Serum Creatinine, ESRD and Death |
|||||
| Doubling of Serum Creatinine |
21.6% |
26.0% |
25.3% |
7.8% to 39.4% |
0.006 |
| ESRD |
19.6% |
25.5% |
28.6% |
11.5% to 42.4% |
0.002 |
| Death |
21.0% |
20.3% |
-1.7% |
-26.9% to 18.6% |
0.884 |
| |
No. of Patients |
Primary Composite Endpoint |
ESRD |
||||
| Losartan potassium tablets Event Rate % |
Placebo Event Rate % |
Hazard Ratio (95% CI) |
Losartan potassium tablets Event Rate % |
Placebo Event Rate % |
Hazard Ratio (95% CI) |
||
| 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 |
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 |
40.0 |
39.0 |
0.983 (0.647, 1.495) |
17.6 |
21.0 |
0.831 (0.456, 1.516) |
| Hispanic |
277 |
55.0 |
54.0 |
1.003 (0.728, 1.380) |
30.0 |
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 are contraindicated in patients who are hypersensitive to any component of this product.
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 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 m (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Pharmacodynamics and Clinical Effects and DOSAGE AND ADMINISTRATION).
† Demographics = (89% caucasian, 64% female)†† Demographics = (90% caucasian, 51% female)
| |
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 |
| Study 1 † |
HCTZ |
Losartan |
Lisinopril |
| Cough |
25% |
17% |
69% |
| |
|
|
|
| Study 2 †† |
Placebo |
Losartan |
Lisinopril |
| Cough |
35% |
29% |
62% |
|
|
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 |
