LOSARTAN POTASSIUM  - losartan potassium tablet, film coated 
Aurobindo Pharma Limited

----------

Losartan Potassium Tablets USP

USE IN PREGNANCY


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.

DESCRIPTION


1 p o H


Chemical Structure





CLINICAL PHARMACOLOGY

Mechanism of Action


1 2 1 1 2 In vitro 1 1

Pharmacokinetics




14 In vitro





max

14 14

Special Populations

Pediatric


Table 1


Table 1 Pharmacokinetic Parameters in Hypertensive Adults and Children Age 6 to 16 Following Multiple Dosing 
* Mean ± standard deviation
Harmonic mean and standard deviation
Median
 
 
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

Parent
Active Metabolite
Parent
Active Metabolite
   AUC0-24*(ng•h/mL)    
442 ± 173
1685 ± 452
368 ± 169
1866 ± 1076
   C max (ng/mL)*
224 ± 82
212 ± 73
141 ± 88
222 ± 127
   T1/2 (h)
2.1 ± 0.7
7.4 ± 2.4
2.3 ± 0.8
5.6 ± 1.2
   TPEAK (h)
0.9
3.5
2
4.1
   CLREN (mL/min)*
56 ± 23
20 ± 3
53 ± 33
17 ± 8

DOSAGE AND ADMINISTRATION, Preparation of Suspension

Geriatric and Gender


DOSAGE AND ADMINISTRATION

Race


PRECAUTIONS, Race  CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke, Race

Renal Insufficiency


WARNINGS, Hypotension — Volume-Depleted Patients DOSAGE AND ADMINISTRATION

Hepatic Insufficiency


DOSAGE AND ADMINISTRATION

Drug Interactions


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%.

Pharmacodynamics and Clinical Effects

Adult Hypertension














Pediatric Hypertension


DOSAGE AND ADMINISTRATION, Preparation of Suspension th

Reduction in the Risk of Stroke






Figure 1 Table 2 Figure 2 Table 2

Figure 1: Primary endpoint of time to cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction in the groups treated with losartan potassium and atenolol


Figure 2: Fatal/nonfatal stroke in the groups treated with losartan potassium and atenolol

Table 2

Table 2 Incidence of Primary Endpoint Events
* Adjusted for baseline Framingham risk score and level of electrocardiographic left ventricular hypertrophy
Rate per 1000 patient-years of follow-up
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
 
Losartan Potassium
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





Figure 3
Figure 3 Primary Endpoint Events† within Demographic Subgroups

Race


INDICATIONS AND USAGE

Hypertension


Hypertensive Patients with Left Ventricular Hypertrophy


PRECAUTIONS, Race CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke, Race

CONTRAINDICATIONS


WARNINGS

Fetal/Neonatal Morbidity and Mortality




2

Hypotension — Volume-Depleted Patients


DOSAGE AND ADMINISTRATION

PRECAUTIONS

General

Hypersensitivity


ADVERSE REACTIONS, Postmarketing Experience.

Impaired Hepatic Function


DOSAGE AND ADMINISTRATION CLINICAL PHARMACOLOGY, Pharmacokinetics

Impaired Renal Function






Electrolyte Imbalance


Information for Patients




Potassium Supplements


PRECAUTIONS, Drug Interactions

Drug Interactions


CLINICAL PHARMACOLOGY, Drug Interactions

Lithium


Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors




Carcinogenesis, Mutagenesis, Impairment of Fertility




in vitro in vitro in vivo in vitro in vitro

Pregnancy

Teratogenic Effects


Pregnancy Categories C (first trimester) and D (second and third trimesters)

WARNINGS, Fetal/Neonatal Morbidity and Mortality

Nursing Mothers



Pediatric Use


2 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations Pharmacodynamics and Clinical Effects, DOSAGE AND ADMINISTRATION

Geriatric Use


Race


CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke

ADVERSE REACTIONS

Hypertension







 
   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









Body as a Whole: Cardiovascular: Digestive: Hematologic: Metabolic: Musculoskeletal: Nervous System/Psychiatric: Respiratory: Skin: Special Senses: Urogenital:


* Demographics = (89% caucasian, 64% female)
Demographics = (90% caucasian, 51% female)
   Study 1*
   HCTZ   
   Losartan   
   Lisinopril   
   Cough
25%
17%
69%
   Study 2
Placebo
Losartan
Lisinopril
   Cough
35%
29%
62%



Pediatric Patients


Hypertensive Patients with Left Ventricular Hypertrophy


Postmarketing Experience




Digestive:


General Disorders and Administration Site Conditions:


Hemic:


Hypersensitivity:


Metabolic and Nutrition: 


Musculoskeletal:


Nervous system disorders:


Respiratory:


Skin:

Laboratory Test Findings


Creatinine, Blood Urea Nitrogen


PRECAUTIONS, Impaired Renal Function

Hemoglobin and Hematocrit


Liver Function Tests


OVERDOSAGE


2



DOSAGE AND ADMINISTRATION

Adult Hypertensive Patients




WARNINGS, Hypotension — Volume-Depleted Patients PRECAUTIONS, General

CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension

CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Hypertension

Pediatric Hypertensive Patients ≥6 years of age


Preparation of Suspension CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations Pharmacodynamics and Clinical Effects, WARNINGS, Hypotension —Volume-Depleted Patients

2 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations Pharmacodynamics and Clinical Effects, PRECAUTIONS

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




Hypertensive Patients with Left Ventricular Hypertrophy




CLINICAL PHARMACOLOGY, Pharmacodynamics and Clinical Effects, Reduction in the Risk of Stroke

HOW SUPPLIED




Losartan Potassium Tablets USP, 25 mg





Losartan Potassium Tablets USP, 50 mg






Losartan Potassium Tablets USP, 100 mg






Store at



Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited


PATIENT INFORMATION ABOUT


LOSARTAN POTASSIUM TABLETS USP
Rx only

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.

What are losartan potassium tablets USP?


 




High Blood Pressure (hypertension).


Left Ventricular Hypertrophy (LVH)

Who should not take losartan potassium tablets USP?

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





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


How should I take losartan potassium tablets USP?

What are the possible side effects of losartan potassium tablets USP?








not

How do I store losartan potassium tablets USP?

General information about losartan potassium tablets USP




What are the ingredients in losartan potassium tablets USP?


Active ingredient:

Inactive ingredients:



Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited


PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 100 mg (90 Tablet Bottle)


NDC 65862-203-90
Losartan Potassium Tablets USP
100 mg
Rx only           90 Tablets
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 100 mg (90 Tablet Bottle)

LOSARTAN POTASSIUM 
losartan potassium   tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65862-201
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LOSARTAN POTASSIUM (LOSARTAN) LOSARTAN POTASSIUM 25 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE MONOHYDRATE  
STARCH, CORN  
HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED  
MAGNESIUM STEARATE  
HYDROXYPROPYL CELLULOSE  
HYPROMELLOSE 2910 (6 CPS)  
TITANIUM DIOXIDE  
FD&C BLUE NO. 2  
D&C YELLOW NO. 10  
WATER  
Product Characteristics
Color GREEN Score no score
Shape OVAL (Biconvex) Size 8mm
Flavor Imprint Code E;45
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 65862-201-90 90 TABLET In 1 BOTTLE None
2 65862-201-99 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090083 10/08/2010

LOSARTAN POTASSIUM 
losartan potassium   tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65862-202
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LOSARTAN POTASSIUM (LOSARTAN) LOSARTAN POTASSIUM 50 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE MONOHYDRATE  
STARCH, CORN  
HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED  
MAGNESIUM STEARATE  
HYDROXYPROPYL CELLULOSE  
HYPROMELLOSE 2910 (6 CPS)  
TITANIUM DIOXIDE  
FD&C BLUE NO. 2  
D&C YELLOW NO. 10  
WATER  
Product Characteristics
Color GREEN Score no score
Shape OVAL (Biconvex) Size 10mm
Flavor Imprint Code E;46
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 65862-202-30 30 TABLET In 1 BOTTLE None
2 65862-202-90 90 TABLET In 1 BOTTLE None
3 65862-202-99 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090083 10/08/2010

LOSARTAN POTASSIUM 
losartan potassium   tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65862-203
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LOSARTAN POTASSIUM (LOSARTAN) LOSARTAN POTASSIUM 100 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
LACTOSE MONOHYDRATE  
STARCH, CORN  
HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED  
MAGNESIUM STEARATE  
HYDROXYPROPYL CELLULOSE  
HYPROMELLOSE 2910 (6 CPS)  
TITANIUM DIOXIDE  
FD&C BLUE NO. 2  
D&C YELLOW NO. 10  
WATER  
Product Characteristics
Color GREEN Score no score
Shape OVAL (Biconvex) Size 13mm
Flavor Imprint Code E;47
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 65862-203-30 30 TABLET In 1 BOTTLE None
2 65862-203-90 90 TABLET In 1 BOTTLE None
3 65862-203-99 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090083 10/08/2010

Labeler - Aurobindo Pharma Limited (650082092)
Establishment
Name Address ID/FEI Operations
Aurobindo Pharma Limited 918917642 MANUFACTURE
Revised: 04/2010 Aurobindo Pharma Limited