e 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 COZAAR have been established in hypertensive pediatric patients aged 6 to 16 years. There are no data on the effect of COZAAR 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 numberof patients receiving COZAAR 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 COZAAR. 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 COZAAR 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.)
ADVERSE REACTIONS
Hypertension
COZAAR has been eva luated 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 COZAAR was well-tolerated. The overall inci
