8 USE IN SPECIFIC POPULATIONS
The limited available data with CARDURA in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. However, untreated hypertension during pregnancy can result in increased maternal risks [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed when doxazosin was orally administered to pregnant rabbits and rats during the period of organogenesis at doses of up to 41 and 20 mg/kg, respectively (exposures in rabbits and rats were 10 and 4 times, respectively, the human AUC exposures with a 12 mg/day therapeutic dose). A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Disease-associated maternal and/or embryo/fetal risk
Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Radioactivity was found to cross the placenta following oral administration of labelled doxazosin to pregnant rats. Studies in pregnant rabbits and rats at daily oral doses of up to 41 and 20 mg/kg, respectively (plasma drug concentrations of 10 and 4 times, respectively, the human AUC exposures with a 12 mg/day therapeutic dose), have revealed no evidence of adverse developmental effects. A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival. In peri- and postnatal studies in rats, postnatal development at maternal doses of 40 or 50 mg/kg/day of doxazosin (about 8 times human AUC exposure with a 12 mg/day therapeutic dose) was delayed, as evidenced by slower body weight gain and slightly later appearance of anatomical features and reflexes.
There is limited information on the presence of CARDURA in human milk [see Data]. There is no information on the effects of CARDURA on the breastfeed infant or the effects on milk production.
8.5 Geriatric Use
Benign Prostatic Hyperplasia (BPH)
The safety and effectiveness profile of CARDURA was similar in the elderly (age ≥ 65 years) and younger (age < 65 years) patients.
Clinical studies of CARDURA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
8.6 Hepatic Impairment
CARDURA is extensively metabolized in the liver. Hepatic impairment is expected to increase exposure to doxazosin. Use of CARDURA in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. Monitor blood pressure and for symptoms of hypotension in patients with lesser degrees of hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].