ing and continuing through gestation day 7. Male rats were given oral doses 4 weeks prior to mating, during mating (3 weeks) and 2 weeks post-mating. No effects were observed in male or female fertility at 5 and 25 mg/kg/day (exposures up to 3 times those resulting with a human oral dose of 180 mg/day based on AUC comparison). At 75 mg/kg/day, there were slight adverse effects (slight decreases in body weight and food consumption) in males and females.
Pregnancy Category C
In pregnant female rats given oral gavage doses of 2, 25, 50 mg/kg/day during gestation no teratogenicity was observed at doses up to 50 mg/kg/day (exposure 4 times those resulting with a human oral dose of 180 mg/day based on AUC comparison). Decreased fetal body weights were observed at all doses (less than 1 to 4 times a human oral dose of 180 mg/day based on AUC comparison) in conjunction with maternal toxicity (decreased food consumption and body weight gain).
In pregnant female rabbits given oral gavage doses of 2, 12, 25 mg/kg/day during gestation no adverse fetal effects were observed (exposures less than with a human oral dose of 180 mg/day based on AUC comparisons). Reductions in maternal food consumption and body weight gain were seen at doses of 12 and 25 mg/kg/day.
In pregnant rats given oral gavage doses of 5, 15, 25 mg/kg/day during gestation through lactation no adverse fetal or pup (post-weaning) effects were observed at 5 mg/kg/day (exposures less than with a human therapeutic dose of 180 mg/day based on AUC comparisons). Higher doses of 15 and 25 mg/kg/day (exposures 2-3 times a human oral dose of 180 mg/day based on AUC comparisons) were accompanied by maternal signs of hypocalcemia (periparturient mortality and early postnatal pup loss), and reductions in postnatal maternal and pup body-weight gain. Sensipar® has been shown to cross the placental barrier in rabbits.
There are no adequate and well-controlled studies in pregnant women. Sensipar® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactating Women
Studies in rats have shown that Sensipar® is excreted in the milk with a high milk-to-plasma ratio. It is not known whether this drug is excreted in human milk. Considering these data in rats and because many drugs are excreted in human milk and because of the potential for clinically significant adverse reactions in infants from Sensipar®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the lactating woman.
Pediatric Use
The safety and efficacy of Sensipar® in pediatric patients have not been established.
Geriatric Use
Of the 1136 patients enrolled in the Sensipar® phase 3 clinical program, 26% were ≥ 65 years old, and 9% were ≥ 75 years old. No differences in the safety and efficacy of Sensipar® were observed in patients greater or less than 65 years of age (see DOSAGE AND ADMINISTRATION, Geriatric Patients).
ADVERSE EVENTS
Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis
In 3 double-blind placebo-controlled clinical trials, 1126 CKD patients on dialysis received study drug (656 Sensipar®, 470 placebo) for up to 6 months. The most frequently reported adverse events (incidence of at least 5% in the Sensipar® group and greater than placebo) are provided in Table 2. The most frequently reported events in the Sensipar® group were nausea, vomi
