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No significant fetal ossification effects were seen in rabbits treated with oral doses up to 10 mg/ kg/ day during gestation (approximately 6.7 times the 30-mg/ day human dose based on surface area, mg/ m 2 ). However, in rabbits treated with 10 mg/ kg/ day, 1 of 14 litters were aborted and 1 of 14 litters were delivered prematurely. Similar to other bisphosphonates, treatment during mating and gestation with doses as low as 3.2 mg/ kg/ day (approximately 1 time the 30-mg/ day human dose based on surface area, mg/ m 2 ) has resulted in periparturient hypocalcemia and mortality in pregnant rats allowed to deliver. Bisphosphonates are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, and animal data suggest that uptake of bisphosphonates into fetal bone is greater than into maternal bone. Therefore, there is a theoretical risk of fetal harm (e. g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been established. Text Continues Below
There are no adequate and well-controlled studies of ACTONEL in pregnant women. ACTONEL should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. Nursing Women Risedronate was detected in feeding pups exposed to lactating rats for a 24-hour period post-dosing, indicating a small degree of lacteal transfer. It is not known whether risedronate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from bisphosphonates, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the patients receiving ACTONEL in postmenopausal osteoporosis studies (see CLINICAL STUDIES), 47% were between 65 and 75 years of age, and 17% were over 75. The corresponding proportions were 26% and 11% in glucocorticoid-induced osteoporosis trials, and 40% and 26% in Paget's disease trials. No overall differences in efficacy or safety were observed between these patients and younger patients but greater sensitivity of some older individuals cannot be ruled out. Use in Men Safety and effectiveness have been demonstrated in clinical studies in men receiving ACTONEL both for Paget's disease and for treatment and prevention of glucocorticoid-induced osteoporosis. However, the safety and effectiveness in men for osteoporosis due to other causes have not been established.
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