Pamidronate Disodium Other names: Pamidronic acid

Pamidronic acid should not be used during pregnancy.

Pamidronic acid may cause fetal harm when administered to a pregnant woman.

There are no adequate and well-controlled studies in pregnant women.

Bolus intravenous studies conducted in rats and rabbits determined that pamidronic acid produces maternal toxicity and embryo/fetal effects when given during organogenesis at doses of 0.6 to 8.3 times the highest recommended human dose for a single intravenous infusion. As it has been shown that pamidronic acid can cross the placenta in rats and has produced marked maternal and nonteratogenic embryo/fetal effects in rats and rabbits, it should not be given to women during pregnancy.

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 vs oral) on this risk has not been established.

It is not known whether pamidronic acid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when pamidronic acid is administered to a nursing woman.

In a 104-week carcinogenicity study (daily oral administration) in rats, there was a positive dose response relationship for benign adrenal pheochromocytoma in males (P<0.00001). Although this condition was also observed in females, the incidence was not statistically significant. When the dose calculations were adjusted to account for the limited oral bioavailability of pamidronic acid in rats, the lowest daily dose associated with adrenal pheochromocytoma was similar to the intended clinical dose. Adrenal pheochromocytoma was also observed in low numbers in the control animals and is considered a relatively common spontaneous neoplasm in the rat. Pamidronic acid (daily oral administration) was not carcinogenic in an 80-week study in mice.

Pamidronic acid was nonmutagenic in six mutagenicity assays: Ames test, Salmonella and Escherichia/ liver-microsome test, nucleusanomaly test, sister-chromatid-exchange study, point-mutation test, and micronucleus test in the rat.

In rats, decreased fertility occurred in first-generation offspring of parents who had received 150 mg/kg of pamidronic acid orally; however, this occurred only when animals were mated with members of the same dose group. Pamidronic acid has not been administered intravenously in such a study.