Pramlintide

Pregnancy Category C.

No adequate and well-controlled studies have been conducted in pregnant women. Studies in perfused human placenta indicate that pramlintide has low potential to cross the maternal/fetal placental barrier. Embryofetal toxicity studies with pramlintide have been performed in rats and rabbits. Increases in congenital abnormalities (neural tube defect, cleft palate, exencephaly) were observed in fetuses of rats treated during organogenesis with 0.3 and 1.0 mg/kg/day (10 and 47 times the exposure resulting from the human dose of 360 mcg/day based on area under the plasma concentration curve [AUC], respectively). Administration of doses up to 0.3 mg/kg/day of pramlintide (9 times the human dose of 360 mcg/day based on AUC) to pregnant rabbits had no adverse effects in embryo fetal development; however, animal reproduction studies are not always predictive of human response. Pramlintide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown whether pramlintide is excreted in human milk. Many drugs, including peptides, are excreted in human milk. Therefore, pramlintide should be administered to nursing women only if it is determined by the healthcare professional that the potential benefit outweighs the potential risk to the infant.

Carcinogenesis

A two-year carcinogenicity study was conducted in CD-1 mice with doses of 0.2, 0.5, and 1.2 mg/kg/day of pramlintide (32, 67, and 159 times the exposure resulting from the human dose of 360 mcg/day based on area under the plasma concentration curve or AUC, respectively). No drug-induced tumors were observed. A two-year carcinogenicity study was conducted in Sprague-Dawley rats with doses of 0.04, 0.2, and 0.5 mg/kg/day of pramlintide (3, 9, and 25 times the exposure resulting from the human dose of 360 mcg/day based on AUC, respectively). No drug-induced tumors were observed in any organ.

Mutagenesis

Pramlintide was not mutagenic in the Ames test and did not increase chromosomal aberration in the human lymphocytes assay. Pramlintide was not clastogenic in the in vivo mouse micronucleus test or in the chromosomal aberration assay utilizing Chinese hamster ovary cells.

Impairment of Fertility

Administration of 0.3, 1, or 3 mg/kg/day of pramlintide (8, 17, and 82 times the exposure resulting from the human dose of 360 mcg/day of mcg based on body surface area) had no significant effects on fertility in male or female rats. The highest dose of 3 mg/kg/day resulted in dystocia in 8/12 female rats secondary to significant decreases in serum calcium levels.