Included as part of the PRECAUTIONS section.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a 26-week carcinogenicity study in Tg.rasH2 mice at daily oral doses of lactitol up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area), there were no drug-related neoplasms.
Published studies indicated that lactitol was negative in the Ames test, chromosome aberration test with cultured mammalian cells, and in vivo mouse micronucleus test.
Published studies indicated that lactitol did not cause any adverse effect on fertility and early embryonic development in rats at doses up to 10 g/kg/day (about 4.6 times the recommended daily human dose based on body surface area).
Use In Specific Populations
Lactitol is minimally absorbed systemically following oral administration [see CLINICAL PHARMACOLOGY], and it is unknown whether maternal use will result in fetal exposure to the drug. Available data from case reports on lactitol use in pregnant women are insufficient to evaluate for any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal developmental studies, no effects on embryo-fetal development were observed with oral administration of lactitol to rats and rabbits during organogenesis at doses much higher than the maximum recommended human dosage.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Reproduction studies have been performed in pregnant rats at oral doses of lactitol up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) and in pregnant rabbits at oral doses up to 1 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area) administered during the period of organogenesis. These studies did not reveal any evidence of harm to the fetus due to lactitol.
In a pre-and postnatal development study in rats, lactitol, administered from gestation day 6 to lactation day 20, did not cause any adverse effect on pre and postnatal development up to 2 g/kg/day (about 0.93 times the recommended daily human dose based on body surface area).
There are no data on the presence of lactitol in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Lactitol is minimally absorbed systemically following oral administration [see CLINICAL PHARMACOLOGY]. It is unknown whether the minimal systemic absorption of lactitol by adults will result in a clinically relevant exposure to breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the motherâ€™s clinical need for PIZENSY and any potential adverse effects on the breastfed infant from PIZENSY or from the underlying maternal condition.
The safety and effectiveness of PIZENSY have not been established in pediatric patients.
Of the 807 patients who received PIZENSY in clinical trials, 202 (25%) were 65 years of age or older, and 59 (7%) were 75 years of age or older. No overall differences in safety or effectiveness of PIZENSY were observed between geriatric patients and younger patients.