Uridine triacetate

Risk Summary

There are no available data on uridine triacetate use in pregnant women to inform a drug-associated risk. When administered orally to pregnant rats during the period of organogenesis, uridine triacetate at doses similar to the maximum recommended human dose (MRHD) of 120 mg/kg per day was not teratogenic and did not produce adverse effects on embryo-fetal development [see Data].

The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. 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.

Data

Animal Data

In an embryo-fetal development study, uridine triacetate was administered orally to pregnant rats during the period of organogenesis at doses up to 2000 mg/kg per day (about 2.7 times the maximum recommended human dose (MRHD) of 120 mg/kg per day on a body surface area basis). There was no evidence of teratogenicity or harm to the fetus and no effect on maternal body weight and overall health.

Risk Summary

There are no data on the presence of uridine triacetate in human milk, the effect on the breastfed infant or the effect on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for uridine triacetate and any potential adverse effects on the breastfed infant from uridine triacetate or from the underlying maternal condition.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of uridine triacetate.

Uridine triacetate was not genotoxic in the Ames test, the mouse lymphoma assay and the mouse micronucleus test.

Orally administered uridine triacetate did not affect fertility or general reproductive performance in male and female rats at doses up to 2000 mg/kg per day (about 2.7 times the maximum recommended human dose (MRHD) of 120 mg/kg per day on a body surface area basis).

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions and using a wide range of doses, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of uridine triacetate was assessed in 4 patients with hereditary orotic aciduria ranging in age from 3 to 19 years (3 male, 1 female) who received 60 mg/kg of uridine triacetate once daily for six weeks. All patients continued to receive uridine triacetate for at least 24 months at dosages of up to 120 mg/kg once daily. No adverse reactions were reported with uridine triacetate.