nystatin-a1 and Abnormalities--Drug-Induced

The aim of the study was to investigate the teratogenicity of oral nystatin treatment during pregnancy in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. In total, 38,151 pregnant women who delivered newborn infants without any defects (control group) and 22,843 pregnant women who had foetuses or newborns with congenital abnormalities (CA) (case group) were included in the study. 106 (0.5%) case and 143 (0.4%) control pregnant women were treated with oral nystatin (crude OR with 95% CI = 1.2, 1.0-1.6). A teratogenic potential of nystatin was seen in 1 CA-group (hypospadias) in 2 different approaches of the study (case-control and total control--CA groups comparison) during the critical period of this congenital abnormality. The conclusion of the study is that treatment with oral nystatin during pregnancy presents little teratogenic risk to the foetus, but the possible association between hypospadias and nystatin needs further study.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Adult; Birth Weight; Case-Control Studies; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Humans; Hypospadias; Incidence; Infant, Newborn; Infant, Premature; Male; Nystatin; Odds Ratio; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Probability; Reference Values; Registries; Risk Assessment; Teratogens

Nyotran is a liposomally encapsulated i.v. formulation of the antifungal polyene nystatin. This drug was evaluated in a series of reproductive toxicity studies, according to the guidelines outlined by the International Conference on Harmonization (ICH). A fertility and early embryonic development study (SEG I) and a prenatal and postnatal development (SEG III) study were conducted in rats, and embryo-fetal development (SEG II) studies were conducted in rats and rabbits. Nyotran was administered iv in all studies. In SEG I and SEG III, rats were administered daily doses of 0.5, 1.5, or 3.0 mg/kg Nyotran. In both studies, parental mortality and toxicity in the 3.0 mg/kg dose group necessitated the lowering of the high dose to 2.0 mg/kg/day. Parental toxicity, in the form of decreased body weights, decreased food consumption, and piloerection were also observed at the 1.5 mg/kg/day dose level in the SEG I and SEG III studies. Despite the parentally toxic doses in the SEG I study, there was no effect of Nyotran on F0 male or female fertility or early embryonic development of F1 offspring. In the SEG III study, lactational body weights of the F1 generation were decreased at all Nyotran dose levels. There was no effect on pre-wean developmental landmarks, but post-wean development was affected by Nyotran administration at all dosage levels. Preputional separation was delayed in the 1.5 and 3.0/2.0 mg/kg/day F1 offspring, auditory startle function was decreased in F1 females at all dose levels, and motor activity was decreased in male F1 offspring at all dose levels. However, there were no treatment-related effects on the subsequent mating of the F1 generation and resulting F2 offspring. In SEG II studies, rats and rabbits were also administered 0.5, 1.5, or 3.0 mg/kg/day of Nyotran during gestation. The high dose in these SEG II studies was not lowered, as the maternal animals were able to tolerate the shorter duration of dosing. Maternal effects in rabbits were observed only in the high-dose group and were limited to decreased food consumption and decreased absolute and relative liver weight. Decreased food consumption in high-dose dams and clinical weight loss in some animals at the mid- and high-dose levels evidenced maternal toxicity in rats. Nyotran did not have any effect on Caesarian section parameters in either rats or rabbits and no effect on the incidence of fetal malformations in rabbits. A statistically significant increase in mild hydrocephaly, obs

Topics: Abnormalities, Drug-Induced; Amphotericin B; Animals; Antifungal Agents; Behavior, Animal; Drug Carriers; Eating; Female; Liposomes; Liver; Male; Motor Activity; Nystatin; Organ Size; Pregnancy; Rabbits; Rats; Rats, Sprague-Dawley; Reproduction; Toxicity Tests

The effect of nystatin and mycoheptyne on pregnancy and fetus of rats of Wister line was studied after single and multiple oral administrations of the drugs. Nystatin was used in single doses of 3000, 500 and 100 mg/kg. In chronic experiments the dose was 500 mg/kg. It was found that nystatin had a slight abortive effect when used during the whole period of pregnancy. Mycoheptyne was used in single doses of 1000, 100 and 20 mg/kg. In chronic experiments the dose was 100 mg/kg. It was noted that mycoheptyne had a higher toxic effect on the pregnant rats than nystatin. The animal death and abortus were observed more often. The level of the changes depended on the dose, time and period of the antibiotic use. No defects in the rat fetus were found.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Antifungal Agents; Carboxymethylcellulose Sodium; Corpus Luteum; Dose-Response Relationship, Drug; Embryo Implantation; Female; Fetal Death; Fetus; Histological Techniques; Nystatin; Pregnancy; Rats; Time Factors