In embryo-fetal development studies, oral administration of gepirone to pregnant rats (75, 150, and 300 mg/kg) or pregnant rabbits (50, 100, and 200 mg/kg) during the period of organogenesis resulted in decreased embryofetal growth, body weights, and lengths, with accompanying skeletal variations at mid and high doses; the mid doses are 18 and 24 times the maximum recommended human dose (MRHD) on a mg/m² basis in rats and rabbits, respectively. No malformations were seen in these studies. The developmental no observed adverse effect level (NOAEL) was 9 and 12 times the MRHD on a mg/m2 basis in rats and rabbits, respectively.^L48295

When pregnant rats were treated with gepirone (10, 20, and 40 mg/kg) from late gestation through weaning, decreased birth weights were seen at mid and high doses; the mid-dose is twice the MRHD. Increased offspring mortality during the first 4 days after birth and persistent reduction in body weight were observed at all doses; the lowest dose is approximately equal to the MRHD on a mg/m² basis. The no-effect dose for fetal effects was not determined in this study.^L48295

When gepirone was administered orally to male and female rats prior to and throughout mating, gestation, and lactation at doses of 5, 27, 64, and 150 mg/kg/day, increased stillbirths were seen at ?64 mg/kg. Early postnatal mortality was increased at 150 mg/kg (18 times the MRHD on a mg/m² basis). The NOAEL (27 mg/kg) for stillbirths was associated with a maternal dose 3 times the MRHD on a mg/m² basis. Fetal weights were decreased at 27 mg/kg (3 times the MRHD on a mg/m2 basis) and fetal lengths were decreased at 64 mg/kg (8 times the MRHD on a mg/m² basis) and above. Pup weights were decreased at birth, throughout lactation and weaning, and until at least 14 weeks of age, with delays of some developmental landmarks, at 64 mg/kg and above. The NOAEL for growth and development (5 mg/kg) was associated with a maternal dose below the MRHD on a mg/m2 basis.^L48295

In the pediatric trial patients, there was a higher occurrence of vomiting in pediatric patients (13%) compared to adults (6.6%).
Antidepressants, such as gepirone, increase the risk of suicidal thoughts and behaviors in pediatric patients.^L48295

In clinical studies, cases of acute ingestions of up to 454 mg (6.25 times the maximum recommended dose) of gepirone alone or in combination with other drugs, were reported. Signs and symptoms reported with an overdose of gepirone at doses up to 454 mg included vomiting and transient incomplete bundle branch block; an unknown dose of gepirone produced an altered level of consciousness and a 60-second convulsion.^L48295

No specific antidotes for gepirone are known. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.^L48295

No evidence of carcinogenic potential was observed in lifetime carcinogenicity studies performed in rats and mice at doses up to 43.6 and 317.8 mg/kg/day, respectively. These doses are approximately 6 and 18 times the MRHD, respectively, on a mg/m² basis.^L48295

Gepirone showed no mutagenicity in three different in vitro genotoxicity assays (bacterial gene mutation, mammalian gene mutation, or DNA repair). No clastogenicity was observed in a rat micronucleus assay.^L48295

When gepirone was administered orally to male and female rats prior to and throughout mating at daily doses of 5, 27, 64, and 150 mg/kg, the latency to mating was increased at doses of 64 mg/kg (8 times the MRHD on a mg/m² basis) and above.^L48295