Piperaquine phosphate: Reproduction studies

In embryofetal studies in rat and rabbit Piperaquine phosphate (PQP) was not teratogenic at the maximal tolerated dose, even in presence of fetal exposure.In peri- post-natal study in rat, PQP did not interfere with the course of delivery at the dose of 5 mg/kg/day (treatment Gestation Day(GD)6-Lactation Day(LD)21) as well as up to the dose of 20 mg/kg/day (treatment GD6–17 and LD1–21). PQP at the dose of 80 mg/kg, induced prolonged gestation, dystocic delivery and increase perinatal mortality both with interruption of treatment (GD6 to GD17 and LD1–21) and with continuous dosing (GD19-LD21).PQP did not interfere with lactation and pup growth and development, in presence of clear exposure during suckling period, irrespective of the dose and treatment schedules.It was not possible to identify the mechanism leading to the delivery delay. In a comparative study using other antimalarials, only Mefloquine gave similar findings to PQP.

► PQP was not teratogenic both in rats and rabbits.
► PQP did not interfere with the course of delivery up to the dose of 20 mg/kg/day.
► PQP did interfere with the course of delivery at the dose of 80 mg/kg/day.
► Prolonged gestation, dystocic delivery and perinatal mortality were observed.
► PQP did not interfere with lactation and pup growth and development at any dose.