Jardiance Duo Use In Pregnancy & Lactation

Fertility: No studies on the effect on human fertility have been conducted with JARDIANCE DUO or its individual components.
Nonclinical studies in animals with the individual components do not indicate direct or indirect harmful effects with respect to fertility.
Empagliflozin: Studies in rats at doses up to 700 mg/kg/day, do not indicate direct or indirect harmful effects with respect to fertility. In female rats this dose was 90- and 155-fold the systemic AUC exposure anticipated with a human dose of 10 and 25 mg.
Metformin hydrochloride: Fertility of male or female rats was unaffected by metformin when administered at doses up to 600 mg/kg/day, which is approximately 2 times the maximum recommended human daily dose based on body surface area comparisons.
Pregnancy: There are limited data from the use of JARDIANCE DUO or its individual components in pregnant women.
It is recommended to avoid the use of JARDIANCE DUO during pregnancy unless clearly needed.
A study in pregnant rats did not reveal teratogenicity or other adverse effects on embryofetal development with co-administration of empagliflozin and metformin at oral doses up to 100/200 mg/kg/day, yielding exposures of approximately 35- and 14-times the clinical AUC exposure of empagliflozin associated with the 5 and 12.5 mg twice daily doses, respectively, and 4-times the clinical AUC exposure of metformin associated with the 1000 mg twice daily dose. At a dose of 300/600 mg/kg/day, associated with 49-times the exposure to empagliflozin and 8-times the exposure to metformin in humans at the maximum recommended dose, teratogenicity attributable to the metformin component was observed.
Empagliflozin: Empagliflozin administered during the period of organogenesis was not teratogenic at doses up to 300 mg/kg in the rat or rabbit, which corresponds to approximately 48- and 122-times or 128- and 325-times the clinical dose of empagliflozin based on AUC exposure associated with the 12.5 mg and 5 mg twice daily doses, respectively. Doses of empagliflozin causing maternal toxicity in the rat also caused the malformation of bent limb bones at exposures approximately 155- and 393-times the clinical dose associated with the 12.5 mg and 5 mg twice daily doses, respectively. Maternally toxic doses in the rabbit also caused increased embryofetal loss at doses approximately 139- and 353-times the clinical dose associated with the 12.5 mg and 5 mg twice daily doses, respectively.
Empagliflozin administered to female rats from gestation day 6 to lactation day 20 resulted in reduced weight gain in offspring at ≥30 mg/kg/day yielding maternal exposures approximately 4- and 11-times those in humans associated with 12.5 mg and 5 mg twice daily doses, respectively.
Specialised studies in rats with other members of the pharmacological class have shown toxicity to the developing kidney in the time period corresponding to the second and third trimesters of human pregnancy. Similar effects have been seen for empagliflozin at approximately 11-times the clinical dose of empagliflozin based on AUC exposure associated with the 12.5 mg twice daily dose. These findings were absent after a 13 week drug-free recovery period.
Metformin hydrochloride: Metformin was not teratogenic in rats at a dose of 200 mg/kg/day associated with a systemic exposure 4 times that in patients at the maximum recommended human dose (2000 mg metformin per day). At higher doses (500 and 1000 mg/kg/day, associated with 11 and 23 times the clinical exposure at the MRHD), teratogenicity of metformin was observed in the rat which was mostly evident as an increase in the incidence of skeletal malformations.
Lactation: Metformin is excreted into human breast milk. No adverse effects were observed in breastfed newborns/infants. It is unknown whether empagliflozin is excreted in human milk.
Available nonclinical data in animals have shown excretion of empagliflozin in milk. Reduced body weight was observed in rats exposed to empagliflozin in utero and through the consumption of maternal milk (see Pregnancy as previously mentioned). Adverse effects on renal development have been observed in juvenile rats treated with other members of this pharmacological class. Similar effects were seen with empagliflozin but the findings were absent after a 13 week drug-free recovery. A risk to human newborns/infants cannot be excluded. It is recommended to discontinue breast feeding during treatment with JARDIANCE DUO.