weights and renal tubular and pelvic dilatation at 100 mg / kg / day , which approximates 13-times the maximum clinical dose of 25 mg , based on AUC . These findings were not observed after a 13 week drug-free recovery period . These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development . In embryo-fetal development studies in rats and rabbits , empagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans . Doses up to 300 mg / kg / day , which approximates 48-times ( rats ) and 128-times ( rabbits ) the maximum clinical dose of 25 mg ( based on AUC ), did not result in adverse developmental effects . In rats , at higher doses of empagliflozin causing maternal toxicity , malformations of limb bones increased in fetuses at 700 mg / kg / day or 154-times the 25 mg maximum clinical dose . In the rabbit , higher doses of empagliflozin resulted in maternal and fetal toxicity at 700 mg / kg / day , or 139-times the 25 mg maximum clinical dose . In preand postnatal development studies in pregnant rats , empagliflozin was administered from gestation day 6 through to lactation day 20 ( weaning ) at up to 100 mg / kg / day ( approximately 16 times the 25 mg maximum clinical dose ) without maternal toxicity . Reduced body weight was observed in the offspring at greater than or equal to 30 mg / kg / day ( approximately 4 times the 25 mg maximum clinical dose ). Lactation : Risk Summary : There is no information regarding the presence of JARDIANCE in human milk , the effects of JARDIANCE on the breastfed infant or the effects on milk production . Empagliflozin is present in the milk of lactating rats [ see Data ]. Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur , there may be risk to the developing human kidney . Because of the potential for serious adverse reactions in a breastfed infant , advise women that use of JARDIANCE is not recommended while breastfeeding . Data : Empagliflozin was present at a low level in rat fetal tissues after a single oral dose to the dams at gestation day 18 . In rat milk , the mean milk to plasma ratio ranged from 0.634 -5 , and was greater than one from 2 to 24 hours post-dose . The mean maximal milk to plasma ratio of 5 occurred at 8 hours post-dose , suggesting accumulation of empagliflozin in the milk . Juvenile rats directly exposed to empagliflozin showed a risk to the developing kidney ( renal pelvic and tubular dilatations ) during maturation . Pediatric Use : The safety and effectiveness of JARDIANCE in pediatric patients under 18 years of age have not been established . Geriatric Use : No JARDIANCE dosage change is recommended based on age . In studies assessing the efficacy of empagliflozin in improving glycemic control in patients with type 2 diabetes , a total of 2721 ( 32 %) patients treated with empagliflozin were 65 years of age and older , and 491 ( 6 %) were 75 years of age and older . JARDIANCE is expected to have diminished glycemic efficacy in elderly patients with renal impairment [ see Use in Specific Populations ].
The risk of volume depletion-related adverse reactions increased in patients who were 75 years of age and older to 2.1 %, 2.3 %, and 4.4 % for placebo , JARDIANCE 10 mg , and JARDIANCE 25 mg . The risk of urinary tract infections increased in patients who were 75 years of age and older to 10.5 %, 15.7 %, and 15.1 % in patients randomized to placebo , JARDIANCE 10 mg , and JARDIANCE 25 mg , respectively [ see Warnings and Precautions and Adverse Reactions ]. Renal Impairment : The efficacy and safety of JARDIANCE were evaluated in a study of patients with mild and moderate renal impairment . In this study , 195 patients exposed to JARDIANCE had an eGFR between 60 and 90 mL / min / 1.73 m 2 , 91 patients exposed to JARDIANCE had an eGFR between 45 and 60 mL / min / 1.73 m 2 and 97 patients exposed to JARDIANCE
had an eGFR between 30 and 45 mL / min / 1.73 m 2 . The glucose lowering benefit of JARDIANCE 25 mg decreased in patients with worsening renal function . The risks of renal impairment [ see Warnings and Precautions ], volume depletion adverse reactions and urinary tract infection-related adverse reactions increased with worsening renal function . In a large cardiovascular outcomes study , there were 1819 patients with
eGFR below 60 mL / min / 1.73 m 2 . The cardiovascular death findings in this subgroup were consistent with the overall findings . The efficacy and safety of JARDIANCE have not been established in patients with severe renal impairment , with ESRD , or receiving dialysis . JARDIANCE is not expected to be effective in these patient populations [ see Contraindications and Warnings and Precautions ]. Hepatic Impairment : JARDIANCE may be used in patients with hepatic impairment .
OVERDOSAGE : In the event of an overdose with JARDIANCE , contact the Poison Control Center . Employ the usual supportive measures ( e . g ., remove unabsorbed material from the gastrointestinal tract , employ clinical monitoring , and institute supportive treatment ) as dictated by the patient ’ s clinical status . Removal of empagliflozin by hemodialysis has not been studied .
Additional information can be found at www . hcp . jardiance . com
Copyright © 2016 Boehringer Ingelheim International GmbH ALL RIGHTS RESERVED
JAR-BS-12 / 16 PC-JAR-0632-PROF
58 ! ! ! ! ! ! ! ! ! ! www . PhysiciansOfficeResource . com