Physicians Office Resource Volume 11 Issue 01 - Page 64

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 Copyright © 2016 Boehringer Ingelheim International GmbH ALL RIGHTS RESERVED JAR-BS-12/16 PC-JAR-0632-PROF 58! ! ! ! ! ! ! ! ! !