QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(十九)
[see Data]. However, due to speciesspecific differences in lactation physiology, the clinical relevance of these data is not clear. Since humankidney 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 reactionsin a breastfed infant, advise women that use of QTERNMET XR is not recommended whilebreastfeeding.
Data
Dapagliflozin
Dapagliflozin was present at a milk/plasma ratio of 0.49, indicating that dapagliflozin and its metabolitesare transferred into milk at a concentration that is approximately 50% of that in maternal plasma. Juvenilerats directly exposed to dapagliflozin showed a risk to the developing kidney (renal pelvic and tubular
dilatations) during maturation.
Saxagliptin
Saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drugconcentrations.
Metformin hydrochloride
Published clinical lactation studies report that metformin is present in human milk which resulted ininfant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratioranging between 0.13 and 1. However, the studies were not designed to definitely establish the risk of useof metformin during lactation because of small sample size and limited adverse event data collected ininfants.
8.3 Females and Males of Reproductive Potential
Discuss the potential for unintended pregnancy with premenopausal women as therapy with metforminmay result in ovulation in some anovulatory women.
8.4 Pediatric Use
Safety and effectiveness of QTERNMET XR in patients under 18 years of age have not been established.
8.5 Geriatric Use
Because metformin is eliminated by the kidney and because elderly patients are more likely to havedecreased renal function, more frequent assessment of renal function is recommended in elderly patients[see WARNINGS AND PRECAUTIONS (5.1)].
Dapagliflozin
A total of 1424 (24%) of the 5936 dapagliflozin-treated patients were 65 years and older and 207 (3.5%)patients were 75 years and older in a pool of 21 double-blind, controlled, clinical safety and efficacystudies of dapagliflozin. After controlling for level of renal function (eGFR), in clinical studies withdapagliflozin, efficacy was similar for patients under age 65 years and those 65 years and older. Inpatients 65 years and older, a higher proportion of patients treated with dapagliflozin had adversereactions related to volume depletion and renal impairment or failure compared to patients treated withplacebo [see WARNINGS AND PRECAUTIONS (5.3)].
Saxagliptin
In the seven, double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of4751 (42.0%) of the 11,301 patients randomized to saxagliptin were 65 years and over, and 1210 (10.7%)were 75 years and over. No overall differences in safety or effectiveness were observed between subjects≥65 years old and younger subjects. While this clinical experience has not identified differences inresponses between the elderly and younger patients, greater sensitivity of some older individuals cannotbe ruled out.
Metformin hydrochloride
Controlled clinical studies of metformin did not include sufficient numbers of elderly patients todetermine whether they respond differently from younger patients, although other reported clinicalexperience has not identified d |
