Saxagliptin and dapagliflozin are 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 QTERN is not recommended while breastfeeding.

Data

Dapagliflozin

Dapagliflozin was present at a milk/plasma ratio of 0.49, indicating that dapagliflozin and its metabolites are transferred into milk at a concentration that is approximately 50% of that in maternal plasma. Juvenile rats 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 drug concentrations.

8.4 Pediatric Use

Safety and effectiveness of QTERN in patients under 18 years of age have not been established.

8.5 Geriatric Use

Because elderly patients are more likely to have decreased renal function, care should be taken when using QTERN in the elderly based on renal function [see Dosage and Administration (3.2)].

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 efficacy studies of dapagliflozin. After controlling for level of renal function (eGFR), in clinical studies with dapagliflozin, efficacy was similar for patients under age 65 years and those 65 years and older. In patients 65 years and older, a higher proportion of patients treated with dapagliflozin had adverse reactions related to volume depletion and renal impairment or failure compared to patients treated with placebo [see Warnings and Precautions (5.3)].

Saxagliptin

In the seven, double-blind, controlled clinical safety and efficacy trials of saxagliptin, a total of 4751 (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 in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

8.6 Patients with Renal Impairment

Discontinue QTERN in patients if eGFR falls persistently below 60 mL/min/1.73 m2. QTERN is contraindicated in patients with moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m2), ESRD, or on dialysis [see Dosage and Administration (3.2), Contraindications (4), and Warnings and Precautions (5.5)].

8.7 Patients with Hepatic Impairment

QTERN may be used in patients with hepatic impairment. However, the benefit-risk for the use of QTERN in patients with severe hepatic impairment should be individually assessed since safety and efficacy have not been studied in this population [see Clinical Pharmacology].

9. OVERDOSAGE 

There is no information available on overdose with QTERN. In the event of an overdose, contact the Poison Control Center. Appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. Saxagliptin and its major metabol