and Males of Reproductive Potential
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Add-on Therapy with Dapagliflozin plus Saxagliptin in Patients
on Metformin
14.2 Add-on Therapy with Saxagliptin in Patients on Dapagliflozin
plus Metformin
14.3 Cardiovascular Safety Trial
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not listed.
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FULL PRESCRIBING INFORMATION
WARNING: LACTIC ACIDOSIS
• Postmarketing cases of metformin-associated lactic acidosis have resulted in death,hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metforminassociatedlactic acidosis is often subtle, accompanied only by nonspecific symptoms such asmalaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociatedlactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter),anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvateratio; and metformin plasma levels generally >5 mcg/mL [see WARNINGS ANDPRECAUTIONS (5.1)].
•Risk factors for metformin-associated lactic acidosis include renal impairment, concomitantuse of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years oldor greater, having a radiological study with contrast, surgery and other procedures, hypoxicstates (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
• Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high riskgroups are provided in the full prescribing information [see DOSAGE AND
ADMINISTRATION (2.2), CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS(5.1), DRUG INTERACTIONS (7) and USE IN SPECIFIC POPULATIONS (8.6, 8.7)].
• If metformin-associated lactic acidosis is suspected, immediately discontinue QTERNMET XRand institute general supportive measures in a hospital setting. Prompt hemodialysis isrecommended [see WARNINGS AND PRECAUTIONS (5.1)].
1 INDICATIONS AND USAGE
QTERNMET XR (dapagliflozin, saxagliptin, and metformin hydrochloride) extended-release tablets isindicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetesmellitus.
Limitations of Use
QTERNMET XR is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
QTERNMET XR initiation is intended only for patients currently taking metformin.
2 DOSAGE AND ADMINISTRATION
2.1 Prior to Initiation of QTERNMET XR
Assess renal function before initiating QTERNMET XR therapy and periodically thereafter [seeWARNINGS AND PRECAUTIONS (5.1, 5.6) and USE IN SPECIFIC POPULATIONS (8.5, 8.6)].
In patients with volume depletion, correct this condition prior to initiation of QTERNMET XR [seeWARNINGS AND PRECAUTIONS (5.4, 5.6) and USE IN SPECIFIC POPULATIONS (8.5, 8.6)].
2.2 Dosage
Individual
