QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(十五)
rved. At Week 24, the mean changes frombaseline in hematocrit were −0.33% in the placebo group and 2.30% in the 10 mg dapagliflozin group. ByWeek 24, hematocrit values >55% were reported in 0.4% of placebo-treated patients and 1.3% of 10 mgdapagliflozin -treated patients.
Increase in Serum Inorganic Phosphorus
Dapagliflozin
In a pool of 13 placebo-controlled studies with dapagliflozin, increases from baseline in mean serumphosphorus levels were reported at Week 24 in dapagliflozin-treated patients compared with placebotreatedpatients (mean increase of 0.13 versus −0.04 mg/dL, respectively). Higher proportions of patientswith marked laboratory abnormalities of hyperphosphatemia (≥5.6 mg/dL for age 17-65 years or≥5.1 mg/dL for age ≥66 years) were reported on dapagliflozin at Week 24 (0.9% versus 1.7% for placeboand 10 mg dapagliflozin, respectively).
Increase in Low-Density Lipoprotein Cholesterol
Patients treated with combination therapy demonstrated a mean percent increase from baselineLDL-cholesterol (ranging from 2.1 to 6.9%).
Elevations in Creatine KinaseAn imbalance in the number of subjects who experienced serum creatine kinase (CK) elevations >10x theupper limit of normal (a marker of muscle injury/necrosis) was observed in 5 subjects (1%) treated withcombination therapy. The elevations were transient. Rhabdomyolysis was reported for one of those
subjects for which no obvious cause was identified.
Decrease in Serum Bicarbonate
In a study of concomitant therapy of 10 mg dapagliflozin with exenatide extended-release (on abackground of metformin), four patients (1.7%) on concomitant therapy had a serum bicarbonate value ofless than or equal to 13 mEq/L compared to one each (0.4%) in the dapagliflozin and exenatide-extendedrelease treatment groups [see WARNINGS AND PRECAUTIONS (5.5)].
Vitamin B12 Concentrations
Metformin
In clinical trials of metformin of 29-week duration, a decrease to subnormal levels of previously normalserum vitamin B12 levels was observed in approximately 7% of patients.
6.2 Postmarketing Experience
Additional adverse reactions have been identified during post approval use of dapagliflozin, saxagliptin,and metformin. Because the following reactions are reported voluntarily from a population of uncertainsize, it is generally not possible to reliably estimate their frequency or establish a causal relationship to
drug exposure.
Dapagliflozin
• Ketoacidosis
• Acute Kidney Injury and Impairment in Renal Function
• Urosepsis and pyelonephritis
• Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
• Rash
Saxagliptin
• Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions
• Pancreatitis
• Severe and disabling arthralgia
• Bullous pemphigoid
Metformin
• Cholestatic, hepatocellular, and mixed hepatocellular liver injury
7 DRUG INTERACTIONS
Table 4: Clinically Relevant Interactions Affecting Drugs Coadministered with
QTERNMET XR
Strong Inhibitors of CYP3A4/5 Enzymes
Clinical Impact Ketoconazole significantly increased saxagliptin exposure. Similar significantincreases in plasma concentrations of saxagliptin are anticipated with otherstrong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir,itraconazole, nefazodone, n |
