XIGDUO XR(dapagliflozin and metformin HCl extended-release)tablets
Pharmacological Class:
Sodium-glucose co-transporter 2 inhibitor (SGLT2) + biguanide.

Active Ingredient(s):
Dapagliflozin, metformin HCl ext-rel; 5mg/500mg, 5mg/1000mg, 10mg/500mg, 10mg/1000mg; tablets.

Company
AstraZeneca Pharmaceuticals
Indication(s):
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both ­dapagliflozin and metformin is appropriate. Limitations of use: not for treating type 1 diabetes or diabetic ketoacidosis.

Pharmacology:
Dapagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion. Metformin HCl decreases hepatic glucose production, intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Clinical Trials:
There have been no clinical efficacy studies conducted with Xigduo XR combination tablets to characterize its effect on HbA1c reduction. Xigduo XR is considered to be bioequivalent to coadministered dapagliflozin and metformin HCl extended-release (XR) tablets.

The coadministration of dapagliflozin + metformin XR tablets has been studied in treatment-naive patients inadequately controlled on diet and exercise alone; and in patients with type 2 diabetes inadequately controlled on metformin. Treatment with dapagliflozin + metformin at all doses produced clinically and statistically significant improvements in HbA1c and fasting plasma glucose vs. placebo plus metformin as initial or add-on therapy.

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
Individualize. Swallow whole. Take once daily in the AM with food; increase dose gradually. Maximum daily dose: 10mg/2000mg.

Children:
<18 years: not established.

Contraindication(s):
Moderate-to-severe renal impairment (SCr ≥1.5mg/dL [men], ≥1.4mg/dL [women] or eGFR <60mL/min/1.73m2). Metabolic acidosis, diabetic ketoacidosis.

Warnings/Precautions:
Confirm normal renal function before starting and monitor thereafter (esp. in elderly). Discontinue if lactic acidosis (dehydration, sepsis), hypoxemia (shock, acute MI or CHF), renal impairment, or hypersensitivity reactions occur. Avoid in hepatic impairment. Correct volume depletion before initiating. Monitor for symptomatic hypotension after starting therapy (esp. elderly, renal impairment, or on loop diuretics). Elderly, debilitated, uncompensated strenuous exercise, malnourished or deficient caloric intake, adrenal or pituitary insufficiency, or alcohol intoxication: increased risk of hypoglycemia. Temporarily suspend for surgery; restart once oral intake resumes and renal function normalized. Discontinue prior to any intravascular radiocontrast study; withhold for 48 hours after procedure. Monitor for genital mycotic infections, hematology (esp. serum Vit. B12), increases in LDL-C; treat if occur. Active bladder cancer: do not use. Pregnancy (Category C). Nursing mothers: not recommended.

Interaction(s)
Cationic drugs eliminated by renal tubular secretion (eg, amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin); may increase metformin levels; monitor. Diuretics, steroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, CCBs, and isoniazid may cause hyperglycemia. Avoid excessive alcohol. Concomitant drugs that may affect renal function or metformin disposition; monitor and adjust dose. Concomitant insulin or insulin secretagogue: consider a lower dose of insulin/insulin secretagogue to reduce risk of hypoglycemia. Beta-blockers may mask hypoglycemia. May cause false (+) urine glucose tests or unreliable measurements of 1, 5-AG assay; use alternative methods to monitor glycemic control.

Adverse Reaction(s)
Female genital mycotic infections, nasopharyngitis, UTI, diarrhea, headache, influenza, nausea, vomiting.

How Supplied:
XR tabs 5mg/ 500mg, 10mg/500mg—30, 500; 5mg/1000mg—30, 60, 90, 400; 10mg/1000mg—30, 90, 400

LAST UPDATED:
3/2/2015
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac8a0f7b-9f69-4495-abbc-3a47cd75a859