Presentation and Status in Health Basket
56 X 5/1000 mg
28 X 10/1000 mg
– Healthcare providers should individualize the starting dose of XIGDUO XR based on the patient’s current treatment.
– XIGDUO XR should be taken once daily in the morning with food with gradual dose escalation to reduce the gastrointestinal (GI) side effects due to metformin.
– XIGDUO XR tablets must be swallowed whole and never crushed, cut, or chewed. Occasionally, the inactive ingredients of XIGDUO XR will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet.
– Dosing may be adjusted based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 10 mg dapagliflozin and 2000 mg metformin HCl.
– Patients taking an evening dose of metformin XR should skip their last dose before starting XIGDUO XR.
– In patients with volume depletion, correcting this condition prior to initiation of XIGDUO XR is recommended.
Patients with Renal Impairment: No dosage adjustment for XIGDUO XR is indicated in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m² or greater).
Assessment of renal function is recommended prior to initiation of XIGDUO XR therapy and periodically thereafter.
XIGDUO XR should not be used in patients with moderate to severe renal impairment (defined as eGFR <60 mL/min/1.73 m² or CrCl <60 mL/min, or end‐stage renal disease [ESRD]).
XIGDUO XR (dapagliflozin and metformin HCl extended‐release) is indicated as an 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: XIGDUO XR is not recommended for patients with type 1 diabetes mellitus or diabetic ketoacidosis.
Moderate to severe renal impairment (e.g., serum creatinine levels ≥1.5 mg/dL for men, ≥1.4 mg/dL for women, or eGFR <60 mL/min/1.73 m² or CrCl <60 mL/min), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
History of a serious hypersensitivity reaction to dapagliflozin or hypersensitivity to metformin hydrochloride.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.
Lactic acidosis: Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation.
The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure. The onset of lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate.
If acidosis is suspected, XIGDUO XR should be discontinued and the patient hospitalized immediately.
Hypoxic States: Cardiovascular collapse (shock), acute congestive heart failure, acute myocardial infarction, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on XIGDUO XR therapy, the drug should be promptly discontinued.
Renal Impairment: Metformin is known to be substantially excreted by the kidney and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Therefore, XIGDUO XR is contraindicated in patients with moderate to severe renal impairment.
Hypotension: Dapagliflozin causes intravascular volume contraction. Symptomatic hypotension can occur after initiating dapagliflozin, particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), elderly patients, or patients on loop diuretics.
Before initiating XIGDUO XR in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms of hypotension after initiating therapy.
Ketoacidosis: Reports of ketoacidosis, a serious life‐threatening condition requiring urgent hospitalization have been identified in postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus taking sodium glucose co‐transporter‐2 (SGLT2) inhibitors, including dapagliflozin. XIGDUO XR is not indicated for the treatment of patients with type 1 diabetes mellitus.
Urosepsis and Pyelonephritis: Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated. Consider risk to benefit in patient with history of recurrent urinary tract infections. Patients should be advised of an increased risk of urinary tract infections.
Impaired Hepatic Function: Metformin use in patients with impaired hepatic function has been associated with some cases of lactic acidosis. Therefore, XIGDUO XR should generally be avoided in patients with hepatic impairment.
Alcohol Intake: Alcohol potentiates the effect of metformin on lactate metabolism. Patients should be warned against excessive alcohol intake while receiving XIGDUO XR.
Surgical Procedures: Use of XIGDUO XR should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal or mildly impaired.
Change in Clinical Status of Patients with Previously Controlled Type 2 Diabetes: A patient with type 2 diabetes, previously well controlled on XIGDUO XR, who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of lactic acidosis. Evaluation should include serum electrolytes, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If lactic acidosis occurs, XIGDUO XR must be stopped immediately and other appropriate corrective measures initiated.
See prescribing information for full details.
Hypotension, Ketoacidosis, Urosepsis and Pyelonephritis, Use with Medications Known to Cause Hypoglycemia, Vitamin B12 Concentrations, Genital Mycotic Infections, Increases in Low‐Density Lipoprotein Cholesterol (LDL‐C), Bladder Cancer.
See prescribing information for full details.
Positive Urine Glucose Test
Dapagliflozin: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.
Interference with 1,5-anhydroglucitol (1,5-AG) Assay
Dapagliflozin: Monitoring glycemic control with 1,5‐AG assay is not recommended as measurements of 1,5‐AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.
Metformin hydrochloride: Cationic drugs (e.g., amiloride, cimetidine, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion
theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. A 40% increase in exposure (AUC) of metformin when coadministered with cimetidine was observed in normal healthy volunteers. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of XIGDUO XR and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
Use with Other Drugs
Metformin hydrochloride: Some medications can predispose to hyperglycemia and may lead to loss of glycemic control. These medications include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products,
estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving XIGDUO XR, the patient should be observed closely for loss of glycemic control. When such drugs are withdrawn from a patient receiving XIGDUO XR, the patient should be observed closely for hypoglycemia.
In healthy volunteers, the pharmacokinetics of metformin and propranolol, and of metformin and ibuprofen were not affected when coadministered in single‐dose interaction studies.
Pregnancy and Lactation
Pregnancy: Pregnancy Category C. There are no adequate and well‐controlled studies of XIGDUO XR or its individual components in pregnant women.
Lactation: It is not known whether XIGDUO XR is excreted in human milk. Data in juvenile rats directly exposed to dapagliflozin showed risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. Since human kidney maturation occurs in utero and in the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dapagliflozin, a decision should be made whether to discontinue nursing or to discontinue XIGDUO XR, taking into account the importance of the drug to the mother.
See prescribing information for full details.
Dapagliflozin: There were no reports of overdose during the clinical development program for dapagliflozin. In the event of an overdose, contact the Poison Control Center. It is also reasonable to employ supportive measures as dictated by the patient’s clinical status. The removal of dapagliflozin by hemodialysis has not been studied.
Metformin hydrochloride: Overdose of metformin hydrochloride has occurred, including ingestion of amounts >50 grams.
Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
Storage: Store below 30°C.