Synjardy Xr

  • Diabetes

Synjardy Xr Generic Name & Formulations

General Description

Empagliflozin, metformin HCl ext-rel; 5mg/1000mg, 10mg/1000mg, 12.5mg/1000mg, 25mg/1000mg; tabs.

Pharmacological Class

Sodium-glucose co-transporter 2 (SGLT2) inhibitor + biguanide.

See Also

How Supplied

Tabs—60, 180; XR tabs 5mg/1000mg, 12.5mg/1000mg—60, 180; 10mg/1000mg, 25mg/1000mg—30, 90

Generic Availability


Mechanism of Action

Empagliflozin inhibits SGLT2 reducing renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Synjardy Xr Indications


Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

Limitations of Use

Not recommended in those with type 1 diabetes; may increase risk of diabetic ketoacidosis. Not recommended in those with heart failure without T2DM due to the metformin component.

Synjardy Xr Dosage and Administration


See full labeling. Swallow whole. Individualize. Take once daily with morning meal; increase dose gradually. Max daily dose: 25mg/2000mg. Renal impairment: initiation is not recommended if eGFR <45mL/min/1.73m2.


<18yrs: not established.

Synjardy Xr Contraindications


Severe renal impairment (eGFR <30mL/min/1.73m2), ESRD, or on dialysis. Metabolic acidosis, diabetic ketoacidosis.

Synjardy Xr Boxed Warnings

Boxed Warning

Lactic acidosis.

Synjardy Xr Warnings/Precautions


Increased risk of metformin-associated lactic acidosis in renal or hepatic impairment, concomitant use of certain drugs (eg, cationic drugs), ≥65yrs of age, undergoing radiological contrast study, surgery and other procedures, hypoxic states, and excessive alcohol intake; discontinue if lactic acidosis is suspected. Discontinue at time of, or prior to intravascular iodinated contrast imaging in patients with eGFR <60mL/min/1.73m2, history of hepatic impairment, alcoholism, heart failure, or will be given intra-arterial contrast; reevaluate eGFR 48hrs after procedure and restart therapy if renally stable. Correct volume depletion before initiating. Increased risk for volume depletion or hypotension in those with renal impairment (eGFR <60mL/min/1.73m2), elderly, or on loop diuretics. Assess volume status and renal function prior to initiation; monitor during therapy; more frequently in elderly. Assess for ketoacidosis in presence of signs/symptoms of metabolic acidosis, regardless of blood glucose levels; discontinue if suspected, evaluate and treat; consider risk factors before initiation (eg, pancreatic insulin deficiency, caloric restriction, alcohol abuse). Consider temporarily discontinuing prior to scheduled surgery (for ≥3 days) or other clinical situations (eg, prolonged fasting due to illness or post-surgery). Necrotizing fasciitis of the perineum (Fournier's gangrene); discontinue and treat immediately if suspected; use alternative antidiabetic. Increased risk of genital mycotic infections, UTIs (including urosepsis, pyelonephritis); monitor and treat as appropriate. Discontinue if hypersensitivity reaction occurs; treat promptly and monitor until resolve. Measure hematologic parameters annually and Vit. B12 levels at 2–3 year intervals. Hepatic impairment, pregnancy (during 2nd & 3rd trimesters), nursing mothers: not recommended.

Synjardy Xr Pharmacokinetics



  • Peak plasma concentrations were reached at 1.5 hours post-dose.
  • Steady-state mean plasma AUC and Cmax were 1,870 nmol∙h/L and 259 nmol/L, respectively, with 10 mg empagliflozin once daily treatment, and 4,740 nmol∙h/L and 687 nmol/L, respectively, with 25 mg empagliflozin once daily treatment.

Metformin ER:

  • Time to reach maximum plasma metformin concentration: ~7 to 8 hours.
  • Low-fat and high-fat meals increased the systemic exposure (as measured by AUC) from metformin extended-release tablets by about 38% and 73%, respectively, relative to fasting.



  • Apparent steady-state volume of distribution: estimated 73.8 L.
  • Plasma protein binding: 86.2%.


  • Apparent volume of distribution of immediate-release metformin HCl 850 mg tablet: 654 ± 358 L.



  • Glucuronidation by UGT2B7, UGT1A3, UGT1A8, UGT1A9.



  • Renal (54.4%), fecal (41.2%). Half-life: 12.4 hours.
  • Apparent oral clearance: 10.6 L/h.


  • Renal (~90%). Half-life: ~6.2 hours (plasma); ~17.6 hours (blood).

Synjardy Xr Interactions


Increased risk of lactic acidosis with topiramate, other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, dichlorphenamide); monitor. Concomitant cationic drugs that interfere with renal tubular transport systems (eg, ranolazine, vandetanib, dolutegravir, cimetidine) may increase metformin levels; monitor. Avoid excessive alcohol. Diuretics, steroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, CCBs, and isoniazid may cause hyperglycemia. Greater potential for volume depletion with concomitant diuretics. β-blockers may mask hypoglycemia. May need a lower dose of concomitant insulin or insulin secretagogue (eg, sulfonylurea) to reduce risk of hypoglycemia. Empagliflozin may antagonize serum lithium concentrations; monitor levels more frequently. Empagliflozin will lead to false (+) urine glucose tests or unreliable measurements of 1, 5-AG assay; use alternative methods to monitor glycemic control.

Synjardy Xr Adverse Reactions

Adverse Reactions

UTIs, female genital mycotic infections, diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, headache; hypotension, ketoacidosis, renal impairment, angioedema; rare: Fournier's gangrene.

Synjardy Xr Clinical Trials

See Literature

Synjardy Xr Note

Not Applicable

Synjardy Xr Patient Counseling

See Literature