Empagliflozin/​Metformin

DEA Class; Rx

Common Brand Names; Synjardy, Synjardy XR

Indicated for the treatment of type 2 diabetes mellitus in combination with diet and exercise when treatment with both empagliflozin and metformin is appropriate.

Moderate-to-severe renal disease (eGFR <45 mL/min/1.73 m²), end-stage renal disease, or dialysis

Acute or chronic metabolic acidosis, including diabetic ketoacidosis (treat ketoacidosis with insulin)

History of serious hypersensitivity reaction to empagliflozin or metformin

• Urinary tract infection (7.6-9.3%)
• Decreased vitamin B12 levels (7%)
• Increased LDL-C (4.6-6.5%)
• Female genital mycotic infections (5.4-6.4%)
• Dyslipidemia (2.9-3.9%)
• Increased urination (3.2-3.4%)
• Male genital mycotic infections (1.6-3.1%)
• Nausea (1.1-2.3%)
• Hypoglycemia, with monotherapy (1.4-1.8%)
• <1%
• Volume depletion
• Impaired renal function
• Ketoacidosis
• Urosepsis and pyelonephritis
• Angioedema
• Skin reactions (e.g., rash, urticaria)
• Cholestatic, hepatocellular, and mixed hepatocellular liver injury
• Acute kidney injury
• Constipation
• Necrotizing fasciitis of the perineum (Fournier’s gangrene)

Lactic acidosis is a metabolic complication that can occur due to metformin accumulation during treatment and is fatal in ~50% of cases (see Black Box Warnings)

Serious hypersensitivity reactions, (eg, angioedema) in patients receiving treatment reported postmarketing; discontinue therapy and treat promptly if it occurs per standard of care

Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4ºF or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary

Empagliflozin causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, elderly patients, patients with low systolic blood pressure, or patients taking diuretics; before initiating therapy, assess for volume contraction and correct volume status if indicated; monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected

Withholding of food and fluids during surgical or other procedures may increase risk for volume depletion, hypotension and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake

Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; when such events occur, discontinue therapy

Administration of intravascular iodinated contrast agents in metformin­treated patients has led to an acute decrease in renal function and occurrence of lactic acidosis; stop treatment at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between <60 mL/min/1.73 m²; in patients with a history of hepatic impairment, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast; re-evaluate eGFR 48 hours after imaging procedure, and restart therapy if renal function is stable

Not recommended during second and third trimester of pregnancy based on animal data

Limited available data with use in pregnant women is not sufficient to determine a drug-associated risk for major birth defects and miscarriages

Metformin may result in ovulation in some anovulatory women; discuss the potential for unintended pregnancy with premenopausal women

There is no information regarding presence in human milk, the effects on breastfed infant or on milk production

Empagliflozin/metformin Hydrochloride

tablet, immediate-release

• 5mg/500mg
• 5mg/1000mg
• 12.5mg/500mg
• 12.5mg/1000mg

tablet, extended-release

• 5mg/1000mg
• 10mg/1000mg
• 12.5mg/1000mg
• 25mg/1000mg