Description: Antidiabetic Agents; Biguanide; Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
“ALERT: US Boxed Warning
Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate), ≥65 years, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information.
If metformin-associated lactic acidosis is suspected, immediately discontinue empagliflozin/metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.”
CSA NA – FDA Approved – REMS (N) – Can Ship
How Does It Work
SGLT2 is in the proximal renal tubules of the nephron (a functional unit of the kidney) and is the main site of the reabsorption of filtered glucose. Empagliflozin inhibits this transporter which lowers glucose reabsorption and lowers the renal threshold for glucose resulting in its urinary excretion thereby lowering plasma glucose concentrations.
Metformin is believed to exhibit multiple mechanisms of action which ultimately decreases gluconeogenesis (hepatic glucose production) in the liver, decreases intestinal absorption of glucose, and improves the insulin sensitivity of muscle which increases peripheral glucose uptake and overall utilization. Metformin also exhibits an anti-androgenic effect in women with insulin resistance
Indications For Use
Diabetes mellitus type 2
Before starting Empagliflozin+Metformin, Synjardy makes sure your physician is aware of any allergies, medications you currently take, if you have kidney disease, liver disease, heart failure, a history of diabetic ketoacidosis, have had bariatric surgery, are pregnant or breastfeeding. Empagliflozin+Metformin, Synjardy has been associated with rare but serious adverse reactions such as the increased risk of bone fracture, genital mycotic infections, hypersensitivity reaction, hypotension, ketoacidosis, lactic acidosis, necrotizing fasciitis, increased risk of lower limb amputation, acute kidney injury, urinary tract infections, and vitamin B12 deficiency.
Initial: Individualize initial dose based on patient’s current antidiabetic regimen. May gradually increase the dose based on effectiveness and tolerability.
Patients on metformin: Empagliflozin 10 mg/day plus a similar total daily dose of metformin, administered in 2 divided doses (immediate release) or once daily (extended release).
Patients on empagliflozin: Metformin 1 g/day plus a similar total daily dose of empagliflozin, administered in 2 divided doses (immediate release) or once daily (extended release).
Maximum: Empagliflozin 25 mg/metformin 2 g/day, administered in 2 divided doses (immediate release) or once daily (extended release).
Pharmacist Tips On Using
How to Take: Follow instructions provided by physician/pharmacy label, take consistently at same times each day unless otherwise directed, store at room temperature. Monitor blood pressure when initiating due to diuretic effect. Administer IR tablets twice daily with meals or extended-release tablets once daily with breakfast. ER tablets should not be split, crushed, chewed, or dissolved.
You Need to Avoid: Do not skip a standard diabetic foot care regimen. Must monitor for wounds or signs of a new infection, ulcers, sores, or new pain or tenderness. A trial involving a similar medication (canagliflozin) showed a higher frequency of lower limb amputations compared to placebo so caution must be taken. There is no direct evidence of empagliflozin having this effect but due to similarities, it should be taken seriously. Avoid volume depletion or dehydration due to the diuretic effect of this medication. Alcohol should be avoided due to the increased risk of lactic acidosis from metformin use.
Empagliflozin – Urinary tract infection (due to sugar content in urine – more common in females due to shorter urethra), increased urine output, genitourinary fungal infection (more common in females), dyslipidemia, nausea, thirst
Metformin – Diarrhea, nausea, vomiting, flatulence, infection
(Note this is not a complete list of side effects only common ones)
Frequently Asked Questions
What is hypoglycemia?
Hypoglycemia is a condition of low blood sugar (>3.9mmol/L-Canada; 70mg/dL-US) which is considered a medical emergency whereas hyperglycemia is a slowly progressive condition. It generally occurs with irregularities in diet, exercise, and medications in diabetic patients. It is preferably treated with simple sugars such as dextrose; regular table sugar can work but is slower acting as it needs to be digested and if blood sugar is extremely low this delay can be a problem. Hypoglycemia has a large host of progressive symptoms from hunger, headache, nausea, sweating, palpitations, mood swings, irritability to seizure, coma and in severe cases, death.