Synjardy Generic Name & Formulations
Mechanism of Action
Adjunct to diet and exercise to improve glycemic control in adults and pediatric patients ≥10yrs 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 Dosage and Administration
Adults and Children
<10yrs: not established. See full labeling. Individualize. ≥10yrs: Take twice daily with meals; increase dose gradually. Max daily dose: 25mg/2000mg. Renal impairment: initiation is not recommended if eGFR <45mL/min/1.73m2.
Synjardy Boxed Warnings
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.
- 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.
- Absolute bioavailability of immediate-release metformin HCl 500 mg tablet under fasting conditions is ~50 to 60%.
- 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.
- 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).
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 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 Clinical Trials
Synjardy Patient Counseling