Overview
11 DESCRIPTION SYNJARDY and SYNJARDY XR tablets for oral use contain: empagliflozin and metformin HCl. Empagliflozin Empagliflozin is an inhibitor of the SGLT2. The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S). Its molecular formula is C 23 H 27 ClO 7 and the molecular weight is 450.91.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action SYNJARDY or SYNJARDY XR SYNJARDY and SYNJARDY XR contain: empagliflozin, a SGLT2 inhibitor, and metformin HCl, a biguanide. Empagliflozin Empagliflozin is an inhibitor of SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion. Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule.
Indications
- 1 INDICATIONS AND USAGE SYNJARDY SYNJARDY is a combination of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor and metformin hydrochloride (HCl) immediate-release, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. SYNJARDY XR SYNJARDY XR is a combination of empagliflozin, a SGLT2 inhibitor and metformin HCl extended-release, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus .
Common Doses
- 25 mg
- 000 mg
- 45 mL
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. ( 2.1 ) Individualize the starting dosage based on the patient's current regimen and renal function. ( 2.2 , 2.3 , 2.4 ) The maximum recommended dosage is 25 mg/day of empagliflozin and 2,000 mg/day of metformin HCl. ( 2.2 , 2.3 ) Initiation of SYNJARDY or SYNJARDY XR is not recommended in patients with an eGFR less than 45 mL/min/1.73 m 2 , due to the metformin HCl component. ( 2.
Black Box Warning
WARNING: LACTIC ACIDOSIS 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/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels...
Contraindications
- 4 CONTRAINDICATIONS SYNJARDY and SYNJARDY XR are contraindicated in patients with: severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ]. acute or chronic metabolic acidosis, including diabetic ketoacidosis [see Warnings and Precautions (5.1) ]. hypersensitivity to empagliflozin, metformin HCl or any of the excipients in SYNJARDY or SYNJARDY XR, reactions such as angioedema have occurred [see Warnings and Precautions (5.7) ] . Severe renal impairment (eGFR below 30 mL/min/1.
Side Effects
- 6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ] Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.2) ] Volume Depletion [see Warnings and Precautions (5.3) ] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS See Table 4 for clinically relevant interactions with SYNJARDY or SYNJARDY XR. Table 4 Clinically Relevant Interactions with SYNJARDY or SYNJARDY XR Carbonic Anhydrase Inhibitors Clinical Impact Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with SYNJARDY or SYNJARDY XR may increase the risk of lactic acidosis. Intervention Consider more frequent monitoring of these patients.