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SYNJARDY (empagliflozin and metformin hydrochloride) tablets,
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SYNJARDY safely and effectively. See full prescribing information for SYNJARDY.
SYNJARDY ® (empagliflozin and metformin hydrochloride) tablets, for oral use
Initial U.S. Approval: 2015
WARNING: LACTIC ACIDOSIS
See full prescribing information for complete boxed warning.
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Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. (5.1)
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Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, 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. (5.1)
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If lactic acidosis is suspected, discontinue SYNJARDY and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. (5.1)
RECENT MAJOR CHANGES
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Indications and Usage (1) |
7/2016 |
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Boxed Warning |
7/2016 |
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Dosage and Administration (2) |
7/2016 |
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Contraindications (4) |
7/2016 |
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Warnings and Precautions (5) |
7/2016 |
INDICATIONS AND USAGE
SYNJARDY is a combination of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor and metformin, a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both empagliflozin and metformin is appropriate. (1)
Limitation of Use:
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Not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis (1.1)
DOSAGE AND ADMINISTRATION
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Individualize the starting dose of SYNJARDY based on the patient’s current regimen (2.1)
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The maximum recommended dose is 12.5 mg empagliflozin/1000 mg metformin twice daily (2.1)
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Take twice daily with meals, with gradual dose escalation to reduce the gastrointestinal side effects due to metformin (2.1)
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Assess renal function before initiating. SYNJARDY is contraindicated in patients with an eGFR below 45 mL/min/1.73 m2 (2.2, 4)
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SYNJARDY may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets:
5 mg empagliflozin/500 mg metformin hydrochloride
5 mg empagliflozin/1000 mg metformin hydrochloride
12.5 mg empagliflozin/500 mg metformin hydrochloride
12.5 mg empagliflozin/1000 mg metformin hydrochloride (3)
CONTRAINDICATIONS
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Moderate to severe renal impairment (eGFR below 45 mL/min/1.73 m2), end stage renal disease, or dialysis (4, 5.1, 5.4)
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Metabolic acidosis, including diabetic ketoacidosis (1, 4, 5.1)
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History of serious hypersensitivity reaction to empagliflozin or metformin (4)
WARNINGS AND PRECAUTIONS
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Lactic acidosis: See boxed warning (5.1)
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Hypotension: Before initiating SYNJARDY assess and correct volume status in patients with renal impairment, the elderly, in patients with low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy. (5.2)
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Ketoacidosis: Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue SYNJARDY, eva luate and treat promptly. Before initiating SYNJARDY, consider risk factors for ketoacidosis. Patients on SYNJARDY may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis. (5.3)
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Impairment in renal function: Monitor renal function during therapy. (5.4)
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Urosepsis and Pyelonephritis: eva luate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated (5.5)
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Hypoglycemia: Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating SYNJARDY (5.6)
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Genital mycotic infections: Monitor and treat as appropriate (5.7)
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Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually. (5.8)
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Increased LDL-C: Monitor and treat as appropriate (5.9)
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Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with SYNJARDY. (5.10)
ADVERSE REACTIONS
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Most common adverse reactions associated with empagliflozin (5% or greater incidence) were urinary tract infection and female genital mycotic infections. (6.1)
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Most common adverse reactions associated with metformin (>5%) are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or 1-800-459-9906 TTY, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring. (7.2)
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Drugs that are eliminated by renal tubular secretion (e.g., cationic drugs such as cimetidine), may increase the accumulation of metformin. Consider more frequent monitoring. (7.2)
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Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake. (7.2)
USE IN SPECIFIC POPULATIONS
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