Synjardy XR
SYNJARDY XR- empagliflozin and metformin hydrochloride tablet, extended release
Boehringer Ingelheim Pharmaceuticals, Inc.
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 generally >5 mcg/mL [see Warnings and Precautions (5.1)].
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., 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 [see Dosage and Administration (2.1), Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7), and Use in Specific Populations (8.6, 8.7)].
If metformin-associated lactic acidosis is suspected, immediately discontinue SYNJARDY XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1)].
1 INDICATIONS AND USAGE
SYNJARDY XR is a combination of empagliflozin and metformin hydrochloride (HCl) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease [see Clinical Studies (14)].
Limitation of Use
SYNJARDY XR is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients [see Warnings and Precautions (5.2)].
2 DOSAGE AND ADMINISTRATION
2.1 Prior to Initiation of SYNJARDY XR
- Assess renal function before initiating SYNJARDY XR and as clinically indicated [see Warnings and Precautions (5.1, 5.3)].
- In patients with volume depletion, correct this condition before initiating SYNJARDY XR [see Warnings and Precautions (5.3) and Use in Specific Populations (8.5, 8.6)].
2.2 Recommended Dosage and Administration
- Individualize the starting dose of SYNJARDY XR based on the patient’s current regimen:
- In patients on metformin HCl, switch to SYNJARDY XR containing a similar total daily dose of metformin HCl and a total daily dose of empagliflozin 10 mg;
- In patients on empagliflozin, switch to SYNJARDY XR containing the same total daily dose of empagliflozin and a total daily dose of metformin HCl extended-release 1000 mg;
- In patients already treated with empagliflozin and metformin HCl, switch to SYNJARDY XR containing the same total daily doses of empagliflozin and a similar total daily dose of metformin HCl.
- Monitor effectiveness and tolerability, and adjust dosing as appropriate, not to exceed the maximum recommended daily dose of empagliflozin 25 mg and metformin HCl 2000 mg.
- The dose of metformin HCl should be gradually escalated to reduce the gastrointestinal side effects due to metformin.
- Take SYNJARDY XR orally once daily with a meal in the morning
- Swallow SYNJARDY XR tablets whole. Do not split, crush, dissolve, or chew.
- SYNJARDY XR 10 mg/1000 mg and 25 mg/1000 mg tablets should be taken as a single tablet once daily. SYNJARDY XR 5 mg/1000 mg and 12.5 mg/1000 mg tablets should be taken as two tablets together once daily.
2.3 Dosage Recommendations in Patients with Renal Impairment
- Initiation of SYNJARDY XR is not recommended in patients with an eGFR less than 45 mL/min/1.73 m2 , due to the metformin component.
- SYNJARDY XR is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 or in patients on dialysis [see Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].
2.4 Discontinuation for Iodinated Contrast Imaging Procedures
Discontinue SYNJARDY XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR less than 60 mL/min/1.73 m2 ; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart SYNJARDY XR if renal function is stable [see Warnings and Precautions (5.1)].
3 DOSAGE FORMS AND STRENGTHS
SYNJARDY XR Tablets:
| Empagliflozin Strength | Metformin HCl Strength | Color/Shape | Tablet Markings |
|---|---|---|---|
| 5 mg | 1000 mg | olive green, oval, biconvex, film-coated tablet | Printed on one side in black ink with the Boehringer Ingelheim company logo and “S5” on the top line and “1000 M” on the bottom line. |
| 10 mg | 1000 mg | orange, oval, biconvex, film-coated tablet | Printed on one side in black ink with the Boehringer Ingelheim company logo and “S10” on the top line and “1000 M” on the bottom line. |
| 12.5 mg | 1000 mg | blue, oval, biconvex, film-coated tablet | Printed on one side in black ink with the Boehringer Ingelheim company logo and “S12” on the top line and “1000 M” on the bottom line. |
| 25 mg | 1000 mg | light green, oval, biconvex, film-coated tablet | Printed on one side in black ink with the Boehringer Ingelheim company logo and “S25” on the top line and “1000 M” on the bottom line. |
4 CONTRAINDICATIONS
SYNJARDY XR is contraindicated in patients with:
- Severe renal impairment (eGFR less than 30 mL/min/1.73 m2), end stage renal disease, or dialysis [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 or any of the excipients in SYNJARDY XR, reactions such as angioedema have occurred [see Warnings and Precautions (5.8)].
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