Synjardy 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 (5.4) ] Hypoglycemia [see Warnings and Precautions (5.5) ] Lower Limb Amputation [see Warnings and Precautions (5.6) ] Hypersensitivity Reactions [see Warnings and Precautions (5.7) ] Vitamin B 12 Deficiency [see Warnings and Precautions (5.8) ] Most common adverse reactions associated with empagliflozin (5% or greater incidence) were urinary tract infections and female genital mycotic infections.

( 6.1 ) Most common adverse reactions associated with metformin HCl (>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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of concomitantly administered empagliflozin (daily dosage 10 mg or 25 mg) and metformin HCl (mean daily dosage of approximately 1,800 mg) has been evaluated in 3,456 adult patients with type 2 diabetes mellitus treated for 16 to 24 weeks, of which 926 patients received placebo, 1,271 patients received a daily dosage of empagliflozin 10 mg, and 1,259 patients received a daily dosage of empagliflozin 25 mg.

Discontinuation of therapy due to adverse events across treatment groups was 3.0%, 2.8%, and 2.9% for placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.

Adverse Reactions in a Clinical Trial with Empagliflozin (Add-On Combination Therapy with Metformin HCl and Sulfonylurea) for Glycemic Control in Adults with Type 2 Diabetes Mellitus In a 24-week placebo-controlled trial of empagliflozin 10 mg or 25 mg administered once daily added to metformin HCl and sulfonylurea, adverse reactions reported in ≥5% of empagliflozin-treated patients and more commonly than in placebo-treated patients are presented in Table 1 (see also Table 4 ).

Table 1 Adverse Reactions Reported in ≥5% of Adults with Type 2 Diabetes Mellitus Treated with Empagliflozin added on to Metformin HCl plus Sulfonylurea and Greater than with Placebo in a 24-week Placebo Controlled Clinical Trial Adverse Reactions Placebo (%) n=225 Empagliflozin 10 mg (%) n=224 Empagliflozin 25 mg (%) n=217 Hypoglycemia 9.8 15.6 12.9 Urinary tract infection 6.7 9.4 6.9 Nasopharyngitis 4.9 8.0 6.0 Empagliflozin Clinical Trials in Adults with Type 2 Diabetes Mellitus The data in Table 2 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with basal insulin in adult patients with type 2 diabetes mellitus.

Empagliflozin was used as monotherapy in one trial and as add-on therapy in four trials [see Clinical Studies (14.1) ] .