1 INDICATIONS AND USAGE Glimepiride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see Clinical Studies (14.1)] .

Limitations of Use Glimepiride tablets should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, as it would not be effective in these settings.

Glimepiride is a sulfonylurea indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1) .

Limitations of Use: Not for treating type 1 diabetes mellitus or diabetic ketoacidosis ( 1 ).

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail below and elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions (5.1) ] Hemolytic anemia [see Warnings and Precautions (5.3) ] Common adverse reactions in clinical trials (≥5% and more common than with placebo) include hypoglycemia, headache, nausea, and dizziness (6.1) .

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc.

at 1(844) 874-7464 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.

Approximately 2,800 patients with type 2 diabetes have been treated with glimepiride in the controlled clinical trials.

In these trials, approximately 1,700 patients were treated with glimepiride for at least 1 year.

In clinical trials, the most common adverse reactions with glimepiride were hypoglycemia, dizziness, asthenia, headache, and nausea.

Table 1 summarizes adverse events, other than hypoglycemia, that were reported in 11 pooled placebo-controlled trials, whether or not considered to be possibly or probably related to study medication.

Treatment duration ranged from 13 weeks to 12 months.

Terms that are reported represent those that occurred at an incidence of ≥5% among glimepiride-treated patients and more commonly than in patients who received placebo.

Table 1: Eleven Pooled Placebo-Controlled Trials ranging from 13 weeks to 12 months: Adverse Events (excluding hypoglycemia) Occurring in ≥5% of Glimepiride-treated Patients and at a Greater Incidence than with Placebo* Glimepiride N=745 % Placebo N=294 % Headache 8.2 7.8 Accidental Injury † 5.8 3.4 Flu Syndrome 5.4 4.4 Nausea 5 3.4 Dizziness 5 2.4 * Glimepiride doses ranged from 1 to 16 mg administered daily † Insufficient information to determine whether any of the accidental injury events were associated with hypoglycemia Hypoglycemia In a randomized, double-blind, placebo-controlled monotherapy trial of 14 weeks duration, patients already on sulfonylurea therapy underwent a 3-week washout period then were randomized to glimepiride 1 mg, 4 mg, 8 mg, or placebo.

Patients randomized to glimepiride 4 mg or 8 mg underwent forced-titration from an initial dose of 1 mg to these final doses, as tolerated [see Clinical Studies (14.1) ].

The overall incidence of possible hypoglycemia (defined by the presence of at least one symptom that the investigator believed might be related to hypoglycemia; a concurrent glucose measurement was not required) was 4% for glimepiride 1 mg, 17% for glimepiride 4 mg, 16% for glimepiride 8 mg and 0% for placebo.

All of these events were self-treated.

In a randomized, double-blind, placebo-controlled monotherapy trial of 22 weeks duration, patients received a starting dose of either 1 mg glimepiride or placebo daily.

The dose of glimepiride was titrated to a target fasting plasma glucose of 90 to 150 mg/dL.

Final daily doses of glimepiride were 1, 2, 3, 4, 6, or 8 mg [see Clinical Studies (14.1) ] .

The overall incidence of possible hypoglycemia (as defined above for the 14-week trial) for glimepiride vs.

placebo was 19.7% vs.

3.2%.

All of these events were self-treated.

Weight gain Glimepiride, like all sulfonylureas, can cause weight gain [see Clinical Studies (14.1) ] .

Allergic Reactions In clinical trials, allergic reactions, such as pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occurred in less than 1% of glimepiride-treated patients.

These may resolve despite continued treatment with glimepiride.

There are postmarketing reports of more serious allergic reactions (e.g., dyspnea, hypotension, shock) [see Warnings and Precautions (5.2) ] .

Laboratory Tests Elevated serum alanine aminotransferase (ALT) In 11 pooled placebo-controlled trials of glimepiride, 1.9% of glimepiride-treated patients and 0.8% of placebo-treated patients developed serum ALT greater than 2 times the upper limit of the reference range.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of glimepiride.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious hypersensitivity reactions, including anaphylaxis, angioedema, and Stevens-Johnson syndrome [see Warnings and Precautions (5.2) ] Hemolytic anemia in patients with and without G6PD deficiency [see Warnings and Precautions (5.3) ] Impairment of liver function (e.g., with cholestasis and jaundice), as well as hepatitis, which may progress to liver failure Porphyria cutanea tarda, photosensitivity reactions and allergic vasculitis Leukopenia, agranulocytosis, aplastic anemia, and pancytopenia Thrombocytopenia (including severe cases with platelet count less than 10,000/µL) and thrombocytopenic purpura Hepatic porphyria reactions and disulfiram-like reactions Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH), most often in patients who are on other medications or who have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone Dysgeusia Alopecia