Glimepiride

GLIMEPIRIDE- glimepiride tablet
Northwind Pharmaceuticals

Indications & Usage Section

Glimepiride tablets USP 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)].

1.1 Important Limitation of Use

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


Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

Dosage & Administration Section

2.1 Recommended Dosing

Glimepiride tablets USP should be administered with breakfast or the first main meal of the day.

The recommended starting dose of glimepiride tablets USP is 1 mg or 2 mg once daily. Patients at increased risk for hypoglycemia (e.g., the elderly or patients with renal impairment) should be started on 1 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.5,8.6)].

After reaching a daily dose of 2 mg, further dose increases can be made in increments of 1 mg or 2 mg based upon the patient’s glycemic response. Uptitration should not occur more frequently than every 1–2 weeks. A conservative titration scheme is recommended for patients at increased risk for hypoglycemia [see Warnings and Precautions (5.1)and Use in Specific Populations (8.5, 8.6)].

The maximum recommended dose is 8 mg once daily.

Patients being transferred to glimepiride tablets USP from longer half-life sulfonylureas (e.g., chlorpropamide) may have overlapping drug effect for 1–2 weeks and should be appropriately monitored for hypoglycemia.

Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

Dosage Forms & Strengths Section

Glimepiride tablet is formulated as tablets of:

1 mg (Light pink capsule shaped flat faced, bevelled edged tablets with breakline on both sides and debossed with ‘I’ and ‘1’ on either side of breakline only on one side)
2 mg (Yellow coloured capsule shaped flat faced, bevelled edged tablets with breakline on both sides and debossed with ‘I’ and ‘2’ on either side of breakline only on one side)
4 mg (White capsule shaped flat faced, bevelled edged tablets with breakline on both sides and debossed with ‘I’ and ‘4’ on either side of breakline only on one side)


Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

Contraindications Section

Glimepiride tablets USP are contraindicated in patients with a history of a hypersensitivity reaction to:

Glimepiride or any of the product’s ingredients [see Warnings and Precautions (5.2)].

Sulfonamide derivatives: Patients who have developed an allergic reaction to sulfonamide derivatives may develop an allergic reaction to glimepiride tablets. Do not use glimepiride tablets in patients who have a history of an allergic reaction to sulfonamide derivatives.

Reported hypersensitivity reactions include cutaneous eruptions with or without pruritus as well as more serious reactions (e.g. anaphylaxis, angioedema, Stevens-Johnson Syndrome, dyspnea) [see Warnings and Precautions (5.2)and Adverse Reactions (6.2)].

Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

Warnings & Precautions Section

5.1 Hypoglycemia

All sulfonylureas, including glimepiride, can cause severe hypoglycemia [see Adverse Reactions (6.1 )]. The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. These impairments may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death.

Patients must be educated to recognize and manage hypoglycemia. Use caution when initiating and increasing glimepiride doses in patients who may be predisposed to hypoglycemia (e.g., the elderly, patients with renal impairment, patients on other anti-diabetic medications). Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic impairment are particularly susceptible to the hypoglycemic action of glucose-lowering medications. Hypoglycemia is also more likely to occur when caloric intake is deficient, after severe or prolonged exercise, or when alcohol is ingested.

Early warning symptoms of hypoglycemia may be different or less pronounced in patients with autonomic neuropathy, the elderly, and in patients who are taking beta-adrenergic blocking medications or other sympatholytic agents. These situations may result in severe hypoglycemia before the patient is aware of the hypoglycemia.

5.2 Hypersensitivity Reactions

There have been postmarketing reports of hypersensitivity reactions in patients treated with glimepiride, including serious reactions such as anaphylaxis, angioedema, and Stevens-Johnson Syndrome. If a hypersensitivity reaction is suspected, promptly discontinue glimepiride, assess for other potential causes for the reaction, and institute alternative treatment for diabetes.

5.3 HemolyticAnemia

Sulfonylureas can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Because glimepiride is a sulfonylurea, use caution in patients with G6PD deficiency and consider the use of a non-sulfonylurea alternative. There are also postmarketing reports of hemolytic anemia in patients receiving glimepiride who did not have known G6PD deficiency [see Adverse Reactions (6.2)].

5.4 Increased Risk of Cardiovascular Mortality with Sulfonylureas

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term, prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups

UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2–1/2 times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glimepiride and of alternative modes of therapy

Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.

5.5 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glimepiride or any other anti-diabetic drug.


Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

Adverse Reactions Section

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)]

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

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.

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
%

*
Glimepiride doses ranged from 1–16 mg administered daily

Insufficient information to determine whether any of the accidental injury events were associated with hypoglycemia

Headache 8.2 7.8
Accidental Injury † 5.8 3.4
Flu Syndrome 5.4 4.4
Nausea 5.0 3.4
Dizziness 5.0 2.4

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% 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 90–150 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 serumALT greater than 2 times the upper limit of the reference range.

6.2 Post marketing Experience

The following adverse reactions have been identified during post-approval 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, thrombocytopenia, aplastic anemia, and pancytopenia
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

Please review the manufacturer’s complete drug information available from the FDA at www.fda.gov
Permanent Link: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4419ca50-539c-47e8-ab00-dbb45c7c1814

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