Glimepiride 3 mg

Description

Glimepiride tablets, USP are an oral sulfonylurea formulation containing the active ingredient glimepiride. The chemical structure of glimepiride is defined as 1-[[p-2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) ethylphenyl]sulfonyl]-3-(trans-4-methylcyclohexyl) urea, with a molecular formula of C24H34N4O5S and a molecular weight of 490.62 g/mol.

The active ingredient is presented as a white to almost white, crystalline, odorless to practically odorless powder that is practically insoluble in water. Each tablet contains glimepiride along with several inactive ingredients, including lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, and sodium starch glycolate. Additionally, the 3 mg formulation of Glimepiride tablets includes Ferric Oxide Yellow as an inactive component.

Uses and Indications

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

Limitations of use include that glimepiride is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. There are no teratogenic or nonteratogenic effects associated with glimepiride.

Dosage and Administration

The recommended starting dose for the medication is 1 or 2 mg administered once daily. Dosing may be increased in increments of 1 or 2 mg, but such adjustments should not occur more frequently than every 1 to 2 weeks, and should be guided by the patient's glycemic response. The maximum recommended dose is 8 mg once daily.

Administration should occur with breakfast or the first meal of the day to optimize absorption and efficacy.

In patients who are at increased risk for hypoglycemia, such as the elderly or those with renal impairment, it is advised to initiate treatment with a starting dose of 1 mg and to titrate the dose slowly to minimize the risk of adverse effects.

Contraindications

Use of this product is contraindicated in patients with hypersensitivity to glimepiride or any of its ingredients. Additionally, it is contraindicated in individuals with hypersensitivity to sulfonamide derivatives due to the potential for cross-reactivity and adverse reactions.

Warnings and Precautions

Severe hypoglycemia may occur with glimepiride, necessitating careful patient selection, appropriate dosing, and clear instructions, particularly for at-risk populations such as the elderly and individuals with renal impairment. Caution is advised when glimepiride is used in conjunction with other anti-diabetic medications, as this may further increase the risk of hypoglycemia.

Hypersensitivity reactions have been reported in postmarketing surveillance, including anaphylaxis, angioedema, and Stevens-Johnson Syndrome. Should a hypersensitivity reaction be suspected, glimepiride must be discontinued immediately. Healthcare professionals should evaluate the patient for other potential causes of the reaction and consider alternative diabetes treatments.

Patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolytic anemia when treated with glimepiride. In such cases, a non-sulfonylurea alternative should be considered to mitigate this risk.

There is a potential increased risk of cardiovascular mortality associated with the use of sulfonylureas, including glimepiride. It is essential for healthcare providers to inform patients about the risks, benefits, and available treatment alternatives.

Currently, there are no clinical studies that provide conclusive evidence regarding macrovascular risk reduction with glimepiride or any other anti-diabetic medication. Therefore, healthcare professionals should remain vigilant and discuss the implications of macrovascular outcomes with their patients.

Side Effects

Patients may experience a range of adverse reactions while using glimepiride, which can be categorized into common and serious reactions.

Common adverse reactions include hypoglycemia, headache, nausea, and dizziness. Hypoglycemia, while common, can also be severe, particularly in at-risk populations such as the elderly and those with renal impairment. It is crucial to ensure proper patient selection, dosing, and instructions when prescribing glimepiride, especially when used in conjunction with other anti-diabetic medications.

Serious adverse reactions reported include hypersensitivity reactions, which have been documented in postmarketing reports and may manifest as anaphylaxis, angioedema, or Stevens-Johnson Syndrome. If a hypersensitivity reaction is suspected, glimepiride should be promptly discontinued, and alternative diabetes treatments should be considered. Additionally, hemolytic anemia may occur in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency, necessitating the consideration of non-sulfonylurea alternatives.

There is a potential increased risk of cardiovascular mortality associated with sulfonylureas, and patients should be informed of the risks, benefits, and available treatment alternatives. Furthermore, no clinical studies have conclusively established evidence of macrovascular risk reduction with glimepiride or any other anti-diabetic drug.

Other important notes include the possibility of hypersensitivity to glimepiride or its ingredients, as well as to sulfonamide derivatives. Overdosage of glimepiride can lead to severe hypoglycemia, which constitutes a medical emergency requiring immediate treatment. Mild hypoglycemic episodes can be managed with oral glucose, while severe cases may necessitate glucagon or intravenous glucose. Continuous observation and additional carbohydrate intake may be required, as hypoglycemia can recur after initial recovery.

In pediatric patients, the profile of adverse reactions appears similar to that observed in adults. Clinical trials indicated that 4% of pediatric patients treated with glimepiride experienced hypoglycemic events, with blood glucose values falling below 36 mg/dL, compared to 1% in those treated with metformin. Notably, one patient in each treatment group experienced a severe hypoglycemic episode.

Elderly patients are at an increased risk for renal impairment, and hypoglycemia may be more challenging to recognize in this population. Caution is advised when initiating or adjusting the dose of glimepiride in elderly patients.

Lastly, neonates born to women with gestational diabetes who were treated with sulfonylureas during pregnancy may face an increased risk of complications, including admission to neonatal intensive care, respiratory distress, hypoglycemia, birth injury, and being large for gestational age. Prolonged severe hypoglycemia lasting 4 to 10 days has been reported in neonates whose mothers received sulfonylureas at the time of delivery.

Drug Interactions

Certain medications can significantly influence glucose metabolism, necessitating careful management of glimepiride therapy.

Pharmacodynamic Interactions Miconazole has been identified to cause severe hypoglycemia when used concurrently with glimepiride. Close monitoring of blood glucose levels is advised in patients receiving this combination.

Pharmacokinetic Interactions Interactions involving cytochrome P450 2C9 may also impact glimepiride's efficacy. Both inhibitors and inducers of this enzyme can alter glimepiride plasma concentrations, potentially affecting glycemic control. Therefore, it is recommended that healthcare providers monitor patients closely for changes in blood glucose levels when initiating or discontinuing such agents.

Additionally, the coadministration of colesevelam may reduce the absorption of glimepiride. To mitigate this interaction, glimepiride should be administered at least 4 hours prior to colesevelam. This timing helps ensure optimal therapeutic effectiveness of glimepiride.

Packaging & NDC

The table below lists all NDC Code configurations of Glimepiride 3 mg (glimepiride), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Glimepiride is not recommended for use in pediatric patients due to its adverse effects on body weight and the risk of hypoglycemia. The pharmacokinetics of a single 1 mg dose of glimepiride was assessed in a study involving 30 patients aged 10 to 17 years with type 2 diabetes.

In a single-blind, 24-week trial, the safety and efficacy of glimepiride were evaluated in 272 patients aged 8 to 17 years, who were randomized to receive either glimepiride (n=135) or metformin (n=137). Glimepiride was initiated at a dose of 1 mg, with titration to 2, 4, or 8 mg (mean final dose of 4 mg) by Week 12. Hypoglycemic events, defined as blood glucose values <36 mg/dL, were reported in 4% of pediatric patients treated with glimepiride, compared to 1% in those treated with metformin.

Geriatric Use

In clinical trials involving glimepiride, 30% of participants were aged 65 years and older. While no overall differences in safety or effectiveness were observed between elderly patients and their younger counterparts, it is important to note that greater sensitivity to the medication may be present in some older individuals.

Pharmacokinetic studies have shown no significant differences in the metabolism of glimepiride between patients with type 2 diabetes aged 65 years or younger and those older than 65 years. However, glimepiride is primarily excreted by the kidneys, and elderly patients are more likely to experience renal impairment, which may necessitate careful monitoring and potential dose adjustments.

Additionally, hypoglycemia can be particularly challenging to recognize in geriatric patients, increasing the risk of adverse events. Therefore, it is advised to exercise caution when initiating therapy with glimepiride or when increasing the dosage in this population. Regular monitoring for signs of hypoglycemia and renal function is recommended to ensure patient safety.

Pregnancy

Available data from a small number of published studies and postmarketing experience with glimepiride use in pregnancy over decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal outcomes. However, sulfonylureas, including glimepiride, cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia. Therefore, glimepiride should be discontinued at least two weeks before the expected delivery to mitigate these risks.

Poorly controlled diabetes in pregnancy poses significant risks to both the mother and fetus. The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes and an HbA1c >7%, escalating to as high as 20% to 25% in those with an HbA1c >10%. The estimated background risk of miscarriage in this population remains unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Poorly controlled diabetes increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Additionally, it heightens the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Neonates of women with gestational diabetes treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may experience respiratory distress, hypoglycemia, birth injury, and be large for gestational age. Prolonged severe hypoglycemia, lasting 4 to 10 days, has been reported in neonates born to mothers receiving a sulfonylurea at the time of delivery.

In animal studies, there was no increase in congenital anomalies; however, an increase in fetal deaths occurred in rats and rabbits at glimepiride doses 50 times (rats) and 0.1 times (rabbits) the maximum recommended human dose (based on body surface area). This fetotoxicity was observed only at doses inducing maternal hypoglycemia and is believed to be directly related to the pharmacologic (hypoglycemic) action of glimepiride.

Lactation

Breastfed infants of lactating mothers using glimepiride should be monitored for symptoms of hypoglycemia. It is currently unknown whether glimepiride is excreted in human milk, and there are no data available regarding its effects on milk production. However, glimepiride has been detected in rat milk, and during prenatal and postnatal studies in rats, significant concentrations of glimepiride were found in both breast milk and the serum of the pups.

The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for glimepiride and any potential adverse effects on the breastfed child. Monitoring for signs of hypoglycemia in breastfed infants is essential, with symptoms including jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, and seizures.

Additionally, offspring of rats exposed to high levels of glimepiride during pregnancy and lactation exhibited skeletal deformities, including shortening, thickening, and bending of the humerus, which were attributed to nursing from mothers treated with glimepiride.

Renal Impairment

To minimize the risk of hypoglycemia, the recommended starting dose of glimepiride for patients with type 2 diabetes and renal impairment is 1 mg daily. A multiple-dose titration study involving 16 patients with renal impairment assessed doses ranging from 1 mg to 8 mg daily over a period of 3 months, with baseline creatinine clearance values between 10 and 60 mL/min.

Pharmacokinetic evaluations from this study indicated that the relative total clearance of glimepiride increased in patients with impaired kidney function. Additionally, both the multiple-dose titration study and a single-dose study revealed that the elimination of the two major metabolites of glimepiride was reduced in patients with renal impairment. These findings underscore the importance of careful dosing adjustments and monitoring in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

An overdosage of glimepiride, similar to other sulfonylureas, can lead to significant hypoglycemia. Healthcare professionals should be vigilant for symptoms of hypoglycemia, which may range from mild to severe.

In cases of mild hypoglycemia, treatment can be effectively managed with the administration of oral glucose. However, severe hypoglycemic reactions are classified as medical emergencies and necessitate immediate intervention.

For patients experiencing severe hypoglycemia, particularly those presenting with coma, seizures, or neurological impairment, treatment options include the administration of glucagon or intravenous glucose. It is crucial to monitor the patient closely following initial treatment, as hypoglycemia may recur even after apparent clinical recovery. Continued observation and the provision of additional carbohydrate intake may be required to ensure the patient's safety and stability.

Nonclinical Toxicology

Studies conducted in rats at doses of up to 5000 parts per million (ppm) in complete feed, which is approximately 340 times the maximum recommended human dose based on surface area, for a duration of 30 months, demonstrated no evidence of carcinogenesis. In contrast, administration of glimepiride in mice over a 24-month period resulted in a dose-related increase in the formation of benign pancreatic adenomas, attributed to chronic stimulation of the pancreas. Notably, no adenoma formation was observed in mice at a dose of 320 ppm in complete feed, equivalent to 46 to 54 mg/kg body weight/day, which is at least 28 times the maximum human recommended dose of 8 mg once daily based on surface area.

Glimepiride was found to be non-mutagenic in a comprehensive array of in vitro and in vivo mutagenicity studies, including the Ames test, somatic cell mutation assays, chromosomal aberration tests, unscheduled DNA synthesis evaluations, and the mouse micronucleus test. Furthermore, there was no observed effect of glimepiride on male mouse fertility in animals exposed to doses up to 2500 mg/kg body weight, which exceeds 1,500 times the maximum recommended human dose based on surface area. Similarly, glimepiride did not impact the fertility of male and female rats administered doses up to 4000 mg/kg body weight, approximately 4,000 times the maximum recommended human dose based on surface area.

Postmarketing Experience

No specific postmarketing experience details are available in the extracted data. As such, there are no reported adverse events or case reports to summarize at this time.

Patient Counseling

Patients should be informed about the symptoms and treatment of hypoglycemia, as well as the conditions that may predispose them to this condition. It is essential for healthcare providers to explain how to recognize the signs of hypoglycemia and the appropriate steps to take if they experience these symptoms.

Healthcare providers should also advise patients that hypoglycemia can impair their ability to concentrate and react, which may pose risks in situations where these abilities are critical, such as driving or operating machinery. Patients should be made aware of the importance of monitoring their blood sugar levels and recognizing when they may need to take action to prevent hypoglycemia.

Additionally, patients should be informed about the potential for hypersensitivity reactions associated with glimepiride. They should be advised to seek medical treatment immediately if they experience any signs of a hypersensitivity reaction and to discontinue the use of glimepiride if such a reaction occurs.

Storage and Handling

The product is supplied in well-closed containers equipped with safety closures. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients should be educated on recognizing and managing hypoglycemia, as early warning symptoms may vary or be less pronounced in individuals with autonomic neuropathy, the elderly, and those taking beta-adrenergic blocking medications or other sympatholytic agents. It is essential for patients to be informed about the potential risks and benefits of glimepiride, as well as alternative treatment options.

Postmarketing experience has revealed reports of hypersensitivity reactions associated with glimepiride, including serious conditions such as anaphylaxis, angioedema, and Stevens-Johnson Syndrome. Additionally, there have been instances of hemolytic anemia in patients treated with glimepiride who did not have a known G6PD deficiency.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Glimepiride 3 mg as submitted by Lifsa Drugs LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)