glimepiride 4 MG Oral Tablet

Generic Name: GLIMEPIRIDE
Brand Name: Glimepiride
  • Substance Name(s):
  • GLIMEPIRIDE

DRUG INTERACTIONS

7 Certain medications may affect glucose metabolism, requiring glimepiride tablets dose adjustment and close monitoring of blood glucose ( 7.1).

Miconazole: Severe hypoglycemia can occur when glimepiride and oral miconazole are used concomitantly.

( 7.2).

Cytochrome P450 2C9 interactions: Inhibitors and inducers of cytochrome P450 2C9 may affect glycemic control by altering glimepiride plasma concentrations ( 7.3).

Colesevelam: Coadministration may reduce glimepiride absorption.

Glimepiride should be administered at least 4 hours prior to colesevelam ( 2.1, 7.4).

7.1 Drugs Affecting Glucose Metabolism A number of medications affect glucose metabolism and may require glimepiride tablets dose adjustment and particularly close monitoring for hypoglycemia or worsening glycemic control.

The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H 2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors.

When these medications are administered to a patient receiving glimepiride, monitor the patient closely for hypoglycemia.

When these medications are withdrawn from a patient receiving glimepiride, monitor the patient closely for worsening glycemic control.

The following are examples of medications that may reduce the glucose-lowering effect of sulfonylureas including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid.

When these medications are administered to a patient receiving glimepiride, monitor the patient closely for worsening glycemic control.

When these medications are withdrawn from a patient receiving glimepiride, monitor the patient closely for hypoglycemia.

Beta-blockers, clonidine, and reserpine may lead to either potentiation or weakening of glimepiride’s glucose-lowering effect.

Both acute and chronic alcohol intake may potentiate or weaken the glucose-lowering action of glimepiride in an unpredictable fashion.

The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic drugs such as beta-blockers, clonidine, guanethidine, and reserpine.

7.2 Miconazole A potential interaction between oral miconazole and sulfonylureas leading to severe hypoglycemia has been reported.

Whether this interaction also occurs with other dosage forms of miconazole is not known.

7.3 Cytochrome P450 2C9 Interactions There may be an interaction between glimepiride and inhibitors (e.g., fluconazole) and inducers (e.g., rifampin) of cytochrome P450 2C9.

Fluconazole may inhibit the metabolism of glimepiride, causing increased plasma concentrations of glimepiride which may lead to hypoglycemia.

Rifampin may induce the metabolism of glimepiride, causing decreased plasma concentrations of glimepiride which may lead to worsening glycemic control.

7.4 Concomitant Administration of Colesevelam Colesevelam can reduce the maximum plasma concentration and total exposure of glimepiride when the two are coadministered.

However, absorption is not reduced when glimepiride is administered 4 hours prior to colesevelam.

Therefore, glimepiride should be administered at least 4 hours prior to colesevelam.

OVERDOSAGE

10 An overdosage of glimepiride tablets, as with other sulfonylureas, can produce severe hypoglycemia.

Mild episodes of hypoglycemia can be treated with oral glucose.

Severe hypoglycemic reactions constitute medical emergencies requiring immediate treatment.

Severe hypoglycemia with coma, seizure, or neurological impairment can be treated with glucagon or intravenous glucose.

Continued observation and additional carbohydrate intake may be necessary because hypoglycemia may recur after apparent clinical recovery [see Warnings and Precautions ( 5.1) ].

DESCRIPTION

11 Glimepiride tablets USP, are an oral sulfonylurea that contains the active ingredient glimepiride USP.

Chemically, glimepiride USP is identified as 1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) ethyl]phenyl]sulfonyl]-3-(trans-4-methylcyclohexyl)urea (C 24H 34N 4O 5S) with a molecular weight of 490.62.

Glimepiride USP is a white to almost white, soluble in dimethyl formamide, sparingly soluble in methylene chloride, practically insoluble in water.

The structural formula is: Glimepiride tablets meets USP drug release test 2.

Glimepiride tablets USP, contain the active ingredient glimepiride USP and the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium starch glycolate.

In addition, glimepiride 1 mg tablets contain ferric oxide red, glimepiride 2 mg tablets contain lake blend green (contains D&C yellow # 10 aluminium lake and FD&C blue #1/ brilliant blue FCF aluminium lake) and glimepiride 4 mg tablets contain lake blend blue (contains D&C yellow # 10 aluminium lake and FD&C blue # 1/ brilliant blue FCF aluminium lake).

Glimepiride structural formula

CLINICAL STUDIES

14 14.1 Monotherapy A total of 304 patients with type 2 diabetes already treated with sulfonylurea therapy participated in a 14-week, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of glimepiride monotherapy.

Patients discontinued their sulfonylurea therapy then entered a 3-week placebo washout period followed by randomization into 1 of 4 treatment groups: placebo (n=74), glimepiride tablets 1 mg (n=78), glimepiride tablets 4 mg (n=76) and glimepiride tablets 8 mg (n=76).

All patients randomized to glimepiride tablets started 1 mg daily.

Patients randomized to glimepiride tablets 4 mg or 8 mg had blinded, forced titration of the glimepiride tablets dose at weekly intervals, first to 4 mg and then to 8 mg, as long as the dose was tolerated, until the randomized dose was reached.

Patients randomized to the 4 mg dose reached the assigned dose at Week 2.

Patients randomized to the 8 mg dose reached the assigned dose at Week 3.

Once the randomized dose level was reached, patients were to be maintained at that dose until Week 14.

Approximately 66% of the placebo-treated patients completed the trial compared to 81% of patients treated with glimepiride 1 mg and 92% of patients treated with glimepiride 4 mg or 8 mg.

Compared to placebo, treatment with glimepiride tablets 1 mg, 4 mg and 8 mg daily provided statistically significant improvements in HbA 1C compared to placebo (Table 3).

Table 3.

14-week Monotherapy Trial Comparing Glimepiride to Placebo in Patients Previously Treated With Sulfonylurea Therapy a Placebo (N=74) Glimepiride 1 mg (N=78) 4 mg (N=76) 8 mg (N=76) HbA 1C (%) n=59 n=65 n=65 n=68 Baseline (mean) 8 7.9 7.9 8 Change from Baseline (adjusted mean b) 1.5 0.3 -0.3 -0.4 Difference from Placebo (adjusted mean b) 95% confidence interval -1.2* (-1.5, -0.8) -1.8* (-2.1, -1.4) -1.8* (-2.2, -1.5) Mean Baseline Weight (kg) n=67 n=76 n=75 n=73 Baseline (mean) 85.7 84.3 86.1 85.5 Change from Baseline (adjusted mean b) -2.3 -0.2 0.5 1 Difference from Placebo (adjusted mean b) 95% confidence interval 2* (1.4, 2.7) 2.8* (2.1, 3.5) 3.2* (2.5, 4) aIntent-to-treat population using last observation on study bLeast squares mean adjusted for baseline value *p<0.001 A total of 249 patients who were treatment-naïve or who had received limited treatment with antidiabetic therapy in the past were randomized to receive 22 weeks of treatment with either glimepiride (n=123) or placebo (n=126) in a multicenter, randomized, double-blind, placebo-controlled, dose-titration trial.

The starting dose of glimepiride tablets was 1 mg daily and was titrated upward or downward at 2-week intervals to a goal FPG of 90 to 150 mg/dL.

Blood glucose levels for both FPG and PPG were analyzed in the laboratory.

Following 10 weeks of dose adjustment, patients were maintained at their optimal dose (1, 2, 3, 4, 6 or 8 mg) for the remaining 12 weeks of the trial.

Treatment with glimepiride provided statistically significant improvements in HbA 1C and FPG compared to placebo (Table 4).

Table 4.

22-Week Monotherapy Trial Comparing Glimepiride to Placebo in Patients Who Were Treatment-Naïve or Who Had No Recent Treatment with Antidiabetic Therapy a Placebo (N=126) Glimepiride (N=123) HbA 1C (%) n=97 n=106 Baseline (mean) 9.1 9.3 Change from Baseline (adjusted mean b) -1.1* -2.2* Difference from Placebo (adjusted mean b) 95% confidence interval -1.1* (-1.5, -0.8) Body Weight (kg) n=122 n=119 Baseline (mean) 86.5 87.1 Change from Baseline (adjusted mean b) -0.9 1.8 Difference from Placebo (adjusted mean b) 95% confidence interval 2.7 (1.9, 3.6) aIntent to treat population using last observation on study bLeast squares mean adjusted for baseline value *p<0.0001

HOW SUPPLIED

16 /STORAGE AND HANDLING Glimepiride tablets USP, are available in the following strengths and package sizes: Glimepiride tablets USP, 1 mg are peach, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “320” separating “3” and “20” with bisect line scoring on the other side and are supplied in unit dose packages of 30 (5 x 6) NDC 68084-788-25 Glimepiride tablets USP, 2 mg are green, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “321” separating “3” and “21” with bisect line scoring on the other side and are supplied in unit dose packages of 100 (10 x 10) NDC 68084-326-01 Glimepiride tablets USP, 4 mg are blue, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “322” separating “3” and “22” with bisect line scoring on the other side and are supplied in unit dose packages of 100 (10 x 10) NDC 68084-327-01 Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

GERIATRIC USE

8.5 Geriatric Use In clinical trials of glimepiride, 1053 of 3491 patients (30%) were >65 years of age.

No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

There were no significant differences in glimepiride pharmacokinetics between patients with type 2 diabetes ≤65 years (n=49) and those >65 years (n=42) [see Clinical Pharmacology ( 12.3) ].

Glimepiride is substantially excreted by the kidney.

Elderly patients are more likely to have renal impairment.

In addition, hypoglycemia may be difficult to recognize in the elderly [see Dosage and Administration ( 2.1) and Warnings and Precautions ( 5.1) ].

Use caution when initiating glimepiride and increasing the dose of glimepiride tablets in this patient population.

DOSAGE FORMS AND STRENGTHS

3 Glimepiride tablets USP, are formulated as tablets of: Glimepiride tablets USP, 1 mg are peach, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “320” separating “3” and “20” with bisect line scoring on the other side.

Glimepiride tablets USP, 2 mg are green, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “321” separating “3” and “21” with bisect line scoring on the other side.

Glimepiride tablets USP, 4 mg are blue, oval, flat beveled edged, uncoated tablets debossed “RDY” on one side and “322” separating “3” and “22” with bisect line scoring on the other side.

Tablets (scored): 1 mg, 2 mg, 4 mg ( 3)

MECHANISM OF ACTION

12.1 Mechanism of Action Glimepiride primarily lowers blood glucose by stimulating the release of insulin from pancreatic beta cells.

Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.

INDICATIONS AND USAGE

1 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) ].

Glimepiride tablets are a sulfonylurea indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ( 1.1).

Important Limitations of Use: Not for treating type 1 diabetes mellitus or diabetic ketoacidosis ( 1.1).

1.1 Important 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.

PEDIATRIC USE

8.4 Pediatric Use The pharmacokinetics, efficacy and safety of glimepiride have been evaluated in pediatric patients with type 2 diabetes as described below.

Glimepiride tablets are not recommended in pediatric patients because of its adverse effects on body weight and hypoglycemia.

The pharmacokinetics of a 1 mg single dose of glimepiride was evaluated in 30 patients with type 2 diabetes (male = 7; female = 23) between ages 10 and 17 years.

The mean (± SD) AUC (0-last) (339±203 ng•hr/mL), C max (102±48 ng/mL) and t 1/2 (3.1±1.7 hours) for glimepiride were comparable to historical data from adults (AUC (0-last) 315±96 ng•hr/mL, C max 103±34 ng/mL and t 1/2 5.3±4.1 hours).

The safety and efficacy of glimepiride in pediatric patients was evaluated in a single-blind, 24-week trial that randomized 272 patients (8 to 17 years of age) with type 2 diabetes to glimepiride (n=135) or metformin (n=137).

Both treatment-naïve patients (those treated with only diet and exercise for at least 2 weeks prior to randomization) and previously treated patients (those previously treated or currently treated with other oral antidiabetic medications for at least 3 months) were eligible to participate.

Patients who were receiving oral antidiabetic agents at the time of study entry discontinued these medications before randomization without a washout period.

Glimepiride was initiated at 1 mg, and then titrated up to 2, 4 or 8 mg (mean last dose 4 mg) through Week 12, targeting a self-monitored fasting fingerstick blood glucose < 126 mg/dL.

Metformin was initiated at 500 mg twice daily and titrated at Week 12 up to 1000 mg twice daily (mean last dose 1365 mg).

After 24 weeks, the overall mean treatment difference in HbA 1c between glimepiride and metformin was 0.2%, favoring metformin (95% confidence interval -0.3% to +0.6%).

Based on these results, the trial did not meet its primary objective of showing a similar reduction in HbA 1c with glimepiride compared to metformin.

Table 2.

Change from Baseline in HbA 1C and Body Weight in Pediatric Patients Taking Glimepiride or Metformin Metformin Glimepiride Treatment-Naïve Patients* N=69 N=72 HbA 1C (%) Baseline (mean) 8.2 8.3 Change from baseline (adjusted LS mean) + -1.2 -1 Adjusted Treatment Difference** (95%CI) 0.2 (-0.3; 0.6) Previously Treated Patients* N=57 N=55 HbA 1C (%) Baseline (mean) 9 8.7 Change from baseline (adjusted LS mean) + -0.2 0.2 Adjusted Treatment Difference** (95%CI) 0.4 (-0.4; 1.2) Body Weight (kg)* N=126 N=129 Baseline (mean) 67.3 66.5 Change from baseline (adjusted LS mean)+ 0.7 2 Adjusted Treatment Difference** (95% CI) 1.3 (0.3; 2.3) * Intent-to-treat population using last-observation-carried-forward for missing data (Glimepiride, n=127; metformin, n=126) + adjusted for baseline HbA 1c and Tanner Stage ** Difference is glimepiride – metformin with positive differences favoring metformin The profile of adverse reactions in pediatric patients treated with glimepiride was similar to that observed in adults [see Adverse Reactions ( 6) ].

Hypoglycemic events documented by blood glucose values <36 mg/dL were observed in 4% of pediatric patients treated with glimepiride and in 1% of pediatric patients treated with metformin.

One patient in each treatment group experienced a severe hypoglycemic episode (severity was determined by the investigator based on observed signs and symptoms).

PREGNANCY

8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of glimepiride in pregnant women.

In animal studies there was no increase in congenital anomalies, but 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, observed only at doses inducing maternal hypoglycemia, is believed to be directly related to the pharmacologic (hypoglycemic) action of glimepiride and has been similarly noted with other sulfonylureas.

Glimepiride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Because data suggest that abnormal blood glucose during pregnancy is associated with a higher incidence of congenital abnormalities, diabetes treatment during pregnancy should maintain blood glucose as close to normal as possible.

Nonteratogenic Effects: Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers receiving a sulfonylurea at the time of delivery.

NUSRING MOTHERS

8.3 Nursing Mothers It is not known whether glimepiride tablets are excreted in human milk.

During pre- and post-natal studies in rats, significant concentrations of glimepiride were present in breast milk and the serum of the pups.

Offspring of rats exposed to high levels of glimepiride during pregnancy and lactation developed skeletal deformities consisting of shortening, thickening, and bending of the humerus during the postnatal period.

These skeletal deformations were determined to be the result of nursing from mothers exposed to glimepiride.

Based on these animal data and the potential for hypoglycemia in a nursing infant, a decision should be made whether to discontinue nursing or discontinue glimepiride, taking into account the importance of glimepiride to the mother.

WARNING AND CAUTIONS

5 WARNINGS AND PRECAUTIONS Hypoglycemia: May be severe.

Ensure proper patient selection, dosing, and instructions, particularly in at-risk populations (e.g., elderly, renally impaired) and when used with other anti-diabetic medications ( 5.1).

Hypersensitivity Reactions: Postmarketing reports include anaphylaxis, angioedema and Stevens-Johnson Syndrome.

Promptly discontinue glimepiride, assess for other causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes ( 5.2).

Hemolytic Anemia: Can occur if glucose 6-phosphate dehydrogenase (G6PD) deficient.

Consider a non-sulfonylurea alternative.

( 5.3).

Potential Increased Risk of Cardiovascular Mortality with Sulfonylureas: Inform patient of risks, benefits and treatment alternatives ( 5.4).

Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with glimepiride or any other anti-diabetic drug ( 5.5).

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 tablets 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 Hemolytic Anemia Sulfonylureas can cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.

Because glimepiride tablets are 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.

INFORMATION FOR PATIENTS

17 PATIENT COUNSELING INFORMATION 17.1 Information for Patients Inform patients about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose.

Inform patients about the potential side effects of glimepiride including hypoglycemia and weight gain.

Explain the symptoms and treatment of hypoglycemia as well as conditions that predispose to hypoglycemia.

Patients should be informed that the ability to concentrate and react may be impaired as a result of hypoglycemia.

This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.

Patients with diabetes should be advised to inform their healthcare provider if they are pregnant, contemplating pregnancy, breastfeeding, or contemplating breastfeeding.

Rx only PACKAGING INFORMATION American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Dr.

Reddy’s Laboratories Limited as follows: (1 mg / 30 UD) NDC 68084-788-25 packaged from NDC 55111-320 (2 mg / 100 UD) NDC 68084-326-01 packaged from NDC 55111-321 (4 mg / 100 UD) NDC 68084-327-01 packaged from NDC 55111-322 Distributed by: American Health Packaging Columbus, OH 43217 8232601/1215OS

DOSAGE AND ADMINISTRATION

2 Recommended starting dose is 1 or 2 mg once daily.

Increase in 1 or 2 mg increments no more frequently than every 1 to 2 weeks based on glycemic response.

Maximum recommended dose is 8 mg once daily ( 2.1).

Administer with breakfast or first meal of the day ( 2.1).

Use 1 mg starting dose and titrate slowly in patients at increased risk for hypoglycemia (e.g., elderly, patients with renal impairment) ( 2.1).

2.1 Recommended Dosing Glimepiride tablets should be administered with breakfast or the first main meal of the day.

The recommended starting dose of glimepiride tablets are 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 to 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 from longer half-life sulfonylureas (e.g., chlorpropamide) may have overlapping drug effect for 1 to 2 weeks and should be appropriately monitored for hypoglycemia.

When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced.

Therefore, glimepiride tablets should be administered at least 4 hours prior to colesevelam.