Glimepiride 3 Mg - Glimepiride tablet

Glimepiride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see

• 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 Recommended Dosing

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

  The recommended starting dose of glimepiride tablets 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 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.
  )
• Administer with breakfast or first meal of the day. (
  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 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 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.
  )
• Use 1 mg starting dose and titrate slowly in patients at increased risk for hypoglycemia (e.g., elderly, patients with renal impairment). (
  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 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 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.
  )

Glimepiride is formulated as tablets of:

• 3 mg (Pale yellow colored, flat capsule shaped uncoated tablets having break line on both faces and GM and 3 engraved on either side of break line on one face.)

• Pediatric Patients: Not recommended because of adverse effects on body weight and hypoglycemia. (
  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 is 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 to 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 to 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-naive 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 HbA1c 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 HbA1c with glimepiride compared to metformin.

  Table 2: Change from Baseline in HbA1C and Body Weight in Pediatric Patients Taking Glimepiride or Metformin
  	Metformin	Glimepiride
  Treatment-Naive Patients*	N=69	N=72
  HbA1C (%)
  Baseline (mean)	8.2	8.3
  Change from baseline (adjusted LS mean)+	-1.2	-1.0
  Adjusted Treatment Difference‡(95%CI)	0.2 (-0.3; 0.6)
  Previously Treated Patients*	N=57	N=55
  HbA1C (%)
  Baseline (mean)	9.0	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	2.0
  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 HbA1cand 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).
  )
• Geriatric or Renally Impaired Patients: At risk for hypoglycemia with glimepiride. Use caution in dose selection and titration, and monitor closely. (
  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 in this patient population.
  ,
  8.6 Renal Impairment

  To minimize the risk of hypoglycemia, the recommended starting dose of glimepiride is 1 mg daily for all patients with type 2 diabetes and renal impairment [see

  Dosage and Administration (2.1)

  and

  Warnings and Precautions (5.1)

  ]

  .

  A multiple-dose titration study was conducted in 16 patients with type 2 diabetes and renal impairment using doses ranging from 1 mg to 8 mg daily for 3 months. Baseline creatinine clearance ranged from 10 to 60 mL/min. The pharmacokinetics of glimepiride were evaluated in the multiple-dose titration study and the results were consistent with those observed in patients enrolled in a single-dose study. In both studies, the relative total clearance of glimepiride increased when kidney function was impaired. Both studies also demonstrated that the elimination of the two major metabolites was reduced in patients with renal impairment [see

  Clinical Pharmacology (12.3)

  ].
  )

• 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 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.
  ).
• Hypersensitivity Reactions: Postmarketing reports include anaphylaxis, angioedema and Stevens-Johnson Syndrome. If a reaction is suspected, promptly discontinue glimepiride, assess for other potential causes for the reaction, and institute alternative treatment for diabetes. (
  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

  [see Adverse Reactions (6.2)].

  If a hypersensitivity reaction is suspected, promptly discontinue glimepiride, assess for other potential causes for the reaction, and institute alternative treatment for diabetes.
  )
• Hemolytic Anemia: Can occur if glucose 6-phosphate dehydrogenase (G6PD) deficient. Consider a non-sulfonylurea alternative. (
  5.3 Hemolytic Anemia

  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)

  ].
  )
• Potential Increased Risk of Cardiovascular Mortality with Sulfonylureas: Inform patient of risks, benefits and treatment alternatives. (
  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 and a half 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.
  )
•  Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with glimepiride or any other anti-diabetic drug (
  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.
  ).