glimepiride 1 MG Tablet Oral
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When these medications are withdrawn from a patient receiving glimepiride, monitor the patient closely for worsening glycemic control.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 24 H 34 N 4 O 5 S) with a molecular weight of 490.62.
Glimepiride USP is a white to almost white powder, 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).
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 Intent-to-treat population using last observation on study 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 Least squares mean adjusted for baseline value ) 1.5 0.3 -0.3 -0.4 Difference from Placebo (adjusted mean ) 95% confidence interval -1.2 p<0.001 (-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 ) -2.3 -0.2 0.5 1 Difference from Placebo (adjusted mean ) 95% confidence interval 2 (1.4, 2.7) 2.8 (2.1, 3.5) 3.2 (2.5, 4) 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 Intent to treat population using last observation on study Placebo (N=126) Glimepiride (N=123) HbA 1C (%) n=97 n=106 Baseline (mean) 9.1 9.3 Change from Baseline (adjusted mean Least squares mean adjusted for baseline value ) -1.1 p<0.0001 -2.2 Difference from Placebo (adjusted mean ) 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 ) -0.9 1.8 Difference from Placebo (adjusted mean ) 95% confidence interval 2.7 (1.9, 3.6)
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) ].
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 tablets are 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 ).
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 Intent-to-treat population using last-observation-carried-forward for missing data (Glimepiride, n=127; metformin, n=126) N=69 N=72 HbA 1C (%) Baseline (mean) 8.2 8.3 Change from baseline (adjusted LS mean) adjusted for baseline HbA1c and Tanner Stage -1.2 -1 Adjusted Treatment Difference Difference is glimepiride – metformin with positive differences favoring metformin (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) 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 Risk Summary 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 tablets should be discontinued at least two weeks before expected delivery (see Clinical Considerations).
Poorly controlled diabetes in pregnancy is also associated with risks to the mother and fetus (see Clinical Considerations).
In animal studies (see Data), there were no effects on embryo-fetal development following administration of glimepiride to pregnant rats and rabbits at oral doses approximately 4,000 times and 60 times the maximum human dose based on body surface area, respectively.
However, fetotoxicity was observed in rats and rabbits at doses 50 times and 0.1 times the maximum human dose, respectively.
The estimated background risk of major birth defects is 6% to 10% in women with pregestational diabetes with a HbA 1c >7% and has been reported to be as high as 20% to 25% in women with a HbA 1c >10%.
The estimated background risk of miscarriage for the indicated population is 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.
Clinical Considerations Disease-associated maternal and/or embryo-fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications.
Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia-related morbidity.
Fetal/neonatal adverse reactions Neonates of women with gestational diabetes who are treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop 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 and has been reported with the use of agents with a prolonged half-life.
Observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly.
Dose adjustments during pregnancy and the postpartum period Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at the time of delivery, glimepiride tablets should be discontinued at least two weeks before expected delivery (see Fetal/Neonatal Adverse Reactions).
Data Animal data 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 was observed only at doses inducing maternal hypoglycemia and is believed to be directly related to the pharmacologic (hypoglycemic) action of glimepiride, as has been similarly noted with other sulfonylureas.
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.
If a reaction is suspected, promptly discontinue glimepiride, assess for other potential causes for the reaction, and institute 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 [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.
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 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.
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 Hypoglycemia Explain the symptoms and treatment of hypoglycemia as well as conditions that predispose to hypoglycemia.
Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia and that this may present a risk in situations where these abilities are especially important, such as driving or operating other machinery [see Warnings and Precautions (5.1) ].
Hypersensitivity Reactions Inform patients that hypersensitivity reactions may occur with glimepiride and that if a reaction occurs to seek medical treatment and discontinue glimepiride [see Warnings and Precautions (5.2) ].
Pregnancy Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1) ].
Lactation Advise breastfeeding women taking glimepiride tablets to monitor breastfed infants for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures) [see Use in Specific Populations (8.2) ].
Rx only
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.