Glimepiride

Class: Sulfonylureas
VA Class: HS502
Molecular Formula: C₂₄H₃₄N₄O₅S
CAS Number: 93479-97-1
Brands: Amaryl, Avandaryl

Special Alerts:

[UPDATED 02/04/2011] FDA notified healthcare professionals and patients that information on the cardiovascular risks (including heart attack) of rosiglitazone has been added to the physician labeling and patient Medication Guide. This information was first announced by FDA on September 23, 2010 as part of new restrictions for prescribing and use of this drug.

Rosiglitazone is sold as a single-ingredient product under the brand name Avandia. Rosiglitazone is also sold as a combination product under the brand name Avandamet (contains rosiglitazone and metformin) and under the brand name Avandaryl (contains rosiglitazone and glimepiride).

In addition to describing the cardiovascular risks, the drug labels have been revised to state that rosiglitazone and rosiglitazone-containing medicines should only be used:

• 
  

  In patients already being treated with these medicines

  
  


• 
  

  In patients whose blood sugar cannot be controlled with other anti-diabetic medicines and who, after consulting with their healthcare professional, do not wish to use pioglitazone-containing medicines (Actos, Actoplus Met, Actoplus Met XR, or Duetact).

  
  

For more information visit the FDA website at: and .

[Posted 09/23/2010] ISSUE: FDA notified healthcare professionals and patients that it will significantly restrict the use of the diabetes drug rosiglitazone (Avandia) to patients with Type 2 diabetes who cannot control their diabetes on other medications. These new restrictions are in response to data that suggest an elevated risk of cardiovascular events, such as heart attack and stroke, in patients treated with rosiglitazone

BACKGROUND: Rosiglitazone is in a class of drugs known as thiazolidinediones, or TZDs. It is intended to be used in conjunction with diet and exercise to improve glucose (blood sugar) control in patients with Type 2 diabetes mellitus. Rosiglitazone also is available in combination with other diabetes medications, metformin under the brand name Avandamet or glimepiride under the brand name Avandaryl.

RECOMMENDATION: FDA will require that GSK develop a restricted access program for rosiglitazone under a risk evaluation and mitigation strategy, or REMS. Under the REMS, rosiglitazone will be available to new patients only if they are unable to achieve glucose control on other medications and are unable to take pioglitazone (Actos), the only other drug in this class. Current users of rosiglitazone who are benefiting from the drug will be able to continue using the medication if they choose to do so.

Doctors will have to attest to and document their patients' eligibility; patients will have to review statements describing the cardiovascular safety concerns associated with this drug and acknowledge they understand the risks. The agency anticipates that the REMS will limit use of rosiglitazone significantly. For more information visit the FDA website at: and .

Introduction

Antidiabetic agent; sulfonylurea.^{1 53}

Uses for Glimepiride

Diabetes Mellitus

Used alone or in combination with one or more other oral antidiabetic agents or insulin as an adjunct to diet and exercise for the management of type 2 (noninsulin-dependent) diabetes mellitus (NIDDM).^{1 5 54 100 101 102 103 104 105 106 107 c}

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Use fixed combination with rosiglitazone (Avandaryl) when treatment with rosiglitazone and glimepiride is appropriate.^c Safety and efficacy of switching to the fixed combination of glimepiride and rosiglitazone in patients with type 2 diabetes mellitus previously receiving other oral antidiabetic agents not established.¹¹⁴

Metformin is the preferred initial oral antidiabetic agent for patients with type 2 diabetes mellitus.¹¹⁸ Sulfonylureas are one of several second-line classes of agents used with other antidiabetic agents (e.g., metformin) in patients who are inadequately controlled on their current therapy.¹¹⁸

Not effective as sole therapy in patients with type 1 diabetes mellitus or diabetic acidosis, ketosis, or coma; insulin is necessary.^{1 14 28 29 42 45 114 d}

Not routinely recommended in hospitalized patients with diabetes mellitus.³¹ Long duration of action precludes rapid dosage adjustments.^{1 31} Increased risk of hypoglycemia in hospitalized diabetic patients with irregular eating patterns.³¹

Glimepiride Dosage and Administration

General

• 
  

  Adjust dosage according to tolerance and fasting glucose determinations.^{1 114} Monitor regularly (e.g., fasting blood or plasma glucose determinations) to determine therapeutic response and minimum effective dosage.^{1 114} Undertake any change in therapy with care and monitor appropriately.¹¹⁴ Monitor glycosylated hemoglobin (hemoglobin A_1c, HbA_1c) every 3–6 months to determine the patient’s continued response to therapy.^{1 114}

  
  


• 
  

  Use lowest effective dosage (either as monotherapy or combined with metformin hydrochloride or insulin) to reduce both fasting glucose concentrations and HbA_1c values to normal or near normal.^{1 17 18 24 31 28}

  
  


• 
  

  Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  
  

  If inadequate glycemic control and/or secondary failure occurs during monotherapy with glimepiride, initiate add-on therapy with metformin, insulin, or rosiglitazone (e.g., as the fixed combination of glimepiride and rosiglitazone).^{1 114} With concomitant glimepiride and metformin therapy, adjust dosage to the minimum effective level for each drug.¹

  
  


• 
  

  When initiating therapy, consider the benefit-to-risk ratio of monotherapy versus combination therapy.^c

  
  

Administration

Oral Administration

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Administer glimepiride alone or in fixed combination with rosiglitazone once daily with the first main meal.^{1 5 6 114 d}

If a dose is missed, take the missed dose as soon as it is remembered.^d If the missed dose is remembered at the time of the next dose, skip missed dose and resume the regular schedule.^d Do not double dose to replace missed dose.^d

Dispensing errors have occurred involving Amaryl (the trade name for glimepiride) and Reminyl (the former trade name for galantamine hydrobromide, an acetylcholinesterase inhibitor used for treatment of Alzheimer’s dementia).^{111 112} Serious adverse events (e.g., severe hypoglycemia, death) have occurred because glimepiride was used in patients for whom the drug was not prescribed.¹¹¹ Exercise extra care in ensuring the accuracy of both oral and written prescriptions for these drugs.^{111 112} To avoid future dispensing errors, the manufacturer of Reminyl changed the trade name for galantamine hydrobromide from Reminyl to Razadyne.¹¹³

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

With the fixed combination of glimepiride and rosiglitazone maleate, dosage of rosiglitazone component expressed in terms of rosiglitazone.¹¹⁴

Adults

Diabetes Mellitus

Glimepiride Monotherapy

Oral

Initially, 1–2 mg once daily for previously untreated patients or patients transferred from other antidiabetic agents.¹ In patients receiving 1 mg daily, increase dosage to 2 mg daily after 1–2 weeks if adequate glycemic control has not been achieved.⁵³ Increase dosage in increments of no more than 2 mg daily at 1- to 2-week intervals up to a maximum of 8 mg once daily.¹ Usual maintenance dosage is 1–4 mg once daily.^{1 53}

Maximum initial dosage should not exceed 2 mg once daily.¹

Glimepiride/Rosiglitazone Fixed-combination Therapy (Avandaryl)

Oral

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Previously untreated patients: Usual initial dosage is 1 mg of glimepiride and 4 mg of rosiglitazone once daily.¹²⁰

Patients inadequately controlled on sulfonylurea or rosiglitazone monotherapy: Initially, 1 or 2 mg of glimepiride and 4 mg of rosiglitazone once daily.¹¹⁴

In patients previously receiving thiazolidinedione monotherapy, allow approximately 1–2 weeks to assess therapeutic response to newly initiated glimepiride component before adjusting dosage.¹¹⁴ If additional glycemic control is needed after 1–2 weeks, increase dosage of the glimepiride component in increments of ≤2 mg.^c Assess response to increase in glimepiride component after 1–2 weeks to determine need for further dosage adjustment.^c If additional glycemic control is needed, increase dosage of glimepiride and rosiglitazone until adequate glycemic control is achieved or maximum daily dosage of 8 mg of rosiglitazone and 4 mg of glimepiride is reached.^c

In patients previously receiving sulfonylurea monotherapy, allow 2 weeks to observe reduction in blood glucose concentrations and 2–3 months to observe full therapeutic response to newly initiated rosiglitazone component.¹¹⁴ If additional glycemic control is needed after 8–12 weeks, increase dosage of the rosiglitazone component.^c If additional glycemic control is needed 2–3 months after an increase in rosiglitazone component, increase dosage of glimepiride and rosiglitazone.^c

For replacement of concurrent therapy with the drugs given as separate tablets, dosage of the fixed combination is based on the patient’s current dosages of glimepiride and/or rosiglitazone.¹¹⁴

If hypoglycemia occurs, reduce dosage of glimepiride component.¹¹⁴

Concomitant Glimepiride and Insulin Therapy

Oral

Initially, 8 mg once daily and a low insulin dosage in patients whose fasting plasma or serum glucose concentration exceeds 150 mg/dL despite appropriate oral antidiabetic monotherapy, diet, and exercise.^{1 31}

Adjust insulin dosage upward at approximately weekly intervals until adequate glycemic control is achieved.^{1 31 53} Periodic adjustments in insulin dosage may be necessary during continued combination therapy.¹

Initial Dosage in Patients Transferred from Other Sulfonylurea Agents

Oral

Initially, 1–2 mg once daily.^{1 1 2} May discontinue other sulfonylurea agents immediately.^{1 2 3 96} During transfer from chlorpropamide (a sulfonylurea with a long elimination half-life), monitor closely for hypoglycemia during the initial 1–2 weeks of the transition period.¹

The initial dosage of glimepiride during transfer from other therapy should not exceed 2 mg daily.¹

Prescribing Limits

Adults

Diabetes Mellitus

Oral

Glimepiride monotherapy: Maximum 8 mg daily.¹

Fixed combination with rosiglitazone: Maximum 4 mg of glimepiride and 8 mg of rosiglitazone daily.¹¹⁴

Special Populations

Hepatic Impairment

Glimepiride monotherapy: Initially, 1 mg once daily.¹ Conservative initial and maintenance dosages recommended.¹

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily.¹¹⁴ Conservative initial and maintenance dosages recommended in patients with mild hepatic impairment; these individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.^c Do not initiate therapy with fixed combination of glimepiride and rosiglitazone in patients with clinical evidence of active liver disease or elevated serum aminotransferase concentrations (ALT >2.5 times ULN).¹¹⁴

Renal Impairment

Glimepiride monotherapy: Initially, 1 mg once daily.¹ Titrate dosage upward based on fasting glucose concentrations.¹ Dosages >1 mg daily may not be required if Cl_cr <22 mL/minute.^{1 8}

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily.¹¹⁴ Conservative initial and maintenance dosages recommended; individuals with renal impairment may be particularly sensitive to the hypoglycemic effects of glimepiride.^c

Geriatric Patients

Geriatric individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.^{1 114 c}

Glimepiride monotherapy: Initially, 1 mg once daily.¹ Titrate dosage upward with care.^{1 114} Conservative initial and maintenance dosages recommended.^{1 53 114}

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily.¹¹⁴ Conservative initial and maintenance dosages recommended.^c

Adrenal Insufficiency

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily.¹¹⁴ Conservative initial and maintenance dosages recommended; these individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.^c

Debilitated or Malnourished Patients

These individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.^{1 c}

Glimepiride monotherapy: Initially, 1 mg once daily.¹ Conservative initial and maintenance dosages recommended.¹

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily.¹¹⁴ Conservative initial and maintenance dosages recommended.^c

Cautions for Glimepiride

Contraindications

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  Known hypersensitivity to glimepiride or any ingredient in formulation.^{1 114 d}

  
  


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  Diabetic ketoacidosis, with or without coma.^{1 114}

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Increased cardiovascular mortality reported with certain other antidiabetic agents (i.e., tolbutamide, phenformin).^{1 99 114} However, the American Diabetes Association (ADA) considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.^{31 58 64 99}

General Precautions

Hypoglycemia

Possible severe hypoglycemia, especially in geriatric, debilitated, or malnourished patients and those with adrenal, pituitary, hepatic, or renal insufficiency.^{1 114} Increased risk of hypoglycemia with strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other oral antidiabetic agents (e.g., rosiglitazone, metformin).^{1 114}

Hypoglycemia may be difficult to recognize in geriatric patients and in those receiving β-adrenergic blocking agents.^{1 114}

Appropriate patient selection and careful dosing are important to avoid glimepiride-induced hypoglycemia.^{1 114}

Loss of Glycemic Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery); administration of insulin may be required.^{1 114} May reinstitute oral antidiabetic therapy after an acute episode has resolved.¹¹⁴

Efficacy of therapy may decrease over time (secondary failure).¹ Addition of metformin or insulin to therapy may be required.^{1 54} (See Diabetes Mellitus under Uses.)

Use of Fixed Combinations

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

When used in fixed-combination with rosiglitazone, consider the cautions, precautions, and contraindications associated with rosiglitazone.¹¹⁴

Specific Populations

Pregnancy

Category C.^{1 114}

Many experts recommend use of insulin during pregnancy to maintain optimum control of blood glucose concentrations.^{1 114 c}

Lactation

Distributed into milk in rats; other sulfonylureas distributed into human milk.¹ Use not recommended.^{1 114} If oral antidiabetic therapy discontinued and diet alone is inadequate for optimal glycemic control, consider institution of insulin.^{1 114}

Pediatric Use

Glimepiride: Safety and efficacy not established in children <16 years of age.^{1 53}

Fixed combination with rosiglitazone: Safety and efficacy not established in children <18 years of age.^{114 d}

ADA states that use of oral antidiabetic agents may be considered in children with type 2 diabetes mellitus because of the greater compliance and convenience and lack of evidence demonstrating better efficacy of insulin for type 2 diabetes mellitus.⁹³

Geriatric Use

No substantial differences in safety, efficacy, or pharmacokinetics relative to younger adults, but increased sensitivity cannot be ruled out.¹

Possible increased risk of adverse effects due to age-related decreases in renal function.¹ Renal function monitoring recommended, and care should be taken in dosage selection.¹ (See Geriatric Patients under Dosage and Administration.)

Increased risk of hypoglycemia; may be difficult to recognize in geriatric patients.¹

Hepatic Impairment

Monitor liver function in all patients receiving glimepiride in fixed combination with rosiglitazone prior to initiation of therapy and periodically thereafter.¹¹⁴ Monitor more frequently if used in patients with mild hepatic impairment (ALT ≤2.5 times the ULN).¹¹⁴ Recheck ALT as soon as possible if ALT increases to >3 times the ULN.¹¹⁴ Discontinue therapy with fixed combination if ALT remains elevated at >3 times ULN.¹¹⁴ Check liver function if manifestations suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine) occur.¹¹⁴ Decision to continue therapy pending results of laboratory tests should be guided by clinician judgment.¹¹⁴ Discontinue if jaundice develops.¹¹⁴

Increased risk of hypoglycemia; conservative dosing recommended.¹ (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance.¹

Increased risk of hypoglycemia; conservative dosing recommended.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Dizziness, asthenia, headache, nausea.¹

Interactions for Glimepiride

Metabolized by CYP2C9.^{1 114}

Drugs Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors and inducers of CYP2C9; possible alteration in metabolism of glimepiride.^{1 114}

Protein-bound Drugs

Potential pharmacokinetic interaction (increased hypoglycemic effect).^{1 114} (See Specific Drugs under Interactions.)

Close observation recommended when initiating or discontinuing concomitant therapy with a highly protein-bound drug.¹

Drugs with Hyperglycemic Effects

Potential pharmacologic interaction (loss of glycemic control).^{1 114}

Close observation recommended when initiating or discontinuing concomitant therapy.^{1 114}

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors (e.g., ramipril)	No evidence of clinically important adverse interactions in clinical studies1 114
Antifungals, oral (i.e., miconazole)	Increased hypoglycemic effect; severe hypoglycemia reported1 114	Not known whether interaction occurs with IV, topical, or vaginal antifungal dosage forms1 114
β-Adrenergic blocking agents (e.g., propranolol)	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114 Increased peak plasma concentrations and half-life and decreased clearance of glimepiride with concomitant propranolol1 114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114 Exercise caution with concomitant therapy114 No evidence of clinically important adverse interactions in clinical studies1 114
Calcium-channel blockers	No evidence of clinically important adverse interactions in clinical studies1
Chloramphenicol	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114
Corticosteroids	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
Coumarin anticoagulants (e.g., warfarin)	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114 No change in warfarin protein binding with concomitant administration but slight decrease in pharmacodynamic response1 114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114 No clinically important pharmacokinetic interaction with warfarin reported1
Diuretics (e.g., thiazides)	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
Estrogens	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114 No evidence of clinically important adverse interactions in clinical studies1
Fluconazole	Increased AUC and half-life of glimepiridea	Concomitant use may increase the risk of hypoglycemiaa
H2-receptor antagonists (e.g., cimetidine, ranitidine)	No clinically important pharmacokinetic interactions observed.1 114
HMG-CoA reductase inhibitors (statins)	No evidence of clinically important adverse interactions in clinical studies1
Hormonal contraceptives	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
Isoniazid	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
MAO inhibitors	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114
Niacin	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
NSAIAs	Potential for increased hypoglycemic effect1 114 No evidence of clinically important adverse interactions in clinical studies1	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114
Phenothiazines	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1
Phenytoin	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114
Probenecid	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114
Rifampin	Decreased AUC and half-life of glimepirideb No clinically important pharmacodynamic interactions reportedb
Salicylates (e.g., aspirin)	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114 Increased glimepiride clearance with concomitant aspirin (1 g 3 times daily); no change in blood glucose concentrations or evidence of hypoglycemia1 114	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114 No evidence of clinically important adverse interactions in clinical studies1
Sulfonamides	Highly protein-bound drugs may displace glimepiride from plasma proteins and potentiate hypoglycemic effect1 114 No evidence of clinically important adverse interactions in clinical studies1	Observe carefully for hypoglycemic effects when initiating concomitant therapy or loss of glycemic control when discontinuing such therapy1 114
Sympathomimetic agents	Potential for decreased hypoglycemic effect1 114	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1
Thyroid hormones	Potential for decreased hypoglycemic effect1 114 No evidence of clinically important adverse interactions in clinical studies1	Observe carefully for loss of glycemic control when initiating concomitant therapy or hypoglycemic effects when discontinuing such therapy1 114

Glimepiride Pharmacokinetics

Absorption

Bioavailability

Completely absorbed; oral bioavailability of 100%.^{1 114} Peak blood concentrations attained within 2–3 hours.^{1 114}

Fixed-combination preparation containing 4 mg of glimepiride and 4 mg of rosiglitazone is bioequivalent to the individual components administered separately at the same dosages in fasted state.^c

Onset

Time to maximum effect about 2–3 hours.¹

Duration

Glucose-lowering effect persists for 24 hours.¹

Food

Food increases the time to peak blood concentrations by about 12%.¹ The mean peak blood concentration and AUC are decreased by 8 and 9%, respectively.¹

Special Populations

Pediatric patients: Peak serum concentrations and AUC attained in children and adolescents 10–17 years of age were comparable to values in adults.^c

Distribution

Extent

Volume of distribution: 8.8 L (113 mL/kg).¹

Not known if glimepiride is distributed into human milk.¹

Plasma Protein Binding

>99.5%.^{1 114}

Elimination

Metabolism

Metabolized by CYP2C9 and by cytosolic enzymes to active and inactive metabolites.^{1 114}

Elimination Route

Excreted in urine (60%) and feces (40%) predominantly as metabolites.^{1 114}

Half-life

Averages 5.3 hours after a single dose in healthy individuals.¹ Averages 9.2 hours in patients with type 2 diabetes mellitus at steady state.¹

Special Populations

Renal impairment: Decreased serum drug concentrations and increased concentrations and half-lives of the metabolites.¹

Geriatric patients: At steady state, lower mean AUC (13%) and increased clearance (11%) compared with younger patients.¹¹⁴

Stability

Storage

Oral

Tablets

Glimepiride: Well-closed containers at 15–30°C.¹

Fixed combination of glimepiride and rosiglitazone: Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).^{114 d}

ActionsActions

• 
  

  Reduces both fasting and postprandial blood glucose concentrations and HbA_1c in a dose-dependent manner.^{1 5 6 20}

  
  


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  Lowers blood glucose concentration principally by stimulating postprandial secretion of endogenous insulin from the beta cells of the pancreas.^{1 9 10 11 28 54 114} Also enhances peripheral sensitivity to insulin.^{1 2 3 5 6 49 50 114}

  
  


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  Provides overall glycemic control without appreciably increasing fasting insulin secretion.^{1 2 3 5 6 49 50}

  
  


• 
  

  Ineffective in the absence of functioning beta cells.¹

  
  

Advice to Patients

• 
  

  Inform patients of the potential risks and advantages of glimepiride therapy and of alternative forms of treatment.^{1 114}

  
  


• 
  

  Importance of taking the medication each morning with breakfast or with the first main meal.^{1 114}

  
  


• 
  

  Importance of adhering to diet and exercise regimen.^{1 13 15 16 114 d}

  
  


• 
  

  Importance of hygiene and avoidance of infection.³¹

  
  


• 
  

  Advise patients about the nature of diabetes mellitus, prevention and detection of complications, and importance of glycemic control.^{18 31 22}

  
  


• 
  

  Importance of appropriate management of hypoglycemia and hyperglycemia.¹ Risks of hypoglycemia.^{1 114} Importance of patients and responsible family members understanding symptoms and treatment of hypoglycemic reactions and identifying conditions that predispose to the development of such reactions.^{1 114}

  
  


• 
  

  Importance of regular monitoring of blood glucose (preferably self-monitoring) and of HbA_1c.^{1 114 d}

  
  


• 
  

  Discuss potential for alterations in dosage requirements in special situations (e.g., illness, fever, trauma, infection, surgery); importance of informing clinician promptly if such situations occur.^d

  
  


• 
  

  Importance of understanding primary and secondary failure to therapy.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 d}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements,¹ as well as any concomitant illnesses (e.g., type 1 diabetes mellitus, kidney or liver disease).^d

  
  


• 
  

  Advise patients receiving β-adrenergic blocking agents about potential risk for hypoglycemia.¹¹⁴

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Glimepiride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	1 mg*	Amaryl (with povidone; scored)	Sanofi-Aventis
		2 mg*	Amaryl (with povidone; scored)	Sanofi-Aventis
		4 mg*	Amaryl (with povidone; scored)	Sanofi-Aventis

Glimepiride Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	2 mg with Rosiglitazone Maleate 4 mg (of rosiglitazone)	Avandaryl	GlaxoSmithKline
		2 mg with Rosiglitazone Maleate 8 mg (of rosiglitazone)	Avandaryl	GlaxoSmithKline
		4 mg with Rosiglitazone Maleate 4 mg (of rosiglitazone)	Avandaryl	GlaxoSmithKline
		4 mg with Rosiglitazone Maleate 8 mg (of rosiglitazone)	Avandaryl	GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Amaryl 1MG Tablets (SANOFI-AVENTIS U.S.): 30/$33.2 or 90/$71.49

Amaryl 2MG Tablets (SANOFI-AVENTIS U.S.): 30/$43.42 or 90/$102.15

Amaryl 4MG Tablets (SANOFI-AVENTIS U.S.): 30/$67.09 or 90/$176.55

Avandaryl 4-1MG Tablets (GLAXO SMITH KLINE): 30/$155.31 or 90/$434.86

Avandaryl 4-2MG Tablets (GLAXO SMITH KLINE): 30/$156.67 or 90/$447.65

Avandaryl 4-4MG Tablets (GLAXO SMITH KLINE): 30/$155.31 or 90/$434.86

Duetact 30-2MG Tablets (TAKEDA PHARMACEUTICALS): 30/$263.99 or 90/$766.95

Duetact 30-4MG Tablets (TAKEDA PHARMACEUTICALS): 30/$245.98 or 90/$685.99

Glimepiride 1MG Tablets (PERRIGO PHARMACEUTICALS): 30/$12.99 or 60/$19.98

Glimepiride 2MG Tablets (DR.REDDY'S LABORATORIES INC.): 90/$18.99 or 180/$37.98

Glimepiride 4MG Tablets (PERRIGO PHARMACEUTICALS): 30/$14.99 or 90/$41.99

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warr