Glimepiride (Lexi-Drugs)

Pronunciation

(GLYE me pye ride)

Brand Names: US

Amaryl

Brand Names: Canada

Amaryl [DSC]; APO-Glimepiride; GEN-Glimepiride; NOVO-Glimepiride [DSC]; PMS-Glimepiride [DSC]; RATIO-Glimepiride [DSC]; SANDOZ Glimepiride

Pharmacologic Category

Antidiabetic Agent, Sulfonylurea

Dosing: Adult

Diabetes mellitus, type 2: Oral:

Initial: 1 to 2 mg once daily, administered with breakfast or the first main meal; based on response, may increase dose by 1 to 2 mg every 1 to 2 weeks up to maximum of 8 mg once daily.

Conversion from therapy with long half-life agents: Observe patient carefully for hypoglycemia for 1 to 2 weeks when converting from a longer half-life agent (eg, chlorpropamide) to glimepiride due to overlapping hypoglycemic effects.

Dosing: Geriatric

Diabetes mellitus, type 2: Oral: Initial: 1 mg once daily; dose titration and maintenance dosing should be conservative to avoid hypoglycemia.

Dosing: Renal Impairment: Adult

Initial: 1 mg once daily; dose titration and maintenance dosing should be conservative to avoid hypoglycemia. Consider alternative therapy if eGFR <15 mL/minute/1.73 m2 (Alsahli 2015).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Titrate carefully due to potential for increased hypoglycemia in patients with hepatic impairment.

Use: Labeled Indications

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Clinical Practice Guidelines

Diabetes Mellitus:

American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE), “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm – 2018 Executive Summary,” January 2018

American Diabetes Association, “Standards of Medical Care in Diabetes – 2018,” January 2018

American Diabetes Association/European Association for the Study of Diabetes, “Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD),” December 2018

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Administration: Oral

Administer once daily with breakfast or first main meal of the day. Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.

Dietary Considerations

Take with breakfast or the first main meal of the day. Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage/Stability

Store at 25°C (77°F); excursions permitted between 20°C and 25°C (68°F and 77°F)

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, headache, flu-like symptoms, or weight gain. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe dizziness, passing out, shortness of breath, severe loss of strength and energy, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  High alert medication:
  International issues:
Contraindications

Hypersensitivity to glimepiride, any component of the formulation, or sulfonamides

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding; type 1 diabetes; diabetic ketoacidosis (with or without coma); severe renal or hepatic impairment

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS 1998), have not supported an association. In patients with established atherosclerotic cardiovascular disease (ASCVD), other agents are preferred (ADA 2019).

• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal or hepatic function; use with caution.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.

• Hepatic impairment: Use with caution; patients with hepatic impairment are more likely to develop hypoglycemia.

• Renal impairment: Use with caution and reduce dosage; patients with renal impairment are more likely to develop hypoglycemia.

• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Special populations:

• CYP2C9 genotype: Systemic exposure of glimepiride is increased in patients with CYP2C9*3 allele (Niemi 2002).

• Elderly: Use with caution; elderly patients are more likely to develop hypoglycemia.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis.

Geriatric Considerations

Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported with glimepiride. Age, hepatic impairment, and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How “tightly” to control a geriatric patient’s blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient’s functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% to 8.5% is acceptable for elderly patients depending on the level of comorbities, functional and cognitive status, and living situation (eg, caregiver present to assist, long-term care facility). For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control (ADA 2018b).

Pregnancy Considerations

Severe hypoglycemia lasting 4 to 10 days has been noted in infants born to mothers taking a sulfonylurea at the time of delivery. Information related to the use of glimepiride during pregnancy is limited (Balaguer Santamaria 2000; Kalyoncu 2005). If exposure during pregnancy occurs, discontinue at least 2 weeks prior to delivery.

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2018c; Metzger 2007). To prevent adverse outcomes prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2018c; Blumer 2013). Agents other than glimepiride are currently recommended to treat diabetes in pregnant women (ADA 2018c).

Breast-Feeding Considerations

It is not known if glimepiride is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Monitor the breastfed infant for signs of hypoglycemia.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%: Endocrine & metabolic: Hypoglycemia (4% to 20%)

1% to 10%:

Central nervous system: Dizziness (2%), headache

Gastrointestinal: Nausea (5%)

Hepatic: Increased serum ALT (2%)

Respiratory: Flu-like symptoms (5%)

Miscellaneous: Accidental injury (6%)

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, accommodation disturbance (early treatment), agranulocytosis, alopecia, anaphylaxis, angioedema, aplastic anemia, cholestatic jaundice, diarrhea, disulfiram-like reaction, dysgeusia, dyspnea, erythema, gastrointestinal pain, hemolytic anemia, hepatic failure, hepatic insufficiency, hepatic porphyria, hepatitis, hypersensitivity, hypersensitivity angiitis, hyponatremia, hypotension, immune thrombocytopenia, leukopenia, maculopapular rash, morbilliform rash, pancytopenia, porphyria cutanea tarda, pruritus, shock, SIADH, skin photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, urticaria, vomiting, weight gain

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2C9 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Risk C: Monitor therapy

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Risk C: Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Carbocisteine: Sulfonylureas may enhance the adverse/toxic effect of Carbocisteine. Specifically, sulfonylureas may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Risk C: Monitor therapy

Chloramphenicol (Systemic): May decrease the metabolism of Sulfonylureas. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Colesevelam: May decrease the serum concentration of Glimepiride. Management: Administer glimepiride at least 4 hours prior to colesevelam. Risk D: Consider therapy modification

Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Fluconazole: May increase the serum concentration of Sulfonylureas. Management: Seek alternatives when possible. If used together, monitor closely for increased effects of sulfonylureas if fluconazole is initiated/dose increased, or decreased effects if fluconazole is discontinued/dose decreased. Risk D: Consider therapy modification

Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination

Metreleptin: May enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Risk D: Consider therapy modification

Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Risk D: Consider therapy modification

Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

RaNITIdine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Sulfonylureas. Management: Seek alternatives to these combinations when possible. Monitor closely for diminished therapeutic effects of sulfonylureas if rifampin is initiated/dose increased, or enhanced effects if rifampin is discontinued/dose decreased. Risk D: Consider therapy modification

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Sulfonamide Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Thiazolidinediones: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Food Interactions

Ethanol may cause rare disulfiram reactions. Management: Monitor patients.

Gene Testing May Be Considered
Monitoring Parameters

Monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), blood glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2018a]), renal function

Reference Range

Recommendations for glycemic control in nonpregnant adults with diabetes (ADA 2018a):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics)

Preprandial capillary blood glucose: 80 to 130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

Recommendations for glycemic control in older adults (≥65 years) with diabetes (ADA 2018b):

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences)

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health)

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health)

Advanced Practitioners Physical Assessment/Monitoring

Assess any allergies prior to beginning therapy.

Nursing Physical Assessment/Monitoring

Allergy history should be assessed prior to beginning therapy.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Amaryl: 1 mg [scored]

Amaryl: 2 mg, 4 mg [scored; contains fd&c blue #2 aluminum lake]

Generic: 1 mg, 2 mg, 4 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Amaryl: 1 mg [DSC]

Amaryl: 2 mg [DSC], 4 mg [DSC] [contains FD&C BLUE #2 ALUMINUM LAKE]

Generic: 1 mg, 2 mg, 4 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • A10BB12
Generic Available (US)

Yes

Pricing: US

Tablets (Amaryl Oral)

1 mg (per each): $1.59

2 mg (per each): $2.58

4 mg (per each): $4.87

Tablets (Glimepiride Oral)

1 mg (per each): $0.40 – $1.08

2 mg (per each): $0.64 – $1.75

4 mg (per each): $1.22 – $3.30

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacodynamics/Kinetics

Onset of action: Peak effect: Blood glucose reductions: 2 to 3 hours

Duration: 24 hours

Absorption: 100%

Distribution: Vd: 8.8 L

Protein binding: >99.5%

Metabolism: Hepatic oxidation via CYP2C9 to M1 metabolite (~33% activity of parent compound); further oxidative metabolism to inactive M2 metabolite

Half-life elimination: 5 to 9 hours

Time to peak, plasma: 2 to 3 hours

Excretion: Urine (60%, 80% to 90% as M1 and M2 metabolites); feces (40%, 70% as M1 and M2 metabolites)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: As renal function declines, glimepiride serum levels decrease and metabolite (M1 and M2) AUC and half-lives increase. Patients with CrCl <20 mL/minute had 2.3-fold higher AUC of M1 (an active metabolite) compared to patients with CrCl >50 mL/minute.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Patients with diabetes should be questioned by the dental professional at each dental visit to assess their risk for stress-induced hypoglycemia. The dental professional should inquire about the patient’s routine (ie, work, sleep schedule, eating patterns), history of hypoglycemia, time of last medication dose, last meal, and most recent blood sugar assessment. Keep a supply of glucose tablets and other carbohydrates in the office to prepare for a hypoglycemic event. Seek medical attention when necessary (American Diabetes Association, 2018).

Effects on Bleeding

No information available to require special precautions

FDA Approval Date
November 30, 1995
References

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American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64.[PubMed 29370047]

American Diabetes Association (ADA). Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1. Accessed February 11, 2019.

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“A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53.[PubMed 992232]

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Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249.[PubMed 24194617 ]

Brackett CC, Singh H, Block JH. Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. Pharmacotherapy. 2004;24(7):856-870.[PubMed 15303450]

“Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65.[PubMed 9742977]

“Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53.[PubMed 9742976]

Johnson KK, Green DL, Rife JP, Limon L. Sulfonamide cross-reactivity: fact or fiction? [published correction appears in Ann Pharmacother. 2005;39(7-8):1373]. Ann Pharmacother. 2005;39(2):290-301.[PubMed 15644481]

Kalyoncu NI, Yaris F, Kadioglu M, et al. Pregnancy outcome following exposure to orlistat, ramipril, glimepiride in a woman with metabolic syndrome. Saudi Med J. 2005;26(3):497-499.[PubMed 15806235]

Kirkman M, Briscoe VJ, Clark N, et al, “Diabetes in Older Adults: A Consensus Report,” J Am Geriatr Soc, 2012; doi: 10.1111/jgs.12035.[PubMed 23106132]

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Niemi M, Cascorbi I, Timm R, et al, “Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes,” Clin Pharmacol Ther, 2002, 72(3):326-32.[PubMed 12235454]

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UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) [published correction appears in: Lancet. 1999;354(9178):602]. Lancet. 1998;352(9131):837-853.[PubMed 9742976]

Brand Names: International

Acotril (PH); Aforglim (PH); Amadiab (ID); Amagreen (KR); Amapirid (UA); Amarax (TH); Amarel (FR); Amarine (TW); Amaryl (AE, AR, AT, AU, BB, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, ID, IE, IL, IN, IS, IT, JM, JO, KE, KR, KW, LB, LK, LR, LT, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, PA, PE, PK, PL, PR, PT, PY, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, ZA, ZM, ZW); Amarylle (BE, LU); Amepirise (TW); Amorin (KR); Arya (PH); Aylide (AU); Azulix (BR, PH); Azulix-1 (BH, LK); Azulix-2 (BH, ZW); Azulix-4 (BH); Betaglid (HR); Betastimul (EG); Canzeal (VN); Daniglim (EG); Daol (CR, DO, GT, HN, NI, PA, SV); Diaglime (ID); Diaglip (TH); Dialosa (GR, SG); Diameril (QA); Diapirid (UA); Diapride (AU, BH, HK, JO, KW, LB, LK, SG); Diaryl (KR); Dimaril (UA); Dimirel (AU); Efinex (CR, DO, GT, HN, NI, PA, SV); Endial (AR); Euglim (IN); Fertin (LV); Getryl (PH); Getzalim (VN); Glaryl (BD, EG); Glazer (TH); Glemaz (EC); Glemep (BD); Glim (BH, QA); Glimaccord (NZ); Glimaryl (ET, HK, MY, QA, TW); Glimed 1 (LK); Glimep (KR); Glimepid (KR); Glimepigen (KR); Glimeryl (HK, JO); Glimide (PE); Glimirid (BD); Glimuilin-2 (ZW); Glimulin (VN); Glimxl (HK); Gliparil (TH); Glipiryl (ZW); Glorion (BH); Glucozen (PH); Gludine (KR); Gluvas (ID); Glypride (AE, QA); Hanmaryl (KR); Hexan (PY); K-Glim (LK); Losu-3 (TH); Mapryl (ID); Melital (AE); Mepigryl (KR); Mericle (KR); Metrix (ID); Miaryl (KR, MY); Neoacotril (PH); Norizec (PH); Oltar (LV); Orbide (LB); Pimaryl (ID); Sinperan (CR, DO, GT, HN, NI, PA, SV); Solosa (ID, PH); Sulfast (PH); Velacom (ID); Versibet (ID)

Glimepiride (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(GLYE me pye ride)

Brand Names: US

Amaryl

Brand Names: Canada

Amaryl

What is this drug used for?
  • It is used to lower blood sugar in patients with high blood sugar (diabetes).
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to glimepiride or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Acidic blood problem or type 1 diabetes.
  • If the patient is a child. Do not give this drug to a child.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • If you have a sulfa (sulfonamide) allergy, talk with your doctor.
  • Low blood sugar may happen with this drug. Very low blood sugar can lead to seizures, passing out, long lasting brain damage, and sometimes death. Talk with the doctor.
  • Check your blood sugar as you have been told by your doctor.
  • Be careful if you have G6PD deficiency. Anemia may happen.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
  • Talk with your doctor before you drink alcohol.
  • If you also take colesevelam, take it at least 4 hours after you take this drug.
  • It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
  • This drug may raise the chance of death from heart disease. Talk with your doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Very bad dizziness or passing out.
  • Shortness of breath.
  • Feeling very tired or weak.
  • Low blood sugar can happen. The chance of low blood sugar may be raised when this drug is used with other drugs for high blood sugar (diabetes). Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call your doctor right away if you have any of these signs. Follow what you have been told to do if you get low blood sugar. This may include taking glucose tablets, liquid glucose, or some fruit juices.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Upset stomach.
  • Dizziness.
  • Feeling tired or weak.
  • Headache.
  • Flu-like signs.
  • Weight gain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Take with a meal.
  • Take with the first meal of the day, if taking once a day.
  • Take this drug at the same time of day.
  • Follow the diet and workout plan that your doctor told you about.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it, with a meal.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.