Dosing and uses of Amaryl (glimepiride)
Adult dosage forms and strengths
tablet
- 1mg
- 2mg
- 4mg
Type 2 Diabetes Mellitus
Initial: 1-2 mg PO qAM after breakfast or with first meal; may increase dose by 1-2 mg every 1-2 weeks; not to exceed 8 mg/day
Conversion from other oral hypoglycemic agents
- Observe patients carefully for 1-2 weeks when being converted from long half-life sulfonylureas to glimepiride, because of potential for overlapping of hypoglycemic effects
Dosing considerations
- Use in monotherapy or, if glycemic response to glimepiride is inadequate at maximum dose, with insulin or metformin
Dosing Modifications
Renal impairment: 1 mg PO qDay; titrate dose based on fasting blood glucose levels
Hepatic impairment: Not studied; not recommended in severe impairment; initiate therapy with 1 mg PO qDay and titrate carefully
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Prolonged hypoglycemia reported with use; titrate dose conservatively; monitor for hypoglycemic or hyperglycemic symptoms
Type 2 Diabetes Mellitus
1 mg PO qDay; titrate dose at weekly intervals to avoid hypoglycemia
Amaryl (glimepiride) adverse (side) effects
>10%
Hypoglycemia (4-20%)
1-10%
Dizziness (1.7%)
Asthenia (1.6%)
Headache (1.5%)
Nausea (1.1%)
<1%
Allergic skin reactions
Erythema
Morbilliform or maculopapular eruptions
Pruritus
Urticaria
Diarrhea
Gastrointestinal pain
Vomiting
Agranulocytosis
Anemia
Aplastic anemia
Leukopenia
Pancytopenia
Thrombocytopenia, hemolytic
Cholestasis
Elevation of liver enzyme levels
Hepatic porphyria reactions
Jaundice (rare)
Disulfiram-like reactions
Hyponatremia
Postmarketing Reports
Serious hypersensitivity reactions, including anaphylaxis, angioedema, and Stevens- Johnson Syndrome
Hemolytic anemia in patients with and without G6PD deficiency
Hepatic impairment (eg, cholestasis, jaundice), as well as hepatitis, which may progress to liver failure
Porphyria cutanea tarda, photosensitivity reactions and allergic vasculitis
Leukopenia, agranulocytosis, aplastic anemia, and pancytopenia
Thrombocytopenia (including severe cases with platelet count <10,000/mcL) and thrombocytopenic purpura
Hepatic porphyria reactions and disulfiram-like reactions
Hyponatremia and SIADH, most often in patients on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone
Warnings
Contraindications
Hypersensitivity; sulfa allergy
Type 1 diabetes
Diabetic ketoacidosis (with or without coma)
Complicated gestational diabetes mellitus
Cautions
Patients with risk of severe hypoglycemia: Elderly, debilitated, or malnourished; adrenal or pituitary insufficiency; patients with stress due to infection, fever, trauma, or surgery
If patient is exposed to stress, it may be necessary to discontinue glimepiride and initiate insulin
Use caution in hepatic/renal impairment
Pregnancy, lactation
Increased risk of cardiovascular mortality
Persons allergic to other sulfonamide derivatives may develop allergic reaction to glimepiride
Hypoglycemia may be difficult to recognize in patients with autonomic neuropathy
Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents
Fluid retention, which may exacerbate or lead to heart failure, may occur
Combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk of other cardiovascular effects
Potential risk of ischemic cardiovascular (CV) events relative to placebo reported in meta-analysis studies, but not confirmed in long-term CV outcome trial versus metformin or sulfonylurea
Dose-related edema, weight gain, and anemia may occur
Macular edema reported
Increased incidence of bone fracture reported
Postmarketing reports for glimepiride include anaphylaxis, angioedema, and Stevens-Johnson syndrome; promptly discontinue glimepiride, assess for other causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in milk unknown; avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Amaryl (glimepiride)
Mechanism of action
Initial effect to increase insulin secretion from beta cells; may also decrease rate of hepatic glucose production and increase insulin receptor sensitivity
Absorption
Bioavailability: 100%
Initial effect: 1 hr
Peak plasma time: 2-3 hr
Max effect: 2-4 hr
Duration: 24 hr
Distribution
Vd: 8.8 L
Protein bound: 99.5%
Metabolism
Metabolized extensively by hepatic P450 enzyme CYP2C9 to less-active metabolites
Metabolites: Cyclohexyl hydroxy methyl derivative (M1; mildly active) and the carboxyl derivative (M2; inactive)
Elimination
Half-life: 5-9 hr
Total body clearance: 47.8 mL/min
Excretion: Urine (60%); feces (40%)
