glimepiride

glimepiride

(glye meh' per ide)

Amaryl

Pregnancy Category C

Drug classes

Antidiabetic

Sulfonylurea (second generation)

Therapeutic actions

Stimulates insulin release from functioning beta cells in the pancreas; may improve binding between insulin and insulin receptors or increase the number of insulin receptors; thought to be more potent in effect than first-generation sulfonylureas.

Indications

·        As an adjunct to diet to lower blood glucose in patients with type 2 (non–insulin-dependent) diabetes mellitus whose hypoglycemia cannot be controlled by diet and exercise alone

·        In combination with metformin or insulin to better control glucose as an adjunct to diet and exercise in patients with type 2 diabetes mellitus

Contraindications and cautions

·        Contraindicated with allergy to sulfonylureas; diabetes complicated by fever, severe infections, severe trauma, major surgery, ketosis, acidosis, coma (insulin is indicated in these conditions); type 1 (insulin-dependent) diabetes, serious hepatic or renal impairment, uremia, thyroid or endocrine impairment, glycosuria, hyperglycemia associated with primary renal disease; labor and delivery—if glimepiride is used during pregnancy, discontinue drug at least 1 mo before delivery; lactation, safety not established.

·        Use cautiously with pregnancy.

Available forms

Tablets—1, 2, 4 mg

Dosages

ADULTS

Usual starting dose is 1–2 mg PO once daily with breakfast or first meal of the day; usual maintenance dose is 1–4 mg PO once daily, depending on patient response and glucose levels. Do not exceed 8 mg/day.

·        Combination with insulin therapy: 8 mg PO daily with first meal of the day with low-dose insulin.

·        Transfer from other hypoglycemic agents: No transition period is necessary.

PEDIATRIC PATIENTS

Safety and efficacy not established.

PATIENTS WITH RENAL IMPAIRMENT

Usual starting dose is 1 mg PO once daily; titrate dose carefully, lower maintenance doses may be sufficient to control blood sugar.

Pharmacokinetics

Route	Onset	Peak
Oral	2–3 hr	2–3 hr

Metabolism: Hepatic; T_1/2: 5.5–7 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Bile, urine

Adverse effects

·        CNS: Drowsiness, asthenia, nervousness, tremor, insomnia

·        CV: Increased risk of cardiovascular mortality (possible)

·        Endocrine: Hypoglycemia, SIADH

·        GI: Anorexia, nausea, vomiting, epigastric discomfort, heartburn, diarrhea

·        Hematologic: Leukopenia, thrombocytopenia, anemia

·        Hypersensitivity: Allergic skin reactions, eczema, pruritus, erythema, urticaria, photosensitivity, fever, eosinophilia, jaundice

·        Other: Diuresis, tinnitus, fatigue, weight gain

Interactions

Drug-drug

·        Increased risk of hypoglycemia with androgens, anticoagulants, azole antifungals, chloramphenicol, clofibrate, fenfluramine, fluconazole, gemfibrozil, H₂blockers, magnesium salts, MAOIs, methyldopa, oxyphenbutazone, phenylbutazone, probenecid, salicylates, sulfinpyrazone, sulfonamides, TCAs, urinary acidifiers

·        Decreased effectiveness of both glimepiride and diazoxide if taken concurrently

·        Increased risk of hyperglycemia with rifampin, thiazides

·        Risk of hypoglycemia and hyperglycemia with ethanol; "disulfiram reaction" has also been reported

·        Possible decreased hypoglycemic effect with beta blockers, calcium channel blockers, cholestyramine, corticosteroids, diazoxide, estrogens, hydantoins, hormonal contraceptives, isoniazid, nicotinic acid, phenothiazines, rifampin, sympathomimetics, thiazide diuretics, thyroid agents, urinary alkalinizers

Drug-alternative therapy

·        Increased risk of hypoglycemia if taken with juniper berries, ginseng, garlic, fenugreek, coriander, dandelion root, celery

Nursing considerations

Assessment

·        History: Allergy to sulfonylureas; diabetes complicated by fever, severe infections, severe trauma, major surgery, ketosis, acidosis, coma (insulin is indicated in these conditions); type 1 diabetes, serious hepatic or renal impairment, uremia, thyroid or endocrine impairment, glycosuria, hyperglycemia associated with primary renal disease; pregnancy

·        Physical: Skin color, lesions; T; orientation, reflexes, peripheral sensation; R, adventitious sounds; liver evaluation, bowel sounds; urinalysis, BUN, serumcreatinine, LFTs, blood glucose, CBC

Interventions

·        Monitor urine or serum glucose levels frequently to determine effectiveness of drug and dosage being used.

·        WARNING: Transfer to insulin therapy during periods of high stress (eg infections, surgery, trauma).

·        Use IV glucose if severe hypoglycemia occurs as a result of overdose.

·        Arrange for consultation with dietitian to establish weight-loss program and dietary control.

·        Arrange for thorough diabetic teaching program, including disease, dietary control, exercise, signs and symptoms of hypoglycemia and hyperglycemia, avoidance of infection, hygiene.

Teaching points

·        Take this drug once a day with breakfast or the first main meal of the day.

·        Do not discontinue this drug without consulting your health care provider; continue with diet and exercise program for diabetes control.

·        Monitor urine or blood for glucose and ketones as prescribed.

·        Do not use this drug if you are pregnant.

·        Avoid alcohol while using this drug.

·        Report fever, sore throat, unusual bleeding or bruising, rash, dark urine, light-colored stools, hypoglycemic or hyperglycemic reactions.

Adverse effects in Italic are most common; those in Bold are life-threatening.