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Uses

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).

Use fixed combination with rosiglitazone (Avandaryl^®) when treatment with rosiglitazone and glimepiride is appropriate. 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.

Metformin is the preferred initial oral antidiabetic agent for patients with type 2 diabetes mellitus. 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.

Not effective as sole therapy in patients with type 1 diabetes mellitus or diabetic acidosis, ketosis, or coma; insulin is necessary.

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

Dosage and Administration

General

• Adjust dosage according to tolerance and fasting glucose determinations. Monitor regularly (e.g., fasting blood or plasma glucose determinations) to determine therapeutic response and minimum effective dosage. Undertake any change in therapy with care and monitor appropriately. Monitor glycosylated hemoglobin (hemoglobin A_1c, HbA_1c) every 3–6 months to determine the patient’s continued response to therapy.
• 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.
• 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). With concomitant glimepiride and metformin therapy, adjust dosage to the minimum effective level for each drug.
• When initiating therapy, consider the benefit-to-risk ratio of monotherapy versus combination therapy.

Administration

Oral Administration

Administer glimepiride alone or in fixed combination with rosiglitazone once daily with the first main meal.

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

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). Serious adverse events (e.g., severe hypoglycemia, death) have occurred because glimepiride was used in patients for whom the drug was not prescribed. Exercise extra care in ensuring the accuracy of both oral and written prescriptions for these drugs. To avoid future dispensing errors, the manufacturer of Reminyl^® changed the trade name for galantamine hydrobromide from Reminyl^® to Razadyne^®.

Dosage

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

Adults

Diabetes Mellitus

Glimepiride Monotherapy

Oral

Initially, 1–2 mg once daily for previously untreated patients or patients transferred from other antidiabetic agents. In patients receiving 1 mg daily, increase dosage to 2 mg daily after 1–2 weeks if adequate glycemic control has not been achieved. 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. Usual maintenance dosage is 1–4 mg once daily.

Maximum initial dosage should not exceed 2 mg once daily.

Glimepiride/Rosiglitazone Fixed-combination Therapy (Avandaryl^®)

Oral

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

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

In patients previously receiving thiazolidinedione monotherapy, allow approximately 1–2 weeks to assess therapeutic response to newly initiated glimepiride component before adjusting dosage. If additional glycemic control is needed after 1–2 weeks, increase dosage of the glimepiride component in increments of ≤2 mg. Assess response to increase in glimepiride component after 1–2 weeks to determine need for further dosage adjustment. 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.

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. If additional glycemic control is needed after 8–12 weeks, increase dosage of the rosiglitazone component. If additional glycemic control is needed 2–3 months after an increase in rosiglitazone component, increase dosage of glimepiride and rosiglitazone.

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.

If hypoglycemia occurs, reduce dosage of glimepiride component.

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.

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

Initial Dosage in Patients Transferred from Other Sulfonylurea Agents

Oral

Initially, 1–2 mg once daily. May discontinue other sulfonylurea agents immediately. 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.

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

Prescribing Limits

Adults

Diabetes Mellitus

Oral

Glimepiride monotherapy: Maximum 8 mg daily.

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

Special Populations

Dosage in Hepatic Impairment

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

Fixed-combination preparation with rosiglitazone: Initially, 1 mg of glimepiride and 4 mg of rosiglitazone daily. Conservative initial and maintenance dosages recommended in patients with mild hepatic impairment; these individuals may be particularly sensitive to the hypoglycemic effects of glimepiride. 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).

Dosage in Renal Impairment

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

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

Geriatric Patients

Geriatric individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.

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

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

Adrenal Insufficiency

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

Debilitated or Malnourished Patients

These individuals may be particularly sensitive to the hypoglycemic effects of glimepiride.

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

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