Amaryl (Glimepiride) - Indications and Dosage

INDICATIONS AND USAGE

AMARYL is indicated as an adjunct to diet and exercise to lower the blood glucose in patients with noninsulin-dependent (Type 2) diabetes mellitus (NIDDM) whose hyperglycemia cannot be controlled by diet and exercise alone. AMARYL may be used concomitantly with metformin when diet, exercise, and AMARYL or metformin alone do not result in adequate glycemic control.

AMARYL is also indicated for use in combination with insulin to lower blood glucose in patients whose hyperglycemia cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic agent. Combined use of glimepiride and insulin may increase the potential for hypoglycemia.

In initiating treatment for noninsulin-dependent diabetes, diet and exercise should be emphasized as the primary form of treatment. Caloric restriction, weight loss, and exercise are essential in the obese diabetic patient. Proper dietary management and exercise alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. In addition to regular physical activity, cardiovascular risk factors should be identified and corrective measures taken where possible.

If this treatment program fails to reduce symptoms and/or blood glucose, the use of an oral sulfonylurea or insulin should be considered. Use of AMARYL must be viewed by both the physician and patient as a treatment in addition to diet and exercise and not as a substitute for diet and exercise or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet and exercise alone may be transient, thus requiring only short-term administration of AMARYL.

During maintenance programs, AMARYL monotherapy should be discontinued if satisfactory lowering of blood glucose is no longer achieved. Judgments should be based on regular clinical and laboratory evaluations. Secondary failures to AMARYL monotherapy can be treated with AMARYL-insulin combination therapy.

In considering the use of AMARYL in asymptomatic patients, it should be recognized that blood glucose control in Type 2 diabetes has not definitely been established to be effective in preventing the long-term cardiovascular and neural complications of diabetes. However, the Diabetes Control and Complications Trial (DCCT) demonstrated that control of HbA_1c and glucose was associated with a decrease in retinopathy, neuropathy, and nephropathy for insulin-dependent diabetic (IDDM) patients.

DOSAGE AND ADMINISTRATION

There is no fixed dosage regimen for the management of diabetes mellitus with AMARYL or any other hypoglycemic agent. The patient's fasting blood glucose and HbA_1c must be measured periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of adequate blood glucose lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels should be performed to monitor the patients response to therapy.

Short-term administration of AMARYL may be sufficient during periods of transient loss of control in patients usually controlled well on diet and exercise.

Usual Starting Dose

The usual starting dose of AMARYL as initial therapy is 1–2 mg once daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1 mg once daily, and should be titrated carefully. (See PRECAUTIONS Section for patients at increased risk.)

No exact dosage relationship exists between AMARYL and the other oral hypoglycemic agents. The maximum starting dose of AMARYL should be no more than 2 mg.

Failure to follow an appropriate dosage regimen may precipitate hypoglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy.

Usual Maintenance Dose

The usual maintenance dose is 1 to 4 mg once daily. The maximum recommended dose is 8 mg once daily. After reaching a dose of 2 mg, dosage increases should be made in increments of no more than 2 mg at 1–2 week intervals based upon the patient's blood glucose response. Long-term efficacy should be monitored by measurement of HbA_1c levels, for example, every 3 to 6 months.

AMARYL-Metformin Combination Therapy

If patients do not respond adequately to the maximal dose of AMARYL monotherapy, addition of metformin may be considered. Published clinical information exists for the use of other sulfonylureas including glyburide, glipizide, chlorpropamide, and tolbutamide in combination with metformin.

With concomitant AMARYL and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant AMARYL and metformin therapy, the risk of hypoglycemia associated with AMARYL therapy continues and may be increased. Appropriate precautions should be taken.

AMARYL-Insulin Combination Therapy

Combination therapy with AMARYL and insulin may also be used in secondary failure patients. The fasting glucose level for instituting combination therapy is in the range of >150 mg/dL in plasma or serum depending on the patient. The recommended AMARYL dose is 8 mg once daily administered with the first main meal. After starting with low-dose insulin, upward adjustments of insulin can be done approximately weekly as guided by frequent measurements of fasting blood glucose. Once stable, combination-therapy patients should monitor their capillary blood glucose on an ongoing basis, preferably daily. Periodic adjustments of insulin may also be necessary during maintenance as guided by glucose and HbA_1c levels.

Specific Patient Populations

AMARYL (glimepiride tablets) is not recommended for use in pregnancy or nursing mothers. Data are insufficient to recommend pediatric use of AMARYL. In elderly, debilitated, or malnourished patients, or in patients with renal or hepatic insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. (See CLINICAL PHARMACOLOGY, Special Populations and PRECAUTIONS, General.)

Patients Receiving Other Oral Hypoglycemic Agents

As with other sulfonylurea hypoglycemic agents, no transition period is necessary when transferring patients to AMARYL. Patients should be observed carefully (1–2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to AMARYL due to potential overlapping of drug effect.

HOW SUPPLIED

AMARYL tablets are available in the following strengths and package sizes:

1 mg (pink, flat-faced, oblong with notched sides at double bisect, imprinted with "AMA RYL" on one side)
Bottles of 100 (NDC 0039-0221-10)

2 mg (green, flat-faced, oblong with notched sides at double bisect, imprinted with "AMA RYL" on one side)
Bottles of 100 (NDC 0039-0222-10)

4 mg (blue, flat-faced, oblong with notched sides at double bisect, imprinted with "AMA RYL" on one side)
Bottles of 100 (NDC 0039-0223-10)