Getryl

Glimepiride.

Glimepiride is an oral blood glucose-lowering drug of the sulfonylurea class. Glimepiride is 1-[[p-[2-(3-Ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido) ethyl]-sulphonyl]-3-(trans-4-methylcyclohexyl)urea. The molecular formula is C₂₄H₃₄N₄O₅S.

Oral hypoglycemic agent.
Pharmacology: Mechanism of Action: The primary mechanism of action of glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic β-cells.
In addition, extra-pancreatic effects (eg, reduction of basal hepatic glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play a role in the activity of glimepiride.
However, as with other sulfonylureas, the mechanism by which glimepiride lowers blood glucose during long-term administration has not been clearly established.
Pharmacokinetics: After oral administration, glimepiride is completely absorbed from the GI tract. The oral bioavailability is approximately 100%. Peak plasma concentrations occur in 2-3 hrs. More than 99% of the drug is bound to plasma proteins. Glimepiride is completely metabolized by oxidative biotransformation into 2 main metabolites, a hydroxy derivative and a carboxy derivative.
The elimination t_½ after multiple doses is about 5-8 hrs. Approximately 60% of dose is eliminated in the urine and 40% in the feces.
Specific Populations: Renal Insufficiency: A single-dose clinical study of glimepiride showed that glimepiride serum levels decreased as renal function decreased. However, metabolites serum levels (mean AUC values) increased. The apparent terminal t_½ for glimepiride did not change, while the half-lives for metabolites increased as renal function decreased. Mean urinary excretion of metabolites as percent of dose, however, decreased.

Adjunct to diet and exercise to lower the blood glucose in patients with non-insulin dependent (Type 2) diabetes mellitus (NIDDM) whose hyperglycemia cannot be controlled by diet and exercise alone.
Getryl may be used concomitantly with metformin when diet, exercise and getryl or metformin alone do not result in adequate glycemic control.
Getryl 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.

In initiating treatment for NIDDM, diet and exercise should be emphasized as the primary form of treatment. There is no fixed dosage regimen for the management of diabetes mellitus with Getryl 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.
Short-term administration of Getryl may be sufficient during periods of transient loss of control in patients usually controlled well on diet and exercise.
Usual Starting Dose: 1-2 mg once daily, administered with breakfast or the 1st 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. The maximum starting dose of glimepiride should not be >2 mg.
Usual Maintenance Dose: 1-4 mg once daily. The maximum recommended dose is 8 mg once daily. After reaching a dose of 2 mg, dose increases should be made in increments of >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 eg, every 3-6 months.
Getryl-Metformin Combination Therapy: If patients do not respond adequately to the maximum dose of Getryl monotherapy, addition of metformin may be considered.
With concomitant Getryl and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug.
Getryl-Insulin Combination Therapy: Combination therapy with Getryl 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.
Recommended Getryl Dose: 8 mg once daily administered with the 1st 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.
Special Populations: In elderly, debilitated or malnourished patients, or in patients with hepatic insufficiency, the initial dosing, dose increments and maintenance dosage should be conservative to avoid hypoglycemic reactions.
Renally Impaired Patients: In patients with mild to moderate renal impairment, a starting dose of 1 mg once daily must not be exceeded. The dose may then be carefully titrated upwards if necessary based on fasting blood glucose levels in increments of 1 mg at intervals of 1-2 weeks.

Patients with diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.

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, ie, inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, ie, loss of adequate blood glucose lowering response. After an initial period of effectiveness glycosylated hemoglobin levels should be performed to monitor the patient's response to therapy.
Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage and instructions are important to avoid hypoglycemic episodes.
Debilitated patients, malnourished patients and patients with adrenal, pituitary, renal or hepatic insufficiency are paticularly susceptible to the hypoglycemic action of sulfonylureas and should therefore be carefully monitored. The dosage of glimepiride should be carefully adjusted in these patients.
Hepatic insufficiency may cause increased serum concentrations of glimepiride and may diminish gluconeogenic capacity, both of which increase the risk of severe hypoglycemic reactions.
Alcohol ingestion, severe or prolonged exercise, deficient caloric intake or use of >1 antidiabetic agent may predispose patients to the development of hypoglycemia.
Loss of Control of Blood Glucose: When a patient stabilized on any diabetic regimen is exposed to stress eg, fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to add insulin in combination with glimepiride or even use insulin monotherapy.
Use in pregnancy: Glimepiride is not recommended for use during pregnancy.
Use in lactation: It is not known whether glimepiride is distributed into human breast milk. However, some sulfonylureas are distributed into human breast milk. Because of its potential to cause hypoglycemia in nursing infants, glimepiride is not recommended for use by nursing mothers.
Use in children: Glimepiride is not recommended for use in children.

Use in pregnancy: Glimepiride is not recommended for use during pregnancy.
Use in lactation: It is not known whether glimepiride is distributed into human breast milk. However, some sulfonylureas are distributed into human breast milk. Because of its potential to cause hypoglycemia in nursing infants, glimepiride is not recommended for use by nursing mothers.

Glimepiride is generally well-tolerated. However, following are the side effects reported during treatment with glimepiride.
Hypoglycemia: The greatest potential risk with all sulfonylureas.
Visual Reactions: There may be temporary visual impairment (eg, changes in accommodation and/or blurred vision) due to the change in blood glucose levels, especially at the start of treatment.
Gastrointestinal Reactions: Occasionally, GI symptoms eg, nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain and diarrhea may occur.
Hematologic Reactions: Rarely, thrombocytopenia and in isolated cases, leukopenia may develop. In isolated instances, thrombocytopenic purpura, agranulocytosis, pancytopenia due to myelosuppression, eosinophilia, hemolytic anemia, aplastic anemia, erythrocytopenia and granulocytopenia may occur.
Dermatologic Reactions: Occasionally, allergic or pseudo-allergic skin reactions (eg, pruritus, erythema, urticaria, erythematous and maculo-papular and bullous skin eruptions or psoriasiform drug eruption) may occur in patients treated with sulfonylureas.
Hepatic Reactions: Increased liver enzymes (AST, ALT), abnormal liver function, cholestasis, cholestatic aernia, hepatitis, granulomatous hepatitis, bilirubinemia and liver failure have been reported with sulfonylureas in isolated cases.
Electrolyte Disturbance: In isolated cases, hyponatremia has been reported in patients receiving glimepiride and other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or to increase release of antidiuretic hormone.
Others: Isolated cases of allergic vasculitis have been reported with sulfonylureas.

The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including NSAIDs and other drugs that are highly protein bound, eg, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, MAOIs and β-adrenergic blocking agents. When these drugs are administered to a patient receiving glimepiride, the patient should be observed closely for hypoglycemia.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, and isoniazid. When these drugs are administered to a patient receiving glimepiride, the patient should be closely observed for loss of control.
Glimepiride is metabolized by cytochrome P-450 2C9 (CYP2C9). This should be taken into account when glimepiride is co-administered with inducers, inhibitors or substrate of CYP2C9 (eg, rifampicin, fluconazole, amiodarone, tolbutamide, diclofenac, ibuprofen, naproxen).
H₂-receptor antagonists, β-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
Concomitant treatment with a β-receptor blocker, clonidine, guanethidine or reserpine may mask the warning symptoms of a hypoglycemic attack.
Acute and chronic alcohol intake may either potentiate or attenuate the activity of glimepiride in an unpredictable fashion.

Store at temperatures not exceeding 30°C. Protect from sunlight and moisture.

Antidiabetic Agents

A10BB12 - glimepiride ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.

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