GETFORMIN Tablet

INDICATIONS

GETFORMIN (Glimepiride + Metformin HCI) is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes whose diabetes is not adequately controlled with glimepiride or metformin HCl alone, or for those patients who have initially responded to glimepiride or metformin HCI alone and require additional glycemic control.

DOSAGE & ADMINISTRATION

Dosage must be Individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended dose. The maximum daily dose of metformin is 2000mg and of glimepiride is 8mg. The tablets should be swallowed whole and not crushed or chewed. The tablet is taken once daily with meals to a maximum of 4 tablets/day or as directed by the physician.

Glimepiride + Metformin HCI combination is contraindicated in patients with

- known hypersensitivity to sulphonylurea or biguanide or any component of the drug.

- Insulin-dependent diabetes mellitus,

- Renal or hepatic failure

- Alcoholism

- NIDDM complicated by severe ketosis and acidosis,

- Diabetes pre-coma and coma,

- Patients undergoing surgery, after severe trauma or during infections,

- Chronic obstructive pulmonary disease,

- Coronary heart disease, cardiac failure,

- Peripheral vascular disease,

- Pregnancy and lactation.

Gastrointestinal disturbances - Nausea, diarrhea, gastric pain, constipation, vomiting, metallic taste in mouth.

Dermatological effects - Rash, pruritus, urticaria, erythema and flushing.

Miscellaneous - Headache and dizziness.

Glimepiride appears to be associated with a low incidence of hypoglycemia. It has also been found to have low propensity to cause adverse cardiovascular effects. Impaired gastrointestinal absorption of vitamin B12 and folic acid has been associated with long term metformin therapy. Rarely, metformin administration has resulted in lactic acidosis.

Glimepiride

- The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory drugs and other drugs that are highly protein bound, such as salicylates, sulfonamides, chloramphenicol, coumarins, probenecid, monoamine oxidase inhibitors, and beta-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 metabolised by cytochrome P4502C9 (CYP2C9). This should be taken into account when glimepiride is coadministered with inducers, inhibitors or substrates of CYP2C9 (e.g. rifampicin, fluconazole, amiodarone, tolbutamide, diclofenac, ibuprofen, naproxen).

- H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.

- Acute and chronic alcohol intake may either potentiate or attenuate the activity of glimepiride in an unpredictable fashion.

Metformin HCI:

Drug interactions of metformin is seen with phenprocoumon, hyperglycemic agent (e.g. thiazides, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and isoniazid), alcohol, furosemide, nifedipine and cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and cimetidine, vancomycin). The absorption of metformin may be reduced by acarbose and guar gum.

Pregnancy and lactation are contraindicated.

General

Hypoglycemia may occur if the patient’s dietary intake is reduced or after accidental or deliberate overdose or after severe exercise, trauma and stress. Hypoglycemic symptoms can be reduced by prescribing a diabetic meal plan. Immediate intervention should be done if signs and symptoms of hypoglycemia occur.

Adjust dose of drug according to blood and urinary glucose levels during the first few months.

The patient's fasting blood glucose and HbA1c must be measured periodically to determine the minimum effective dose for the patient. After an Initial period of effectiveness glycosylated hemoglobin levels should be performed to monitor the patient's response to therapy.

Lactic acidosis

Lactic acidosis is rare, but serious metabolic complication that can occur due to metformin accumulation. The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.

Renal function

As metformin is excreted by the kidney, serum creatinine levels should be determined before initiating treatment and regularly thereafter.

Pediatric use

Safety and effectiveness of the drug in children have not been established.

Glimepiride:

Glimepiride is a third-generation sulphonylurea. The primary mechanism of action of Glimepiride appears to be dependent on stimulating the release of Insulin from functioning pancreatic beta cells.

In addition, extra-pancreatic effects (e.g. reduction of basal hepatic glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play role in the activity of Glimepiride.

Metformin HCI:

Metformin hydrochloride is a biguanide anti-diabetic, which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its mode of action is thought to be multifactorial and includes delayed uptake of glucose from the intestinal tract, increased peripheral glucose utilization mediated by increased insulin sensitivity and inhibition of increased hepatic and renal gluconeogenesis. Sulfonylureas and biguanides act complementary to each other. Both compounds have an additive anti-hyperglycemic effect without increasing the adverse effects of either pharmacological class.