Repaglinide is an oral blood-glucose-lowering drug of the meglitinide class used in the management of Type 2 diabetes mellitus (NIDDM). Repaglinide works by causing pancreas to release more insulin into the blood stream which possesses rapid onset of action and rapid elimination.
Repaglinide is indicated as an adjunct to diet and exercise to lower the blood glucose in patients with type 2 diabetes mellitus (NIDDM) whose hyperglycemia cannot be controlled satisfactorily by diet and exercise alone. It is also indicated for use in combination with Metformin to lower blood glucose in patients whose hyperglycemia cannot be controlled by exercise, diet, and either Repaglinide or Metformin alone.
Repaglinide binds to specific receptors in the cell membrane leading to the closure of ATP dependent K+ channels and the depolarisation of cell membrane. This in turn, leads to Ca++ influx, increased intracellular Ca++ and the stimulation of insulin secretion.
For patients not previously treated or whose HbA1c is <8%, the starting dose should be 0.5 mg before each meal.
For patients previously treated with blood glucose-lowering drugs and whose HbA1c is >8%, the initial dose is 1 or 2 mg before each meal.
Repaglinide should be taken immediately or up to 30 minutes before each meal.
Dosage should be adjusted according to response at intervals of 1-2 weeks; up to 4 mg may be given as a single-dose, maximum 16 mg daily.
The dose of Repaglinide may need to be adjusted, if taken with other medications. The possible interactions of Repaglinide with other drugs are:
Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Repaglinide clearance and longer half life.
Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Repaglinide metabolism and shorten its effect.
Cimetidine has no significant effect on Repaglinide absorption or clearance.
Repaglinide has no significant effect on Digoxin, Theophyllin, or Warfarin.
Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Repaglinide and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Repaglinide may increase the risk of hypoglycaemia.
The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.
Repaglinide is contraindicated in patients with:
Diabetic ketoacidosis, with or without coma.
Type 1 diabetes mellitus and
Known hypersensitivity to the drug or its inactive ingredients.
The most common side effects of Repaglinide are hypoglycemia and related symptoms. Others include upper respiratory tract infections, diarrhea, constipation, nausea and vomiting. Hypersensitivity reactions include rashes and urticaria.
Safety in pregnant women has not been established. Repaglinide should be used during pregnancy only if it is clearly needed. It is not known whether Repaglinide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Repaglinide, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Insulin should be substituted during concurrent illness (such as myocardial infarction, coma, infection, and trauma) and during surgery. All oral blood glucose-lowering drugs are capable of producing hypoglycemia. Repaglinide should be administered with meals to lessen the risk of hypoglycemia.
Patients receiving up to 80 mg of Repaglinide developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.
