Each tablet contains Repaglinide 1.0 mg.
The tablet can be divided into equal doses.
Excipients/Inactive Ingredients: Poloxamer 188, microcrystalline cellulose, croscarmellose sodium, magnesium stearate.
Pharmacology: Pharmacodynamics: Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta-cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations.
Repaglinide closes ATP-dependent potassium channels in the beta-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the beta-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle.
Pharmacokinetics: Repaglinide is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 hr. The mean bioavailability is about 60%. Repaglinide is highly bound to plasma proteins and has a plasma elimination half-life of about 1 hr. It undergoes almost complete hepatic metabolism involving the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. The metabolites, which are inactive, are excreted in the bile. Higher plasma concentrations and prolonged half-life of repaglinide may occur in patients with renal impairment (creatinine clearance less than 40 mL/minute) or chronic liver disease.
Pranstad 1 is used as monotherapy as an adjunct to diet and exercise for the management of type 2 (non-insulin dependent) diabetes mellitus (NIDDM) in patients whose hyperglycemia cannot be controlled by diet, and exercise alone.
Pranstad 1 also may be used in combination with metformin in patients who do not achieve adequate glycemic control with diet, exercise and monotherapy with metformin, a sulfonylurea, repaglinide or a thiazolidinedione antidiabetic agent.
Starting dose: For patients not previously treated or whose HbA1C is <8%: The starting dose should be 0.5 mg with each meal preprandial.
For patients previously treated with blood glucose-lowering drugs and whose HbA1C is ≥8%: The initial dose is 1 or 2 mg with each meal preprandial.
Dose Adjustment: Dosing adjustments should be determined by blood glucose response, usually fasting blood glucose.
The preprandial dose should be doubled up to 4 mg with each meal until satisfactory blood glucose response is achieved. At least one week should elapse to assess response after each dose adjustment.
The recommended dose range is 0.5 to 4 mg. Pranstad 1 may be dosed preprandially 2, 3 or 4 times a day in response to changes in the patient's meal pattern. The maximum recommended daily dose is 16 mg.
Patients receiving other oral hypoglycemic agents: Patients can be transferred directly from other oral hypoglycaemic agents to repaglinide. The recommended maximum starting dose of patients transferred to repaglinide is 1 mg given before main meals.
Combination with metformin: Dosage of each drug should be adjusted to obtain adequate glycemic control, using the minimum effective dosage of each drug.
Specific Patient Groups: Patients with severe renal impairment e.g., creatinine clearance of 20-40 mL/minute should initiate therapy with a repaglinide dose of 0.5 mg with subsequent careful dosage titration.
No clinical studies have been performed in children and adolescents <18 years or in patients >75 years of age. Therefore, treatment is not recommended in these patient groups.
Administration: Pranstad 1 is administered orally given within 15 minutes of each meal but may be given as early as 30 minutes prior to each meal up to immediately preceding each meal.
Acute repaglinide overdosage is manifested principally as hypoglycemia.
Hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery. There is no evidence that repaglinide is dialyzable using hemodialysis.
Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of (concentrated 50%) glucose solution. This should be followed by a continuous infusion of more dilute (concentrated 10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL.
Patients with known hypersensitivity to the drug.
Patients with type 1 diabetes.
Patients with diabetes complicated by acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma; insulin should be used to treat these conditions.
Repaglinide is not indicated for use in combination with NPH-insulin.
All oral blood glucose-lowering drugs including repaglinide are capable of producing hypoglycemia.
Hepatic insufficiency may cause elevated repaglinide blood levels and may diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemia.
Elderly, debilitated or malnourished patients and those with adrenal, pituitary, hepatic or severe renal insufficiency may be particularly susceptible to the hypoglycemic action of glucose lowering drugs.
Hypoglycemia may be difficult to recognize in the elderly and in people taking beta-adrenergic-blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested or when more than one glucose-lowering drug is used.
When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection or surgery, a loss of glycemic control may occur. At such times, repaglinide may be necessary to discontinue and administer insulin.
Effects on the ability to drive and use machines: Patients should be advised to take precautions to avoid hypoglycemia whilst driving.
This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycemia or have frequent episodes of hypoglycemia. The advisability of driving should be considered in these circumstances.
Pregnancy: The safety of repaglinide in pregnant women has not been established and the drug should be used during pregnancy only when clearly needed.
Since abnormal maternal blood glucose concentrations during pregnancy may be associated with a higher incidence of congenital abnormalities, most experts recommend that insulin be used during pregnancy to maintain optimum control of blood glucose concentration.
Lactation: Because of the potential for repaglinide to cause hypoglycemia and resultant skeletal changes in nursing infants may exist, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. If repaglinide is discontinued and diet therapy alone does not provide adequate glycemic control, insulin therapy should be instituted.
Common (1/100 ≤ ADR < 1/10): Metabolism:
Upper respiratory tract infection, sinusitis, rhinitis, bronchitis.
Arthralgia, back pain.
Uncommon (1/1,000 ≤ ADR < 1/100): Gastrointestinal:
Constipation, vomiting, dyspepsia.
Paresthesia, chest pain, urinary tract infection, allergy.
Drugs effecting hepatic microsomal enzymes: Concomitant administration of repaglinide with drugs that induce the CYP3A4 or CYP2C8 isoenzyme (such as troglitazone, rifampin, barbiturates and carbamazepine) may theoretically increase repaglinide metabolism.
Concomitant administration of repaglinide with drugs that inhibit the CYP2C8 isoenzyme e.g., gemfibrozil, trimethoprim or montelukast, may increase the drug's plasma concentrations.
Protein-bound drugs: Salicylates or other nonsteroidal anti-inflammatory agents (NSAIAs), sulfonamides, probenecid, chloramphenicol, oral anticoagulants (e.g., warfarin), monoamine oxidase inhibitors, certain HMG-CoA reductase inhibitors, and beta-adrenergic-blocking agents. When such drugs are initiated or withdrawn in patients receiving repaglinide, the patient should be observed for evidence of hypoglycemia or loss of glycemic control.
Other drugs: Drugs that cause hyperglycemia and may exacerbate glycemic control in patients with diabetes mellitus include corticosteroids, niacin, thiazides and other diuretics, oral contraceptives, sympathomimetics, thyroid preparations, estrogens, phenytoin, phenothiazines, calcium-channel blocking agents and isoniazid.
Do not store above 30°C. Store in a well-closed container, in a dry place, protect from light.
Shelf-Life: 36 months from the date of manufacturing.
A10BX02 - repaglinide ; Belongs to the class of other blood glucose lowering drugs excluding insulins. Used in the treatment of diabetes.
Tab 1 mg (white, round-shaped, scored on one side, plain on the other side) x 3 x 10's, 6 x 10's.