PRALINIDE 1mg
Tablets

Anti-diabetic agents

  • Chemical Composition

    Repaglinide 1 mg

  • Packing

    30Tablets

  • Medical Id

    T62

  • License Number

    25/2008

  • License date

    5/2/2008

Mechanism Of Action Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations. Repaglinide closes ATP-dependent potassium channels in the β-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the β--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.
INDICATIONS : PRALINIDE 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. If glucose control has not been achieved after a suitable trial of combination therapy, consideration should be given to discontinuing these drugs and using insulin. Judgments should be based on regular clinical and laboratory evaluations. In initiating treatment for patients with type 2 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 blood glucose-lowering agent or insulin should be considered. Use of PRALINIDE must be viewed by both the physician and patient as a treatment in addition to diet, and not as a substitute for diet or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of PRALINIDE. During maintenance programs, PRALINIDE should be discontinued if satisfactory lowering of blood glucose is no longer achieved. Judgments should be based on regular clinical and laboratory evaluations. In considering the use of PRALINIDE or other antidiabetic therapies, it should be recognized that blood glucose control in type 2 diabetes has not been definitely established to be effective in preventing the long-term cardiovascular and neural complications of diabetes. However, in patients with Type 1 diabetes, the Diabetes Control and Complications Trial (DCCT) demonstrated that improved glycemic control, as reflected by HbA1c and fasting glucose levels, was associated with a reduction in the diabetic complications retinopathy, neuropathy, and nephropathy.
CONTRAINDICATIONS PRALINIDE is contraindicated in patients with diabetic ketoacidosis, with or without coma (this condition should be treated with insulin), and patients with Type1 diabetes. Known hypersensitivity to the drug or its inactive ingredients.
Side EFFECTS PRALINIDE side effects that may occur include increased heartbeat, headache, sweating, tremor, excessive hunger, changes in vision, nervousness, tiredness, or nasal or chest congestion. Less common and rare side effects may include allergic reactions, angina (chest pain), tooth problems, tightness in chest, trouble in breathing, vomiting, and wheezing.
WARNINGS Hypoglycemia: All oral blood glucose-lowering drugs are capable of producing hypoglycemia. Proper patient selection, dosage, and instructions to the patients are important to avoid hypoglycemic episodes. 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. The frequency of hypoglycemia is greater in patients with type 2 diabetes who have not been previously treated with oral blood glucose-lowering drugs (naïve) or whose HbA1c is less than 8%. PRALINIDE should be administered with meals to lessen the risk of hypoglycemia. Loss of control of blood glucose: 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, it may be necessary to discontinue PRALINIDE and administer insulin. The effectiveness of any hypoglycemic drug in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when the drug is first given. Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.
DRUG INTERACTIONS : In vitro data indicate that repaglinide metabolism may be inhibited by antifungal agents like ketoconazole and miconazole, and antibacterial agents like erythromycin (cytochrome P-450 enzyme system 3A4 inhibitors). Drugs that induce the cytochrome P450 enzyme system 3A4 may increase repaglinide metabolism; such drugs include rifampin, barbiturates, and carbamezapine. In vivo data from a study that evaluated the co-administration of a cytochrome P450 enzyme inhibitor, clarithromycin, with repaglinide resulted in a clinically significant increase in repaglinide plasma levels. This increase in repaglinide plasma levels may necessitate a repaglinide dose adjustment. In vivo data from a study that evaluated the co-administration of gemfibrozil with repaglinide in healthy subjects resulted in a significant increase in repaglinide blood levels. Patients taking PRALINIDE should not start taking gemfibrozil; patients taking gemfibrozil should not start taking PRALINIDE. Concomitant use may result in enhanced and prolonged blood glucose-lowering effects of repaglinide. Caution should be used in patients already on PRALINIDE and gemfibrozil - blood glucose levels should be monitored and PRALINIDE dose adjustment may be needed. Rare postmarketing events of serious hypoglycemia have been reported in patients taking PRALINIDE and gemfibrozil together. Gemfibrozil and itraconazole had a synergistic metabolic inhibitory effect on PRALINIDE. Therefore, patients taking PRALINIDE and gemfibrozil should not take itraconazole. Protein bound drugs (eg. NSAIDs, salicylates, sulfonamides, propenecid, MAO inhibitors, beta adrenergic blocking agents) may potentiate hypoglycemic effects of repaglinide. Drug \ Clinical Laboratory Test Interactions: Less common adverse clinical or laboratory events observed in clinical trials included elevated liver enzymes, thrombocytopenia, leukopenia, and anaphylactoid reactions
Pregnancy And lactations The safety of PRALINIDE administration throughout pregnancy or lactation cannot be established. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made as to whether PRALINIDE should be discontinued in nursing mothers, or if mothers should discontinue nursing. If PRALINIDE is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered. No adequate human studies on the effects of repaglinide on the fetus have been done. Therefore, physician must weigh the potential benefits and the risks of this medication when considering its use in pregnant women
Dosage And Administration : There is no fixed dosage regimen for the management of type 2 diabetes with PRALINIDE. The patient's blood glucose should be monitored 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 an adequate blood glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels are of value in monitoring the patient's longer term response to therapy. Short-term administration of PRALINIDE may be sufficient during periods of transient loss of control in patients usually well controlled on diet. PRALINIDE doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. Starting Dose: For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. 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 preprandially. Dose Adjustment: Dosing adjustments should be determined by blood glucose response, usually fasting blood glucose. Postprandial glucose levels testing may be clinically helpful in patients whose premeal blood glucose levels are satisfactory but whose overall glycemic control (HbA1c) is inadequate. 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 mg to 4 mg taken with meals. PRALINIDE 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: When PRALINIDE is used to replace therapy with other oral hypoglycemic agents, PRALINIDE may be started on the day after the final dose is given. Patients should then be observed carefully for hypoglycemia due to potential overlapping of drug effects. When transferred from longer half-life sulfonylurea agents (e.g., chlorpropamide) to repaglinide, close monitoring may be indicated for up to one week or longer. Combination Therapy: If PRALINIDE monotherapy does not result in adequate glycemic control, metformin or a thiazolidinedione may be added. If metformin or thiazolidinedione monotherapy does not provide adequate control, PRALINIDE may be added. The starting dose and dose adjustments for PRALINIDE combination therapy is the same as for PRALINIDE monotherapy. The dose of each drug should be carefully adjusted to determine the minimal dose required to achieve the desired pharmacologic effect. Failure to do so could result in an increase in the incidence of hypoglycemic episodes. Renal insufficiency. Patients with type 2 diabetes who have severe renal function impairment should initiate PRALINIDE therapy with the 0.5 mg dose – subsequently, patients should be carefully titrated. Hepatic insufficiency. PRALINIDE should be used cautiously in patients with impaired liver function. Longer intervals between dose adjustments should be utilized to allow full assessment of response.
OVERDOSE 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 (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dl.
Storage Conditions Store below 30° C. Keep out of reach of children, Protect from moisture