Repanid2 mg

Repanid is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Monotherapy: Repanid is FDA-approved for use alone when diet and exercise alone do not adequately control blood glucose.
• Combination therapy: Repanid is FDA-approved for use in combination with metformin, or with thiazolidinediones (e.g. pioglitazone), in patients whose type 2 diabetes is not adequately controlled on either agent alone.

Repanid is not indicated for type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Each film-coated tablet contains Repaglinide as the active ingredient, commonly available in strengths of 0.5 mg, 1 mg, and 2 mg. Tablets also contain standard inactive excipients such as microcrystalline cellulose, calcium hydrogen phosphate, maize starch, polacrilin potassium, povidone, glycerol, magnesium stearate, and coloring agents that vary by strength.

Repanid is a short-acting, rapid-onset oral antidiabetic agent belonging to the meglitinide (carbamoylmethyl benzoic acid derivative) class. Unlike sulfonylureas, Repanid has a rapid onset and short duration of action, which allows it to be dosed flexibly with meals to control post-prandial glucose excursions.

Repanid is chemically distinct from sulfonylureas and is used specifically to lower blood glucose that rises after eating, mimicking the body's natural early-phase insulin response to meals.

Repanid belongs to the meglitinide class of oral antidiabetic agents (non-sulfonylurea insulin secretagogues), used in the management of type 2 diabetes mellitus.

Mechanism of Action

Repaglinide lowers blood glucose by stimulating insulin release from the beta cells of the pancreas. It closes ATP-dependent potassium channels in the beta-cell membrane by binding at a site distinct from the sulfonylurea binding site. This channel closure depolarizes the cell, opening calcium channels; the resulting calcium influx induces insulin secretion.

Pharmacokinetics

• Onset: Rapid; insulinotropic effect occurs within about 30 minutes of dosing.
• Absorption: Rapidly absorbed after oral dosing; peak plasma concentration reached within about 1 hour.
• Duration: Short-acting; plasma levels decline rapidly, and glucose-lowering effect wanes within a few hours, mirroring meal-related insulin need.
• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4, with a minor contribution from CYP2C8, to inactive metabolites.
• Excretion: Mainly via bile/feces, with a small fraction renally excreted.
• Half-life: Approximately 1 hour.

• Take Repanid by mouth shortly before eating (within 15–30 minutes of the start of a meal).
• Take 2, 3, or 4 times daily, matching the number of meals eaten that day.
• Skip the dose if a meal is skipped; take an extra dose if an extra meal is added.
• Swallow the tablet whole with water; do not chew or crush unless advised otherwise.
• Do not take Repanid between meals or without an accompanying meal.

Gemfibrozil (Contraindicated Combination)

Concomitant use of Repanid with gemfibrozil is contraindicated. Gemfibrozil markedly inhibits the CYP2C8-mediated metabolism of Repanid, causing a large increase in Repanid plasma concentrations and a substantially increased risk of severe and prolonged hypoglycemia. This combination should be avoided entirely.

Other CYP2C8 and CYP3A4 Interactions

Drugs that inhibit CYP2C8 (e.g. trimethoprim, deferasirox) or CYP3A4 (e.g. ketoconazole, itraconazole, clarithromycin, certain protease inhibitors) can increase Repanid plasma levels and hypoglycemia risk; use with caution and monitor blood glucose closely. Drugs that induce CYP3A4/CYP2C8 (e.g. rifampin, phenytoin, carbamazepine) may reduce Repanid effectiveness.

Other Antidiabetic and Glucose-Lowering Agents

Combining Repanid with insulin, sulfonylureas, or other agents that lower blood glucose increases the risk of hypoglycemia; dose adjustment and closer monitoring are needed.

Drugs That May Increase Hypoglycemia Risk

NSAIDs, salicylates, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, and alcohol may potentiate the glucose-lowering effect of Repanid.

Drugs That May Cause Hyperglycemia

Corticosteroids, thiazide diuretics, thyroid hormones, sympathomimetics, and estrogens/oral contraceptives may reduce the glucose-lowering effect of Repanid, requiring dose review.

Cyclosporine

Cyclosporine can increase Repanid exposure; if co-administered, initiate Repanid cautiously and monitor glucose closely.

Common

• Hypoglycemia (the most common adverse effect; see Precautions and Warnings)
• Upper respiratory tract infection
• Headache
• Nausea, diarrhea, constipation, abdominal pain
• Arthralgia, back pain

Less Common / Serious

• Allergic reactions (rash, pruritus, urticaria; rarely anaphylaxis or severe cutaneous reactions)
• Elevated liver enzymes (rare reports of hepatic dysfunction)
• Cardiovascular events have been reported in trials; causal relationship to Repanid not firmly established

Pregnancy: Data on the use of Repanid in pregnant women are limited. Poorly controlled diabetes during pregnancy is itself associated with increased maternal and fetal risk, and insulin is generally the preferred agent for glycemic control during pregnancy. Repanid should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; consult a physician before use.

Lactation: It is not known whether Repanid is excreted in human breast milk; animal studies suggest excretion into milk. Because of the potential for hypoglycemia in a nursing infant, Repanid is generally not recommended during breastfeeding unless a physician determines the benefit outweighs the risk; alternative glucose-lowering therapy is usually preferred while breastfeeding.

Hypoglycemia

Like other insulin secretagogues, Repanid can cause hypoglycemia. Risk is increased by skipping or delaying meals, strenuous exercise, alcohol intake, hepatic or renal impairment, malnutrition, and use with other glucose-lowering drugs. Patients must be counseled on the "no meal, no dose" rule and taught to recognize and manage hypoglycemia symptoms.

Hepatic Impairment

Use with caution and extended dose intervals in hepatic impairment; contraindicated in severe hepatic impairment (see Contraindications).

Cardiovascular Considerations

As with other antidiabetic agents, individualized glycemic targets and monitoring are recommended, particularly in patients with cardiovascular disease.

Loss of Glycemic Control

Effectiveness may diminish over time (secondary failure) or be reduced temporarily during periods of stress (fever, trauma, infection, surgery); temporary insulin therapy may be required in such situations.

General

Repanid is not a substitute for diet and exercise in the management of type 2 diabetes; these measures should continue during treatment. Blood glucose and periodic HbA1c monitoring are recommended.

Overdose of Repanid can cause an exaggerated glucose-lowering effect, leading to hypoglycemia, which may present with sweating, tremor, palpitations, confusion, and, in severe cases, seizures or loss of consciousness.

Mild hypoglycemia can usually be managed with oral glucose or sugar-containing food. Severe or symptomatic overdose requires immediate medical attention — contact a physician, emergency services, or a poison control center right away. Do not attempt to manage a severe overdose at home; because Repanid has a short duration of action, close monitoring of blood glucose is required, and glucose administration or supportive care may need to be continued for an extended period.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric

Safety and efficacy of Repanid in patients under 18 years of age have not been established; use in children is not recommended.

Elderly

Elderly patients may be more sensitive to the glucose-lowering effect of Repanid; initiate therapy conservatively and titrate cautiously due to increased hypoglycemia risk.

Renal Impairment

Use a conservative starting dose (0.5 mg with meals) with cautious titration in patients with renal impairment, including those on dialysis, due to increased hypoglycemia risk (see Dosage and Administration).

Hepatic Impairment

Use with caution and extended titration intervals in hepatic impairment; contraindicated in severe hepatic impairment.

Pregnancy and Lactation

See Pregnancy and Lactation section.

Repanid is generally used long-term as part of ongoing management of type 2 diabetes, for as long as it continues to provide adequate glycemic control alongside diet and exercise. Duration is determined by the prescribing physician based on periodic blood glucose and HbA1c monitoring; therapy may be adjusted, combined with other agents, or discontinued based on response and tolerability.

Repaglinide is classified as a meglitinide (carbamoylmethyl benzoic acid derivative), a non-sulfonylurea insulin secretagogue used in oral antidiabetic therapy.

Repaglinide stimulates rapid, meal-time insulin release from pancreatic beta cells by binding to a specific site on the ATP-sensitive potassium (K-ATP) channel, distinct from the sulfonylurea binding site. Channel closure depolarizes the beta cell, triggering calcium influx through voltage-gated calcium channels, which in turn stimulates insulin secretion. Because this binding and the resulting insulin release are rapid and short-lived, Repaglinide closely mimics the body's normal early-phase insulin response to a meal, lowering post-prandial glucose with a low risk of prolonged inter-meal hypoglycemia when dosed correctly.

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The safety and efficacy of Repanid in pediatric patients (under 18 years) have not been established. Repanid is not recommended for use in children or adolescents.