NovoNorm^® (Tablets) Instructions for Use

ATC Code

A10BX02 (Repaglinide)

Active Substance

Repaglinide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Oral hypoglycemic agent

Pharmacological Action

Oral hypoglycemic agent. It rapidly reduces blood glucose levels by stimulating the release of insulin from functioning pancreatic beta-cells.

The mechanism of action is associated with the ability to block ATP-dependent channels in the membranes of beta-cells by acting on specific receptors, which leads to cell depolarization and the opening of calcium channels.

As a result, the increased influx of calcium induces insulin secretion by beta-cells.

After taking repaglinide, the insulinotropic response to food intake is observed within 30 minutes, leading to a decrease in blood glucose levels.

No increase in insulin concentration is noted between meals.

In patients with type 2 diabetes mellitus, dose-dependent reduction in blood glucose levels is observed when taking repaglinide in doses from 500 mcg to 4 mg.

Pharmacokinetics

After oral administration, Repaglinide is rapidly absorbed from the gastrointestinal tract, with C_max reached within 1 hour after administration; then the plasma level of repaglinide decreases rapidly and becomes very low after 4 hours.

No clinically significant differences in the pharmacokinetic parameters of repaglinide were noted when taken immediately before a meal, 15 and 30 minutes before a meal, or on an empty stomach.

Plasma protein binding is more than 90%.

V_d is 30 L (which is consistent with distribution in the interstitial fluid).

Repaglinide is almost completely biotransformed in the liver to form inactive metabolites.

Repaglinide and its metabolites are excreted primarily in the bile, less than 8% in the urine (as metabolites), and less than 1% in the feces (unchanged). T_1/2 is about 1 hour.

Indications

Type 2 diabetes mellitus (when diet therapy, weight loss, and physical exercise are ineffective) as monotherapy or in combination with metformin or thiazolidinediones in cases where satisfactory glycemic control cannot be achieved with monotherapy using repaglinide, metformin, or thiazolidinediones.

ICD codes

Dosage Regimen

Administer orally, immediately before main meals (typically 15-30 minutes prior). The regimen is an adjunct to diet and physical exercise.

Initiate therapy at a starting dose of 0.5 mg before each meal. The frequency of administration depends on the number of daily meals; administer up to three or four times per day.

Individually titrate the dose at 1-2 week intervals based on blood glucose monitoring. Adjust the pre-meal dose in steps of 0.5 mg or 1 mg.

The maximum single dose is 4 mg. The maximum recommended daily dose is 16 mg.

For patients previously treated with other oral hypoglycemic agents, initiate with a 1 mg dose. A dose adjustment period is required when switching from other medications.

If a meal is skipped, omit the corresponding dose. If an extra meal is added, administer an additional dose.

For patients with renal impairment or hepatic impairment, initiate therapy at the 0.5 mg dose and titrate cautiously. Closely monitor glycemic control.

Adverse Reactions

Immune system disorders : very rarely – generalized hypersensitivity reactions; frequency unknown – pruritus, skin rash, urticaria.

Metabolism and nutrition disorders: often – hypoglycemia; frequency unknown – hypoglycemic coma, hypoglycemia with loss of consciousness.

Eye disorders: very rarely – visual disturbances, especially at the initial stage of therapy (usually transient).

Gastrointestinal disorders: often – abdominal pain, diarrhea; very rarely – vomiting, constipation; frequency unknown – nausea, pancreatitis.

Hepatobiliary disorders increased activity of “liver” enzymes, severe liver dysfunction, including hepatitis and jaundice.

Other frequency unknown – alopecia, hemolytic anemia, Stevens-Johnson syndrome.

Contraindications

Hypersensitivity to repaglinide; type 1 diabetes mellitus, diabetic ketoacidosis, diabetic precoma and coma; infectious diseases, major surgical interventions and other conditions requiring insulin therapy; severe liver dysfunction; simultaneous use of gemfibrozil; pregnancy, breastfeeding period; age under 18 years and over 75 years.

With caution in mild to moderate liver dysfunction, febrile syndrome, chronic renal failure, alcoholism, general severe condition, malnutrition.

Use in Pregnancy and Lactation

The use of repaglinide during pregnancy is contraindicated. If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction. Should be used with caution in mild to moderate liver dysfunction.

Use in Renal Impairment

Should be used with caution in chronic renal failure,

Pediatric Use

Contraindicated in children and adolescents under 18 years of age, due to the lack of sufficient data on the safety and efficacy of repaglinide in this patient group.

Geriatric Use

Contraindicated in patients over 75 years of age, due to the lack of sufficient data on the safety and efficacy of repaglinide in this patient group.

Special Precautions

Repaglinide is indicated for unsatisfactory glycemic control and persistence of diabetes symptoms despite diet therapy and physical exercise.

In cases of liver or kidney disease, extensive surgical interventions, recent illness or infection, the effectiveness of repaglinide may be reduced.

It is necessary to regularly monitor fasting and postprandial blood glucose concentrations. The patient should be warned about the increased risk of hypoglycemia in cases of alcohol consumption, NSAID use, and fasting.

In debilitated patients or undernourished patients, Repaglinide should be administered at the minimum initial and maintenance doses. To prevent hypoglycemic reactions in this category of patients, the dose should be selected with caution.

Occurring hypoglycemic conditions are usually of moderate severity and are easily controlled by carbohydrate intake. In severe conditions, intravenous glucose administration may be necessary. The likelihood of developing such reactions depends on the dose, dietary habits, intensity of physical exercise, and stress.

It should be taken into account that beta-blockers may mask the symptoms of hypoglycemia.

Effect on ability to drive vehicles and operate machinery

During the use of repaglinide, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Enhancement of the hypoglycemic effect of repaglinide is possible with simultaneous use of gemfibrozil, trimethoprim, rifampicin, clarithromycin, ketoconazole, itraconazole, cyclosporine, deferasirox, clopidogrel, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, salicylates, NSAIDs, octreotide, anabolic steroids, ethanol.

Reduction of the hypoglycemic effect of repaglinide is possible with simultaneous use of oral hormonal contraceptives, thiazide diuretics, corticosteroids, danazol, thyroid hormones, sympathomimetics (when prescribing or discontinuing these drugs, the state of carbohydrate metabolism should be carefully monitored).

When repaglinide is used concomitantly with drugs that are primarily excreted in the bile, the possibility of potential interaction between them should be considered.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.