Novonorm

/ Novo Nordisk

Initial dose: The dosage should be determined by the physician, according to the patient’s requirements. The recommended starting dose is 0.5 mg. One to two weeks should elapse between titration steps (as determined by blood glucose response). If patients are transferred from another oral hypoglycaemic medicinal product, the recommended starting dose is 1 mg.
Maintenance: The recommended maximum single dose is 4 mg taken with main meals. The total maximum daily dose should not exceed 16 mg.
Special populations
Renal impairment: Repaglinide is primarily excreted via the bile and excretion is therefore not affected by renal disorders.
Only 8% of one dose of Repaglinide is excreted through the kidneys and total plasma clearance of the product is decreased in patients with renal impairment. As insulin sensitivity is increased in diabetic patients with renal impairment, caution is advised when titrating these patients.
Hepatic impairment: No clinical studies have been conducted in patients with hepatic insufficiency.
Elderly: No clinical studies have been conducted in patients >75 years of age or in patient with hepatic insufficiency.
Peadiatric population: 
The safety and efficacy of repaglinide in children below 18 years have not been established. No data are available.
Debilitated or malnourished patients: In debilitated or malnourished patient the initial and maintenance dosage should be conversative and careful dose titration is required to avoid hypoglycaemic reactions.
Patients receiving other oral hypoglycaemic agents (OHAs): Patients can be transferred directly from other oral hypoglycaemic medicinal products to repaglinide. However, no exact dosage relationship exists between repaglinide and the other oral hypoglycaemic medicinal products. The recommended maximum starting dose of patients transferred to repaglinide is 1 mg given before main meals.
Repaglinide can be given in combination with metformin, when blood glucose is insufficiently controlled with metformin alone. In this case, the dosage of metformin should be maintained and repaglinide administered concomitantly. The starting dose of repaglinide is 0.5 mg taken before main meals; titration is according to blood glucose response as for monotherapy.
Method of administration: Repaglinide should be taken before main meals (i.e. preprandially). 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 (i.e. preprandially 2, 3, or 4 meals a day). Patients who skip a meal (or add an extra meal) should be instructed to skip (or add) a dose for that meal.

Treatment of Type 2 diabetes. Repaglinide is indicated in patients with Type 2 diabetes (Non Insulin-Dependent Diabetes Mellitus (NIDDM)) whose hyperglycaemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Repaglinide is also indicated in combination with metformin in Type 2 diabetes patients who are not satisfactorily controlled on metformin alone. Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.

Type 1 diabetes (insulin-dependent diabetes mellitus), C-peptide negative. Diabetic keoacidosis, with or without coma. Pregnancy and lactation. Children under 12 years of age. Severe renal or hepatic function disorders. Concomitant therapy with medicdbinal products inhibiting or inducing CYP3A4.

Should only be prescribed if poor blood glucose control and symptoms of diabetes persist despite adquate attempts at dieting, exercise and weight reduction. Can produce hypoglycemia. The blood glucose lowering effect of orally hypoglycemic agents decreases in many patients over time. This may be due to progression of the severity of the diabetes or to diminished responsiveness to the product. This is known as secondary failure. Adjustment of dose and adherence to diet and exercise should be assessed before classifying a patient as a secondary failure. Combination treatment with metformin is associated with an increased risk of hypoglycemia. Patients should be advised to take precautions to avoid hypoglycemia whilst driving.
Pregnancy and lactation: Should be avoided during pregnancy and should not be used in lactating women.

Transient visual disturbances, especially at the commencement of treatment. Abdominal pain, diarrhea, nausea, vomiting and constipation. Increased liver enzymes, hypersensitivity reactions of the skin. Hypoglycemia, secondary failure.

MAOI, non-selective beta blocking agents, ACE-inhibitors, salicylates, NSAIDS, octreotide, alcohol, anabolic steroids.

Pregnancy: There are no studies of repaglinide in pregnant women. Repaglinide should be avoided during pregnancy.
Breast-feeding: There are no studies in breast-feeding women. Repaglinide should not be used in breast-feeding women.
Fertility: Studies in animals have shown reproductive toxicity

Repaglinide has been given with weekly escalating doses from 4 – 20 mg four times daily in a 6 week period. No safety concerns were raised. As hypoglycaemia in this study was avoided through increased calorie intake, a relative overdose may result in an exaggerated glucose lowering effect with the development of hypoglycaemic symptoms (dizziness, sweating, tremor, headache etc.). Should these symptoms occur, adequate action should be taken to correct the low blood glucose (oral carbohydrates). More severe hypoglycaemia with seizure, loss of consciousness or coma should be treated with i.v. glucose.