ded 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 agent 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.
Specific patient groups
Repaglinide is primarily excreted via the bile and excretion is therefore not affected by renal disorders.
Eight percent 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.
No clinical studies have been conducted in patients> 75 years of age or in patients with hepatic insufficiency (see section 4.4).
Repaglinide is not recommended for use in children below age 18 due to a lack of data on safety and/or efficacy.
In debilitated or malnourished patients the initial and maintenance dosage should be conservative 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 agents to repaglinide. However, no exact dosage relationship exists between repaglinide and the other oral hypoglycaemic agents. 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 the 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.
4.3 Contraindications
• Hypersensitivity to repaglinide or to any of the excipients in NovoNorm
• Type 1 diabetes (Insulin-Dependent Diabetes Mellitus: IDDM), C-peptide negative
• Diabetic ketoacidosis, with or without coma
• Severe hepatic function disorder
• Concomitant use of gemfibrozil (see section 4.5).
4.4 Special warnings and precautions for use
General
Repaglinide should only be prescribed if poor blood glucose control and symptoms of diabetes persist despite adequate attempts at dieting, exercise and weight reduction.
Repaglinide like other insulin secretagogues, is capable of producing hypoglycaemia.
The blood glucose-lowering effect of oral hypoglycaemic 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 phenomenon is known as secondary failure, to distinguish it from primary failure, where the drug is ineffective in an individual patient when first given. Adjustment of dose and adherence to diet and exercise should be assessed before classifying a patient as a secondary failure.
Repaglinide acts through a distinct binding site with a short action on the β-cells. Use of repaglinide in case of secondary failure to insulin secretagogues has not been investigated in clinical trials.
Trials investigating the combination with other insulin secretagogues and acarbose have not been performed.
Trials of combina |
