Active Ingredient: Glibenclamide
Glibenclamide is indicated for the treatment of neonatal diabetes mellitus, for use in newborns, infants and children.
Sulphonylureas like glibenclamide have been shown to be effective in patients with mutations in the genes coding for the β-cell ATP-sensitive potassium channel and chromosome 6q24-related transient neonatal diabetes mellitus.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: In case that patient weight is ≤ 10 kg, oral, 0.2 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. Afterwards, in case that patient weight is ≤ 10 kg, oral, between 0.4 milligrams glibenclamide per kilogram of body weight and 0.6 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. The maximum allowed total dose is 0.6 milligrams glibenclamide per kilogram of body weight daily.
Regimen B: In case that patient weight is ≥ 11 kg and patient weight is ≤ 12 kg, oral, 0.2 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. Afterwards, in case that patient weight is ≥ 11 kg and patient weight is ≤ 12 kg, oral, between 0.4 milligrams glibenclamide per kilogram of body weight and 0.5 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. The maximum allowed total dose is 0.5 milligrams glibenclamide per kilogram of body weight daily.
Regimen C: In case that patient weight is ≥ 13 kg and patient weight is ≤ 15 kg, oral, 0.2 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. Afterwards, in case that patient weight is ≥ 13 kg and patient weight is ≤ 15 kg, oral, 0.4 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. The maximum allowed total dose is 0.4 milligrams glibenclamide per kilogram of body weight daily.
Regimen D: In case that patient weight is ≥ 16 kg and patient weight is ≤ 20 kg, oral, 0.2 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. Afterwards, in case that patient weight is ≥ 16 kg and patient weight is ≤ 20 kg, oral, 0.3 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. The maximum allowed total dose is 0.3 milligrams glibenclamide per kilogram of body weight daily.
Regimen E: In case that patient weight is ≥ 20 kg, oral, 0.2 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. Afterwards, in case that patient weight is ≥ 20 kg, oral, between 0.4 milligrams glibenclamide per kilogram of body weight and 1 milligrams glibenclamide per kilogram of body weight, divided daily, 2 doses in total. The maximum allowed total dose is 1 milligrams glibenclamide per kilogram of body weight daily.
Glibenclamide suspension therapy should be initiated by a physician experienced in the treatment of patients with very early onset diabetes.
Maximum recommended posology:
| Body weight (kg) | Maximum recommended posology (expressed as mg/kg/day) where the glibenclamide 0.6 mg/mL strength can be used |
|---|---|
| Up to 10 | 0.6 |
| 11 | 0.5 |
| 12 | 0.5 |
| 13 | 0.4 |
| 14 | 0.4 |
| 15 | 0.4 |
| 16 | 0.3 |
| 17 | 0.3 |
| 18 | 0.3 |
| 19 | 0.3 |
| 20 | 0.3 |
In any other cases, glibenclamide 6 mg/mL should be preferred.
Glibenclamide therapy should be initiated at 0.2 mg/kg per day in two divided doses before feeding (including bottle feeding) and increased by 0.2 mg/kg/day until insulin independence is achieved.
Since glibenclamide is administered with an oral syringe graduated in mL, the calculated daily dose should be expressed in mL by the physician explicitly stating the strength to be used.
The syringe will be chosen (1 mL or 5 mL) based on the volume in mL to be administered for each dose, as prescribed by the physician. The 5 mL syringe has to be used for volumes greater than 1 mL
The nearest volume to the calculated one should be used.
Patients should be closely monitored by their treating physician during the titration phase.
As shown in the literature and in the clinical studies performed with glibenclamide, the average daily dose is expected to be around 0.2 to 0.5 mg/kg/day in most of the patients suffering from neonatal diabetes. Higher doses have occasionally been observed and doses up to 2.8 mg/kg/day have been successfully given without adverse reactions, according to literature. In case of a partial response on lower doses, as shown by reduced insulin requirements, a further dose increase up to 2.8 mg/kg/day may be tried in selected cases.
In some children glycemic control can be better achieved when glibenclamide is administered 3 times or 4 times daily.
If no improvement is seen (unchanged insulin dose, similar glycaemic control and no improvement in neurology), glibenclamide should be discontinued.
During titration period patients' capillary blood-glucose concentration should continue to be monitored four times a day and at bedtime, as insulin requirements may continue to fall, or glibenclamide may need to be titrated. Once steady state is reached, capillary blood glucose does no longer need to be daily monitored except in clinical situations at risk of metabolic unbalance. In all cases, HbA1c must be monitored every three months.
Sometimes, blood-glucose concentration will fall even though the patient is on a fixed dose of glibenclamide. Therefore, to avoid hypoglycaemia, consideration should be given to reducing the dose of glibenclamide or stopping treatment.
Reduction of glibenclamide dose should be anticipated by the treating physician and certainly if the glucose values are going below 4 mmol/L (72 mg/dL).
It may be necessary to adjust the dosage of glibenclamide in patients suffering from intercurrent infections, trauma, shock or anaesthesia:
Patients occasionally may have very high glucose values, i.e. >20 mmol/L (>360 mg/dL). In some cases these high glucose values seem to settle with the normal dose of glibenclamide. However, close monitoring of blood-glucose is required in all cases and adequate measures to restore euglycaemia (e.g. application of a third daily glibenclamide dose or insulin) must be taken.
If a dose is forgotten, there is a risk of hyperglycaemia. Blood-glucose level must be checked immediately and glibenclamide taken as soon as possible. If the blood-glucose level exceeds 16.5 mmol/L, the presence of ketonuria or ketonaemia must also be checked. If ketone bodies are present, an insulin injection must be given rapidly to restore the metabolic situation. The attending specialist should then be contacted.
Since no interaction study between glibenclamide and milk has been performed, and despite absence of food effect on glibenclamide absorption, recommendation is given to administer the suspension 15 minutes before child’s milk feeding.
Administration through a feeding tube should be avoided.
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