Amglidia

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 
AMGLIDIA 0.6 mg/mL oral suspension 
AMGLIDIA 6 mg/mL oral suspension 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
AMGLIDIA 0.6 mg/mL oral suspension 
 
Each mL contains 0.6 mg glibenclamide. 
 
AMGLIDIA 6 mg/mL oral suspension 
 
Each mL contains 6 mg glibenclamide. 
 
Excipient(s) with known effect 
 
Each mL contains 2.8 mg of sodium and 5 mg of benzoate salt. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 

 
Oral suspension. 
White, odourless suspension. 
 
 
4. CLINICAL PARTICULARS 

 
4.1 Therapeutic indications 
 
AMGLIDIA is indicated for the treatment of neonatal diabetes mellitus, for use in newborns, infants 
and children. 
Sulphonylureas like AMGLIDIA 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. 
 
4.2 Posology and method of administration 
 
Glibenclamide suspension therapy should be initiated by a physician experienced in the treatment of 
patients with very early onset diabetes.  
 
Prescription instructions 
Care should be taken when prescribing and administering AMGLIDIA to avoid dosing errors due to 
confusion between milligram (mg) and millilitre (mL). It should be ensured that the proper dose and 
strength are communicated and dispensed. 



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Posology 
 
To avoid exceeding sodium benzoate acceptable daily dose, AMGLIDIA daily dose should not exceed 
1 mL/kg/day. As a consequence, AMGLIDIA 0.6 mg/mL should not be used for posology higher than 
0.6 mg/kg/day. 
 
To limit exposure to sodium benzoate and with respect to the mode of delivery (1 mL and 5 mL oral 
syringes), it is not recommended to use the AMGLIDIA 0.6 mg/mL strength for posologies higher 
than the ones described below: 
 

Body weight (kg) 
Maximum recommended posology (expressed as 
mg/kg/day) where the AMGLIDIA 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, AMGLIDIA 6 mg/mL should be preferred.  
 
AMGLIDIA 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 AMGLIDIA 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 5mL) 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. 
 
Inpatient treatment introduction 
 
Start AMGLIDIA at a dose of 0.2 mg/kg/day, in two administration. Give basal and bolus insulin as 
usual on Day 1. On Day 2, if administered sub-cutaneously, basal insulin can be removed. If on insulin 
pump, reduce basal rate of insulin pump by 50% and reduce further in accordance with capillary 
blood-glucose measurements. Throughout the transfer period, administer bolus insulin or insulin pump 
boluses with meals as required to maintain reasonable glycemic control. From Day 2 until the end of 
the titration phase, if capillary blood glucose is ≥7 mmol/L, increase AMGLIDIA by 0.2 mg/kg/day. If 
capillary blood glucose is < 7 mmol/L, do not increase AMGLIDIA and reduce pre-meal insulin 
boluses by 50%. 
 
Pre-breakfast glucose may be very slow to fall. Pre-lunch or pre-evening meal glucose values fall 
more rapidly and are generally a better marker of response to AMGLIDIA. 
 
Repeat the same protocol every day until insulin independence is achieved. As soon as insulin is 



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discontinued, the dose of AMGLIDIA is adjusted according to capillary blood glucose. 
 
For patients still under insulin at day 6, maintain the dose of AMGLIDIA for at least 4 weeks. This 
may be done as an outpatient.  
 
Patients can be discharged when no longer requiring insulin treatment, when stable on a combination 
of AMGLIDIA and insulin or when stable on insulin alone. 
 
Outpatient treatment introduction 
 
AMGLIDIA should be introduced at a dose of 0.2 mg/kg/day in two administration and dose should 
be progressively increased each week by 0.2 mg/kg/day.  
 
As the dose is increased, it is usually possible to reduce and then stop the insulin dose.  
 
From week 2 onward, if capillary blood glucose is ≥7 mmol/L increase AMGLIDIA by 0.2 mg/kg/day 
and reduce insulin. If capillary blood glucose is < 7 mmol/L reduce insulin.  
 
If blood-glucose value increases after insulin reduction, then increase AMGLIDIA by 0.2 mg/kg/day. 
Insulin reduction should be done using the pre-meal glucose. 
 
Repeat the same protocol every week until insulin independence is achieved. As soon as insulin is 
discontinued, the dose of AMGLIDIA is adjusted according to capillary blood glucose.  
 
If at the end of a 5 to 6-week period, there is no evidence of a response with insulin doses similar to 
those at starting, administration of doses up to 2 mg/kg/day for a week may be tried. (In rare cases, it 
has taken 4 months to wean off insulin completely).  
 
If there is a clear reduction in insulin requirement at this dose of 2 mg/kg/day (reduction in insulin to 
at least 60% of pre-AMGLIDIA dose), then it is worth continuing a higher dose of AMGLIDIA over a 
prolonged period of time in selected cases.  
 
Dosage adjustments and long-term management 
 
As shown in the literature and in the clinical studies performed with AMGLIDIA, 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 AMGLIDIA is administered 3 times or 
4 times daily. 
 
If no improvement is seen (unchanged insulin dose, similar glycaemic control and no improvement in 
neurology), AMGLIDIA 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 
AMGLIDIA 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 (see 
below). In all cases, HbA1c must be monitored every three months. 



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Sometimes, blood-glucose concentration will fall even though the patient is on a fixed dose of 
AMGLIDIA. Therefore, to avoid hypoglycaemia, consideration should be given to reducing the dose 
of AMGLIDIA or stopping treatment.  
 
Reduction of AMGLIDIA 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 AMGLIDIA in patients suffering from intercurrent 
infections, trauma, shock or anaesthesia: 
 

o For major surgery, insulin therapy should replace AMGLIDIA; 
o Hepatic or renal dysfunction may require a reduction in dosage; 
o In exceptional situations of stress (e.g. trauma, surgery, febrile infections), blood-glucose 

regulation may deteriorate, and a temporary change to insulin may be necessary to maintain 
good metabolic control. 
 

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 AMGLIDIA. However, close 
monitoring of blood-glucose is required in all cases (please also refer to recommendations given under 
the heading “dose omission” further below) and adequate measures to restore euglycemia (e. g. 
application of a third daily AMGLIDIA dose or insulin) must be taken. 
 
Amglidia is not bioequivalent with (crushed) tablets containing the same amount of glibenclamide. 
Available data are described in section 5.2. 
 
Dose omission 
 
If a dose is forgotten, there is a risk of hyperglycaemia. Blood-glucose level must be checked 
immediately and AMGLIDIA 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. 
 
Special populations 
 
Renal impairment 
Dose adjustment is required in patients with mild to moderate renal impairment. In those patients, 
treatment should be started at the lowest dose and dosage levels strictly followed, to avoid 
hypoglycaemic reactions (see section 4.4). For severe renal impairment see section 4.3. 
 
Hepatic impairment 
Dose adjustment is required in patients with mild to moderate hepatic impairment. In those patients, 
treatment should be started at the lowest dose and dosage levels strictly followed, to avoid 
hypoglycaemic reactions (see section 4.4). For severe hepatic impairment see section 4.3. 
 
Adults and elderly 
Safety and efficacy of Amglidia in elderly patients has not been established since the medicinal 
product is indicated in the paediatric population. 
 
Paediatric population 
AMGLIDIA is to be used in newborns, infants and children. 
 
At risk patients 
In malnourished patients or those displaying a marked change in their general condition, or whose 
calorie intake is irregular, and in patients with impaired renal or hepatic function, treatment should be 

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started at the lowest dose and dosage levels strictly followed, to avoid hypoglycaemic reactions (see 
section 4.4). 
 
Method of administration  
 
The bottle does not need to be shaken before administration. 
 
This medicinal product is administered orally as a “ready for-use” oral suspension using a graduated 
oral syringe. It is administered directly into the child's mouth. 
 
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. 
 
Only the oral syringe included in the outer carton should be used. 
 
Depending on the volume to be administered orally, there are two types of oral syringes, graduated up 
to 1 mL or up to 5 mL. Each syringe is included in a specific presentation. The appropriate syringe 
(1 mL or 5 mL), included in a specific AMGLIDIA presentation, will be prescribed by the physician 
based on the volume to be administered for each dose. 
The two syringes, respectively included in two different presentations for each strength, are clearly 
distinguishable: 1 mL oral syringe is thin and small while 5 mL syringe is thick and long. 
 
The dose to be administered is obtained by drawing the plunger back as far as the scale marking for 
the dose determined for each child.  The dose in mL per administration and the number of 
administrations per day have to carefully follow the medical prescription. 
 
Administration through a feeding tube should be avoided. 
 
4.3 Contraindications 

 
This medicinal product is contraindicated in the following cases: 

− hypersensitivity to the active substance, other sulphonylureas or sulphonamides or to any of 
the excipients listed in section 6.1; 

− in patients with ketoacidosis, continuous intravenous insulin injection and intravenous 
infusion of physiologic saline remains the benchmark treatment.  

− in patients with porphyria; 
− in patients taking bosentan (see section 4.5) 
− in patients with severe renal impairment 
− in patients with severe hepatic impairment 

 
4.4 Special warnings and precautions for use 

 
Special care should be taken when calculating the dose. Before each administration, it should be 
verified that the correct strength and syringe are used. 
 
AMGLIDIA should not be used in patients with insulin-dependent type 1 diabetes mellitus with 
evidence of auto-immune destruction of beta cells. 
 
Patients with G6PD enzyme deficiency 
 
In patients carrying a G6PD enzyme deficiency, cases of acute haemolytic anaemia have been reported 
with glibenclamide. It should therefore not be prescribed for these patients, and the use of an 
alternative treatment is strongly recommended, if available. If there is no alternative, the decision for 
each patient must consider the danger of haemolysis and the potential benefit expected from the 
treatment. If it is necessary to prescribe this medicinal product, screening should be conducted for the 
occurrence of any haemolysis. 

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Hypoglycaemia 
 
Hypoglycaemia can occur under treatment with hypoglycaemic sulphonamides. This can sometimes 
be severe and prolonged. Hospitalisation may then prove necessary and sugar may have to be 
administered for several days. 
 
Diarrhea, nausea and vomiting 
 
In some patients, there may be an initial diarrhea when the dose of glibenclamide suspension is 
increased but it settles if the dose is maintained. 
In case of nausea glycaemia seems to be maintained and insulin does not need to be re-introduced until 
the patient is able to take the glibenclamide suspension.  
If there is major vomiting, a fast-acting insulin should be used to treat the patient until vomiting stops. 
If there is minor vomiting, an antivomiting medicinal product should be given and treatment with 
AMGLIDIA can be continued. 
 
Biological analyses:  
 
Blood-glucose should be monitored periodically throughout treatment with glibenclamide. 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 glycosylated haemoglobin level should be measured every three months to assess the child's 
metabolic equilibrium. 
 
Renal impairment: 
 
Patients with renal impairment should be monitored periodically during treatment due to the increased 
risk of hypoglycaemia. Dose adjustment is required in patients with mild to moderate renal 
impairment (refer to section 4.2). 
 
Hepatic impairment: 
 
Patients with hepatic impairment should be monitored periodically during treatment due to the 
increased risk of hypoglycaemia. Dose adjustment is required in patients with mild to moderate 
hepatic impairment (refer to section 4.2). 
 
Sodium 
 
This medicinal product contains 2.8 mg of sodium per mL oral suspension, equivalent to 0.1% of the 
WHO recommended daily intake of 2 g sodium for an adult. To be taken into consideration by patients 
on a controlled sodium diet. 
 
Benzoic acid and benzoates (sodium benzoate) 
 
This medicinal product contains 5 mg benzoate salt in each mL oral suspension.  
Increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice 
which may develop into kernicterus (non-conjugated bilirubin deposits in the brain tissue). 
 
4.5 Interaction with other medicinal products and other forms of interaction 

 
No interaction studies have been performed for the two oral suspensions of glibenclamide (0.6 mg/mL 
and 6 mg/mL). 
 
Hypoglycaemia may occur when taking other medicinal products. 



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Highly protein-bound medicinal products, which may also potentiate the hypoglycaemic action of 
glibenclamide due to glibenclamide displacement from plasma proteins, include oral anticoagulants, 
phenytoin, salicylates and other non-steroidal anti-inflammatory agents. 
Weakening of the blood-glucose-lowering effect and, thus, raised blood-glucose levels may occur 
when taking other medicinal products. 
Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, 
guanethidine, and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be 
reduced or absent. The symptoms of hypoglycaemia may also be milder or absent where 
hypoglycaemia develops gradually or where there is autonomic neuropathy. 
 
In very rare cases, an intolerance to alcohol may occur. Both acute and chronic alcohol intake, or 
excessive alcohol ingestion by people who drink occasionally, may attenuate the hypoglycaemic effect 
of glibenclamide or dangerously potentiate it by delaying its metabolic inactivation. Disulfiram-like 
reactions have occurred very rarely following the concomitant use of alcohol and glibenclamide. 
 
Glibenclamide may increase ciclosporin plasma concentration and potentially lead to its increased 
toxicity. Monitoring and dosage adjustment of ciclosporin are therefore recommended when both 
medicinal products are co-administered. 
 
Colesevelam binds to glibenclamide and reduces glibenclamide absorption from the gastrointestinal 
tract. No interaction was observed when glibenclamide was taken at least 4 hours before colesevelam. 
Therefore, glibenclamide should be administered at least 4 hours prior to colesevelam. 
 
A summary of the interactions detailed above and further interactions are summarised in the table 
below. 
 
Active substance Effect of interaction Potential risk 
ACE inhibitors Potentiation of the blood-glucose 

lowering 
Hypoglycaemia 

Acetazolamide Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Adrenaline (epinephrine) 
and other 
sympathomimetic agents 

Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Alcohol Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Attenuate the hypoglycaemic effect of 
glibenclamide or dangerously potentiate 
it by delaying its metabolic inactivation 

Incorrect control of plasma 
glucose 

Anabolic steroids and 
male sex hormones 

Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Barbiturates Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Beta-receptor blockers Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Signs of adrenergic counter-regulation to 
hypoglycaemia may be reduced or absent 

Incorrect control of plasma 
glucose 

Biguanides Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Bosentan Increase liver enzymes Incorrect control of plasma 
glucose 

Calcium channel 
blockers 

Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Chloramphenicol Potentiation of the blood-glucose Hypoglycaemia 



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Active substance Effect of interaction Potential risk 
lowering 

Ciclosporin Increase ciclosporin plasma 
concentration 

Increased toxicity of 
ciclosporin 

Cimetidine Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Clarithromycin Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Clonidine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Potentiation or weakening of the blood-
glucose lowering effect 

Incorrect control of plasma 
glucose 

Signs of adrenergic counter-regulation to 
hypoglycaemia may be reduced or absent 

Incorrect control of plasma 
glucose 

Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Colesevelam Reduction of glibenclamide absorption 
from the gastrointestinal tract 

Incorrect control of plasma 
glucose 

Corticosteroids Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Coumarin derivatives Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Potentiate or weaken the effect of 
coumarin derivatives 

Incorrect dosage of coumarin 
derivatives administered 

Cyclophosphamides Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Diazoxide Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Disopyramide Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Diuretics Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Fenfluramine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Fenyramidol Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Fibrates Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Fluoxetine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Glucagon Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Guanethidine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Signs of adrenergic counter-regulation to 
hypoglycaemia may be reduced or absent 

Incorrect control of plasma 
glucose 

H2-receptor antagonists Potentiation or weakening of the blood-
glucose lowering effect 

Incorrect control of plasma 
glucose 

Heparin Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Ifosfamide Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Insulin Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Isoniazid Weakening of the blood-glucose- Increased blood-glucose levels 



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Active substance Effect of interaction Potential risk 
lowering effect 

Large doses of laxatives Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Long-acting 
sulphonamides 

Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

MAO inhibitors Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Miconazole Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Nicotinic acid (in high 
doses) 

Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Oestrogens Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Other oral antidiabetics Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Oxypentifylline Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Oxyphenbutazone Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Phenothiazine derivatives Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Phenytoin Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Phosphamides Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Probenecid Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Progestogens Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Quinolone antibiotics Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Reserpine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Potentiation or weakening of the blood-
glucose lowering effect 

Incorrect control of plasma 
glucose 

Signs of adrenergic counter-regulation to 
hypoglycaemia may be reduced or absent 

Incorrect control of plasma 
glucose 

Rifampicin Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Thyroid hormones Weakening of the blood-glucose-
lowering effect 

Increased blood-glucose levels 

Salicylates Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Sulfamethoxazole with 
trimethoprim (Co-
trimoxazole) 

Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Tetracycline compounds Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

Tritoqualine Potentiation of the blood-glucose 
lowering 

Hypoglycaemia 

 



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4.6 Fertility, pregnancy and lactation 
 

General aspects 
 
AMGLIDIA is indicated for the treatment of neonatal diabetes in newborns, infants and children.  
 
Women of childbearing potential / Contraception 
 
Women of childbearing potential planning a pregnancy should be switched from oral glibenclamide to 
insulin. Glibenclamide should not be given during pregnancy. 
 
Pregnancy 
 
Based on a limited amount of published data, the use of glibenclamide during the 1st trimester does not 
seem to cause an increase in congenital malformations. With respect to the 2nd and 3rd trimester 
published data did not find fetotoxic effects. 
Animal studies do not indicate a teratogenic potential. 
 
Glibenclamide crosses the placenta mostly in small amounts; however, transfer is highly variable 
among patients. 
 
In pregnant women insulin is recommended for blood sugar control. 
 
Breast-feeding 
 
Published data from 11 glibenclamide-treated mothers indicate that glibenclamide is not excreted in 
human milk and hypoglycemia in the breast-fed newborns was not reported. Breast-feeding seems to 
be compatible, but as a precautious measure monitoring of the fully breast-fed infant’s blood sugar 
level is advisable. 
 
Fertility 
 
Clinical data are not available. 
 
4.7 Effects on ability to drive and use machines 

 
AMGLIDIA has moderate influence on the ability to drive and use machines since glibenclamide may 
increase the risk of hypoglycaemia. This may not be relevant for the target population. However, 
reduced alertness may also be of concern when participating in road traffic. 
 
4.8 Undesirable effects 
 
Summary of the safety profile: 
 
The most frequent adverse reactions are hypoglycemia, transitory diarrhea and abdominal pain. The 
most serious adverse reaction is hypoglycemia (see section 4.4). 
Overall, the safety profile of Glibenclamide is in line with the safety profile of others sulfonylureas. 



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Tabulated list of adverse reactions 
 
Adverse reactions reported with glibenclamide (oral suspension or crushed tablets) in children, in the 
frame of treatment of neonatal diabetes are listed below by system organ class and frequency 
grouping. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be 
estimated from the available data). Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness. 
 
MedDRA system organ class Adverse reactions 

Very common Common 
Blood and lymphatic system disorders Neutropenia  
Metabolism and nutrition disorders Hypoglycaemia  
Gastrointestinal disorders Transitory diarrhea 

Abdominal pain 
Vomiting 
Dyspepsia 

Tooth discoloration 

Investigations Transitory increased transaminases  
 
Description of selected adverse reactions  
 
The following adverse reactions have been observed in a clinical study (Neogli study). This was a 
phase II, single-centre, prospective, open-label, non-randomised study. After enrolment, patients 
continued taking their usual doses of glibenclamide tablets for 1 month. Ten patients were switched to 
glibenclamide oral suspension and treatment with oral suspension continued for 3 months. 
 
Hypoglycaemia  
 
Two cases of severe hypoglycaemia were observed, which were considered related to the medicinal 
product. Symptomatic measures were taken and the situation resolved in the two cases. 
 
Transitory diarrhea, vomiting and abdominal pain and dyspepsia 
 
Two children had abdominal pain (one with transient diarrhea and vomiting during the same episode) 
that were considered related to the medicinal product. Symptomatic measures were taken and the 
medicinal product continued and the situation resolved in the two cases. 
 
One child had dyspepsia, which was considered related to the medicinal product. Symptomatic 
measures were taken and the situation resolved. 
 
Neutropenia and transitory increased transaminases 
 
One child had punctually low leucocytes level, but close to the normal range (neutrophils 1.3×103/µL 
for a lower limit of normal of 1.5×103/µL). 
The same child had a transient and minimal ASAT 73 IU/L, and ALAT 42 IU/L increased (normal 
range below 60 and 40 respectively). These resolved subsequently. 
 
In addition undesirable effects gathered from the use in adults is of importance given the small 
database in children. Those not already mentioned above, which could happen in children as well are  
listed below. 
 
Eye disorders 
 
Transient visual disturbances (blurred vision or accommodation disorder),  especially early in 
treatment,  with or without glycaemic variation. 
 
Skin and subcutaneous tissue disorders 



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In isolated cases, photosensitivity may occur. 
Skin rash, pruritus, urticaria, allergic skin reaction. Bullous eruptions, exfoliative dermatitis, erythema 
multiforme have occasionally been reported in adults. 
 
Immune system disorders 
 
Anaphylactic reaction including dyspnoea, hypotension and shock. 
 
Blood disorders 
 
Blood affections generally reversible when treatment stops. 
Hypereosinophilia, leucopenia, mild or severe thrombocytopenia, which can lead to purpura. 
Rare cases of agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Overdose of sulphonamides can result in hypoglycaemia. 
The symptoms of moderate hypoglycaemia, without loss of consciousness or neurological signs, must 
be completely corrected by taking sugar, adjusting the dose and/or changing dietary behaviour. Close 
monitoring of blood-glucose by the patient’s family must be continued until the family and the 
physician, if he/she had to be contacted, are certain that the patient is out of danger. 
Severe hypoglycaemic reactions, with coma, convulsions or other neurological disorders are possible 
and are medical emergencies requiring immediate treatment as soon as the cause is diagnosed or 
suspected before immediately admitting the patient to hospital. 
 
If a hypoglycaemic coma is diagnosed or suspected, the patient should quickly receive an intravenous 
injection of concentrated glucose solution (0.5 g/kg body weight as a 30% glucose solution). This 
must be followed by continuous infusion of more dilute glucose solution (10%) at the rate needed to 
maintain blood-glucose above 100 mg/dL (100 mg/dL = 5.5 mmol/L). Patients must be closely 
monitored for at least 48 hours and, depending on the patient's condition at this time, the physician 
will decide if additional monitoring is necessary. 
 
Plasma clearance of glibenclamide may be prolonged in patients suffering from liver disease.  
Due to strong binding of glibenclamide to proteins, dialysis is of no benefit to the patient. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs used in diabetes, sulphonylureas, ATC code: A10BB01 
 
Mechanism of action 
 
Sulphonylureas will act on pancreatic beta-cells by inhibiting ATP-sensitive potassium channels. 
The mechanisms of action proposed for this effect include stimulation of insulin release by beta-cells 
of the pancreas. 
The minimum active concentration for the effect is considered to be 30-50 ng/mL glibenclamide. 
 
Pharmacodynamic effects 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


14 

Glibenclamide, a second-generation, short half-life sulphonylurea, is a hypoglycaemic agent that 
reduces blood-glucose by stimulating insulin release by the pancreas; this effect depends on the 
presence of active beta-cells or beta-cells made active by glibenclamide in the pancreatic islets in 
certain cases of neonatal diabetes. 
 
Stimulation of insulin secretion by glibenclamide in response to a meal is of major significance. 
Administering glibenclamide to a diabetic enhances the post-prandial insulinotropic response. Post-
prandial responses involving secretion of insulin and peptide-C continue to be enhanced after at least 
6 months of treatment and even over many years in the case of neonatal diabetes by potassium channel 
disorders. 
 
Glibenclamide has 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. 
 
Clinical efficacy and safety 
 
Treatment using sulphonylureas in neonatal diabetes linked to potassium channel disorders is 
supported by published studies showing measurable improvements in glycaemic control and 
suggesting neuro-psychomotor and neuro-psychological deficiencies, which are greater in younger 
patients. 
 
From data published in the literature, treatment with sulfonylurea is reported to be successful in 
approximately 90% of the patients with neonatal diabetes associated with K-ATP channel mutations. 
The average dose reported in the literature (clinical trials and case reports) is of approximately 0.5 
mg/kg/day. When limited to clinical trials or prospective data collections only, the average dose 
decreases to 0.2 to 0.3 mg/kg/day. Higher doses have occasionally been reported in the literature with 
doses as high as 2.8 mg/kg/day without undesirable effects and with full transfer off insulin. 
 
In a phase II, single-centre, prospective, open-label, non-randomised study, acceptability, efficiency 
and tolerance of the switch from crushed tablets to Amglidia suspension were measured. Ten patients 
(7 boys/3 girls) with KCNJ11 mutation, with median age 2.7 years (0.3 to 16.2) andmedian duration of 
glibenclamide therapy 2.3 years (6 days to 11.3 years) were treated.  
Daily doses ranged from 0.1 to 0.8 mg/kg for glibenclamide tablets (median dose, 0.3 mg/kg) and 
from 0.1 to 0.6 mg/kg for oral suspension (median 0.1 to 0.2 mg/kg/day over the study period) given 
in 2 to 4 administration per day). 
 
After switching from glibenclamide tablets to AMGLIDIA suspension, there was no significant 
change in glycaemic control as evidenced from the similar serum HbA1c (6.5 vs 6.1% at Visits M0 
and M4, respectively; p=0.076) and fructosamine (283.4 vs 271.2 µmol/L at Visits M0 and M4, 
respectively; p=0.55) mean concentrations. 
 
None of patients experienced deterioration in glycaemic control, defined as an increase of HbA1c by 
> 0.5% and exceeding 5.6% in patients with baseline HbA1c ≤ 5.6% or an increase of HbA1c by 
> 0.5% in patients with baseline HbA1c > 5.6%. 
 
A large international long-term term study of treatment for neonatal diabetes due to KCNJ11 
mutations is ongoing and results were reported in 81 patients of the 90 patients originally included 
with a median [interquartile range] follow-up duration of 10.2 years [9.3-10.8 years]. Transfer to 
sulfonylureas occurred in childhood with a median [IQR] at transfer of 4.8 years [1.7 – 11.4 years]. 
Seventy-five patients (93%) remained on sulphonylurea alone at most recent follow-up and 6/81(7%) 
were on sulphonylurea and daily insulin. In patients on sulphonylurea alone, blood glucose control has 
been improved after transfer to sulfonylureas with median [IQR] HbA1c of 5.9% [5.4-6.5%] at 1 year 
vs 8.0 % [7.2-9.2 %] before transfer (p< 0.0001), and remained very well controlled after 10 years  
with a median [IQR] HbA1c of 6.4% [5.9-7.2 %].  
 



15 

The median [IQR] dose of sulfonylurea fell over the follow-up with a median [IQR] dose of 
0.30 mg/kg/day [0.14-0.53] mg/kg/day at one year and of 0.23 mg/kg/day [0.12-0.41 mg/kg/day] at 10 
years, p=0.03). There were no reported episodes of severe hypoglycaemia. Adverse reactions 
(diarrhoea/nausea/reduced appetite/abdominal pain) were reported in 10/81(12%); these were 
transient, and no patients discontinued sulphonylurea as a result. Microvascular complications were 
reported in 7/81(9%) patients; there were no macrovascular complications. Patients with complications 
were older at age of transfer to sulfonylurea than those without complications (median age at transfer: 
20.5 v 4.1 years, p=0.0005).  Oral glucose tolerance tests and intravenous glucose tolerance tests 
revealed good insulin response to glucose and maintained incretin effect after ten years. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
After oral administration, glibenclamide is absorbed rapidly and induces its effect within 2.5 hours 
with a duration of up to 15 hours, although the elimination half-life is 5 to 10 hours. The food effect on 
the speed or the level of absorption of glibenclamide oral suspension has not been investigated. 
Bioavailability studies have demonstrated that nonmicronised tablets provide serum glibenclamide 
concentrations that are not bioequivalent to those from micronised tablets. 
 
Head to head comparative pharmacokinetic data following the application of glibenclamide 
suspension and micronised tablets are not available. The conversion rate between micronised tablets 
and the suspension has not been established. 
 
A comparative study of relative bioavailability between two suspensions of glibenclamide oral 
suspensions (0.6 mg/mL and 6 mg/mL) and crushed glibenclamide tablets (Daonil 5 mg) showed that 
when glibenclamide oral suspensions were administered, peak plasma concentrations of glibenclamide 
are reached 0.5 hours earlier than that observed with the crushed Daonil tablet (median value after 
administration is 2.5 hours compared to 3 hours). The values for maximum plasma concentrations 
(Cmax) were similar for the two suspensions (201.71 ± 71.43 ng/mL for the 6 mg/mL suspension and 
206.93 ± 67.33 ng/mL for the 0.6 mg/mL suspension). These values were approx. 40% greater than 
those obtained for the crushed tablet (148.34 ± 46.74 ng/mL).  
 
The exposures were respectively similar for the two glibenclamide oral suspensions, and greater than 
those observed after administration of crushed Daonil tablets. The relative bioavailability was 121.6% 
for the 0.6 mg/mL suspension and 114.1% for the 6 mg/mL suspension compared to the crushed 
Daonil tablets. 
 
Population pharmacokinetic approach was used to compare steady state concentrations following 0.9 
mg twice daily in children with body weights between 10 – 30 kg and 1.25 mg twice daily in adults. 
The plasma glibenclamide levels in the simulated paediatric population were approximately 30%-60% 
lower than the adult levels.  With smaller bodyweight the concentration increased but exceeded the 
adult plasma levels in minimal extents only for poor metabolizers. 
 
Distribution 
 
Glibenclamide is strongly bound to plasma albumin (99%), which may account for certain drug 
interactions, but is not easily detached by acidic medicinal products. 
 
Biotransformation and elimination 
 
Glibenclamide is completely metabolised by the liver into 3 inactive metabolites excreted via bile 
(60%) and urine (40%); elimination is complete in 45 to 72 hours. Clinical studies appear to suggest 
that CYP2C9 contributes significantly to glibenclamide metabolism in vivo. 
Liver failure reduces the metabolism of glibenclamide and therefore significantly slows down its 
elimination. 



16 

Biliary excretion of the metabolites increases in the event of kidney failure, proportionally to the 
severity of the change in renal function. Kidney failure does not affect its elimination as long as 
creatinine clearance remains above 30 ml/min. 
 
The elimination half-lives were similar for the two suspensions (almost 8 hours) and a little shorter 
than those observed with the crushed Daonil tablets. 
 
5.3 Preclinical safety data 
 
In repeated dose toxicity studies with oral administration of high doses of glibenclamide, effects on 
pancreatic beta-cells were observed (enlargement of the islets of Langerhans with irregularly 
configured islets and reduction in pancreatic β-cell granulation in rats at doses of ≥ 30 mg/kg/day, 
beta-cell exhaustion as indicated by depletion of insulin-containing granules in rabbits at doses of 
> 100 mg/kg/day). 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
hydroxyethylcellulose 
lactic acid 
purified water 
sodium benzoate (E211)  
sodium citrate  
xanthan gum 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
After first opening 
30 days.  
Keep the bottle tightly closed. 
 
6.4 Special precautions for storage 
 
Keep the bottle in the outer carton in order to protect from light. 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Brown glass bottle (type III) with a child-resistant closure (polypropylene screw cap with polyethylene 
capsule inside) in a carton containing a 1 mL or 5 ml graduated oral syringe of LDPE and 
polypropylene depending on the presentation prescribed and an adaptor (LDPE) to be plugged on the 
bottle after opening for the syringe. 
 
The 1 mL oral syringe is thin and small while the 5 mL syringe is thick and long. 
 
Pack sizes 
 
One bottle of 30 ml suspension and one oral syringe of 1 mL packed in an individual bag and one 
syringe adaptor. 



17 

One bottle of 30 ml suspension and one oral syringe of 5 mL packed in an individual bag and one 
syringe adaptor. 
 
6.6 Special precautions for disposal and other handling 
 
At the first use, the bottle should be opened by unscrewing the child-resistant closure while pressing 
downwards. The adaptor should be inserted firmly into the bottle while holding the bottle the right 
way up. The screw cap should then be replaced on the bottle with the adaptor and not removed during 
the 30-day use. The screw cap should be retightened in order to push the adaptor well into the bottle. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
AMMTeK 
55 rue de Turbigo 
75003 Paris 
France 
Tel: + 33 (0)1 58 28 16 80 
Fax: + 33 (0)1 58 28 16 90 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1279/001 (AMGLIDIA 0.6 mg/mL oral suspension with 1 mL oral syringe) 
EU/1/18/1279/002 (AMGLIDIA 0.6 mg/mL oral suspension with 5 mL oral syringe) 
EU/1/18/1279/003 (AMGLIDIA 6 mg/mL oral suspension with 1 mL oral syringe) 
EU/1/18/1279/004 (AMGLIDIA 6 mg/mL oral suspension with 5 mL oral syringe) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 24th May 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING  
AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



19 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Centre Spécialités Pharmaceutiques 
76-78 Avenue du midi  
63800 Cournon d’Auvergne  
France 
 
Unither Pharmaceutical 
Zone d'Activites Tech Espace 
Avenue Toussaint Catros 
33185 Le Haillan 
FRANCE 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
An updated RMP should be submitted: 

 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
• Additional risk minimisation measures  

 
Prior to launch of Amglidia in each Member State, the Marketing Authorisation Holder (MAH) must 
agree the content and format of an educational material for Amglidia, including communication 
media, distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  



20 

The educational material is aimed at increasing awareness about the four presentations available 
(two strengths of the product, each containing either a 1mL or a 5mL syringe) and at minimising 
the risk of hypoglycaemia in case of mix-ups of the different presentations. 
 
The MAH shall ensure that, in each Member State where Amglidia is marketed, all healthcare 
professionals who are expected to prescribe Amglidia, have access to the following 
educational guide: 
 

• A Prescriber’s Guide, including  the SmPC of Amglidia  attached  
 
The Prescriber’s Guide shall contain the following key messages: 

 
• Amglidia is a suspension to be administered with a provided oral syringe graduated in mL. 

Healthcare professionals or patients should never use another syringe than the one provided in 
the box to avoid dosing errors which could result in serious harm. 

• Amglidia is available in four different boxes corresponding to four different presentations 
(four different strengths): 
 One box for the 0.6 mg/mL strength with one 1mL syringe: yellow colour for outer carton 

and reverse type yellow colour for label  
 One box for the 0.6 mg/mL strength with one 5 mL syringe: yellow colour for outer carton 

and reverse type yellow colour for label  
 One box for the 6 mg/mL strength with one syringe of 1 mL: purple colour for outer 

carton and reverse type purple colour for label  
 One box for the 6 mg/mL strength with one syringe of 5 mL: purple colour for outer 

carton and reverse type purple colour for label  
• The choice of the Amglidia strength should be defined according to the prescribed posology 

and the patient’s body weight. 
• The Amglidia 0.6 mg/mL strength should not be used for posology higher than 0.6 mg/kg/day 

to limit the exposure to the sodium benzoate excipient. Please read the posology and method 
of administration in the SmPC attached to this prescriber’s guide. 

• Choice of the syringe to be used:  
 After the total daily dose and the strength to be used have been defined, the frequency of 

the daily administration should be pointed out and the corresponding volume per 
administration should be calculated. 

 Depending on the volume calculated per administration: 
 If the volume per administration is 1mL or below, the 1mL syringe should be 

prescribed; 
 If the volume per administration is more than 1mL, the 5mL syringe should be 

prescribed. 
• The prescription should state the calculated daily dose in mL, the strength of Amglidia to be 

used, the number of administrations over which the daily dose is divided, as well as the 
volume in mL to be administered for each dose and the size of the syringe to be used.  

• Patients and/or their caretakers should be explained that: 
 They are prescribed a dose of Amglidia in mL according to their body weight. This dose is 

to be administrated with a provided oral syringe graduated in mL.  
 There are 2 presentations for a same strength: one with a syringe of 1mL and one with a 

syringe of 5 mL.  
 Patients or their caretakers should be reminded to use the correct syringe as stated in their 

prescription. 
• If the patient is prescribed a different presentation, the prescriber should highlight to the 

patient the packaging differences between the different presentations (focus on colour 
differentiation, warning statements on carton, thickness and length of the provided syringe). 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



23 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
AMGLIDIA 0.6 mg/mL oral suspension 
AMGLIDIA 6 mg/mL oral suspension 
glibenclamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL contains 0.6 mg glibenclamide. 
Each mL contains 6 mg glibenclamide. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium and benzoate, see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral suspension. 
1 x 30 mL bottle. 
1 oral syringe (1 mL) 
1 oral syringe (5 mL) 
1 syringe adaptor. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
You should only use the syringe which has been prescribed by your doctor. 
Make sure you have the box containing the syringe size prescribed by your doctor. 
If a new presentation of AMGLIDIA is prescribed by your doctor, return back your previous 
presentation and syringe to your pharmacist to avoid mixing up of the syringes. 
 
 



24 

8. EXPIRY DATE 
 
EXP {MM/YYYY} 
After opening, keep the bottle tightly closed after each use and stored for a maximum of 30 days. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the bottle in the outer carton in order to protect from the light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
AMMTeK 
55 rue de Turbigo 
75003 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1279/001 (AMGLIDIA 0.6 mg/mL oral suspension with 1 mL oral syringe) 
EU/1/18/1279/002 (AMGLIDIA 0.6 mg/mL oral suspension with 5 mL oral syringe) 
EU/1/18/1279/003 (AMGLIDIA 6 mg/mL oral suspension with 1 mL oral syringe) 
EU/1/18/1279/004 (AMGLIDIA 6 mg/mL oral suspension with 5 mL oral syringe) 
 
 
13. BATCH NUMBER 
 
 
Lot 
 
 
14. CONDITIONS DE PRESCRIPTION ET DE DÉLIVRANCE 
 
 
15. INDICATIONS D’UTILISATION 
 
 
16. INFORMATION IN BRAILLE 
 
AMGLIDIA 0.6 mg/mL 
AMGLIDIA 6 mg/Ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



25 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



26 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
BOTTLE  
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
AMGLIDIA 0.6 mg/mL oral suspension 
AMGLIDIA 6 mg/mL oral suspension 
glibenclamide 
Oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
Keep out of the sight and reach of children. 
 
 
3. EXPIRY DATE 
 
EXP  
Keep the bottle in the outer carton in order to protect from the light. 
After opening, keep the bottle tightly closed after each use and stored for a maximum of 30 days. 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 mL 
 
 
6. OTHER 
 
Each mL contains 0.6 mg glibenclamide. 
Each mL contains 6 mg glibenclamide. 
 
Contains sodium and benzoate, see leaflet for further information.  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



28 

Package leaflet: Information for the user 
 

AMGLIDIA 6 mg/mL oral suspension 
Glibenclamide 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as those of your child. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 

What is in this leaflet 
 
1. What AMGLIDIA is and what it is used for  
2. What you need to know before you give AMGLIDIA  
3. How to give AMGLIDIA 
4. Possible side effects  
5. How to store AMGLIDIA  
6. Contents of the pack and other information 
 
 
1. What AMGLIDIA is and what it is used for 
 
AMGLIDIA contains the active substance called glibenclamide which belongs to a group of medicines 
called sulphonylureas used for lowering blood sugar (blood-glucose).  
 
AMGLIDIA is used in newborns, infants and children to treat diabetes that occurs at birth (known as 
neonatal diabetes mellitus). Neonatal diabetes is a disease where the child’s body does not release 
enough insulin to control the level of blood sugar; AMGLIDIA is used only in patients who still have 
some ability to make insulin. 
Sulphonylureas like glibenclamide have been shown to be effective in certain genetic mutations 
responsible for the genesis of neonatal diabetes. 
 
You must talk to a doctor if your child does not feel better or if he/she feels worse after a few days. 
 
 
2. What you need to know before you give AMGLIDIA 
 
Do not give AMGLIDIA 
 
- if your child is allergic to glibenclamide or any of the other ingredients of this medicine (listed 

in section 6). 
- if your child has ketoacidosis (high blood levels of acid substances called ketones). 
- if your child suffers from porphyria (inability to break down body chemicals called porphyrins). 
- if your child is treated with bosentan, e.g. a medicine used to treat problems of blood 

circulation. 
- if your child suffers from severe renal dysfunction. 
- if your child suffers from severe liver dysfunction. 
 
Warnings and precautions  
 
Talk to your doctor before your child is given AMGLIDIA. 



29 

Your child’s blood sugar levels may become too low (hypoglycaemia) after taking AMGLIDIA. Tell 
the doctor if your child is pale, sweating, has irregular heart rhythm or seems disoriented, confused or 
unresponsive.  
 
Ask your doctor to determine at which frequency capillary blood sugar should be checked.  
 
G6PD is an enzyme evolved in sugar metabolism. If your child carries a G6PD enzyme deficiency, 
he/she may experiment an abnormal breakdown of red blood cells (acute haemolytic anaemia) after 
taking AMGLIDIA. 
Tell the doctor if you know that your child is affected by G6PD deficiency and contact him/her if you 
notice that your child is pale as compared to usually. 
 
Tell your doctor if your child suffers from renal or liver disorders. 
 
Children and adolescents 
 
AMGLIDIA is to be used for newborns, infants and children. Adolescents are not in need of this oral 
suspension formulation. 
 
Other medicines and AMGLIDIA 
 
Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any 
other medicines.  
 
Interactions of AMGLIDIA with other medicines are presented in the table below: 
 
Medicines Potential effects 
ACE inhibitors (used to treat hypertension) 
(such as captopril and enalapril)  

Blood sugar levels too low 

Acetazolamide (used to treat glaucoma) Increased blood sugar levels 
Adrenaline (epinephrine) and other 
sympathomimetic agents (used to treat 
serious allergic reaction, cardiovascular 
arrest, asthma) 

Increased blood sugar levels 

Alcohol (Alcohol present in medicines) Blood sugar levels too low 
Increased blood sugar levels 
Incorrect control of plasma sugar 

Anabolic steroids and male sex hormones 
(such as testosterone enanthate) (used to treat 
testosterone deficiency) 

Blood sugar levels too low 

Barbiturates (such as phenobarbital used to 
treat epilepsy) 

Increased blood sugar levels 

Beta-receptor blockers (such as propranolol 
used to treat high blood pressure, control 
irregular or fast heart beats, help prevent 
additional heart attack) 

Blood sugar levels too low 
Incorrect control of plasma sugar 
low blood sugar levels may be hidden   

Biguanides (such as metformin) used to treat 
diabetes mellitus 

Blood sugar levels too low 

Bosentan used to treat high blood pressure in 
the blood vessels between the heart and the 
lungs. 

Incorrect control of plasma sugar (see section 2 “Do 
not give AMGLIDIA”) 

Calcium channel blockers (such as nifedipine 
used to treat high blood pressure) 

Increased blood sugar levels 

Chloramphenicol (in case of oral route) is an 
antibiotic used to treat infections 

Blood sugar levels too low 

Ciclosporin used to prevent rejection of the Increased toxicity of ciclosporin 



30 

Medicines Potential effects 
transplanted organ 
Cimetidine used to relieve the symptoms of 
stomach and duodenal ulcers, oesophageal 
reflux disease and the Zollinger-Ellison 
syndrome 

Increased blood sugar levels 

Clarithromycin is an antibiotic used to treat 
certain infections 

Blood sugar levels too low 

Clonidine used to treat arterial hypertension Blood sugar levels too low 
Incorrect control of plasma sugar 
Incorrect control of plasma sugar 
Increased blood sugar levels 

Colesevelam used to lower cholesterol  Incorrect control of plasma sugar 
Corticosteroids (such as prednisone, 
prednisolone) used in various indications 
such as inflammation and asthma 

Increased blood sugar levels 

Coumarin derivatives (such as dicoumarol, 
acenocoumarol) used to decrease the clotting 
ability of the blood 

Blood sugar levels too low 
Incorrect dosage of coumarin derivatives 
administered 

Cyclophosphamides used to treat different 
types of cancer 

Blood sugar levels too low 

Diazoxide used for low blood sugar Increased blood sugar levels 
Disopyramide used to treat an irregularity in 
the heartbeat 

Blood sugar levels too low 

Diuretics (such as furosemide, 
hydrochlorothiazide) used to treat arterial 
hypertension 

Increased blood sugar levels 

Fibrates (such as bezafibrate, fenofibrate, 
gemfibrozil used to lower the level of fats) 

Blood sugar levels too low 

Fluoxetine  used to treat depression and 
anxiety disorders 

Blood sugar levels too low 

Glucagon used to treat high blood-glucose 
level 

Increased blood sugar levels 

Guanethidine used to treat high blood 
pressure 

Blood sugar levels too low 
Incorrect control of plasma sugar 

H2-receptor antagonists used for reducing 
stomach acid (such as ranitidine) to relieve 
the symptoms of stomach and duodenal 
ulcers, oesophageal reflux disease and the 
Zollinger-Ellison syndrome 

Incorrect control of plasma sugar 

Heparin used to decrease the clotting ability 
of the blood 

Blood sugar levels too low 

Ifosfamide used to treat different types of 
cancers 

Blood sugar levels too low 

Insulin used to lower blood sugar level Blood sugar levels too low 
Isoniazid used to treat tuberculosis Increased blood sugar levels 
Large doses of laxatives (such as macrogol) Increased blood sugar levels 
MAO inhibitors (such as iproniazide) used to 
treat depression 

Blood sugar levels too low 

Miconazole used to treat fungal infection Blood sugar levels too low 
Nicotinic acid (in high doses) used to 
decrease high levels of cholesterol and 
triglycerides which are fat-like substances in 
the blood 

Increased blood sugar levels 

Oestrogens (such as 17-beta oestradiol) used Increased blood sugar levels 

https://en.wikipedia.org/wiki/Hydrochlorothiazide


31 

Medicines Potential effects 
for hormonal treatment 
Other oral antidiabetics (such as metformin) 
used to lower blood-glucose level 

Blood sugar levels too low 

Oxypentifylline used to improve peripheral 
blood flow 

Blood sugar levels too low 

Phenothiazine derivatives (such as 
chlorpromazine) used to treat schizophrenia 
and other psychoses 

Increased blood sugar levels 

Phenytoin used to treat epilepsy Increased blood sugar levels 
Probenecid used to treat gout, gouty arthritis Blood sugar levels too low 
Progestogens (such as desogestrel, 
dydrogesterone) used for hormonal treatment 

Increased blood sugar levels 

Quinolone antibiotics (such as nalidixic acid 
and ciprofloxacine) used to treat infections 

Blood sugar levels too low 

Rifampicin used to treat infections including 
tuberculosis 

Increased blood sugar levels 

Sulfamethoxazole with trimethoprim (Co-
trimoxazole) used to treat infections 

Blood sugar levels too low 

Thyroid hormones (such as L-thyroxin) used 
for hormonal treatment 

Increased blood sugar levels 

Salicylates (such as aminosalicylic acid, 
para-aminosalicylic acid used for 
tuberculosis) 

Blood sugar levels too low 

Tetracycline antibiotics (such as doxycycline 
and minocycline) used to treat infections 

Blood sugar levels too low 

 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines. 
 
AMGLIDIA with alcohol 
 
Both acute and chronic alcohol intake may attenuate the hypoglycaemic effect of glibenclamide or 
dangerously potentiate it by delaying its metabolic inactivation. Nausea, vomiting, flushing, dizziness, 
headache, chest and abdominal discomfort, and general hangover-like symptoms among others have 
occurred following the concomitant use of alcohol and glibenclamide. Concomitant use of alcohol and 
glibenclamide should be avoided. 
 
Pregnancy and breast-feeding 
 
This medicine may only be used for the treatment of neonatal diabetes in newborns, infants and 
children. 
This medicine is not intended to be used in pregnant women and patients planning a pregnancy should 
inform their doctor. It is recommended that such patients change treatment to insulin. 
Breast-feeding seems to be compatible, but as a precautious measure monitoring of the fully breast-fed 
infant’s blood sugar level is advisable. 
 
Driving and using machines 
 
Glibenclamide may increase the risk of low blood sugar and therefore have a moderate influence on 
the ability to drive, to take part in road traffic otherwise or use machines. 
 
AMGLIDIA contains sodium and benzoate salt 
 
This medicine contains 2.80 mg of sodium per mL. To be taken into consideration by patients on a 
controlled sodium diet. 



32 

This medicine contains 5 mg benzoate salt in each mL oral suspension. Benzoate salt may increase 
jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks old). 
 
 
3. How to give AMGLIDIA 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Dosage 
 
Glibenclamide therapy should be started by a doctor experienced in the treatment of patients with very 
early onset diabetes.  
 
The dose of AMGLIDIA depends on your child’s body weight, and will be calculated by the doctor as 
an amount (volume) in mL of oral suspension to be measured with the oral syringe (either an 1 mL or 
a 5 mL syringe) supplied with the medicine. Your doctor will prescribe the specific presentation and 
strength including the particular syringe you should use. Do not use any other syringe to administer 
AMGLIDIA. 
It is important you do not adjust yourself the doses of either AMGLIDIA or insulin, unless specifically 
directed to do so by your child’s doctor. 
 
Make sure that you use correct strength of the medicine and the appropriate oral syringe prescribed by 
your doctor to avoid accidental administration of too high or too low amounts. 
 
The starting dose of AMGLIDIA is 0.2 mg of glibenclamide for each kilogram (kg) of body weight 
daily, divided in two doses of 0.1 mg/kg. As the dose is increased, it is usually possible to reduce and 
then stop the dose of insulin the patient is already receiving.  
 
Higher doses of AMGLIDIA can be given as needed and administered in up to four intakes per day, 
based on blood-glucose monitoring, as per titration recommendations given by the referring doctor. 
 
In case of minor vomiting, an antivomiting medicine will be prescribed by your doctor and 
AMGLIDIA can be continued. 
As generally recommended in such situations, if vomiting occurs less than 30 minutes following 
administration of AMGLIDIA, a new dose can be given. If vomiting occurs more than 30 minutes 
following administration of AMGLIDIA, no new dose should be given. Always ask your child’s 
doctor for advice in such circumstances. 
 
In case of major vomiting, ketonemia and ketonuria should be closely monitored by the treating 
doctor. The doctor may start insulin therapy again, when ketonemia or ketonuria were found to be 
responsible for the major vomiting. In case of inability of food or beverage intake, the child should go 
to emergency department to get an insulin and glucose perfusion until vomiting stops. 
 
Method of administration 
 
Always give the medicine before feeding,  
 
The medicine should be given at the same time each day. 
 
In case of milk feeding, recommendation is given to administer the suspension 15 minutes before 
child’s milk feeding. 
 
This medicine is a ready-for-use oral suspension to be given with a marked oral syringe. Only the oral 
syringe included in the carton should be used.  
The 1 mL syringe is thin and small and graduated in steps of 0.05 mL. The 5 mL syringe is thick and 
long and graduated in steps of 0.1 mL. 



33 

Instructions for use 
 
The dose is measured by drawing the plunger of the syringe back until it reaches the marking for the 
dose the doctor has prescribed for your child. The dose in mL per administration and the number of 
administrations per day have to carefully follow the medical prescription. 
 
While the child is awake, position the child in half-sitting position in the hollow of your arm, with the 
child’s head resting on your arm. 
 
Slip about the first 1 cm of the syringe into the child’s mouth and place it against the inside cheek; 
Let the child suck. If the child does not suck, slowly press the plunger of the syringe so that the 
suspension trickles into the mouth. 
 
Do not lay the child down directly after administration. It is recommended to wait for the child has 
swallowed the medicine before reverting back to lying position. 
 
For first use 

1. Open the bottle by unscrewing the child-resistant closure while pressing downwards. 

 
2. Insert the adaptor firmly into the bottle while holding the bottle the right way up. 
3. Replace the screw cap on the bottle with the adaptor. 
4. Retighten the screw cap to push the adaptor well into the bottle. 

For each administration 
1. The bottle does not need to be shaken before administration. The medicine is administered as 

a ready-for-use oral suspension to be given using a specific marked syringe. 
2. Open the bottle by unscrewing the child-resistant closure while pressing downwards (figure 

1). 
3. Holding the bottle the right way up, insert the syringe firmly into the adaptor fitted to the 

bottle (figure 2). 
4. Turn the bottle with the syringe upside down (figure 3). 
5. Draw back the plunger to obtain the desired volume (figure 4A). Then push the plunger to 

remove as many air bubbles as possible from the syringe (figure 4B). Finally, draw back the 
plunger until graduation corresponding to the prescribed dose in mL (figure 4C).  
Note: if air gets into the syringe, empty the syringe into the bottle and start the procedure 
again.  

6. Turn the bottle with the syringe into its upright position. 
7. Remove the syringe from the adaptor. Put the syringe into the child mouth and push the 

plunger to slowly administer the medicine into the mouth.  
8. Close the bottle by tightening the screw cap well on top of the adaptor. 

 The bottle must be closed after each use and stored for a maximum of 30 days. 
9. The syringe must be rinsed thoroughly with water, wiped dry after each use and replaced back 

into the medicine’s carton. The oral syringe in the carton should be used only with this 
medicine. 



34 

 
 
If you give more AMGLIDIA to your child than you should 
See your doctor, nurse or your hospital pharmacist immediately. 
 
There is a risk of hypoglycaemia. You should check capillary blood sugar of your child and follow the 
instructions described in section 4. 
 
If you forget to give AMGLIDIA 
 
If you forget to give AMGLIDIA, there is a risk of high blood sugar.  
 
You must check your child’s blood sugar (capillary blood sugar) and give AMGLIDIA as soon as you 
realise you have forgotten to use it. If your child’s capillary blood sugar exceeds 3 g/L (or 300 mg/dL 
or 16.5 mmol/L), check for the presence of ketonuria with a finger stick or urine stick tests according 
to your child’s doctor recommendations. If ketonuria is detected, you must inject insulin immediately 
according to the procedure defined beforehand with your child’s doctor and contact him/her or his/her 
team for advice. 
 
Do not give a double dose to make up for a forgotten dose. 
 
If you stop giving AMGLIDIA 
There is a risk of high blood sugar.  
 
You should check your child’s blood sugar (capillary blood sugar). Diabetes symptoms may reappear 
and may lead to a serious disturbance of the body’s metabolism with high blood levels of ketones 
(ketoacidosis), dehydration and disturbance of the balance of acids in the body. You should therefore 
never stop the medicine without checking with the doctor looking after your child. Seek advice from 
your doctor. 
 
You will be requested to bring back remaining AMGLIDIA oral suspension to your doctor at each 
consultation. 
 
If you have any further questions on the use of this medicine, ask the doctor of your child or 
pharmacist. 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
 
Too low blood sugar (hypoglycaemia) (very common: may affect more than 1 in 10 people) 
If you take AMGLIDIA, you are at risk of getting too low blood sugar (hypoglycaemia). The signs of 
too low blood sugar may include: 
- shaking, sweating, feeling very anxious or confused, fast heart beat 
- excessive hunger, headache 



35 

If your child starts to become pale, sweating, has irregular heart rhythm or seems disoriented, confused 
or unresponsive, these may be signs that the child’s blood sugar is too low ; you should first solve the 
situation as explained below and you should then talk to your child’s doctor to adapt AMGLIDIA’s 
dose.  
The risk of low blood sugar is increased if the medicine is not taken with a meal, is taken with alcohol, 
or if combined with certain medicines. Such low blood sugar should be managed by taking sugar by 
mouth followed by a snack or meal. If very low blood sugar occurs that affects consciousness, 
emergency services should be called and an intravenous glucose injection performed. After such a 
severe episode of hypoglycaemia, the child and family should see the child’s doctor to check the 
appropriateness of the dose of glibenclamide suspension.  
 
Allergic reactions  
This medicine may cause allergic reactions, which may be serious in isolated cases, including 
difficulties to breath, low blood pressure and shock. If your child presents any of theses symptoms, you 
should immediately go to the nearest emergency department. 
 
Gastro intestinal disorders (very common: may affect more than 1 in 10 people): 

 
- Diarrhea 
- Abdominal (belly) pain 
- Vomiting 
- Stomach ache (Dyspepsia) 
 
Teeth problems (common: may affect up to 1 in 10 people): 

 
- Tooth discoloration. 
 
Abnormal blood test results (very common: may affect more than 1 in 10 people) 
 
Laboratory blood tests may show changes in blood cells (decrease in white blood cells: leucopenia) 
and effects on liver function (brief increase in enzymes called transaminases). 
 
Other side effects: 
 
Tell your doctor or pharmacist if you notice any of the following side effects: 
- Skin rash: itching, nettle rash (urticarial), allergic skin reaction, blistering of the skin, skin 

inflammation. 
- Increase in sensitivity of the skin to sunlight. 
- Transient visual disturbances. 
- Other laboratory blood tests changes: increased levels of the white blood cells called eosinophils 

(hypereosinophilia), mild to severe decrease in blood components called platelets 
(thrombocytopenia) which can lead to subcutaneous bleeding (purpura). 

 
Reporting of side effects 
 
If you notice any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects, you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store AMGLIDIA 
 
Keep this medicine out of the sight and reach of children. 
Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. The 
expiry date refers to the last day of that month. 
Keep the bottle in the outer carton in order to protect from light. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


36 

After first opening, use within 30 days. Keep the bottle tightly closed. 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What AMGLIDIA contains  
- The active substance is glibenclamide. Each mL contains 6 mg glibenclamide. 
- The other ingredients are: xanthan gum, hydroxyethylcellulose, lactic acid, purified water 

sodium citrate and sodium benzoate (E211) (see section 2 “AMGLIDIA contains sodium and 
benzoate”). 

 
What AMGLIDIA looks like and contents of the pack 
 
AMGLIDIA is a white and odourless oral suspension.  
Each carton contains: 
- 1 bottle containing 30 mL oral suspension 
- one 1 mL oral syringe (thin and small) or one 5 mL oral syringe (thick and long) depending on 

the prescribed dose and the volume to be given. The syringe is packed in a transparent bag. 
- one syringe adaptor. 

 
Marketing Authorisation Holder  
 
AMMTek 
55 rue de Turbigo  
75003 Paris 
France 
 
Manufacturer 
 
Unither Développement Bordeaux 
ZA Tech-Espace, Avenue Toussaint-Catros 
33185 Le Haillan 
France 
 
Centre Spécialités Pharmaceutiques 
76-78 Avenue du midi  
63800 Cournon d’Auvergne  
France 
 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 



37 

 
Package leaflet: Information for the user 
AMGLIDIA 0.6 mg/mL oral suspension 

Glibenclamide 
 

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as those of your child. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What AMGLIDIA is and what it is used for  
2. What you need to know before you give AMGLIDIA  
3. How to give AMGLIDIA 
4. Possible side effects  
5. How to store AMGLIDIA  
6. Contents of the pack and other information 
 
 
1. What AMGLIDIA is and what it is used for 
 
AMGLIDIA contains the active substance called glibenclamide which belongs to a group of medicines 
called sulphonylureas used for lowering blood sugar (blood-glucose).  
 
AMGLIDIA is used in newborns, infants and children to treat diabetes that occurs at birth (known as 
neonatal diabetes mellitus). Neonatal diabetes is a disease where the child’s body does not release 
enough insulin to control the level of blood sugar; AMGLIDIA is used only in patients who still have 
some ability to make insulin..  
Sulphonylureas like glibenclamide have been shown to be effective in certain genetic mutations 
responsible for the genesis of neonatal diabetes. 
 
This medicine is an oral suspension, to be taken by mouth, which is a more convenient treatment for 
newborns and young children compared to regular injections of insulin.  
 
You must talk to a doctor if your child does not feel better or if he/she feels worse after a few days. 
 
 
2. What you need to know before you give AMGLIDIA 
 
Do not give AMGLIDIA 
 
- if your child is allergic to glibenclamide or any of the other ingredients of this medicine (listed 

in section 6). 
- if your child has ketoacidosis (high blood levels of acid substances called ketones). 
- if your child suffers from porphyria (inability to break down body chemicals called porphyrins). 
- if your child is treated with bosentan, e.g. a medicine used to treat problems of blood 

circulation. 
- if your child suffers from severe renal dysfunction. 
- if your child suffers from severe liver dysfunction. 
 
Warnings and precautions  
 



38 

Talk to your doctor before your child is given AMGLIDIA. 
 
Your child’s blood sugar levels may become too low (hypoglycaemia) after taking AMGLIDIA. Tell 
the doctor if your child is pale, sweating, has irregular heart rhythm or seems disoriented, confused or 
unresponsive..  
 
Ask your doctor to determine at which frequency capillary blood sugar should be checked. 
G6PD is an enzyme evolved in sugar metabolism. If your child carries a G6PD enzyme deficiency, 
he/she may experiment an abnormal breakdown of red blood cells (acute haemolytic anaemia) after 
taking AMGLIDIA. 
Tell the doctor if you know that your child is affected by G6PD deficiency and contact him/her if you 
notice that your child is pale as compared to usually. 
 
Tell your doctor if your child suffers from renal or liver disorders. 
 
Children and adolescents 
 
AMGLIDIA is to be used for newborns, infants and children. Adolescents are not in need of this oral 
suspension formulation. 
 
Other medicines and AMGLIDIA 
 
Tell your child’s doctor or pharmacist if your child is taking, has recently taken or might take any 
other medicines. 
 
Interactions of AMGLIDIA with other medicines are presented in the table below: 
 
Medicines Potential effects 
ACE inhibitors (used to treat hypertension) 
(such as captopril and enalapril)  

Blood sugar levels too low 

Acetazolamide (used to treat glaucoma) Increased blood sugar levels 
Adrenaline (epinephrine) and other 
sympathomimetic agents (used to treat 
serious allergic reaction, cardiovascular 
arrest, asthma) 

Increased blood sugar levels 

Alcohol (Alcohol present in medicines) Blood sugar levels too low 
Increased blood sugar levels 
Incorrect control of plasma sugar 

Anabolic steroids and male sex hormones 
(such as testosterone enanthate) (used to treat 
testosterone deficiency) 

Blood sugar levels too low 

Barbiturates (such as phenobarbital used to 
treat epilepsy) 

Increased blood sugar levels 

Beta-receptor blockers (such as propranolol 
used to treat high blood pressure, control 
irregular or fast heart beats, help prevent 
additional heart attack) 

Blood sugar levels too low 
Incorrect control of plasma sugar 
low blood sugar levels may be hidden 

Biguanides (such as metformin) used to treat 
diabetes mellitus 

Blood sugar levels too low 

Bosentan used to treat high blood pressure in 
the blood vessels between the heart and the 
lungs. 

Incorrect control of plasma sugar (see section 2 “Do 
not give AMGLIDIA”) 

Calcium channel blockers (such as nifedipine 
used to treat high blood pressure) 

Increased blood sugar levels 

Chloramphenicol (in case of oral route) is an 
antibiotic used to treat infections 

Blood sugar levels too low 



39 

Medicines Potential effects 
Ciclosporin used to prevent rejection of the 
transplanted organ 

Increased toxicity of ciclosporin 

Cimetidine used to relieve the symptoms of 
stomach and duodenal ulcers, oesophageal 
reflux disease and the Zollinger-Ellison 
syndrome 

Increased blood sugar levels 

Clarithromycin is an antibiotic used to treat  
certain infections 

Blood sugar levels too low 

Clonidine  used to treat arterial hypertension Blood sugar levels too low 
Incorrect control of plasma sugar 
Incorrect control of plasma sugar 
Increased blood sugar levels 

Colesevelam  used to lower cholesterol Incorrect control of plasma sugar 
Corticosteroids (such as prednisone, 
prednisolone) used in various indications 
such as inflammation and asthma 

Increased blood sugar levels 

Coumarin derivatives (such as dicoumarol, 
acenocoumarol) used to decrease the clotting 
ability of the blood 

Blood sugar levels too low 
Incorrect dosage of coumarin derivatives 
administered 

Cyclophosphamides used to treat different 
types of cancer 

Blood sugar levels too low 

Diazoxide used for low blood sugar Increased blood sugar levels 
Disopyramide  used to treat an irregularity in 
the heartbeat 

Blood sugar levels too low 

Diuretics (such as furosemide, 
hydrochlorothiazide) used to treat arterial 
hypertension 

Increased blood sugar levels 

Fibrates (such as bezafibrate, fenofibrate, 
gemfibrozil used to lower the level of fats) 

Blood sugar levels too low 

Fluoxetine  used to treat depression and 
anxiety disorders 

Blood sugar levels too low 

Glucagon used to treat high blood-glucose 
level 

Increased blood sugar levels 

Guanethidine used to treat high blood 
pressure 

Blood sugar levels too low 
Incorrect control of plasma sugar 

H2-receptor antagonists used for reducing 
stomach acid (such as ranitidine) to relieve 
the symptoms of stomach and duodenal 
ulcers, oesophageal reflux disease and the 
Zollinger-Ellison syndrome 

Incorrect control of plasma sugar 

Heparin used to decrease the clotting ability 
of the blood 

Blood sugar levels too low 

Ifosfamide used to treat different types of 
cancers 

Blood sugar levels too low 

Insulin used to lower blood sugar level Blood sugar levels too low 
Isoniazid  used to treat tuberculosis Increased blood sugar levels 
Large doses of laxatives (such as macrogol) Increased blood sugar levels 
MAO inhibitors (such as iproniazide) used to 
treat depression 

Blood sugar levels too low 

Miconazole used to treat fungal infection Blood sugar levels too low 
Nicotinic acid (in high doses) used to 
decrease high levels of cholesterol and 
triglycerides which are fat-like substances in 
the blood 

Increased blood sugar levels 



40 

Medicines Potential effects 
Oestrogens (such as 17-beta oestradiol) used 
for hormonal treatment 

Increased blood sugar levels 

Other oral antidiabetics (such as metformin) 
used to lower blood-glucose level 

Blood sugar levels too low 

Oxypentifylline used to improve peripheral 
blood flow 

Blood sugar levels too low 

Phenothiazine derivatives (such as 
chlorpromazine) used to treat schizophrenia 
and other psychoses 

Increased blood sugar levels 

Phenytoin used to treat epilepsy Increased blood sugar levels 
Probenecid used to treat gout, gouty arthritis Blood sugar levels too low 
Progestogens (such as desogestrel, 
dydrogesterone) used for hormonal treatment 

Increased blood sugar levels 

Quinolone antibiotics (such as nalidixic acid 
and ciprofloxacine) used to treat infections 

Blood sugar levels too low 

Rifampicin used to treat infections including 
tuberculosis 

Increased blood sugar levels 

Sulfamethoxazole with trimethoprim (Co-
trimoxazole) used to treat infections 

Blood sugar levels too low 

Thyroid hormones (such as L-thyroxin) used 
for hormonal treatment 

Increased blood sugar levels 

Salicylates (such as aminosalicylic acid, 
para-aminosalicylic acid used for 
tuberculosis) 

Blood sugar levels too low 

Tetracycline antibiotics (such as doxycycline 
and minocycline) used to treat infections 

Blood sugar levels too low 

 
Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other 
medicines. 
 
AMGLIDIA with alcohol 
 
Both acute and chronic alcohol intake may attenuate the hypoglycaemic effect of glibenclamide or 
dangerously potentiate it by delaying its metabolic inactivation. Nausea, vomiting, flushing, dizziness, 
headache, chest and abdominal discomfort, and general hangover-like symptoms among others have 
occurred following the concomitant use of alcohol and glibenclamide. Concomitant use of alcohol and 
glibenclamide should be avoided. 
 
Pregnancy and breast-feeding 
 
This medicine may only be used for the treatment of neonatal diabetes in newborns, infants and 
children. 
This medicine is not intended to be used in pregnant women and patients planning a pregnancy should 
inform their doctor. It is recommended that such patients change treatment to insulin. 
Breast-feeding seems to be compatible, but as a precautious measure monitoring of the fully breast-fed 
infant’s blood sugar level is advisable. 
 
Driving and using machines 
 
Glibenclamide may increase the risk of low blood sugar and therefore have a moderate influence on 
the ability to drive, to take part in road traffic otherwise or use machines.  
 
AMGLIDIA contains sodium and benzoate salt 
This medicine contains 2.80 mg of sodium per mL. To be taken into consideration by patients on a 
controlled sodium diet. 



41 

This medicine contains 5 mg benzoate salt in each mL oral suspension. Benzoate salt may increase 
jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks old). 
 
 
3. How to give AMGLIDIA 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Dosage 
 
Glibenclamide therapy should be started by a doctor experienced in the treatment of patients with very 
early onset diabetes.  
 
The dose of AMGLIDIA depends on your child’s body weight, and will be calculated by the doctor as 
an amount (volume) in mL oral suspension to be measured with the oral syringe (either an 1 mL or a 
5 mL syringe) supplied with the medicine. Your doctor will prescribe the specific presentation and 
strength including the particular syringe you should use. Do not use any other syringe to administer 
AMGLIDIA. 
 
It is important you do not adjust yourself the doses of either AMGLIDIA or insulin, unless specifically 
directed to do so by your child’s doctor. 
 
Make sure that you use correct strength of the medicine and the appropriate oral syringe prescribed by 
your doctor to avoid accidental administration of too high or too low amounts.  
 
The starting dose of AMGLIDIA is 0.2 mg of glibenclamide for each kilogram (kg) of body weight 
daily, divided in two doses of 0.1 mg/kg. As the dose is increased, it is usually possible to reduce and 
then stop the dose of insulin the patient is already receiving. 
 
Higher doses of AMGLIDIA can be given as needed and administered in up to four intakes per day 
based on blood-glucose monitoring, as per titration recommendations given by the referring doctor. 
 
In case of minor vomiting, an antivomiting medicine will be prescribed by your doctor and 
AMGLIDIA can be continued. 
As generally recommended in such situations, if vomiting occurs less than 30 minutes following 
administration of AMGLIDIA, a new dose can be given. If vomiting occurs more than 30 minutes 
following administration of AMGLIDIA, no new dose should be given. Always ask your child’s 
doctor for advice in such circumstances. 
 
In case of major vomiting, ketonemia and ketonuria should be closely monitored by the treating 
doctor. The doctor may start insulin therapy again, when ketonemia or ketonuria were found to be 
responsible for the major vomiting. In case of inability of food or beverage intake, the child should go 
to emergency department to get an insulin and glucose perfusion until vomiting stops. 
 
Method of administration 
 
Always give the medicine 15 minutes before feeding. 
 
The medicine should be given at the same times each day. 
 
In case of milk feeding, recommendation is given to administer the suspension 15 minutes before 
child’s milk feeding. 
 
This medicine is a ready-for-use oral suspension to be given with a marked oral syringe. Only the oral 
syringe included in the carton should be used.  



42 

The 1 mL syringe is thin and small and graduated in steps of 0.05 mL. The 5 mL syringe is thick and 
long and graduated in steps of 0.1 mL. 
 
Instructions for use 
 
The dose is measured by drawing the plunger of the syringe back until it reaches the marking for the 
dose the doctor has prescribed for your child. The dose in mL per administration and the number of 
administrations per day have to carefully follow the medical prescription. 
 
While the child is awake, position the child in half-sitting position in the hollow of your arm, with the 
child’s head resting on your arm. 
 
Slip about the first 1 cm of the syringe into the child’s mouth and place it against the inside cheek; 
Let the child suck. If the child does not suck, slowly press the plunger of the syringe so that the 
suspension trickles into the mouth. 
 
Do not lay the child down directly after administration. It is recommended to wait for the child has 
swallowed the medicine before reverting back to lying position. 
 
For first use 

1. Open the bottle by unscrewing the child-resistant closure while pressing downwards. 

 
2. Insert the adaptor firmly into the bottle while holding the bottle the right way up. 
3. Replace the screw cap on the bottle with the adaptor. 
4. Retighten the screw cap to push the adaptor well into the bottle. 

For each administration 
1. The bottle does not need to be shaken before administration. The medicine is administered as 

a ready-for-use oral suspension to be given using a specific marked syringe. 
2. Open the bottle by unscrewing the child-resistant closure while pressing downwards (figure 

1). 
3. Holding the bottle the right way up, insert the syringe firmly into the adaptor fitted to the 

bottle (figure 2). 
4. Turn the bottle with the syringe upside down (figure 3). 
5. Draw back the plunger to obtain the desired volume (figure 4A). Then push the plunger to 

remove as many air bubbles as possible from the syringe (figure 4B). Finally, draw back the 
plunger until graduation corresponding to the prescribed dose in ml (figure 4C).  
Note: if air gets into the syringe, empty the syringe into the bottle and start the procedure 
again.  

6. Turn the bottle with the syringe into its upright position. 
7. Remove the syringe from the adaptor. Put the syringe into the child mouth and push the 

plunger to slowly administer the medicine into the mouth.  
8. Close the bottle by tightening the screw cap well on top of the adaptor. 

 The bottle must be closed after each use and stored for a maximum of 30 days. 
9. The syringe must be rinsed thoroughly with water, wiped dry after each use and replaced back 

into the medicine’s carton. The oral syringe in the carton should be used only with this 
medicine. 



43 

 
 
If you give more AMGLIDIA to your child than you should 
 
See your doctor, nurse or your hospital pharmacist immediately. 
There is a risk of hypoglycaemia. You should check capillary blood sugar of your child and follow the 
instructions described in section 4. 
 
If you forget to give AMGLIDIA 
 
If you forget to give AMGLIDIA, there is a risk of high blood sugar.  
 
You must check your child’s blood sugar (capillary blood sugar) and give AMGLIDIA as soon as you 
realise you have forgotten to use it. If your child’s capillary blood sugar exceeds 3 g/L (or 300 mg/dL 
or 16.5 mmol/L), check for the presence of ketonuria with a finger stick or urine stick tests according 
to your child’s doctor recommendations. If ketonuria is detected, you must inject insulin immediately 
according to the procedure defined beforehand with your child’s doctor and contact him/her or his/her 
team for advice. 
Do not give a double dose to make up for a forgotten dose. 
 
If you stop giving AMGLIDIA 
 
There is a risk of high blood sugar.  
 
You should check your child’s blood sugar (capillary blood sugar). Diabetes symptoms may reappear 
and may lead to a serious disturbance of the body’s metabolism with high blood levels of ketones 
(ketoacidosis), dehydration and disturbance of the balance of acids in the body. You should therefore 
never stop the medicine without checking with the doctor looking after your child. Seek advice from 
your doctor. 
 
You will be requested to bring back remaining AMGLIDIA oral suspension to your doctor at each 
consultation. 
 
If you have any further questions on the use of this medicine, ask the doctor of your child or 
pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
 
Too low blood sugar (hypoglycaemia) (very common: may affect more than 1 in 10 people) 
 
If you take AMGLIDIA, you are at risk of getting too low blood sugar (hypoglycaemia). The signs of 
too low blood sugar may include: 
- shaking, sweating, feeling very anxious or confused, fast heart beat 



44 

- excessive hunger, headache 
 
If your child starts to become pale, sweating, has irregular heart rhythm or seems disoriented, confused 
or unresponsive, these may be signs that the child’s blood sugar is too low ; you should first solve the 
situation as explained below and you should then talk to your child’s doctor to adapt AMGLIDIA’s 
dose. 
 
The risk of low blood sugar is increased if the medicine is not taken with a meal, is taken with alcohol, 
or if combined with certain medicines. Such low blood sugar should be managed by taking sugar by 
mouth followed by a snack or meal. If very low blood sugar occurs that affects consciousness, 
emergency services should be called and an intravenous glucose injection performed. After such a 
severe episode of hypoglycaemia, the child and family should see the child’s doctor to check the 
appropriateness of the dose of glibenclamide suspension.  
 
Allergic reactions  
 
This medicine may cause allergic reactions, which may be serious in isolated cases, including 
difficulties to breath, low blood pressure and shock. If your child presents any of theses symptoms, you 
should immediately go to the nearest emergency department. 
 
Gastro intestinal disorders (very common: may affect more than 1 in 10 people): 

 
- Diarrhea 
- Abdominal (belly) pain 
- Vomiting 
- Stomach ache (Dyspepsia) 
 
Teeth problems (common: may affect up to 1 in 10 people): 

 
- Tooth discoloration. 
 
Abnormal blood test results (very common: may affect more than 1 in 10 people) 
 
Laboratory blood tests may show changes in blood cells (decrease in white blood cells: leucopenia) 
and effects on liver function (brief increase in enzymes called transaminases). 
 
Other side effects: 
 
Tell your doctor or pharmacist if you notice any of the following side effects: 
- Skin rash: itching, nettle rash (urticarial), allergic skin reaction, blistering of the skin, skin 

inflammation. 
- Increase in sensitivity of the skin to sunlight 
- Transient visual disturbances. 
- Other laboratory blood tests changes: increased levels of the white blood cells called eosinophils 

(hypereosinophilia), mild to severe decrease in blood components called platelets 
(thrombocytopenia), which can lead to subcutaneous bleeding (purpura). 

 
Reporting of side effects 
 
If you notice any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store AMGLIDIA 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


45 

Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and bottle after EXP. The 
expiry date refers to the last day of that month. 
 
Keep the bottle the outer carton in order to protect from light. 
 
After first opening, use within 30 days. Keep the bottle tightly closed. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What AMGLIDIA contains  
 
- The active substance is glibenclamide. Each mL contains 0.6 mg glibenclamide. 
- The other ingredients are: xanthan gum, hydroxyethylcellulose, lactic acid, purified water, 

sodium citrate and sodium benzoate (E211) (see section 2 “AMGLIDIA contains sodium and 
benzoate). 

-  
What AMGLIDIA looks like and contents of the pack 
 
AMGLIDIA is a white and odourless oral suspension.  
 
Each carton contains: 
- 1 bottle containing 30 mL oral suspension 
- one 1 mL oral syringe (thin and small) and or 5 mL oral syringe (thick and long) depending on 

the prescribed dose and the volume to be given. The syringe is packed in a transparent bag. 
- one syringe adaptor. 
 
Marketing Authorisation Holder  
 
AMMTeK 
55 rue de Turbigo  
75003 Paris 
France 
 
Manufacturer 
Unither Développement Bordeaux 
ZA Tech-Espace, Avenue Toussaint-Catros 
33185 Le Haillan 
France 
 
Centre Spécialités Pharmaceutiques 
76-78 Avenue du midi  
63800 Cournon d’Auvergne  
France 
 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET