Amglidia · 4.8 Undesirable effects · 1

HOS-217651 · has-adverse-reaction-information · PDF-Seite 12

Summary of the safety profile The most frequent adverse reactions are hypoglycaemia, transitory diarrhoea and abdominal pain. The most serious adverse reaction is hypoglycaemia (see section 4.4). Overall, the safety profile of glibenclamide is in line with the safety profile of others sulfonylureas. 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. Table 3: Adverse reactions MedDRA system organ class Adverse reactions Very common Common Blood and lymphatic system Neutropenia disorders Eye disorders Vision blurred Metabolism and nutrition disorders Hypoglycaemia Gastrointestinal disorders Transitory diarrhoea, Abdominal Tooth discolouration pain,Vomiting Dyspepsia Investigations Transitory increased transaminases Skin disorders Skin rash Description of selected adverse reactions The following adverse reactions have been observed in a clinical study (Neogli study) and during the extension phase. 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 diarrhoea, vomiting and abd

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HOS-217647 · has-contraindication-information · PDF-Seite 6

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 sodium chloride solution 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

HOS-217646 · has-indication-information · PDF-Seite 2

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.

HOS-217649 · has-interaction-information · PDF-Seite 7

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. 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 dose 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. Summary of interactions A summary of the interactions detailed above and further interactions are summarized in the table below. Table 2 : Summary of interactions Active substance Effect of interaction Potential risk ACE inhibitors Potentiation of the Hypoglycaemia blood-glucose lowering effect Acetazolamide Weakening of the Increased blood-glucose blood-glucose lowering levels effect Adrenaline (epinephrine

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HOS-217650 · has-pregnancy-information · PDF-Seite 11

General aspects AMGLIDIA is indicated for the treatment of neonatal diabetes in newborns, infants and children. Women of childbearing potential 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 first trimester does not seem to cause an increase in congenital malformations. With respect to the second and third 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 hypoglycaemia 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.

HOS-217648 · has-warning-information · PDF-Seite 6

Special care should be taken when calculating the dose. Before each administration, it should be verified that the correct strength and syringe are used (see section 4.2). Glibenclamide 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. Ketoacidosis  Neonatal diabetes is a life-threatening and chronically debilitating condition due to hyperglycemia, which includes symptoms such like thirst, frequent urination, and dehydration. In severe cases this is associated with ketoacidosis which can led to death. Glibenclamide should not be used to treate this life- threatening condition. Continuous intravenous insulin injection and intravenous infusion of physiologic sodium chloride solution remains the benchmark treatment. Hypoglycaemia Hypoglycaemia can occur under treatment with hypoglycaemic sulphonamides. This can sometimes be severe and prolonged. Hospitalisation may then prove necessary and glucose may have to be administered for several days. Diarrhoea, nausea and vomiting In some patients, there may be an initial diarrhoea 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 glibenclamide can be continued. Biological analyses Blood-glucose should be monitored periodically throughout treatment with glibenclamide. If the bl

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