Symptoms
Hypoglycaemia has not been seen with Meglucon Hexal hydrochloride doses of up to 85g, although lactic acidosis has occurred in such circumstances. High overdose of Meglucon Hexal or concomitant risks may lead to lactic acidosis.
Management
Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Meglucon Hexal is haemodialysis.
Hypoglycaemia has not been seen with Meglucon Hexal doses of up to 85 g, although lactic acidosis has occurred in such circumstances. High overdose of Meglucon Hexal or concomitant risks may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and Meglucon Hexal is haemodialysis.
-
- Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis.)
- Severe renal failure (GFR <30 mL/min)
- Acute conditions with the potential to alter renal function such as:
| o dehydration o severe infection o shock |
- Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as:
- Decompensated heart failure o respiratory failure o recent myocardial infarction o shock |
- Hepatic insufficiency, acute alcohol intoxication, alcoholism.
- Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
- Severe renal failure (GFR <30 mL/min)
- Acute conditions with the potential to alter renal function such as:
o dehydration,
o severe infection,
o shock,
- Acute or chronic disease which may cause tissue hypoxia such as:
o cardiac or respiratory failure,
o recent myocardial infarction,
o shock
- Hepatic insufficiency, acute alcohol intoxication, alcoholism
Not applicable.
Not applicable
During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases. To prevent them, it is recommended to take Meglucon Hexal in 2 or 3 daily doses and to increase the doses slowly.
Adverse events are which have been associated with Meglucon Hexal are given below, listed by system organ class and frequency. Undesirable effects are especially likely to occur at treatment onset or at dose increase.
The following adverse reactions may occur under treatment with Meglucon Hexal. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness:
very common (>1/10),
common (>1/100 to <1/10),
uncommon (>1/1000 to<1/100),
rare (>1/10000 to<1/1000),
very rare (<1/10000),
not known (cannot be estimated from the available data).
| System organ class | Frequency | Undesirable effects |
| Metabolism and nutrition disorders | Very rare | Lactic acidosis ( serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis) |
| Nervous system disorders | Common | Taste disturbance |
| Gastrointestinal disorders | Very common | nausea, vomiting, diarrhoea, abdominal pain and loss of appetite i |
| Hepatobiliary disorders | Very rare | liver function test abnormalities or hepatitisii |
| Skin and subcutaneous tissue disorders | Very rare | Skin reactions such as erythema, pruritus, urticaria |
i) These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that Meglucon Hexal be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.
ii) Isolated reports of liver function test abnormalities or hepatitis resolving upon Meglucon Hexal discontinuation
Paediatric population
In published and post marketing data and in controlled clinical studies in a limited paediatric population aged 10-16 years treated during 1 year, adverse event reporting was similar in nature and severity to that reported in adults.
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 Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases. To prevent them, it is recommended to take metformin in 2 or 3 daily doses and to increase slowly the doses.
The following adverse reactions may occur under treatment with metformin. Frequencies are defined as follows: very common: >1/10; common >1/100, <1/10; uncommon >1/1,000, <1/100; rare >1/10,000, <1/1,000; very rare <1/10,000.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Metabolism and nutrition disorders:
very rare:
Lactic acidosis.
Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin. Consideration of such aetiology is recommended if a patient presents with megaloblastic anaemia.
Nervous system disorders:
Common: Taste disturbance
Gastrointestinal disorders:
very common: Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.
Hepatobiliary disorders:
very rare: Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Skin and subcutaneous tissue disorders:
very rare: Skin reactions such as erythema, pruritus, urticaria
Paediatric population
In published and post marketing data and in controlled clinical studies in a limited paediatric population aged 10-16 years treated during 1 year, adverse event reporting was similar in nature and severity to that reported in adults.
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Non clinical data reveal no special hazard for humans based on conventional studies on safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.
Preclinical data reveal no special hazard for humans based on conventional studies on safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity.
Pharmacotherapeutic group: Blood glucose lowering drugs, Biguanides
ATC Code: A10B A02
Mechanism of action
Meglucon Hexal hydrochloride is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Pharmacodynamic effect
Meglucon Hexal hydrochloride may act via 3 mechanisms:
(1) reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis (2) in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilisation (3) delay of intestinal glucose absorption.
Meglucon Hexal hydrochloride stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Meglucon Hexal hydrochloride increases the transport capacity of all types of membrane glucose transporters (GLUT) known to date.
In clinical studies, use of Meglucon Hexal was associated with either a stable body weight or modest weight loss.
In humans, independently of its action on glycaemia, Meglucon Hexal has favourable effects on lipid metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: Meglucon Hexal hydrochloride reduces total cholesterol, LDL cholesterol and triglyceride levels.
Clinical efficacy and safety:
The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in adult patients with type 2 diabetes.
Analysis of the results for overweight patients treated with Meglucon Hexal after failure of diet alone showed:
- a significant reduction of the absolute risk of any diabetes-related complication in the Meglucon Hexal group (29.8 events/1000 patient-years) versus diet alone (43.3 events/1000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/1000 patient-years), p=0.0034;
- a significant reduction of the absolute risk of diabetes-related mortality: Meglucon Hexal 7.5 events/1000 patient-years, diet alone 12.7 events/1000 patient-years, p=0.017;
- a significant reduction of the absolute risk of overall mortality: Meglucon Hexal 13.5 events/1000 patient-years versus diet alone 20.6 events/1000 patient-years (p=0.011), and versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/1000 patient-years (p=0.021);
- a significant reduction in the absolute risk of myocardial infarction: Meglucon Hexal 11 events/1000 patient-years, diet alone 18 events/1000 patient-years (p=0.01).
Benefit regarding clinical outcome has not been shown for Meglucon Hexal used as second-line therapy, in combination with a sulfonylurea.
In type 1 diabetes, the combination of Meglucon Hexal hydrochloride and insulin has been used in selected patients, but the clinical benefit of this combination has not been formally established.
Paediatric population
Controlled clinical studies in a limited paediatric population aged 10-16 years treated during 1 year demonstrated a similar response in glycaemic control to that seen in adults.
Pharmacotherapeutic group: Blood Glucose lowering drugs, excl Insulins, Biguanides ATC code: A10BA02
Mechanism of action
Meglucon Hexal is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Meglucon Hexal may act via 3 mechanisms:
(1) reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis
(2) in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilization
(3) and delay of intestinal glucose absorption.
Meglucon Hexal stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Meglucon Hexal increases the transport capacity of all types of membrane glucose transporters (GLUTs) known to date.
In humans, independently of its action on glycaemia, Meglucon Hexal has favourable effects on lipid metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: Meglucon Hexal reduces total cholesterol, LDL cholesterol and triglyceride levels.
In clinical studies, use of metformin was associated with either a stable body weight or modest weight loss.
Clinical efficacy:
The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in adult patients with type 2 diabetes.
Analysis of the results for overweight patients treated with Meglucon Hexal after failure of diet alone showed:
o a significant reduction of the absolute risk of any diabetes-related complication in the Meglucon Hexal group (29.8 events/ 1000 patient-years) versus diet alone (43.3 events/ 1000 patient-years), p=0.0023, and versus the combined sulfonylurea and insulin monotherapy groups (40.1 events/ 1000 patient-years), p=0.0034;
o a significant reduction of the absolute risk of diabetes-related mortality: Meglucon Hexal 7.5 events/1000 patient-years, diet alone 12.7 events/1000 patient-years, p=0.017;
o a significant reduction of the absolute risk of overall mortality: Meglucon Hexal 13.5 events/ 1000 patient-years versus diet alone 20.6 events/ 1000 patient -years (p=0.011), and versus the combined sulfonylurea and insulin monotherapy groups 18.9 events/ 1000 patient-years (p=0.021);
o a significant reduction in the absolute risk of myocardial infarction: Meglucon Hexal 11 events/ 1000 patient-years, diet alone 18 events/ 1000 patient-years (p=0.01)
Benefit regarding clinical outcome has not been shown for Meglucon Hexal used as second-line therapy, in combination with a sulfonylurea.
In type 1 diabetes, the combination of Meglucon Hexal and insulin has been used in selected patients, but the clinical benefit of this combination has not been formally established.
Paediatric population
Controlled clinical studies in a limited paediatric population aged 10-16 years treated during 1 year demonstrated a similar response in glycaemic control to that seen in adults.
Absorption:
After an oral dose of Meglucon Hexal hydrochloride, Tmax is reached approximately in 2.5 hours. Absolute bioavailability of a 500mg or 850mg Meglucon Hexal hydrochloride tablet is approximately 50-60% in healthy subjects. After an oral dose, the non-absorbed fraction recovered in faeces was 20-30%.
After oral administration, Meglucon Hexal hydrochloride absorption is saturable and incomplete. It is assumed that the pharmacokinetics of Meglucon Hexal absorption is non-linear.
At the recommended Meglucon Hexal doses and dosing schedules, steady state plasma concentrations are reached within 24 to 48 hours and are generally less than 1μg/ml. In controlled clinical trials, maximum Meglucon Hexal hydrochloride plasma levels (Cmax) did not exceed 5μg/ml, even at maximum doses.
Food decreases the extent and slightly delays the absorption of Meglucon Hexal. Following administration of a dose of 850mg, a 40% lower plasma peak concentration, a 25% decrease in AUC (area under the curve) and a 35 minute prolongation of time to peak plasma concentration were observed. The clinical relevance of these findings is unknown.
Distribution:
Plasma protein binding is negligible. Meglucon Hexal hydrochloride partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean volume of distribution (Vd) ranged between 63-276L.
Biotransformation:
Meglucon Hexal hydrochloride is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination:
Renal clearance of Meglucon Hexal is >400ml/min, indicating that Meglucon Hexal is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of Meglucon Hexal in plasma.
Characteristics in specific groups of patients
Renal impairment
The available data in subjects with moderate renal insufficiency are scarce and no reliable estimation of the systemic exposure to Meglucon Hexal in this subgroup as compared to subjects with normal renal function could be made. Therefore, the dose adaptation should be made upon clinical efficacy/tolerability considerations.
Paediatric population:
Single dose study: After single doses of Meglucon Hexal hydrochloride 500mg, paediatric patients have shown similar pharmacokinetic profiles to that observed in healthy adults.
Multiple dose study: Data are restricted to one study. After repeated doses of 500mg twice daily for 7 days, in paediatric patients, the peak plasma concentration (Cmax) and systemic exposure (AUC0-t) were reduced by approximately 33% and 40%, respectively, compared to diabetic adults who received repeated doses of 500mg twice daily for 14 days. As the dose is individually titrated based on glycaemic control, this is of limited clinical relevance.
Absorption:
After an oral dose of Meglucon Hexal maximum plasma concentration (Cmax) is reached in approximately 2.5 hours (Tmax). Absolute bioavailability of a 500 mg or 850 mg Meglucon Hexal tablet is approximately 50-60 % in healthy subjects. After an oral dose, the non-absorbed fraction recovered in faeces was 20-30 %.
After oral administration, Meglucon Hexal absorption is saturable and incomplete. It is assumed that the pharmacokinetics of Meglucon Hexal absorption is non-linear.
At the recommended Meglucon Hexal doses and dosing schedules, steady state plasma concentrations are reached within 24 to 48 hours and are generally less than 1 microgram/ml. In controlled clinical trials, maximum Meglucon Hexal plasma levels (Cmax) did not exceed 4 microgram/ml, even at maximum doses.
Food decreases the extent and slightly delays the absorption of Meglucon Hexal. Following administration of a dose of 850 mg, a 40 % lower plasma peak concentration, a 25 % decrease in AUC (area under the curve) and a 35 minute prolongation of time to peak plasma concentration were observed. The clinical relevance of these findings is unknown.
Distribution:
Plasma protein binding is negligible. Meglucon Hexal partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean volume of distribution (Vd) ranged between 63-276 l.
Biotransformation:
Meglucon Hexal is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination:
Renal clearance of Meglucon Hexal is >400 ml/min, indicating that Meglucon Hexal is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of Meglucon Hexal in plasma.
Pediatric population
Single dose study: After single doses of Meglucon Hexal 500 mg, paediatric patients have shown similar phamacokinetic profile to that observed in healthy adults.
Multiple dose study: Data are restricted to one study. After repeated doses of 500 mg twice daily for 7 days in paediatric patients the peak plasma concentration (Cmax) and systemic exposure (AUC0-t) were reduced by approximately 33% and 40%, respectively compared to diabetic adults who received repeated doses of 500 mg twice daily for 14 days. As the dose is individually titrated based on glycaemic control, this is of limited clinical relevance.
Lactic acidosis
Lactic acidosis, a very rare, but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Meglucon Hexal accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
Reported cases of lactic acidosis in patients on Meglucon Hexal have occurred primarily in diabetic patients with impaired renal failure or acute worsening of renal function. Special caution should be paid to situations where renal function may become impaired, for example in case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), or when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID). In the acute conditions listed, Meglucon Hexal should be temporarily discontinued.
Other associated risk factors should be considered to avoid lactic acidosis such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia (such as decompensated heart failure, acute myocardial infarction).
The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps, digestive disorders as abdominal pain and severe asthenia. Patients should be instructed to notify these signs immediately to their physicians if they occur, notably if patients had a good tolerance to Meglucon Hexal before. Meglucon Hexal should be discontinued, at least temporarily, until the situation is clarified. Reintroduction of Meglucon Hexal should then be discussed taking into account the benefit/risk ratio in an individual basis as well as renal function.
Diagnosis:
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in Meglucon Hexal treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis.
Patients and/or care-givers should be informed on the risk of lactic acidosis.
Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH (< 7.35), increased plasma lactate levels (>5 mmol/l) and an increased anion gap and lactate/pyruvate ratio. In case of lactic acidosis, the patient should be hospitalised immediately.
Physicians should alert the patients on the risk and on the symptoms of lactic acidosis.
Renal function
As Meglucon Hexal is excreted by the kidney, creatinine clearance (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) or eGFR should be determined before initiating treatment and regularly thereafter:
- at least annually in patients with normal renal function;
- at least two to four times a year in patients with serum creatinine levels at the lower limit of normal and in elderly subjects.
Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy, diuretic therapy or when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).
In these cases, it is also recommended to check renal function before initiating treatment with Meglucon Hexal.
Cardiac function
Patients with heart failure are more at risk of hypoxia and renal insufficiency. In patients with stable chronic heart failure, Meglucon Hexal may be used with a regular monitoring of cardiac and renal function.
For patients with acute and unstable heart failure, Meglucon Hexal is contraindicated.
Administration of iodinated contrast media
Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in Meglucon Hexal accumulation and an increased risk of lactic acidosis.5.
In patients with moderate renal impairment (eGFR between 45 and 60 ml/min/1.73m2), Meglucon Hexal must be discontinued 48 hours before administration of iodinated contrast media and not be reinstituted until at least 48 hours afterwards and only after renal function has been re-evaluated and has not deteriorated further.
Surgery
Meglucon Hexal must be discontinued at the time of surgery under general, spinal or epidural anaesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.
Paediatric population
The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with Meglucon Hexal is initiated.
No effect of Meglucon Hexal on growth and puberty has been detected during controlled clinical studies of one year duration, but no long term data on these specific points are available. Therefore, a careful follow-up of the effect of Meglucon Hexal hydrochloride on these parameters, in Meglucon Hexal hydrochloride treated children, especially pre-pubescent children, is recommended.
Children aged between 10 and 12 years:
Only 15 subjects aged between 10 and 12 years were included in the controlled clinical studies conducted in children and adolescents. Although efficacy and safety of Meglucon Hexal in these children did not differ from efficacy and safety in older children and adolescents, particular caution is recommended when prescribing to children aged between 10 and 12 years.
Other precautions
All patients should continue their diet with a regular distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
The usual laboratory tests for diabetes monitoring should be performed regularly.
Meglucon Hexal hydrochloride alone does not cause hypoglycaemia, but caution is advised when it is used in combination with insulin or other oral antidiabetics (e.g. sulphonylureas or meglitinides).
Excipient warnings
This product contains:
- Sodium methyl and propyl parahydroxybenzoates. These may cause allergic reactions (possibly delayed).
- Liquid maltitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
- Sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine. Sucrose may also be harmful to teeth.
- Sodium - 7mg per 5ml dose. To be taken into consideration by patients on a controlled sodium diet.
- Potassium - 14.5mg per 5ml dose. To be taken into consideration by patients with reduced kidney function or patients on controlled potassium diets.
- Sodium sulphite. This may rarely cause severe hypersensitivity (allergic) reactions and bronchospasm.
- Ethanol. This medicinal product contains small amounts of ethanol (alcohol), less than 100mg per 10ml.
Lactic acidosis:
Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended.
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis.
Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH (< 7.35), increased plasma lactate levels (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.
Administration of iodinated contrast agents
Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis.5.
Renal function
Surgery
Metformin must be discontinued at the time of surgery under general, spinal or epidural anesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.
Paediatric population
The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with Meglucon Hexal is initiated.
No effect of Meglucon Hexal on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of Meglucon Hexal on these parameters in Meglucon Hexal-treated children, especially pre-pubescent children, is recommended.
Children aged between 10 and 12 years:
Only 15 subjects aged between 10 and 12 years were included in the controlled clinical studies conducted in children and adolescents. Although efficacy and safety of Meglucon Hexal in these children did not differ from efficacy and safety in older children and adolescents, particular caution is recommended when prescribing to children aged between 10 and 12 years.
Other precautions:
All patients should continue their diet with a regular distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
The usual laboratory tests for diabetes monitoring should be performed regularly.
Meglucon Hexal alone does not cause hypoglycaemia, but caution is advised when it is used in combination with insulin or oral antidiabetics (e.g. sulfonylureas or meglitinides).
Meglucon Hexal has no influence on the ability to drive and use machines.
Meglucon Hexal monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
However, patients should be alerted to the risk of hypoglycaemia when Meglucon Hexal is used in combination with other antidiabetic agents (e.g. sulphonylureas, insulin, meglitinides).
Meglucon Hexal monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
However, patients should be alerted to the risk of hypoglycaemia when meformin hydrochloride is used in combination with other antidiabetic agents (sulfonylureas, insulin or meglitinides).
Any unused product or waste material should be disposed of in accordance with local requirements.
Any unused product or waste material should be disposed off in accordance with local requirements.
