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Sulfonylureas

Glimepiride is a sulfonylurea antidiabetic agent which decreases blood glucose concentration. The primary mechanism of action of Glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. Glimepiride acts in concert with glucose by improving the sensitivity of beta cells to physiological glucose stimulus, resulting in insulin secretion. In addition, extrapancreatic effects like reduction of basal hepatic glucose production, increased peripheral tissue sensitivity to insulin and glucose uptake may also play role in the activity of Glimepiride. In non-fasting diabetic patients, the hypoglycaemic action of a single dose of Glimepiride persists for 24 hours.

In principle, the dosage of Glimepiride is governed by the desired blood sugar level. The dosage of Glimepiride must be the lowest which is sufficient to achieve the desired metabolic control. The initial and the maintenance doses are set based on the results of regular check of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.

Initial dose and dose titration: the usual initial dose is 1 mg once daily, if necessary, the daily dose can be increased. Any increase can be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of 1 to 2 weeks, and carried out stepwise, as follows: 1 mg -> 2 mg -> 3 mg -> 4 mg -> 6 mg.

Dose in patients with well controlled diabetes: the usual dose range in patients with well controlled diabetes is 1 to 4 mg daily.

Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient's current life-style. Normally, a single daily dose is sufficient. This should be taken immediately before a substantial breakfast or if none is taken immediately before the first main meal. It is very important not to skip meals after taking the drug.

Secondary dosage adjustment: As control of diabetes improves, sensitivity to insuiin increases; therefore, Glimepiride requirement may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Glimepiride therapy must be considered. A dose adjustment must also be considered whenever the patient's weight or life-styie changes, or other factors arise which cause an increased susceptibility to hypo or hyperglycaemia.

Changeover from other oral antidiabetics to Glimepiride: There is no exact dosage relationship between Glimepiride and other oral blood sugar lowering agents. When substituting Glimepiride for other such agents, the initial daily dose is 1 mg; this applies even in changeover from maximum dose of other oral blood sugar lowering agents. Any dose increase should be in accordance with guideline given above in 'initial dose and dose titration'. Consideration must be given to the potency and duration of action of the previous blood sugar lowering agent. It may be necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.

Glimepiride tablet must be swallowed with sufficient amount of liquid.

Hypoglycaemia, temporary visual impairment, nausea, vomiting, diarrhoea, abdominal pain, urticaria, fall in blood pressure.

Glimepiride is not suitable for the treatment of insulin dependent (type I) diabetes mellitus, or for the treatment of diabetic ketoacidosis, nor for the treatment of diabetic coma. Glimepiride must not be used in patients hypersensitive to Glimepiride, other sulfonylureas, other sulfonamides, severe hepatic dysfunction, severe impairment of renal function and dialysis patients.

in the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates careful monitoring. If such risk present it may be necessary to adjust the dosage of Glimepiride, Hypoglycaemia can almost be promptly controlled by immediate intake of carbohydrates (glucose or sugar).

Based on experience with Glimepiride and known interactions for other sulfonylureas, the following interactions must be considered.

In addition to insulin and other oral antidiabetic agents, drugs which may potentiate the hypoglycaemic action of Glimepiride include: ACE inhibitors, aminosalicylic acid, anabolic steroids and male sex hormones, azapropazone, chloramphenicol, ciofibrate, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluconazole, fluoxetine, guanethidine, ifosfamide, MAO-inhibitors, miconazole, oxpentifylline (high dose parenteral), oxyphenbutazone, para-aminosalicylic acid, phenylbutazone, probenecid, quinolones, salicylates, sulphinpyrazone, sulfonamide antibiotics, tetracyclines, tritoqualine, trofosfamide.

Drugs which may attenuate the hypoglycaemic action of Glimepiride include:

• Acetazoiamide, barbiturates, calcium channel blockers, corticosteroids, diazoxide, diuretics, glucagon, isoniazid, laxatives, nicotinic acid (high doses), oestrogens, phenothiazines, phenytoin, progestagens, rifampicin, sympathomimetic agents, thyroid hormones.
• H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
• Concomitant treatment with a beta-receptor blocker, clonidine, guanethidine or reserpine may mask the warning symptoms of a hypoglycaemic attack.
• Acute and chronic aicohol intake may either potentiate or attenuate the activity of Glimepiride in an unpredictable fashion.

Glimepiride must not be taken during pregnancy; a changeover to insulin is necessary. Patients planning a pregnancy must inform their physician, and should change over to insulin. Ingestion of Glimepiride with breast milk feeding may harm the child. Therefore, Glimepiride must not be taken by breastfeeding women. Either a changeover or complete discontinuation of breastfeeding is necessary.

Overdosage of sulfonylureas, including Glimepiride, can produce hypoglycaemia. Mild hypoglycaemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycaemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medicai emergencies requiring immediate hospitalization. If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of  concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dl. Patients should be closely monitored for a minimum of 24 to 48 hours, because hypoglycaemia may recur after apparent clinical recovery.

Do not store above 30°C. Keep away from light and out of the reach of children.

Sulfonylureas

Glimepiride is a sulfonylurea antidiabetic agent which decreases blood glucose concentration. The primary mechanism of action of Glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. Glimepiride acts in concert with glucose by improving the sensitivity of beta cells to physiological glucose stimulus, resulting in insulin secretion. In addition, extrapancreatic effects like reduction of basal hepatic glucose production, increased peripheral tissue sensitivity to insulin and glucose uptake may also play role in the activity of Glimepiride. In non-fasting diabetic patients, the hypoglycaemic action of a single dose of Glimepiride persists for 24 hours.

In principle, the dosage of Glimepiride is governed by the desired blood sugar level. The dosage of Glimepiride must be the lowest which is sufficient to achieve the desired metabolic control. The initial and the maintenance doses are set based on the results of regular check of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.

Initial dose and dose titration: the usual initial dose is 1 mg once daily, if necessary, the daily dose can be increased. Any increase can be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of 1 to 2 weeks, and carried out stepwise, as follows: 1 mg -> 2 mg -> 3 mg -> 4 mg -> 6 mg.

Dose in patients with well controlled diabetes: the usual dose range in patients with well controlled diabetes is 1 to 4 mg daily.

Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient's current life-style. Normally, a single daily dose is sufficient. This should be taken immediately before a substantial breakfast or if none is taken immediately before the first main meal. It is very important not to skip meals after taking the drug.

Secondary dosage adjustment: As control of diabetes improves, sensitivity to insuiin increases; therefore, Glimepiride requirement may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Glimepiride therapy must be considered. A dose adjustment must also be considered whenever the patient's weight or life-styie changes, or other factors arise which cause an increased susceptibility to hypo or hyperglycaemia.

Changeover from other oral antidiabetics to Glimepiride: There is no exact dosage relationship between Glimepiride and other oral blood sugar lowering agents. When substituting Glimepiride for other such agents, the initial daily dose is 1 mg; this applies even in changeover from maximum dose of other oral blood sugar lowering agents. Any dose increase should be in accordance with guideline given above in 'initial dose and dose titration'. Consideration must be given to the potency and duration of action of the previous blood sugar lowering agent. It may be necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.

Glimepiride tablet must be swallowed with sufficient amount of liquid.

Hypoglycaemia, temporary visual impairment, nausea, vomiting, diarrhoea, abdominal pain, urticaria, fall in blood pressure.

Glimepiride is not suitable for the treatment of insulin dependent (type I) diabetes mellitus, or for the treatment of diabetic ketoacidosis, nor for the treatment of diabetic coma. Glimepiride must not be used in patients hypersensitive to Glimepiride, other sulfonylureas, other sulfonamides, severe hepatic dysfunction, severe impairment of renal function and dialysis patients.

in the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates careful monitoring. If such risk present it may be necessary to adjust the dosage of Glimepiride, Hypoglycaemia can almost be promptly controlled by immediate intake of carbohydrates (glucose or sugar).

Based on experience with Glimepiride and known interactions for other sulfonylureas, the following interactions must be considered.

In addition to insulin and other oral antidiabetic agents, drugs which may potentiate the hypoglycaemic action of Glimepiride include: ACE inhibitors, aminosalicylic acid, anabolic steroids and male sex hormones, azapropazone, chloramphenicol, ciofibrate, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluconazole, fluoxetine, guanethidine, ifosfamide, MAO-inhibitors, miconazole, oxpentifylline (high dose parenteral), oxyphenbutazone, para-aminosalicylic acid, phenylbutazone, probenecid, quinolones, salicylates, sulphinpyrazone, sulfonamide antibiotics, tetracyclines, tritoqualine, trofosfamide.

Drugs which may attenuate the hypoglycaemic action of Glimepiride include:

• Acetazoiamide, barbiturates, calcium channel blockers, corticosteroids, diazoxide, diuretics, glucagon, isoniazid, laxatives, nicotinic acid (high doses), oestrogens, phenothiazines, phenytoin, progestagens, rifampicin, sympathomimetic agents, thyroid hormones.
• H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
• Concomitant treatment with a beta-receptor blocker, clonidine, guanethidine or reserpine may mask the warning symptoms of a hypoglycaemic attack.
• Acute and chronic aicohol intake may either potentiate or attenuate the activity of Glimepiride in an unpredictable fashion.

Glimepiride must not be taken during pregnancy; a changeover to insulin is necessary. Patients planning a pregnancy must inform their physician, and should change over to insulin. Ingestion of Glimepiride with breast milk feeding may harm the child. Therefore, Glimepiride must not be taken by breastfeeding women. Either a changeover or complete discontinuation of breastfeeding is necessary.

Overdosage of sulfonylureas, including Glimepiride, can produce hypoglycaemia. Mild hypoglycaemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycaemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medicai emergencies requiring immediate hospitalization. If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of  concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dl. Patients should be closely monitored for a minimum of 24 to 48 hours, because hypoglycaemia may recur after apparent clinical recovery.

Do not store above 30°C. Keep away from light and out of the reach of children.

Sulfonylureas

Glimepiride is a sulfonylurea antidiabetic agent which decreases blood glucose concentration. The primary mechanism of action of Glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. Glimepiride acts in concert with glucose by improving the sensitivity of beta cells to physiological glucose stimulus, resulting in insulin secretion. In addition, extrapancreatic effects like reduction of basal hepatic glucose production, increased peripheral tissue sensitivity to insulin and glucose uptake may also play role in the activity of Glimepiride. In non-fasting diabetic patients, the hypoglycaemic action of a single dose of Glimepiride persists for 24 hours.

In principle, the dosage of Glimepiride is governed by the desired blood sugar level. The dosage of Glimepiride must be the lowest which is sufficient to achieve the desired metabolic control. The initial and the maintenance doses are set based on the results of regular check of glucose in blood and urine. Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.

Initial dose and dose titration: the usual initial dose is 1 mg once daily, if necessary, the daily dose can be increased. Any increase can be based on regular blood sugar monitoring, and should be gradual, i.e., at intervals of 1 to 2 weeks, and carried out stepwise, as follows: 1 mg -> 2 mg -> 3 mg -> 4 mg -> 6 mg.

Dose in patients with well controlled diabetes: the usual dose range in patients with well controlled diabetes is 1 to 4 mg daily.

Distribution of doses: Timing and distribution of doses are decided by the physician, in consideration of the patient's current life-style. Normally, a single daily dose is sufficient. This should be taken immediately before a substantial breakfast or if none is taken immediately before the first main meal. It is very important not to skip meals after taking the drug.

Secondary dosage adjustment: As control of diabetes improves, sensitivity to insuiin increases; therefore, Glimepiride requirement may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Glimepiride therapy must be considered. A dose adjustment must also be considered whenever the patient's weight or life-styie changes, or other factors arise which cause an increased susceptibility to hypo or hyperglycaemia.

Changeover from other oral antidiabetics to Glimepiride: There is no exact dosage relationship between Glimepiride and other oral blood sugar lowering agents. When substituting Glimepiride for other such agents, the initial daily dose is 1 mg; this applies even in changeover from maximum dose of other oral blood sugar lowering agents. Any dose increase should be in accordance with guideline given above in 'initial dose and dose titration'. Consideration must be given to the potency and duration of action of the previous blood sugar lowering agent. It may be necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.

Glimepiride tablet must be swallowed with sufficient amount of liquid.

Hypoglycaemia, temporary visual impairment, nausea, vomiting, diarrhoea, abdominal pain, urticaria, fall in blood pressure.

Glimepiride is not suitable for the treatment of insulin dependent (type I) diabetes mellitus, or for the treatment of diabetic ketoacidosis, nor for the treatment of diabetic coma. Glimepiride must not be used in patients hypersensitive to Glimepiride, other sulfonylureas, other sulfonamides, severe hepatic dysfunction, severe impairment of renal function and dialysis patients.

in the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates careful monitoring. If such risk present it may be necessary to adjust the dosage of Glimepiride, Hypoglycaemia can almost be promptly controlled by immediate intake of carbohydrates (glucose or sugar).

Based on experience with Glimepiride and known interactions for other sulfonylureas, the following interactions must be considered.

In addition to insulin and other oral antidiabetic agents, drugs which may potentiate the hypoglycaemic action of Glimepiride include: ACE inhibitors, aminosalicylic acid, anabolic steroids and male sex hormones, azapropazone, chloramphenicol, ciofibrate, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluconazole, fluoxetine, guanethidine, ifosfamide, MAO-inhibitors, miconazole, oxpentifylline (high dose parenteral), oxyphenbutazone, para-aminosalicylic acid, phenylbutazone, probenecid, quinolones, salicylates, sulphinpyrazone, sulfonamide antibiotics, tetracyclines, tritoqualine, trofosfamide.

Drugs which may attenuate the hypoglycaemic action of Glimepiride include:

• Acetazoiamide, barbiturates, calcium channel blockers, corticosteroids, diazoxide, diuretics, glucagon, isoniazid, laxatives, nicotinic acid (high doses), oestrogens, phenothiazines, phenytoin, progestagens, rifampicin, sympathomimetic agents, thyroid hormones.
• H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
• Concomitant treatment with a beta-receptor blocker, clonidine, guanethidine or reserpine may mask the warning symptoms of a hypoglycaemic attack.
• Acute and chronic aicohol intake may either potentiate or attenuate the activity of Glimepiride in an unpredictable fashion.

Glimepiride must not be taken during pregnancy; a changeover to insulin is necessary. Patients planning a pregnancy must inform their physician, and should change over to insulin. Ingestion of Glimepiride with breast milk feeding may harm the child. Therefore, Glimepiride must not be taken by breastfeeding women. Either a changeover or complete discontinuation of breastfeeding is necessary.

Overdosage of sulfonylureas, including Glimepiride, can produce hypoglycaemia. Mild hypoglycaemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycaemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medicai emergencies requiring immediate hospitalization. If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of  concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dl. Patients should be closely monitored for a minimum of 24 to 48 hours, because hypoglycaemia may recur after apparent clinical recovery.

Do not store above 30°C. Keep away from light and out of the reach of children.

Contrast medium for diagnostic procedures

The paramagnetic properties of Gadodiamide provides contrast enhancement during MRI. There were no clinically significant deviations from pre-injection values in haemodynamic and blood and urine laboratory parameters following intravenous injection of gadodiamide in healthy volunteers. However, a minor transient change in serum iron levels 8 to 48 hours after gadodiamide injection was observed.

Gadodiamide does not cross the intact blood-brain barrier. Administration of Gadodiamide causes signal enhancement from areas where blood-brain barrier dysfunction has been induced by pathological processes, and may provide greater diagnostic yield than unenhanced MRI. Lack of enhancement need not indicate absence of pathology since some types of low grade malignancies or inactive MS-plaques fail to enhance; it can be used for differential diagnosis between different pathologies.

No special preparation of the patient is required. Gadodiamide should be drawn into the syringe immediately before use.The vial is intended for one patient only. Contrast medium not used in one examination must be discarded.

CNS (Central Nervous System):

• Adults: The recommended dose of Gadodiamide is 0.2 mL/kg (0.1 mmol/kg) administered as a bolus intravenous injection.
• Pediatric Patients (2-16 years): The recommended dose of Gadodiamide is 0.2 mL/kg (0.1 mmol/kg) administered as a bolus intravenous injection.

Body (Intrathoracic [noncardiac], Intra-abdominal, Pelvic And Retroperitoneal Regions):

• Adult and Pediatric Patients (2-16 years of age): For imaging the kidney, the recommended dose of Gadodiamide is 0.1 mL/kg (0.05 mmol/kg). For imaging the intrathoracic (noncardiac), intra-abdominal, and pelvic cavities, the recommended dose of Gadodiamide is 0.2 mL/kg (0.1 mmol/kg)

Nephrogenic systemic fibrosis, Hypersensitivity reactions

Chronic, severe kidney disease (glomerular filtration rate < 30 ml/ min/1.73 m²), or acute kidney injury prior hypersensitivity reaction, should not be used in patients known to have hypersensitivity to Gadodiamide or its constituents.

Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs among these patients unless the diagnostic information is essential and not available with non-contrast enhanced MRI or other modalities.

The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m²) as well as patients with acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function.

There are no known drug interactions and none well documented.

Pregnancy category B3. No effects of Gadodiamide on reproductive performance were seen in rats at doses up to 1.0 mmol/kg. In rabbits, there is an increased incidence of litters with skeletal or visceral abnormalities at doses up to 0.5 and 1.0 mmol/kg. However, these effects are possibly attributable to maternal toxicity rather than a direct effect of the drug. There are no adequate and well-controlled studies of Gadodiamide in pregnant women. Gadodiamide should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.

Use in Lactation: It is not known whether Gadodiamide is excreted in human milk. Breast-feeding should be discontinued prior to administration and should not be recommenced until at least 24 hours after the administration of Gadodiamide.

Use in Children: The safety and effectiveness of Gadodiamide have been established for whole body magnetic resonance imaging in children from 6 months of age.The safety and effectiveness in infants and neonates have been established in the evaluation of lesions within the brain and spine.

There is no experience with Gadodiamide in children below 6 months of age with severe hepatic or renal disease, or with premature infants below 4 weeks, or those with a post-conceptional age of less than 30 weeks.

Use in elderly patients: Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Clinical consequences of overdose have not been reported and acute symptoms of toxicity are unlikely in patients with a normal renal function. Treatment is symptomatic. There is no antidote for this contrast medium. In patients with delayed elimination due to renal insufficiency and in patients who have received excessive doses, the contrast medium can be eliminated by haemodialysis.

Store at temperatures not exceeding 25° C. Protect from light.

Gliclazide is a medicine that reduces blood sugar levels (oral antidiabetic medicine belonging to the sulphonylurea group). Gliclazide is used in a certain form of diabetes (type 2 diabetes Mellitus) in adults, when diet, exercise and weight loss alone do not have an adequate effect on keeping blood sugar at the correct level.

Sulfonylureas

Gliclazide is a second generation sulfonylurea drug that has hypoglycaemic and potentially useful hematological properties. It stimulates the release of insulin from pancreatic β-cells by facilitating Ca⁺²  transport across the β-cell membranes and decreases hepatic glucose output.

Film-coated tablet: The usual initial dose is 40 to 80 mg daily. The dose can be increased up to 320 mg daily in divided doses when needed. The drug should be taken before meal. For children, Gliclazide is not used because it is contraindicated in juvenile-onset diabetes.

Modified release preparation: Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose is determined by the doctor, depending on your blood and possibly urine sugar levels. Change in external factors (weight reduction, lifestyle, stress) or improvements in the blood sugar control may require changed gliclazide doses.

The recommended daily dose is one to four tablets (maximum 120 mg) in a single intake at breakfast time. This depends on the response to treatment. Gliclazide MR tablet is for oral use. Take your tablet(s) with a glass of water at breakfast time (and preferably at the same time each day). Swallow your whole tablet(s) in one piece. Do not chew or crush. You must always eat a meal after taking your tablet(s).

If a combination therapy of gliclazide with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor a GLP-1 receptor agonist or insulin is initiated your doctor will determine the proper dose of each medicine individually for you. If you notice that your blood sugar levels are high although you are taking the medicine as prescribed, you should contact your doctor or pharmacist.

If you take more Gliclazide tablets than you should: If you take too many tablets, contact your doctor or the nearest hospital Accident & Emergency department immediately. The signs of overdose are those of low blood sugar (hypoglycaemia). The symptoms can be helped by taking sugar (4 to 6 lumps) or sugary drinks straight away, followed by a substantial snack or meal. If the patient is unconscious immediately inform a doctor and call the emergency services. The same should be done if somebody, (for instance a child), has taken the product unintentionally. Unconscious patients must not be given food or drink. It should be ensured that there is always a pre-informed person that can call a doctor in case of emergency.

If you forget to take Gliclazide tablet: It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Gliclazide MR tablet, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gliclazide MR tablet: As the treatment for diabetes is usually lifelong, you should discuss with your doctor before stopping this medicinal product. Stopping could cause high blood sugar (hyperglycaemia) which increases the risk of developing complications of diabetes. If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Gliclazide can cause side effects, although not everybody gets them. The most commonly observed side effect is low blood sugar (hypoglycaemia). If left untreated these symptoms could progress to drowsiness, loss of consciousness or possibly coma. If an episode of low blood sugar is severe or prolonged, even if it is temporarily controlled by eating sugar, you should seek immediate medical attention.

Liver disorders: There have been isolated reports of abnormal iiver function, which can cause yellow skin and eyes. If you get this, see your doctor immediately. The symptoms generally disappear if the medicine is stopped. Your doctor will decide whether to stop your treatment.

Skin disorders: Skin reactions such as rash, redness, itching, hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin. If you develop this, stop taking, seek urgent advice from a doctor and tell him that you are taking this medicine. Exceptionally, signs of severe hypersensitivity reactions have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

Blood disorders: Decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.

Digestive disorders: Abdominal pain, nausea, vomiting, indigestion, diarrhoea, and constipation. These effects are reduced when Gliclazide is taken with a meal as recommended.

Eye disorders: Your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

As for another sulfonylurea, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (for instance jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

Reporting of side effects: If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not take Gliclazide:

• if you are allergic to gliclazide or to other medicines of the same group (sulfonylurea), or to other related medicines (hypoglycaemic sulfonamides)
• if you have insulin-dependent diabetes (type 1)
• if you have ketone bodies and sugar in your urine (this may mean you have diabetic ketoacidosis), a diabetic pre-coma or coma
• if you have severe kidney or liver disease
• if you are taking medicines to treat fungal infections
• if you are breastfeeding

Talk to your doctor before taking Gliclazide. You should observe the treatment plan prescribed by your doctor to achieve proper blood sugar levels. This means, apart from regular tablet intake, to observe the dietary regimen, have physical exercise and, where necessary, reduce weight During gliclazide treatment regular monitoring of your blood (and possibly urine) sugar level and also your glycated haemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of having reduced blood sugar levels (hypoglycaemia) may be increased. So particularly close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

• if you take meals irregularly or skip meals altogether,
• if you are fasting
• if you are malnourished
• if you change your diet
• if you increase your physical activity and carbohydrate intake does not match this increase,
• if you drink alcohol, especially in combination with skipped meals,
• if you take other medicines or natural remedies at the same time,
• if you take too high doses of gliclazide,
• if you suffer from particular hormone-induced disorders (functional disorders of the thyroid gland, pituitary gland or adrenal cortex),
• if your kidney function or liver function is severely decreased.

if you have low blood sugar you may have the following symptoms: headache, intense hunger, nausea, vomiting, weariness, sleep disorders, restlessness, aggressiveness, poor concentration, reduced alertness and reaction time, depression, confusion, speech or visual disorders, tremor, sensory disturbances, dizziness and helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, fast or irregular heartbeat, high blood pressure, sudden strong pain in the chest that may radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may suffer from considerable confusion (delirium), develop convulsions, lose self-control, your breathing may be shallow and your heartbeat slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar vanish very quickly when you consume .some form of sugar, (for instance, glucose tablets, sugar cubes, sweet juice, sweetened tea).

You should therefore always carry some form of sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Please contact your doctor or the nearest hospital if taking sugar does not help or if the symptoms recur.

Symptoms of low blood sugar may be absent, less obvious or develop very slowly or you are not aware in time that your blood sugar level has dropped. This may happen if you are an elderly patient taking certain medicines (for instance those acting on the central nervous system and beta-blockers).

If you are in stressful situations (e.g. accidents, surgical operations, fever etc.) your doctor may temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may occur when gliclazide has not yet sufficiently reduced the blood sugar when you have not complied with the treatment plan prescribed by your doctor if you take St. John’s Wort (Hypericum perforatum) preparations or in special stress situations. These may include thirst, frequent urination, dry mouth, dry itchy skin, skin infections and reduced performance.

Blood glucose disturbances (low blood sugar and high bold sugar) can occur when Gliclazide is prescribed at the same time as medicines to a class of antibiotics called fluoroquinolone, especially in elderly patients. In this case, your doctor will remind you of the importance of monitoring your blood glucose.

If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur. Contact your doctor before taking this medicinal product.

Gliclazide is not recommended for use in children due to lack of data.

Other medicines and Gliclazide: Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

The blood sugar lowering effect of gliclazide may be strengthened and signs of low blood sugar levels may occur when one of the follow ng medicines is taken:

• other medicines used to treat high blood sugar (oral antidiabetics, GLP-1 receptor agonists or insulin),
• antibiotics (sulphonamides, clarithromycin)
• medicines to treat high blood pressure or heart failure (beta-blockers. ACE-inhibitors such as captopril, or enalapril)
• medicines to treat fungal infections (miconazole, fluconazole)
• medicines to treat ulcers in the stomach or duodenum (H2 receptor antagonists),
• medicines to treat depression (monoamine oxidase inhibitors)
• painkiller or antirheumatics (phenylbutazone, ibuprofen)
• medicines containing alcohol

The blood-glucose-lowering effect of gliclazide may be weakened and raised blood sugar levels may occur when one of the following medicines is taken:

• medicines to treat disorders of the central nervous system (chlorpromazine)
• medicines reducing inflammation (corticosteroids)
• medicines to treat asthma or used during labour (intravenous salbutamol, ritodrine and terbutaline)
• medicines to treat breast disorders, heavy menstrual bleeding and endometriosis (danazol)
• St John's Wort- Hypericum perforatum- preparations

Blood glucose disturbance (low blood sugar and high blood sugar) can occur when a medicine belonging to a class of antibiotics called fluoroquinolones is taken at the same time as gliclazide especially in elderly patients.

Gliclazide may increase the effects of medicines that reduce blood clotting (warfarin).

Consult your doctor before you start taking another medicinal product. If you go into hospital tell the medical staff you are taking gliclazide.

Gliclazide with food and drink: Gliclazide can be taken with food and non-alcoholic drinks. Drinking alcohol is not recommended as it can alter the control of your diabetes in an unpredictable manner.

Driving and using machines: Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), or too high (hyperglycaemia) or if you develop visual problems as a result of such conditions. Bear in mind that you could endanger yourself or others (for instance when driving a car or using machines). Please ask your doctor whether you can drive a car if you:

• have frequent episodes of low blood sugar (hypoglycaemia)
• have few or no warning signals of low blood sugar (hypoglycaemia)

Gliclazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Gliclazide is not recommended for use during pregnancy. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You must not take Gliclazide while you are breastfeeding.

Keep out of the reach and sight of children. Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month. Store below 30°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Miglitol is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Alpha-Glucosidase inhibitor

Miglitol reversibly inhibits membrane-bound intestinal α-glucosidase enzymes which hydrolyse oligosaccharides and disaccharides to glucose and other monosaccharides in the small intestinal brush border. It delays carbohydrate breakdown, glucose absorption and reduces postprandial hyperglycaemia.

There is no fixed dosage regimen for the management of diabetes mellitus with Miglitol Tablets or any other pharmacologic agent. Dosage of Miglitol must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dosage of 100 mg 3 times daily. Miglitol should be taken three times daily at the start of each main meal. Miglitol should be started at 25 mg, and the dosage gradually increased both to reduce gastrointestinaladverse effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. During treatment initiation and dose titration one-hour postprandial plasma glucose may be used to determine the therapeutic response to Miglitol and identify the minimum effective dose for the patient.

Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Miglitol, either as monotherapy or in combination with a sulfonylurea.

Initial Dosage: The recommended starting dosage of Miglitol is 25 mg, given orally three times daily at the start of each main meal. However, some patients may benefit by starting at 25 mg once daily to minimize gastrointestinal adverse effects, and gradually increasing the frequency of administration to 3 times daily.

Maintenance Dosage: The usual maintenance dose of Miglitol is 50 mg taken 3 times daily, although some patients may benefit from increasing the dose to 100 mg 3 times daily. To allow adaptation to potential gastrointestinal adverse effects, it is recommended that Miglitol therapy be initiated at a dosage of 25 mg 3 times daily, then gradually titrated upward to allow adaptation. After 4 to 8 weeks of the 25 mg 3 times daily regimen, the dosage should be increased to 50 mg 3 times daily for approximately three months, following which a glycosylated hemoglobin level should be measured to assess therapeutic response. If at that time, the glycosylated hemoglobin level is not satisfactory, the dosage may be further increased to 100 mg 3 times daily, the maximum recommended dosage.

Maximum Dosage: The maximum recommended dosage of Miglitol is 100 mg 3 times daily. In one clinical trial, 200 mg 3 times daily gave additional improved glycemic control but increased the incidence of the gastrointestinal symptoms described above.

Patients Receiving Sulfonylureas: Sulfonylurea agents may cause hypoglycemia. There was no increased incidence of hypoglycemia in patients who took Miglitol in combination with sulfonylurea agents compared to the incidence of hypoglycemia in patients receiving sulfonylureas alone in any clinical trial. However, Miglitol given in combination with a sulfonylurea will cause a further lowering of blood glucose and may increase the risk of hypoglycemia due to the additive effects of the two agents. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made

Should be taken with food. Take with 1st bite of each main meal.

Abdominal pain or discomfort, diarrhoea, flatulence, skin rash.

Patient with diabetic ketoacidosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to this condition, chronic intestinal diseases associated with marked disorders of digestion or absorption and co-existing conditions that may deteriorate as a result of increased intestinal gas formation.

Patient exposed to stress (e.g. fever, trauma, infection, surgery). Renal impairment. Pregnancy and lactation.

Concomitant use with insulin increases the risk of hypoglycaemia. Intestinal adsorbents (e.g. charcoal) and carbohydrate-splitting digestive enzyme supplements (e.g. amylase, pancreatin) may reduce glycaemic effects. May significantly reduce the bioavailability of ranitidine and propranolol.

Category B: Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Store at 25° C.

Miglitol is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Alpha-Glucosidase inhibitor

Miglitol reversibly inhibits membrane-bound intestinal α-glucosidase enzymes which hydrolyse oligosaccharides and disaccharides to glucose and other monosaccharides in the small intestinal brush border. It delays carbohydrate breakdown, glucose absorption and reduces postprandial hyperglycaemia.

There is no fixed dosage regimen for the management of diabetes mellitus with Miglitol Tablets or any other pharmacologic agent. Dosage of Miglitol must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dosage of 100 mg 3 times daily. Miglitol should be taken three times daily at the start of each main meal. Miglitol should be started at 25 mg, and the dosage gradually increased both to reduce gastrointestinaladverse effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. During treatment initiation and dose titration one-hour postprandial plasma glucose may be used to determine the therapeutic response to Miglitol and identify the minimum effective dose for the patient.

Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Miglitol, either as monotherapy or in combination with a sulfonylurea.

Initial Dosage: The recommended starting dosage of Miglitol is 25 mg, given orally three times daily at the start of each main meal. However, some patients may benefit by starting at 25 mg once daily to minimize gastrointestinal adverse effects, and gradually increasing the frequency of administration to 3 times daily.

Maintenance Dosage: The usual maintenance dose of Miglitol is 50 mg taken 3 times daily, although some patients may benefit from increasing the dose to 100 mg 3 times daily. To allow adaptation to potential gastrointestinal adverse effects, it is recommended that Miglitol therapy be initiated at a dosage of 25 mg 3 times daily, then gradually titrated upward to allow adaptation. After 4 to 8 weeks of the 25 mg 3 times daily regimen, the dosage should be increased to 50 mg 3 times daily for approximately three months, following which a glycosylated hemoglobin level should be measured to assess therapeutic response. If at that time, the glycosylated hemoglobin level is not satisfactory, the dosage may be further increased to 100 mg 3 times daily, the maximum recommended dosage.

Maximum Dosage: The maximum recommended dosage of Miglitol is 100 mg 3 times daily. In one clinical trial, 200 mg 3 times daily gave additional improved glycemic control but increased the incidence of the gastrointestinal symptoms described above.

Patients Receiving Sulfonylureas: Sulfonylurea agents may cause hypoglycemia. There was no increased incidence of hypoglycemia in patients who took Miglitol in combination with sulfonylurea agents compared to the incidence of hypoglycemia in patients receiving sulfonylureas alone in any clinical trial. However, Miglitol given in combination with a sulfonylurea will cause a further lowering of blood glucose and may increase the risk of hypoglycemia due to the additive effects of the two agents. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made

Should be taken with food. Take with 1st bite of each main meal.

Abdominal pain or discomfort, diarrhoea, flatulence, skin rash.

Patient with diabetic ketoacidosis, inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to this condition, chronic intestinal diseases associated with marked disorders of digestion or absorption and co-existing conditions that may deteriorate as a result of increased intestinal gas formation.

Patient exposed to stress (e.g. fever, trauma, infection, surgery). Renal impairment. Pregnancy and lactation.

Concomitant use with insulin increases the risk of hypoglycaemia. Intestinal adsorbents (e.g. charcoal) and carbohydrate-splitting digestive enzyme supplements (e.g. amylase, pancreatin) may reduce glycaemic effects. May significantly reduce the bioavailability of ranitidine and propranolol.

Category B: Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Store at 25° C.

Cholera Saline contains different electrolytes which are usually depleted in various conditions e.g. diarrhoea, vomiting, profuse sweating etc. So, this saline is indicated in cholera, also in diarrhoea, vomiting, fluid loss, to replenish and restore the normal electrolyte balance of the body.

Intravenous fluid preparations

The volume and rate of infusion of Cholera Saline depends upon the requirements of the patient and the judgement of the physician. It usually varies with age, weight and clinical condition of the patient.

Administration Procedure:

• Check infusion set and infusion solution prior to use
• Pull moderately to tear off the protective cover of the Eurohead
• Hold lightly the Eurohead but not the bag
• Open the flow regulator fully and hold the giving set on the top white area, but not the membrane venting region
• Insert the spike of the administration set to the Eurohead and fit the connector of the administration set firmly to the needle
• Gradually allow the fluid to flow down to the needle tip and close
• Remove the protective cover of the needle
• Locate the venipuncture site and clean the site with an antiseptic solution, and then insert the needle
• Securely tape the puncture site
• Securely tape the wings and tubing
• Start infusion while adjusting drip speed

Since Cholera Saline contains different electrolytes, it should be infused with caution in patients where electrolyte imbalance may cause detrimental effects, e.g. in pregnancy, renal impairment, heart failure, pulmonary congestion, head injury etc. or in patients receiving potassium sparing diuretics.

Should be stored at controlled room temperature.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Empagliflozin is indicated in:

• As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• To reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.

The recommended dose of Empagliflozin is 10 mg once daily, taken in the morning, with or without food. In patients tolerating Empagliflozin, the dose may be increased to 25 mg once daily. In patients with volume depletion, correcting this condition prior to initiation of Empagliflozin is recommended.

The most common adverse reactions associated with Empagliflozin are urinary tract infections and female genital mycotic infections. Others common side effects includes dehydration, hypotension, weakness, dizziness and increased thirstiness.

Empagliflozin is contraindicated in patients with history of serious hypersensitivity reaction to Empagliflozin or any of its ingredients, severe renal impairment, end-stage renal disease, or dialysis.

Assessment of renal function is recommended prior to initiation of Empagliflozin and periodically thereafter. Empagliflozin should not initiated in patients with an eGFR less than 45 ml/min/1.73 m². No dose adjustment is needed in patients with an eGFR greater than or equal to 45 ml/min/1.73 m².

Diuretics: Co-administration of Empagliflozin with diuretics resulted in increased urine volume. 

Insulin or Insulin Secretagogues: Co-administration of Empagliflozin with insulin or insulin secretagogues increases the risk for hypoglycemia. 

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control. 

Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

There are no adequate and well-controlled studies of Empagliflozin in pregnant women. Empagliflozin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Empagliflozin is excreted in human milk. It is not recommended when breastfeeding.

In the event of an overdose with Empagliflozin the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, perform clinical monitoring, and institute supportive treatment) should be employed. Removal of Empagliflozin by hemodialysis has not been studied.

Keep in a cool & dry place (below 30° C), protected from light & moisture. Keep out of the reach of children.

Medium Acting Insulin

Insulin Human (rDNA) is human insulin made by recombinant DNA technology. It has the same structure and function as natural insulin. Insulin regulates the glucose metabolism and stimulates the ingestion and utilization of glucose by liver, muscle and fat tissue. It also lowers blood glucose by accelerating glycogenesis and inhibiting gluconeogenesis.

Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 start action within 30 minutes after injection, reach peak level within 2-8 hours and last about 24 hours.

The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/kg. In pre-pubertal children it usually varies from 0.7 to 1.0 IU/kg, whereas in insulin resistant cases, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/kg/day.

The dosage form, the dosage and the administration time of the insulin are different due to the individual differences of each patient. In addition, the dosage is also affected by food, working style and exercising intensity. Therefore, patients should use the insulin under doctor's instruction.

An injection should be followed by a meal or snack containing carbohydrates within 30 minutes. Injection is administered subcutaneously in the upper arm, thigh, buttock or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites. Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 are never to be administered intravenously.

Preparation before use:

• Clean your hands.
• Shake or rotate the vial gently to mix the solution uniformly and check if the insulin has the normal appearance.
• In case of using a new vial, flip off the plastic protective cap and wipe the rubber plug with an alcohol swab.
• Draw air into your syringe equal to the amount of insulin needed.
• Puncture the needle into the vial and inject the air.
• Turn the bottle and syringe upside down and withdraw correct dose of insulin into the syringe.
• Before pulling out the needle, check if there are any bubbles remain in the syringe. If so, put the syringe upright and tap the syringe to discharge the air bubbles.

Injection site:

• Choose the area where skin is less tight, such as the upper arm, thigh, buttock or abdomen.
• To avoid tissue damage, choose a site for each injection that is at least 1 cm from the previous injection site.

Injection method:

• Cleanse the skin with alcohol where the injection is to be made.
• Put the needle in such a position as to form 45° angle with the skin.
• Puncture the needle into skin and inject insulin.
• Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected.
• Pull the needle out and apply gentle pressure over the injected site for several seconds.
• Do not rub the injection site.

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycemia or the patients who have allergic reaction to insulin or any of the excipients.

Inadequate dosing or discontinuation especially in type 1 diabetes, may lead to hyperglycemia. Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement. Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycemia.

When using oral contraceptive drug, adrenal cortical hormone, thyroid hormone, etc., the drugs that can result in the rise of blood glucose; you might need to increase the amount of Insulin. When using drugs with hypoglycemic activities, salicylate, sulfanilamide and other anti-depressants, which will result in the decrease of blood glucose, the dosage of insulin should be reduced.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier. Insulin treatment of the nursing mother presents no risk to the baby.

Excessive use of insulin may lead to hypoglycemia during the treatment. Slight to moderate hypoglycemia may suddenly occur. It is important to get immediate treatment when hypoglycemia occurs. If you have frequent hypoglycemia, you should consult your doctor to discuss possible changes in therapy, diet plans, and/or exercise programs to help you avoid hypoglycemia.

Store at 2°C - 8°C in a refrigerator. Do not freeze. In case of insulin for recent use need not be refrigerated, try to keep it in a cool place and keep away from heat and light. The insulin in use can be kept under the room temperature for a month.

Medium Acting Insulin

Insulin Human (rDNA) is human insulin made by recombinant DNA technology. It has the same structure and function as natural insulin. Insulin regulates the glucose metabolism and stimulates the ingestion and utilization of glucose by liver, muscle and fat tissue. It also lowers blood glucose by accelerating glycogenesis and inhibiting gluconeogenesis.

Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 start action within 30 minutes after injection, reach peak level within 2-8 hours and last about 24 hours.

The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/kg. In pre-pubertal children it usually varies from 0.7 to 1.0 IU/kg, whereas in insulin resistant cases, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/kg/day.

The dosage form, the dosage and the administration time of the insulin are different due to the individual differences of each patient. In addition, the dosage is also affected by food, working style and exercising intensity. Therefore, patients should use the insulin under doctor's instruction.

An injection should be followed by a meal or snack containing carbohydrates within 30 minutes. Injection is administered subcutaneously in the upper arm, thigh, buttock or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites. Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 are never to be administered intravenously.

Preparation before use:

• Clean your hands.
• Shake or rotate the vial gently to mix the solution uniformly and check if the insulin has the normal appearance.
• In case of using a new vial, flip off the plastic protective cap and wipe the rubber plug with an alcohol swab.
• Draw air into your syringe equal to the amount of insulin needed.
• Puncture the needle into the vial and inject the air.
• Turn the bottle and syringe upside down and withdraw correct dose of insulin into the syringe.
• Before pulling out the needle, check if there are any bubbles remain in the syringe. If so, put the syringe upright and tap the syringe to discharge the air bubbles.

Injection site:

• Choose the area where skin is less tight, such as the upper arm, thigh, buttock or abdomen.
• To avoid tissue damage, choose a site for each injection that is at least 1 cm from the previous injection site.

Injection method:

• Cleanse the skin with alcohol where the injection is to be made.
• Put the needle in such a position as to form 45° angle with the skin.
• Puncture the needle into skin and inject insulin.
• Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected.
• Pull the needle out and apply gentle pressure over the injected site for several seconds.
• Do not rub the injection site.

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycemia or the patients who have allergic reaction to insulin or any of the excipients.

Inadequate dosing or discontinuation especially in type 1 diabetes, may lead to hyperglycemia. Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement. Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycemia.

When using oral contraceptive drug, adrenal cortical hormone, thyroid hormone, etc., the drugs that can result in the rise of blood glucose; you might need to increase the amount of Insulin. When using drugs with hypoglycemic activities, salicylate, sulfanilamide and other anti-depressants, which will result in the decrease of blood glucose, the dosage of insulin should be reduced.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier. Insulin treatment of the nursing mother presents no risk to the baby.

Excessive use of insulin may lead to hypoglycemia during the treatment. Slight to moderate hypoglycemia may suddenly occur. It is important to get immediate treatment when hypoglycemia occurs. If you have frequent hypoglycemia, you should consult your doctor to discuss possible changes in therapy, diet plans, and/or exercise programs to help you avoid hypoglycemia.

Store at 2°C - 8°C in a refrigerator. Do not freeze. In case of insulin for recent use need not be refrigerated, try to keep it in a cool place and keep away from heat and light. The insulin in use can be kept under the room temperature for a month.

Medium Acting Insulin

Insulin Human (rDNA) is human insulin made by recombinant DNA technology. It has the same structure and function as natural insulin. Insulin regulates the glucose metabolism and stimulates the ingestion and utilization of glucose by liver, muscle and fat tissue. It also lowers blood glucose by accelerating glycogenesis and inhibiting gluconeogenesis.

Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 start action within 30 minutes after injection, reach peak level within 2-8 hours and last about 24 hours.

The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/kg. In pre-pubertal children it usually varies from 0.7 to 1.0 IU/kg, whereas in insulin resistant cases, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/kg/day.

The dosage form, the dosage and the administration time of the insulin are different due to the individual differences of each patient. In addition, the dosage is also affected by food, working style and exercising intensity. Therefore, patients should use the insulin under doctor's instruction.

An injection should be followed by a meal or snack containing carbohydrates within 30 minutes. Injection is administered subcutaneously in the upper arm, thigh, buttock or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites. Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 are never to be administered intravenously.

Preparation before use:

• Clean your hands.
• Shake or rotate the vial gently to mix the solution uniformly and check if the insulin has the normal appearance.
• In case of using a new vial, flip off the plastic protective cap and wipe the rubber plug with an alcohol swab.
• Draw air into your syringe equal to the amount of insulin needed.
• Puncture the needle into the vial and inject the air.
• Turn the bottle and syringe upside down and withdraw correct dose of insulin into the syringe.
• Before pulling out the needle, check if there are any bubbles remain in the syringe. If so, put the syringe upright and tap the syringe to discharge the air bubbles.

Injection site:

• Choose the area where skin is less tight, such as the upper arm, thigh, buttock or abdomen.
• To avoid tissue damage, choose a site for each injection that is at least 1 cm from the previous injection site.

Injection method:

• Cleanse the skin with alcohol where the injection is to be made.
• Put the needle in such a position as to form 45° angle with the skin.
• Puncture the needle into skin and inject insulin.
• Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected.
• Pull the needle out and apply gentle pressure over the injected site for several seconds.
• Do not rub the injection site.

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycemia or the patients who have allergic reaction to insulin or any of the excipients.

Inadequate dosing or discontinuation especially in type 1 diabetes, may lead to hyperglycemia. Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement. Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycemia.

When using oral contraceptive drug, adrenal cortical hormone, thyroid hormone, etc., the drugs that can result in the rise of blood glucose; you might need to increase the amount of Insulin. When using drugs with hypoglycemic activities, salicylate, sulfanilamide and other anti-depressants, which will result in the decrease of blood glucose, the dosage of insulin should be reduced.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier. Insulin treatment of the nursing mother presents no risk to the baby.

Excessive use of insulin may lead to hypoglycemia during the treatment. Slight to moderate hypoglycemia may suddenly occur. It is important to get immediate treatment when hypoglycemia occurs. If you have frequent hypoglycemia, you should consult your doctor to discuss possible changes in therapy, diet plans, and/or exercise programs to help you avoid hypoglycemia.

Store at 2°C - 8°C in a refrigerator. Do not freeze. In case of insulin for recent use need not be refrigerated, try to keep it in a cool place and keep away from heat and light. The insulin in use can be kept under the room temperature for a month.

Medium Acting Insulin

Insulin Human (rDNA) is human insulin made by recombinant DNA technology. It has the same structure and function as natural insulin. Insulin regulates the glucose metabolism and stimulates the ingestion and utilization of glucose by liver, muscle and fat tissue. It also lowers blood glucose by accelerating glycogenesis and inhibiting gluconeogenesis.

Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 start action within 30 minutes after injection, reach peak level within 2-8 hours and last about 24 hours.

The average range of total daily insulin requirement for maintenance therapy in type 1 diabetic patients lies between 0.5 and 1.0 IU/kg. In pre-pubertal children it usually varies from 0.7 to 1.0 IU/kg, whereas in insulin resistant cases, e.g. during puberty or due to obesity, the daily insulin requirement may be substantially higher. Initial dosages for type 2 diabetic patients are often lower, e.g. 0.3 to 0.6 IU/kg/day.

The dosage form, the dosage and the administration time of the insulin are different due to the individual differences of each patient. In addition, the dosage is also affected by food, working style and exercising intensity. Therefore, patients should use the insulin under doctor's instruction.

An injection should be followed by a meal or snack containing carbohydrates within 30 minutes. Injection is administered subcutaneously in the upper arm, thigh, buttock or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites. Insulin Human (rDNA) 30/70 & Insulin Human (rDNA) 50/50 are never to be administered intravenously.

Preparation before use:

• Clean your hands.
• Shake or rotate the vial gently to mix the solution uniformly and check if the insulin has the normal appearance.
• In case of using a new vial, flip off the plastic protective cap and wipe the rubber plug with an alcohol swab.
• Draw air into your syringe equal to the amount of insulin needed.
• Puncture the needle into the vial and inject the air.
• Turn the bottle and syringe upside down and withdraw correct dose of insulin into the syringe.
• Before pulling out the needle, check if there are any bubbles remain in the syringe. If so, put the syringe upright and tap the syringe to discharge the air bubbles.

Injection site:

• Choose the area where skin is less tight, such as the upper arm, thigh, buttock or abdomen.
• To avoid tissue damage, choose a site for each injection that is at least 1 cm from the previous injection site.

Injection method:

• Cleanse the skin with alcohol where the injection is to be made.
• Put the needle in such a position as to form 45° angle with the skin.
• Puncture the needle into skin and inject insulin.
• Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected.
• Pull the needle out and apply gentle pressure over the injected site for several seconds.
• Do not rub the injection site.

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycemia or the patients who have allergic reaction to insulin or any of the excipients.

Inadequate dosing or discontinuation especially in type 1 diabetes, may lead to hyperglycemia. Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement. Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycemia.

When using oral contraceptive drug, adrenal cortical hormone, thyroid hormone, etc., the drugs that can result in the rise of blood glucose; you might need to increase the amount of Insulin. When using drugs with hypoglycemic activities, salicylate, sulfanilamide and other anti-depressants, which will result in the decrease of blood glucose, the dosage of insulin should be reduced.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier. Insulin treatment of the nursing mother presents no risk to the baby.

Excessive use of insulin may lead to hypoglycemia during the treatment. Slight to moderate hypoglycemia may suddenly occur. It is important to get immediate treatment when hypoglycemia occurs. If you have frequent hypoglycemia, you should consult your doctor to discuss possible changes in therapy, diet plans, and/or exercise programs to help you avoid hypoglycemia.

Store at 2°C - 8°C in a refrigerator. Do not freeze. In case of insulin for recent use need not be refrigerated, try to keep it in a cool place and keep away from heat and light. The insulin in use can be kept under the room temperature for a month.

Long Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Dosage is individual and determined in accordance with the needs of the patient. The individual insulin requirement is usually between 0.3 and 1.0 IU/kg day. The daily insulin requirement may be higher in patients with insulin resistance (e.g. during puberty or due to obesity) and lower in patients with residual, endogenous insulin production.

The physician determines one or several daily injections are necessary. Insulatard may be used alone or mixed with fast-acting insulin. In intensive insulin therapy the suspension may be used as basal insulin (evening and/or morning injection) with fast-acting insulin given at meals. In patients with diabetes mellitus optimised glycaemic control delays the onset of late diabetic complications. Close blood glucose monitoring is recommended.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycaemia, Hypersensitivity to human insulin or to any of the excipients

Inadequate dosage or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia. Usually the first symptoms of hyperglycaemia set in gradually, over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal. Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly Usual warning symptoms may disappear in patients with longstanding diabetes.

A number of medicinal products are known to interact with the glucose metabolism. Physicians must therefore take possible interactions into account and should always ask their patients about any medicinal products they take.

The following substances may reduce insulin requirement: Oral hypoglycaemic agents (OHA), monoamine oxidase inhibitors (MAOI), non-selective beta-blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates and alcohol.

The following substances may increase insulin requirement: Thiazides, glucocorticoids, thyroid hormones and beta-sympathomimetics, growth hormone and danazol. Beta-blocking agents may mask the symptoms of hypoglycaemia and delay recovery from hypoglycaemia. Octreotide/lanreotide may both decrease and increase insulin requirement. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier.

A specific overdose of insulin cannot be defined. However, hypoglycaemia may develop over sequential stages

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the container cartridge or vial in the outer carton in order to protect from light.

During use: do not refrigerate. Do not store vials above 25°C and cartridges above 30°C. Protect from excessive heat and sunlight.

Long Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Dosage is individual and determined in accordance with the needs of the patient. The individual insulin requirement is usually between 0.3 and 1.0 IU/kg day. The daily insulin requirement may be higher in patients with insulin resistance (e.g. during puberty or due to obesity) and lower in patients with residual, endogenous insulin production.

The physician determines one or several daily injections are necessary. Insulatard may be used alone or mixed with fast-acting insulin. In intensive insulin therapy the suspension may be used as basal insulin (evening and/or morning injection) with fast-acting insulin given at meals. In patients with diabetes mellitus optimised glycaemic control delays the onset of late diabetic complications. Close blood glucose monitoring is recommended.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin

Hypoglycemia is the most common adverse effect during insulin treatment and symptoms of hypoglycemia may occur suddenly. Few cases of the allergic reaction such as red and swollen or itching are reported. It usually disappears in a few days. In some instances, the allergy may be caused by other reasons rather than insulin, such as disinfectant and poor injection technique.

Hypoglycaemia, Hypersensitivity to human insulin or to any of the excipients

Inadequate dosage or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia. Usually the first symptoms of hyperglycaemia set in gradually, over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry mouth, loss of appetite as well as acetone odour of breath In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal. Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly Usual warning symptoms may disappear in patients with longstanding diabetes.

A number of medicinal products are known to interact with the glucose metabolism. Physicians must therefore take possible interactions into account and should always ask their patients about any medicinal products they take.

The following substances may reduce insulin requirement: Oral hypoglycaemic agents (OHA), monoamine oxidase inhibitors (MAOI), non-selective beta-blocking agents, angiotensin converting enzyme (ACE) inhibitors, salicylates and alcohol.

The following substances may increase insulin requirement: Thiazides, glucocorticoids, thyroid hormones and beta-sympathomimetics, growth hormone and danazol. Beta-blocking agents may mask the symptoms of hypoglycaemia and delay recovery from hypoglycaemia. Octreotide/lanreotide may both decrease and increase insulin requirement. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier.

A specific overdose of insulin cannot be defined. However, hypoglycaemia may develop over sequential stages

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the container cartridge or vial in the outer carton in order to protect from light.

During use: do not refrigerate. Do not store vials above 25°C and cartridges above 30°C. Protect from excessive heat and sunlight.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Used as a diet supplement and sugar substitute.

Oral nutritional preparations

Aspartame is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.

Aspartame is 180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.

According to individual taste. 1 pellet is equivalent in sweetness to 1 tsf of sugar.

Constipation; faecal impaction; haemorrhoids; abdominal discomfort or pain; heartburn; flatulence; nausea; vomiting; diarrhoea; increased bleeding tendency (chronic use); osteoporosis; steatorrhoea (high doses); skin rashes; pruritus of the tongue, skin and perianal region; hyperchloraemic acidosis.

Complete biliary obstruction, hypersensitivity.

If pregnant or breast-feeding, seek advice of a health professional before use.

There are no known drug interactions and none well documented.

Pregnancy Category-C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Gliclazide is a medicine that reduces blood sugar levels (oral antidiabetic medicine belonging to the sulphonylurea group). Gliclazide is used in a certain form of diabetes (type 2 diabetes Mellitus) in adults, when diet, exercise and weight loss alone do not have an adequate effect on keeping blood sugar at the correct level.

Sulfonylureas

Gliclazide is a second generation sulfonylurea drug that has hypoglycaemic and potentially useful hematological properties. It stimulates the release of insulin from pancreatic β-cells by facilitating Ca⁺²  transport across the β-cell membranes and decreases hepatic glucose output.

Film-coated tablet: The usual initial dose is 40 to 80 mg daily. The dose can be increased up to 320 mg daily in divided doses when needed. The drug should be taken before meal. For children, Gliclazide is not used because it is contraindicated in juvenile-onset diabetes.

Modified release preparation: Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose is determined by the doctor, depending on your blood and possibly urine sugar levels. Change in external factors (weight reduction, lifestyle, stress) or improvements in the blood sugar control may require changed gliclazide doses.

The recommended daily dose is one to four tablets (maximum 120 mg) in a single intake at breakfast time. This depends on the response to treatment. Gliclazide MR tablet is for oral use. Take your tablet(s) with a glass of water at breakfast time (and preferably at the same time each day). Swallow your whole tablet(s) in one piece. Do not chew or crush. You must always eat a meal after taking your tablet(s).

If a combination therapy of gliclazide with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor a GLP-1 receptor agonist or insulin is initiated your doctor will determine the proper dose of each medicine individually for you. If you notice that your blood sugar levels are high although you are taking the medicine as prescribed, you should contact your doctor or pharmacist.

If you take more Gliclazide tablets than you should: If you take too many tablets, contact your doctor or the nearest hospital Accident & Emergency department immediately. The signs of overdose are those of low blood sugar (hypoglycaemia). The symptoms can be helped by taking sugar (4 to 6 lumps) or sugary drinks straight away, followed by a substantial snack or meal. If the patient is unconscious immediately inform a doctor and call the emergency services. The same should be done if somebody, (for instance a child), has taken the product unintentionally. Unconscious patients must not be given food or drink. It should be ensured that there is always a pre-informed person that can call a doctor in case of emergency.

If you forget to take Gliclazide tablet: It is important to take your medicine every day as regular treatment works better. However, if you forget to take a dose of Gliclazide MR tablet, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gliclazide MR tablet: As the treatment for diabetes is usually lifelong, you should discuss with your doctor before stopping this medicinal product. Stopping could cause high blood sugar (hyperglycaemia) which increases the risk of developing complications of diabetes. If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Gliclazide can cause side effects, although not everybody gets them. The most commonly observed side effect is low blood sugar (hypoglycaemia). If left untreated these symptoms could progress to drowsiness, loss of consciousness or possibly coma. If an episode of low blood sugar is severe or prolonged, even if it is temporarily controlled by eating sugar, you should seek immediate medical attention.

Liver disorders: There have been isolated reports of abnormal iiver function, which can cause yellow skin and eyes. If you get this, see your doctor immediately. The symptoms generally disappear if the medicine is stopped. Your doctor will decide whether to stop your treatment.

Skin disorders: Skin reactions such as rash, redness, itching, hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin. If you develop this, stop taking, seek urgent advice from a doctor and tell him that you are taking this medicine. Exceptionally, signs of severe hypersensitivity reactions have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

Blood disorders: Decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.

Digestive disorders: Abdominal pain, nausea, vomiting, indigestion, diarrhoea, and constipation. These effects are reduced when Gliclazide is taken with a meal as recommended.

Eye disorders: Your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

As for another sulfonylurea, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (for instance jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

Reporting of side effects: If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not take Gliclazide:

• if you are allergic to gliclazide or to other medicines of the same group (sulfonylurea), or to other related medicines (hypoglycaemic sulfonamides)
• if you have insulin-dependent diabetes (type 1)
• if you have ketone bodies and sugar in your urine (this may mean you have diabetic ketoacidosis), a diabetic pre-coma or coma
• if you have severe kidney or liver disease
• if you are taking medicines to treat fungal infections
• if you are breastfeeding

Talk to your doctor before taking Gliclazide. You should observe the treatment plan prescribed by your doctor to achieve proper blood sugar levels. This means, apart from regular tablet intake, to observe the dietary regimen, have physical exercise and, where necessary, reduce weight During gliclazide treatment regular monitoring of your blood (and possibly urine) sugar level and also your glycated haemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of having reduced blood sugar levels (hypoglycaemia) may be increased. So particularly close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

• if you take meals irregularly or skip meals altogether,
• if you are fasting
• if you are malnourished
• if you change your diet
• if you increase your physical activity and carbohydrate intake does not match this increase,
• if you drink alcohol, especially in combination with skipped meals,
• if you take other medicines or natural remedies at the same time,
• if you take too high doses of gliclazide,
• if you suffer from particular hormone-induced disorders (functional disorders of the thyroid gland, pituitary gland or adrenal cortex),
• if your kidney function or liver function is severely decreased.

if you have low blood sugar you may have the following symptoms: headache, intense hunger, nausea, vomiting, weariness, sleep disorders, restlessness, aggressiveness, poor concentration, reduced alertness and reaction time, depression, confusion, speech or visual disorders, tremor, sensory disturbances, dizziness and helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, fast or irregular heartbeat, high blood pressure, sudden strong pain in the chest that may radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may suffer from considerable confusion (delirium), develop convulsions, lose self-control, your breathing may be shallow and your heartbeat slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar vanish very quickly when you consume .some form of sugar, (for instance, glucose tablets, sugar cubes, sweet juice, sweetened tea).

You should therefore always carry some form of sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Please contact your doctor or the nearest hospital if taking sugar does not help or if the symptoms recur.

Symptoms of low blood sugar may be absent, less obvious or develop very slowly or you are not aware in time that your blood sugar level has dropped. This may happen if you are an elderly patient taking certain medicines (for instance those acting on the central nervous system and beta-blockers).

If you are in stressful situations (e.g. accidents, surgical operations, fever etc.) your doctor may temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may occur when gliclazide has not yet sufficiently reduced the blood sugar when you have not complied with the treatment plan prescribed by your doctor if you take St. John’s Wort (Hypericum perforatum) preparations or in special stress situations. These may include thirst, frequent urination, dry mouth, dry itchy skin, skin infections and reduced performance.

Blood glucose disturbances (low blood sugar and high bold sugar) can occur when Gliclazide is prescribed at the same time as medicines to a class of antibiotics called fluoroquinolone, especially in elderly patients. In this case, your doctor will remind you of the importance of monitoring your blood glucose.

If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur. Contact your doctor before taking this medicinal product.

Gliclazide is not recommended for use in children due to lack of data.

Other medicines and Gliclazide: Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

The blood sugar lowering effect of gliclazide may be strengthened and signs of low blood sugar levels may occur when one of the follow ng medicines is taken:

• other medicines used to treat high blood sugar (oral antidiabetics, GLP-1 receptor agonists or insulin),
• antibiotics (sulphonamides, clarithromycin)
• medicines to treat high blood pressure or heart failure (beta-blockers. ACE-inhibitors such as captopril, or enalapril)
• medicines to treat fungal infections (miconazole, fluconazole)
• medicines to treat ulcers in the stomach or duodenum (H2 receptor antagonists),
• medicines to treat depression (monoamine oxidase inhibitors)
• painkiller or antirheumatics (phenylbutazone, ibuprofen)
• medicines containing alcohol

The blood-glucose-lowering effect of gliclazide may be weakened and raised blood sugar levels may occur when one of the following medicines is taken:

• medicines to treat disorders of the central nervous system (chlorpromazine)
• medicines reducing inflammation (corticosteroids)
• medicines to treat asthma or used during labour (intravenous salbutamol, ritodrine and terbutaline)
• medicines to treat breast disorders, heavy menstrual bleeding and endometriosis (danazol)
• St John's Wort- Hypericum perforatum- preparations

Blood glucose disturbance (low blood sugar and high blood sugar) can occur when a medicine belonging to a class of antibiotics called fluoroquinolones is taken at the same time as gliclazide especially in elderly patients.

Gliclazide may increase the effects of medicines that reduce blood clotting (warfarin).

Consult your doctor before you start taking another medicinal product. If you go into hospital tell the medical staff you are taking gliclazide.

Gliclazide with food and drink: Gliclazide can be taken with food and non-alcoholic drinks. Drinking alcohol is not recommended as it can alter the control of your diabetes in an unpredictable manner.

Driving and using machines: Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), or too high (hyperglycaemia) or if you develop visual problems as a result of such conditions. Bear in mind that you could endanger yourself or others (for instance when driving a car or using machines). Please ask your doctor whether you can drive a car if you:

• have frequent episodes of low blood sugar (hypoglycaemia)
• have few or no warning signals of low blood sugar (hypoglycaemia)

Gliclazide contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Gliclazide is not recommended for use during pregnancy. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You must not take Gliclazide while you are breastfeeding.

Keep out of the reach and sight of children. Do not use this medicine after the expiry date which is stated on the carton and the blister. The expiry date refers to the last day of that month. Store below 30°C. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.