Diabetes

Therapeutic indications

Amaryl® is indicated for the treatment of type 2 diabetes mellitus, when diet, physical exercise and weight reduction alone are not adequate.

POSOLOGY AND METHOD OF ADMINISTRATION

For oral administration. Tablets should be swallowed without chewing with some liquid. Normally a single daily dose of glimepiride is sufficient. It is recommended that this dose be taken shortly before or during a substantial breakfast or - if none is taken - shortly before or during the first main meal. If a dose is forgotten, this should not be corrected by increasing the next dose. The starting dose is 1 mg glimepiride per day. If good control is achieved this dose should be used for maintenance therapy. If control is unsatisfactory the dose should be increased, based on the glycaemic control, in a stepwise manner with an interval of about 1 to 2 weeks between each step, to 2, 3 or 4 mg glimepiride per day.

A dose of more than 4 mg glimepiride per day gives better results only in exceptional cases. The maximum recommended dose is 6 mg glimepiride per day. In patients not adequately controlled with the maximum daily dose of metformin, concomitant glimepiride therapy can be initiated. The combination therapy should be initiated under close medical supervision. In patients not adequately controlled with the maximum daily dose of Amaryl, concomitant insulin therapy can be initiated if necessary. The combination therapy should be initiated under close medical supervision.

Patients can be switched from other oral hypoglycaemic agents, insulin to Amaryl; the recommended starting dose is 1 mg glimepiride per day. Amaryl® use in the paediatric population is not recommended.

CONTRA-INDICATIONS

Hypersensitivity to glimepiride, other sulfonylureas or sulphonamides, or to any of the excipients; insulin-dependent diabetes; diabetic coma; ketoacidosis, severe renal or hepatic function disorders. In case of severe renal or hepatic function disorders, a changeover to insulin is required.

Glimepiride should not be used during the whole pregnancy. In case of treatment by glimepiride, if the patient plans to become pregnant or if a pregnancy is discovered, the treatment should be switched as soon as possible to insulin therapy. Breast-feeding is advised against during treatment with glimepiride.

SPECIAL WARNINGS ANDSPECIAL PRECAUTIONS FOR USE

Amaryl® must be taken shortly before or during a meal. When meals are taken at irregular hours or skipped altogether, treatment with Amaryl® may lead to hypoglycaemia. The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke. Symptoms can almost always be promptly controlled by immediate intake of carbohydrates (sugar). Artificial sweeteners have no effect. Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, require immediate medical treatment and occasionally hospitalisation. Treatment with Amaryl® requires regular monitoring of glucose levels in blood and urine.

In addition determination of the proportion of glycosylated haemoglobin is recommended. Regular hepatic and haematological monitoring (especially leucocytes and thrombocytes) are required during treatment with Amaryl.

In stress-situations (e.g. accidents, acute operations, infections with fever, etc.) a temporary switch to insulin may be indicated. In patients with severe impairment of renal or liver function change over to insulin is indicated. Since glimepiride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-deficiency and a non-sulfonylurea alternative should be considered. Amaryl® contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

INTERACTIONS

Concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole), in some instances hypoglycaemia may occur when one of the following medicinal products is taken, for example: phenylbutazone, azapropazone and oxyfenbutazone, insulin and oral antidiabetic products, such as metformin, salicylates and p-amino-salicylic acid, anabolic steroids and male sex hormones, chloramphenicol, certain long acting sulfonamides, tetracyclines, quinolone antibiotics and clarithromycin, coumarin anticoagulants, fenfluramine, disopyramide, fibrates, ACE inhibitors, fluoxetine, MAO-inhibitors, allopurinol, probenecid, sulfinpyrazone, sympatholytics, cyclophosphamide, trophosphamide and iphosphamides, miconazole, fluconazole, pentoxifylline (high dose parenteral), tritoqualine.

Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following medicinal products is taken, for example: oestrogens and progestogens, saluretics, thiazide diuretics, thyroid stimulating agents, glucocorticoids, phenothiazine derivatives, chlorpromazine, adrenaline and sympathicomimetics, nicotinic acid (high doses) and nicotinic acid derivatives, laxatives (long term use), phenytoin, diazoxide, glucagon, barbiturates and rifampicin, acetazolamide. H2 antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.

Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent. Alcohol intake may potentiate or weaken the hypoglycaemic action of glimepiride in an unpredictable fashion. Glimepiride may either potentiate or weaken the effects of coumarin derivatives. Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract; glimepiride should be administered at least 4 hours prior to colesevelam.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

It should be considered whether it is advisable to drive or operate machinery as the patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.

UNDESIRABLE EFFECTS

Rarely hypoglycaemic reactions can occur, mostly occurring immediately.
For other uncommon, rare and very rare side effects see full Prescribing information.

OVERDOSE

Treatment primarily consists of preventing absorption by inducing vomiting and then drinking water or lemonade with activated charcoal (adsorbent) and sodium-sulphate (laxative).
If large quantities have been ingested, gastric lavage is indicated, followed by activated charcoal and sodium-sulphate.
In case of (severe) overdose hospitalisation in an intensive care department is indicated.
Start the administration of glucose as soon as possible, if necessary by a bolus intravenous injection of 50 ml of a 50% solution, followed by an infusion of a 10% solution with strict monitoring of blood glucose.
Further treatment should be symptomatic.
In particular when treating hypoglycaemia due to accidental intake of Amaryl® in infants and young children, the dose of glucose given must be carefully controlled to avoid the possibility of producing dangerous hyperglycaemia.
Blood glucose should be closely monitored.

PHARMACODYNAMIC PROPERTIES

Pharmacotherapeutic group: Blood glucose lowering drugs, excl. insulins: Sulfonamides, urea derivatives.
ATC Code: A10B B12.

Date of SmPC text revision: 7 October 2013;
Date of abbreviated prescribing information: August 2017;
More detailed Information on request:
Refer to Summary of Product Characteristics or
Sanofi, Japaul House, Plot 8,
Dr. Nurudeen Olowopopo Avenue, Ikeja Central Business District, Agidingbi, Lagos, Nigeria.
Tel: +234 1 2710135/2800994;

Sanofi Office, 2nd Floor Yekeima Square,
No_ 6 George Walker Bush Highway Dzorwulu, Accra.
Tel: +233 302 734772;

For Pharmacovigilance (reporting adverse events), please contact: ng-gh.pv@sanofi.com.

Therapeutic indications

Treatment of diabetes mellitus in adults, adolescents and children aged 2 years and above.

POSOLOGY AND METHOD OF ADMINISTRATION

Posology

Lantus® contains insulin glargine, an insulin analogue, and has a prolonged duration of action.
Lantus® should be administered once daily at any time but at the same time each day.
The dose regimen (dose and timing) should be individually adjusted. In patients with type 2 diabetes mellitus, Lantus® can also be given together with orally active antidiabetic medicinal products.
The potency of this medicinal product is stated in units. These units are exclusive to Lantus® and are not the same as IU or the units used to express the potency of other insulin analogues (see section 5.1).

Method of administration

Lantus® is administered subcutaneously.
Lantus® should not be administered intravenously. The prolonged duration of action of Lantus® is dependent on its injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.
There are no clinically relevant differences in serum insulin or glucose levels after abdominal, deltoid or thigh administration of Lantus. Injection sites must be rotated within a given injection area from one injection to the next.
Lantus® must not be mixed with any other insulin or diluted. Mixing or diluting can change its time/action profile and mixing can cause precipitation.

CONTRA-INDICATIONS

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE

Lantus® is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulin administered intravenously is recommended in such cases.
In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose.

INTERACTIONS

A number of substances affect glucose metabolism and may require dose adjustment of insulin glargine.
Substances that may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.

Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g. clozapine and olanzapine) and protease inhibitors.

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

PREGNANCY AND LACTATION

Pregnancy

The use of Lantus® may be considered during pregnancy, if clinically needed.

Lactation

It is unknown whether insulin glargine is excreted in human milk. No metabolic effects of ingested insulin glargine on the breast-fed newborn/infant are anticipated since insulin glargine as a peptide is digested into aminoacids in the human gastrointestinal tract. Breast-feeding women may require adjustments in insulin dose and diet.

UNDESIRABLE EFFECTS

Hypoglycaemia,, Lipohypertrophy, Injection site reactions

For uncommon, rare and very rare side effects see full prescribing information

OVERDOSE

Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in dose of the medicinal product, meal patterns, or physical activity may be needed.
More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.

PHARMACODYNAMIC PROPERTIES

Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, long-acting.
ATC Code: A10AE04.

Date of abbreviated prescribing information: June 2019;
More detailed Information on request: Refer to Summary of Product Characteristics or
Sanofi, Japaul House, Plot 8,
Dr. Nurudeen Olowopopo Avenue, Ikeja Central Business District, Agidingbi, Lagos, Nigeria.
Tel: +234 1 2710135/2800994;

Sanofi Office, Volta Place,
35 Patrice Lumumba Road, Airport Residential Area, Accra.
Tel: +233 302 734772;

For Pharmacovigilance (reporting adverse events), please contact: ng-gh.pv@sanofi.com.

Therapeutic indications

Treatment of adults, adolescents and children 6 years or older, with diabetes mellitus, where treatment with insulin is required.

POSOLOGY AND METHOD OF ADMINISTRATION

Posology

The potency of this preparation is stated in units. These units are exclusive to Apidra® and are not the same as IU or the units used to express the potency of other insulin analogues (see section 5.1).
Apidra® should be used in regimens that include an intermediate or long acting insulin or basal insulin analogue and can be used with oral hypoglycaemic agents.

The dose of Apidra® should be individually adjusted.

Method of administration

Apidra® 100 Units/ml solution for injection in a vial
Intravenous use
Apidra® can be administered intravenously. This should be carried out by healthcare professionals.
Apidra® must not be mixed with glucose or Ringer’s solution or with any other insulin.

Continuous subcutaneous insulin infusion

CONTRA-INDICATIONS

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypoglycaemia.

SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE

Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, neutral protamine Hagedorn [NPH], lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose. Concomitant oral antidiabetic treatment may need to be adjusted.

INTERACTIONS

Studies on pharmacokinetic interactions have not been performed. Based on empirical knowledge from similar medicinal products, clinically relevant pharmacokinetic interactions are unlikely to occur.
A number of substances affect glucose metabolism and may require dose adjustment of insulin glulisine and particularly close monitoring.

PREGNANCY AND LACTATION

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of insulin glulisine in pregnant women.
Animal reproduction studies have not revealed any differences between insulin glulisine and human insulin regarding pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Caution should be exercised when prescribing to pregnant women. Careful monitoring of glucose control is essential.
It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly.

Lactation

It is unknown whether insulin glulisine is excreted in human milk, but in general insulin does not pass into breast milk and is not absorbed after oral administration.

Breast-feeding mothers may require adjustments in insulin dose and diet.

UNDESIRABLE EFFECTS

Hypoglycaemia, Injection site reactions, Local hypersensitivity reactions.

For uncommon, rare and very rare side effects see full prescribing information

OVERDOSE

Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient constantly carries some sugar lumps, sweets, biscuits or sugary fruit juice.
Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5 mg to 1 mg) given intramuscularly or subcutaneously by a person who has received appropriate instruction, or by glucose given intravenously by a healthcare professional. Glucose must also be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes.
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
After an injection of glucagon, the patient should be monitored in a hospital in order to find the reason for this severe hypoglycaemia and prevent other similar episodes.

PHARMACODYNAMIC PROPERTIES

Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection, fast-acting.
ATC code: A10AB06.

Date of abbreviated prescribing information: September 2018;
More detailed Information on request: Refer to Summary of Product Characteristics or
Sanofi, Japaul House, Plot 8,
Dr. Nurudeen Olowopopo Avenue, Ikeja Central Business District, Agidingbi, Lagos, Nigeria.
Tel: +234 1 2710135/2800994;

Sanofi Office, Volta Place,
35 Patrice Lumumba Road, Airport Residential Area, Accra.
Tel: +233 302 734772;

For Pharmacovigilance (reporting adverse events), please contact: ng-gh.pv@sanofi.com.

Therapeutic indications

This medicinal product is used as an adjunct to appropriate dietary measures for the treatment of non-insulin dependent diabetes, when blood glucose levels cannot be controlled adequately by diet alone.

POSOLOGY AND METHOD OF ADMINISTRATION

Posology

For use in adults only : As for all hypoglycemic agents, the dose should be adjusted to each individual case.
In the event of a transient glycemic imbalance, a short period of treatment with the medicinal product may be sufficient in patients who are usually adequately stabilized by diet.

Subjects aged under 65 years

Initial dose: The recommended initial dose is 1/2 tablet daily, administered before breakfast.

Dose increments: Dose adjustment usually takes place in increments of 1/2 a tablet, based on glycemic response, in divided doses before the 2 or 3 main meals. Each dose increment should be separated by at least several days.

Maintenance treatment: The maximum dosage is 3 tablets daily, divided into 2 or 3 doses before the main meals.

Subjects at risk

Elderly patients aged 65 years and over: The initial dose and the maintenance doses should be cautiously adjusted to reduce the risk of hypoglycemia. Treatment should be initiated with the smallest available dose and gradually increased if necessary (see Section 4.4).

Subjects at risk

In patients who are malnourished or show a considerable deterioration in their general condition, or with irregular calorie intake, and in patients with kidney or liver failure, treatment should be initiated at the lowest dose, and the dose increments scrupulously followed, so as to avoid hypoglycemic reactions (see Section 4.4).

Patients receiving other oral hypoglycemic agents

As for all sulfonylureas, this medicinal product may follow on from another antidiabetic treatment without a transition period. When changing over from a sulfonylurea with a longer half-life (such as chlorpropamide) to this medicinal product, patients should be carefully monitored for several weeks in order to avoid the onset of hypoglycemia, due to the possible overlap of therapeutic effects.

Method of administration

Oral use.

CONTRA-INDICATIONS

This medicinal product is contraindicated in the following situations:
• hypersensitivity to glibenclamide, to other sulfonylureas or to any of the excipients listed in Section 6.1,
• insulin-dependent diabetes, particularly juvenile onset diabetes, diabetic ketoacidosis and diabetic pre-coma,
• severe kidney or liver failure,
• porphyria,
• treatment with miconazole (see Section 4.5),
• breast-feeding.

SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR US

This medicinal product contains lactose. It is not recommended for use in patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome (rare hereditary diseases).

Cases of acute hemolysis have been reported in patients with G6PD deficiency receiving glibenclamide. Prescription is therefore not recommended in these patients, and use of an alternative treatment is strongly recommended if available. If there is no alternative, the decision must take into account the risk of hemolysis and the potential expected benefit of treatment on a case-by-case basis. If prescription of this medicinal product is necessary, monitoring for the possible onset of hemolysis should be performed.

Hypoglycemia

Hypoglycemia may occur with sulfonylureas. The risk appears to be increased with glibenclamide. Some cases of hypoglycemia can be severe and prolonged, therefore requiring hospitalization to bring blood sugar levels back to normal over several days.

In addition, clinical signs of adrenergic counter-regulation may be observed, such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycemic attack may resemble that of a stroke.
Symptoms generally subside after intake of carbohydrates (sugar) or when hypoglycemia has been corrected.
Careful selection of patients, the dosages used, together with adequate patient information are necessary in order to avoid episodes of hypoglycemia.

INTERACTIONS

Phenylbutazone, Alcohol, Danazol, Beta blockers, Fluconazole, ACE inhibitors, Clarithromycin, Erythromycin, Chlorpromazine, Glucocorticosteroids, Beta-2-adrenergic agonists (ritodrine, salbutamol, terbutaline), Bosentan, Somatostatin analogs, Colesevelam.

UNDESIRABLE EFFECTS

Hypoglycemia (see Sections 4.4 and 4.9), mucocutaneous rash, nausea, diarrhea.
like all sulfonylureas, glibenclamide may cause weight gain.

For uncommon, rare and very rare side effects see full prescribing information

OVERDOSE

If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of a concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more diluted (10%) glucose solution at a rate that makes it possible to maintain blood glucose above 100 mg/dl. Patients should be closely monitored for at least 48 hours and, based on the patient's condition at that time, the physician should decide whether additional monitoring is necessary.
Glucagon must not be used as it may cause recurrent hypoglycemia due to secondary insulin hypersecretion.
Plasma clearance of glibenclamide may be prolonged in patients with liver disease. Dialysis is not beneficial to patients as glibenclamide is extensively bound to plasma proteins.

PHARMACOLOGICAL CLASSIFICATION

Pharmacotherapeutic group: BLOOD GLUCOSE LOWERING DRUGS EXCLUDING INSULINS - SULFONYLUREAS.
ATC code: A10BB01 (A: Alimentary tract and metabolism).

Date of SmPC approval: September 2017;
Date of abbreviated prescribing information: October 2018.
More detailed Information on request: Refer to Summary of Product Characteristics or
Sanofi, Japaul House, Plot 8,
Dr. Nurudeen Olowopopo Avenue, Ikeja Central Business District, Agidingbi, Lagos, Nigeria.
Tel: +234 1 2710135/2800994;

Sanofi Office, Volta Place,
35 Patrice Lumumba Road, Airport Residential Area, Accra.
Tel: +233 302 734772;

For Pharmacovigilance (reporting adverse events), please contact: ng-gh.pv@sanofi.com.