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Drug Details

Amaryl

• Drug Class Description
  Sulphonylureas.
• Generic Name
  Glimepiride
• Presentation
  Each tablet contains 1mg, 2mg, 3mg or 4mg of glimepiride
• Description
  Amaryl 1 mg, tablet Amaryl 2 mg, tablet Amaryl 3 mg, tablet Amaryl 4 mg, tablet
• Indications
  

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

• Adult Dosage
  

  For oral administration

  The basis for successful treatment of diabetes is a good diet, regular physical activity, as well as routine checks of blood and urine. Tablets or insulin cannot compensate if the patient does not keep to the recommended diet.

  Dosage is determined by the results of blood and urinary glucose determinations.

  The starting dose is 1 mg glimepiride per day. If good control is achieved this dosage should be used for maintenance therapy.

  For the different dosage regimens appropriate strengths are available.

  If control is unsatisfactory the dosage 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 dosage 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.

  While maintaining the metformin dose, the glimepiride therapy is started with a low dose, and is then titrated up depending on the desired level of metabolic control up to the maximum daily dose. 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. While maintaining the glimepiride dose, insulin treatment is started at low dose and titrated up depending on the desired level of metabolic control. The combination therapy should be initiated under close medical supervision.

  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.

  Tablets should be swallowed whole with some liquid.

  If a patient has a hypoglycaemic reaction on 1 mg glimepiride daily, this indicates that they can be controlled by diet alone.

  In the course of treatment, as an improvement in control of diabetes is associated with higher insulin sensitivity, glimepiride requirements may fall. To avoid hypoglycaemia timely dose reduction or cessation of therapy must therefore be considered. Change in dosage may also be necessary, if there are changes in weight or life style of the patient, or other factors that increase the risk of hypo-or hyperglycaemia.

  Switch over from other oral hypoglycaemic agents to Amaryl

  A switch over from other oral hypoglycaemic agents to Amaryl can generally be done. For the switch over to Amaryl the strength and the half-life of the previous medicinal product has to be taken into account. In some cases, especially in antidiabetics with a long half-life (e.g. chlorpropamide), a wash out period of a few days is advisable in order to minimise the risk of hypoglycaemic reactions due to the additive effect.

  The recommended starting dose is 1 mg glimepiride per day. Based on the response the glimepiride dosage may be increased stepwise, as indicated earlier.

  Switch over from Insulin to Amaryl

  In exceptional cases, where type 2 diabetic patients are regulated on insulin, a changeover to Amaryl may be indicated. The changeover should be undertaken under close medical supervision.

  Special Populations

  Patients with renal or hepatic impairment:

   

• Child Dosage
  

  Children and adolescents:

  There are no data available on the use of glimepiride in patients under 8 years of age. For children aged 8 to 17 years, there are limited data on glimepiride as monotherapy.

  The available data on safety and efficacy are insufficient in the paediatric population and therefore such use is not recommended.

• Contra Indications
  

  Glimepiride is contraindicated in patients with the following conditions:

  • hypersensitivity to glimepiride, other sulfonylureas or sulfonamides 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 change over to insulin is required.
• Special Precautions
  

  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. Possible symptoms of hypoglycaemia include: headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, alertness and reaction time, depression, confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and bradycardia. In addition, signs of adrenergic counter-regulation may be present such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.

  The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.

  Symptoms can almost always be promptly controlled by immediate intake carbohydrates (sugar). Artificial sweeteners have no effect.

  It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur.

  Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, require immediate medical treatment and occasionally hospitalisation.

  Factors favouring hypoglycaemia include:

  - unwillingness or (more commonly in older patients) incapacity of the patient to cooperate,

  - undernutrition, irregular mealtimes or missed meals or periods of fasting,

  - alterations in diet,

  - imbalance between physical exertion and carbohydrate intake,

  - consumption of alcohol, especially in combination with skipped meals,

  - impaired renal function,

  - serious liver dysfunction,

  - overdosage with Amaryl,

  - certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter-regulation of hypoglycaemia (as for example in certain disorders of thyroid function and in anterior pituitary or adrenocortical insufficiency),

  - concurrent administration of certain other medicinal products.

  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.

  No experience has been gained concerning the use of Amaryl in patients with severe impairment of liver function or dialysis patients. In patients with severe impairment of renal or liver function change over to insulin is indicated.

  Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to hemolytic anaemia. 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
  

  If glimepiride is taken simultaneously with certain other medicinal products, both undesired increases and decreases in the hypoglycaemic action of glimepiride can occur. For this reason, other medicinal products should only be taken with the knowledge (or at the prescription) of the doctor.

  Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole)

  Results from an in vivo interaction study reported in literature show that glimepiride AUC is increased approximately 2-fold by fluconazole, one of the most potent CYP2C9 inhibitors.

  Based on the experience with glimepiride and with other sulfonylureas the following interactions have to be mentioned.

  Potentiation of the blood-glucose-lowering effect and, thus, 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 paminosalicylic 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 dosages) 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.

• Adverse Drug Reactions
  

  The following undesirable effects are based on experience with Amaryl and other sulfonylureas.

  Blood and lymphatic system disorders

  Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and pancytopenia, which are in general reversible upon discontinuation of medication.

  Immune system disorders

  Very rare: leukocytoclastic vasculitis, mild hypersensitivity reactions that may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.

  Cross-allergenicity with sulfonylureas, sulfonamides or related substances is possible.

  Metabolism and nutrition disorders

  Rare: hypoglycaemia.

  These hypoglycaemic reactions mostly occur immediately, may be severe and are not always easy to correct. The occurrence of such reactions depends, as with other hypoglycaemic therapies, on individual factors such as dietary habits and dosage. 

  Eye disorders

  Visual disturbances, transient, may occur especially on initiation of treatment, due to changes in blood glucose levels.

  Gastrointestinal disorders

  Very rare: nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pain, which seldom lead to discontinuation of therapy.

  Hepato-biliary disorders

  Hepatic enzymes increased.

  Very rare: hepatic function abnormal (e.g. with cholestasis and jaundice), hepatitis and hepatic failure.

  Skin and subcutaneous tissue disorders

  Hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.

  Investigations

  Very rare: blood sodium decrease.