Glimepiride

Registered South African indications:

• Non-insulin-dependent (Type 2) diabetes mellitus when hyperglycaemia cannot be controlled by diet and exercise alone
  - As an adjunct to diet and exercise to lower blood glucose

Contraindications

• Hypersensitivity to the active ingredients or any of its excipients
• Hypersensitivity to other sulphonylureas, sulfonamides
• Pregnancy
• Breastfeeding
• Impaired liver function
• Insulin-dependent (Type 1) diabetes mellitus
• Use in children

Cautions

• Renal impairment
• Elderly
• Hypoglycaemia
• Undernutrition
• Physiological stress
• Irregular mealtimes, missed meals or periods of fasting
• Alterations in diet
• Imbalance between physical exertion and carbohydrate intake
• Alcohol
• Endocrine abnormalities
• Glucose-6-phosphate dehydrogenase deficiency
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Stress-situations (eg. acute operations, infections with fever)

Forms avail. in SA and covered in this monograph: tab

Non-insulin-dependent (Type 2) diabetes mellitus when hyperglycaemia cannot be controlled by diet and exercise alone
- As an adjunct to diet and exercise to lower blood glucose

Initial dose and dose titration

• Oral (tab): Usual initial dose: 1mg, dly; If needed and guided by regular blood glucose monitoring, titrate at intervals of 1-2 weeks according to the following dose steps: 1mg - 2mg - 3mg - 4mg - 6mg; Max: 8mg/24hrs

Dose range in patients with well-controlled diabetes

• Oral (tab): Usual dose: 1-4mg, daily

Daily doses of more than 6mg are more effective only in a minority of patients

The dosage of glimepiride is determined by the desired blood glucose level. The dosage of glimepiride must be the lowest which is sufficient to achieve the desired metabolic control. During treatment with glimepiride, glucose levels in blood and urine must be measured regularly.
In addition, it is recommended that regular determinations of the proportion of glycated haemoglobin be carried out

Combination therapy with metformin
In patients not adequately controlled with the maximum daily dose of either glimepiride or metformin, combination therapy with both oral antidiabetic agents may be initiated
In patients not adequately controlled with the maximum daily dose of glimepiride, combination therapy with metformin may be initiated. The additional metformin treatment is started with a low dose, which is then titrated up depending on the desired level of metabolic control up to a maximum daily dose. The combination therapy should be initiated under close medical supervision

If a patient forgets to take a dose, this must never be corrected by subsequently taking a larger dose. Measures for dealing with such situations (in particular forgetting a dose or skipping a meal), where a dose cannot be taken at the prescribed time, must be discussed and agreed between physician and patient beforehand

If it is discovered that too high a dose or an extra dose of glimepiride has been taken, a physician must be notified immediately

Glimepiride tablets must be swallowed whole with approximately half a glass of water taken immediately before a substantial breakfast or, if none is taken, immediately before the first main meal

See Additional Prescribing Points for dose adjustments and change over from other antidiabetics to glimepiride

Not established for use in children (see Contraindications)

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Caution; no dose adjustment recommended
  There is limited information available on the use of glimepiride in renal insufficiency. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of glimepiride

Hepatic Impairment

• Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorder

• Headache
• Sleep disorders
• Restlessness
• Aggression
• Impaired alertness and reactions
• Depression
• Confusion
• Speech disorders
• Aphasia
• Tremor
• Paresis
• Sensory disturbances
• Dizziness
• Delirium
• Cerebral convulsion
• Somnolence
• Coma
• Lassitude
• Anxiety

Cardiovascular Disorder

• Bradycardia
• Tachycardia
• Hypertension
• Palpitations
• Angina pectoris
• Cardiac arrhythmias

Respiratory Disorder

• Shallow breathing

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal distension
• Abdominal discomfort
• Abdominal pain
• Sensation of fullness in epigastrium
• Metallic taste
• Dry mouth

Hepatobiliary Disorders

• Cholestasis
• Jaundice
• Hepatitis
• Hepatic failure
• Increased hepatic enzymes

Genitourinary Disorders

• Polyuria

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Ravenous hunger
• Anorexia
• Weight gain
• Intense thirst

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Urticaria
• Photosensitivity
• Steven-Johnson syndrome
• Erythema multiforme
• Exfoliative dermatitis
• Erythema nodosum
• Dry skin
• Sweating 
• Clammy skin

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Leukopenia
• Granulocytopenia
• Agranulocytosis
• Erythropenia
• Haemolytic anaemia 
• Pancytopenia
• Thrombocytopenic purpura
• Leukocytoclastic vasculitis
• Hypersensitivity reactions 
• Cross-allergenicity with sulfonylureas, sulfonamides or related substances

Sensory Disorders

• Visual disturbances

• CYP2C9 inducers
• CYP2C9 inhibitors
• Histamine antagonists
• Beta blockers
• Clonidine
• Reserpine 
• Guanethidine
• Alcohol
• Warfarin
• Colesevelam 
• Oestrogens
• Progestogens
• Saluretics
• Thiazide diuretics
• Thyroid stimulating agents
• Glucocorticoids
• Phenothiazine derivatives
• Chlorpromazine
• Adrenaline 
• Sympathicomimetics
• Nicotinic acid 
• Nicotinic acid derivatives
• Laxatives
• Phenytoin
• Diazoxide
• Glucagon
• Barbiturates
• Rifampicin
• Acetazolamide
• Phenylbutazone
• Azapropazone
• Oxyfenbutazone
• Insulin 
• Oral antidiabetic products
• Salicylates
• Anabolic steroids
• Male sex hormones
• Chloramphenicol
• Long acting sulfonamides
• Tetracyclines
• Quinolone antibiotics
• Clarithromycin
• Fenfluramine
• Disopyramide
• Fibrates
• Angiotensin coverting enzyme inhibitors
• Fluoxetine
• Monoamine oxidase inhibitors
• Allopurinol
• Probenecid 
• Sulfinpyrazone
• Sympatholytics
• Cyclophosphamide
• Trophosphamide
• Iphosphamides
• Miconazole
• Fluconazole
• Pentoxifylline
• Tritoqualine

• Renal function
• Hepatic function
• Full blood count

Distribution of doses

• Timing and distribution of doses are to be decided by the medical practitioner, taking into consideration the patient's current lifestyle
• Normally, a single daily dose of glimepiride is sufficient to provide metabolic control over 24 hours
• It is recommended that this dose 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 the tablet(s) have been taken

Secondary dosage adjustment

• An improvement in the control of diabetes is associated with higher insulin sensitivity; therefore, glimepiride requirements may decrease as treatment proceeds
• To avoid hypoglycaemia, dose reduction or cessation of glimepiride therapy must therefore be considered in time
• Adjustment of dosage must also be considered whenever the patient's weight changes, the patient's lifestyle changes, or other factors arise that increase susceptibility to hypoglycaemia or hyperglycaemia

Change-over from other oral antidiabetics to glimepiride

• There is no exact dosage relationship between glimepiride and other oral antidiabetics. When substituting glimepiride for other oral antidiabetics, it is recommended that the procedure be the same as for initial dosage, starting with daily doses of 1mg
• This applies even in cases where the patient is being switched from the maximum dose of another oral antidiabetic

Glimepiride stimulates the release of insulin from functioning pancreatic beta cells and increases the sensitivity of peripheral tissues to insulin. On the pancreatic cell surface, glimepiride binds to ATP-sensitive potassium channel receptors reducing potassium conductance and causing depolarization of the membrane. This depolarization stimulates calcium ions to move intracellularly and the increased intracellular calcium ion concentration induces the secretion of insulin.

Tablet 1mg

• Accord Glimepiride (Accord Healthcare)
• Amaryl (Sanofi)
• Aspen Glimepiride (Pharmacare)
• Austell Glimepiride (Austell Laboratories)
• Diaglim (Cipla Medpro)
• Euglim (Zydus Healthcare)
• Glamaryl (Withrop Pharma) originator
• Glimepiride Oethmaan (Oethmaan)
• Glimepiride Zydus 1 (Zydus)
• Sandoz Glimepiride (Sandoz)
• Sulphonur (Specpharm)

Tablet 2mg 

• Accord Glimepiride (Accord Healthcare)
• Amaryl (Sanofi)
• Aspen Glimepiride (Pharmacare)
• Austell Glimepiride (Austell Laboratories)
• Diaglim (Cipla Medpro)
• Euglim (Zydus Healthcare)
• Glamaryl (Withrop Pharma) originator
• Glimepiride Oethmaan (Oethmaan)
• Glimepiride Zydus 2 (Zydus)
• Sandoz Glimepiride (Sandoz)
• Sulphonur (Specpharm)

Tablet 4mg 

• Accord Glimepiride (Accord Healthcare)
• Amaryl (Sanofi)
• Aspen Glimepiride (Pharmacare)
• Austell Glimepiride (Austell Laboratories)
• Diaglim (Cipla Medpro)
• Euglim (Zydus Healthcare)
• Glamaryl (Withrop Pharma) originator
• Glimepiride Oethmaan (Oethmaan)
• Glimepiride Zydus 4 (Zydus)
• Sandoz Glimepiride (Sandoz)
• Sulphonur (Specpharm)

COMBINATION PREPARATIONS

Glimepiride/Metformin

Tablet 2mg/500mg

• Amaryl Combi (Sanofi) originator