1. Name of the medicinal product
Glimepiride 2 mg Tablets
2. Qualitative and quantitative composition
Each tablet contains 2 mg of glimepiride.
Each tablet contains 156.765 mg of lactose monohydrate.
For the full list of excipients, see section 6.1
3. Pharmaceutical form
Tablet.
Glimepiride Tablets 2 mg: Light pink coloured oval shaped, uncoated tablets with score line on one side & plain on other side.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
4. Clinical particulars
4.1 Therapeutic indications
Glimepiride is indicated for the treatment of type 2 diabetes mellitus, when diet, physical exercise and weight reduction alone are not adequate.
4.2 Posology and method of administration
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 cannot compensate if the patient does not keep to the recommended diet.
Posology
The 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 glimepiride, concomitant therapy can be initiated if necessary. While maintaining the glimepiride dose, s started at a 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.
5.2 Pharmacokinetic properties
Absorption
The bioavailability of glimepiride after oral administration is complete. Food intake has no relevant influence on absorption, only the absorption rate is slightly diminished. Maximum serum concentrations (Cmax) are reached approx 2.5 hours after oral intake (mean 0.3 μg/ml during multiple dosing of 4 mg/daily) and there is a linear relationship between dose and both Cmax and AUC (area under the time concentration curve).
Distribution
Glimepiride has a very low distribution volume (approx. 8.8 litres), which is roughly equal to the albumin distribution space, high protein binding (>99%) and a low clearance (approx. 48 ml/min).
In animals, glimepiride is excreted in milk. Glimepiride is transferred to the placenta. Passage of the blood-brain barrier is low.
Biotransformation and elimination
Mean dominant serum half-life, which is of relevance for the serum concentrations under multiple-dose conditions, is about 5 to 8 hours. After high doses, slightly longer half-lives were noted.
After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine, and 35% in the faeces. No unchanged substance was detected in the urine. Two metabolites most probably resulting from hepatic metabolism (major enzyme is CYP2C9) were identified both in urine and faeces: the hydroxy derivative and the carboxy derivative. After oral administration of glimepiride, the terminal half-lives of these metabolites were 3 to 6 and 5 to 6 hours respectively.
Comparison of single and multiple once-daily dosing revealed no significant differences in pharmacokinetics, and the intra individual variability was very low. There was no relevant accumulation.
Special populations
Pharmacokinetics were similar in males and females, as well as in young and elderly (above 65 years) patients. In patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding.
Renal elimination of the two metabolites was impaired. Overall no additional risk of accumulation is to be assumed in such patients.
Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Paediatric population
A fed study investigating the pharmacokinetics, safety, and tolerability of a 1 mg single dose of glimepiride in 30 paediatric patients (4 children aged 10-12 years and 26 children aged 12-17 years) with type 2 diabetes showed mean AUC(0-last) , Cmax and t1/2similar to that previously observed in adults.
5.3 Preclinical safety data
Preclinical effects observed occurred at exposures sufficiently in excess of the maximum human exposure as to indicate little relevance to clinical use, or were due to the pharmacodynamic action (hypoglycaemia) of the compound. This finding is based on conventional safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and reproduction toxicity studies. In the latter (covering embryotoxicity, teratogenicity and developmental toxicity), adverse effects observed were considered to be secondary to the hypoglycaemic effects induced by the compound in dams and in offspring.
6. Pharmaceutical particulars
6.1 List of excipients
Lactose monohydrate
Sodium starch glycolate (type A)
Povidone K-30
Magnesium stearate
Iron oxide red (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from moisture. Keep the blister in the outer carton.
6.5 Nature and contents of container
The blisters, of PVC/PVdC, are heat sealed with hard tempered aluminium foil and packaged in a carton with a pack insert. PVC/PVdC/Aluminium blisters are clear/transparent.
Pack sizes: 10, 30, 60, 90, 120 and 180 tablets in blister strips of 10 tablets.
Not all pack size may be marketed.
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