Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Date of revision of text on the SPC: 17-Oct-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In section 4.5       Interaction with other medicinal products and other forms of interaction

 

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 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. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore, glimepiride should be administered at least 4 hours prior to colesevelam.

 

4.8       Undesirable effects

 

The following adverse reactions from clinical investigations were based on experience with Amaryl and other sulfonylureas, were listed below by system organ class and in order of decreasing incidence (very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000; very rare: <1/10,000), not known (cannot be estimated from the available data).

 

Blood and lymphatic system disorders

Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and pancytopenia, which are in general reversible upon discontinuation of medication. Not known: severe thrombocytopenia with platelet count less than 10,000/µl and thrombocytopenic purpura

 

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.

 

Not known: 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 dose (see further under section 4.4).

 

Eye disorders

Not known: 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

Not known: hepatic enzymes increased.

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

 

Skin and subcutaneous tissue disorders

Not known: hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.

 

Investigations

Very rare: blood sodium decrease.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Reasons for adding or updating:

• Change to section 3 - Pharmaceutical form
• Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC: 28-Jun-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In section 3 (Pharmaceutical Form)  The tablet can be divided into equal doses has been added

In section 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 or insulin cannot compensate if the patient does not keep to the recommended diet.

 

Posology

Dose 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 dose should be used for maintenance therapy.

 

For the different dose regimens appropriate strengths are available.

 

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.

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.

 

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 dose 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 dose 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:

See section 4.3.

 

Paediatric population:

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 (see sections 5.1 and 5.2).

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

 

Method of administration

Tablets should be swallowed whole without chewing with some liquid.

Reasons for adding or updating:

• New SPC for new product

Legal Category:POM

Black Triangle (CHM): NO