Gliclazide 40mg tablets

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

Buy It Now

Active ingredient:
Gliclazide
Available from:
Alliance Healthcare (Distribution) Ltd
ATC code:
A10BB09
INN (International Name):
Gliclazide
Dosage:
40mg
Pharmaceutical form:
Tablet
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF:

Read the complete document

1. What Gliclazide tablets are and what

they are used for

Gliclazide tablets contain the active substance

gliclazide, one of a group of medicines called

sulfonylureas. It is an oral hypoglycaemic

medicine (blood sugar lowering drug). Gliclazide

tablets are used to keep blood sugar at the

correct level in adults with non-insulin dependent

diabetes when it is not controlled by diet,

physical exercise and weight loss alone.

2. What you need to know before you

take Gliclazide tablets

Do not take Gliclazide tablets:

If you are allergic to gliclazide or any of the

other ingredients of this medicine (listed

in section 6), to other medicines of the same

group (sulfonylureas), to other related

medicines (hypoglycaemic sulfonamides),

If you have insulin-dependent diabetes (type 1),

If you have ketone bodies and sugar in your

urine (this may mean you have

keto-acidosis), a diabetic pre-coma or coma,

If you have severe kidney or liver disease,

If you are taking miconazole (a treatment for

fungal infections) (see Other medicines and

Gliclazide tablets),

If you are breast-feeding (see Pregnancy and

breast-feeding).

Children and adolescents

Gliclazide tablets are not recommended for use

in children.

Warnings and precautions

Talk to your doctor before taking Gliclazide

tablets. You should observe the treatment plan

prescribed by your doctor to achieve proper

blood sugar levels. This means, apart from

regular tablet intake, you observe the dietary

regimen, have physical exercise and, where

necessary, reduce weight.

During gliclazide treatment regular monitoring of

your blood (and possibly urine) sugar level and

also your glycated haemoglobin (HbA1c) is

necessary.

In the first few weeks of treatment the risk of

having reduced blood sugar levels (hypo-

glyceamia) may be increased. So particularly

close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

if you take meals irregularly or skip meals

altogether, if you are fasting,

if you are malnourished,

if you change your diet,

if you increase your physical activity and

carbohydrate intake does not match this

increase,

if you drink alcohol, especially in combination

with skipped meals,

if you take other medicines or natural

remedies at the same time,

if you take too high doses of gliclazide,

if you suffer from particular hormone-induced

disorders (functional disorders of the thyroid

gland, of the pituitary gland or adrenal cortex),

if your kidney function or liver function is

severely decreased.

If you have low blood sugar you may have the

following symptoms: headache, intense hunger,

nausea, vomiting, weariness, sleep disorders,

restlessness, aggressiveness, poor concentration,

reduced alertness and reaction time, depression,

confusion, speech or visual disorders, tremor,

sensory disturbances, dizziness, and helplessness.

The following signs and symptoms may also

occur: sweating, clammy skin, anxiety, fast or

irregular heart beat, high blood pressure,

sudden strong pain in the chest that may

radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may

suffer from considerable confusion (delirium),

develop convulsions, lose self-control, your

breathing may be shallow and your heart beat

slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar

vanish very quickly when you consume some

form of sugar, e.g. glucose tablets, sugar cubes,

sweet juice, sweetened tea. You should therefore

always carry some form of sugar with you

(glucose tablets, sugar cubes). Remember that

artificial sweeteners are not effective.

Please contact your doctor or the nearest

hospital if taking sugar does not help or if the

symptoms recur.

Symptoms of low blood sugar may be absent,

less obvious or develop very slowly or you are

not aware in time that your blood sugar level has

dropped. This may happen if you are an elderly

patient taking certain medicines (e.g. those acting

on the central nervous system and beta blockers).

If you are in stress-situations (e.g. accidents,

surgical operations, fever etc.) your doctor may

temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia)

may occur when gliclazide has not yet sufficiently

reduced the blood sugar, when you have not

complied with the treatment plan, if you take St

John's Wort (Hypericum perforatum) preparations

(see Other medicines and Gliclazide tablets),

or in special stress situations. These may include

thirst, frequent urination, dry mouth, dry itchy

skin, skin infections and reduced performance.

If these symptoms occur, you must contact your

doctor or pharmacist.

While taking Gliclazide tablets you should:

follow a regular diet: it is important to eat

regular meals, including breakfast and never

to miss or delay a meal,

take your medicine regularly

(see How to take Gliclazide tablets),

check your blood glucose regularly as

recommended by your doctor.

Blood glucose disturbances (low blood sugar

and high blood sugar) can occur when

gliclazide is prescribed at the same time as

medicines belonging to a class of antibiotics

called fluoroquinolones, especially in elderly

patients. In this case, your doctor will remind

you the importance of monitoring your blood

glucose.

If you have a family history of or know you have

the hereditary condition glucose-6-phosphate

dehydrogenase (G6PD) deficiency (abnormality

of red blood cells), contact your doctor before

taking this medicinal product.

Other medicines and Gliclazide tablets

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines.

The blood sugar lowering effect of gliclazide

may be strengthened and signs of low blood

sugar levels may occur when one of the

following medicines is taken:

other medicines used to treat high blood

sugar (oral antidiabetics, GLP-1 receptor

inhibitors or insulin),

antibiotics (e.g. sulfonamides, clarithromycin),

medicines to treat high blood pressure or

heart failure (beta blockers, ACE-inhibitors

such as captopril or enalapril),

medicines to treat fungal infections

(miconazole, fluconazole),

medicines to treat ulcers in the stomach or

duodenum (H2 receptor antagonists),

medicines to treat depression (monoamine

oxidase inhibitors),

painkillers or anti-rheumatics

(phenylbutazone, ibuprofen),

medicines containing alcohol.

The blood glucose lowering effect of gliclazide

may be weakened and raised blood sugar

levels may occur when one of the following

medicines is taken:

medicines to treat disorders of the central

nervous system (chlorpromazine),

medicines reducing inflammation

(corticosteroids),

PACKAGE LEAFLET – INFORMATION FOR THE USER

Gliclazide 40 mg tablets

Gliclazide

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

What is in this leaflet

Gliclazide 40 mg tablets will be referred to as Gliclazide tablets throughout.

What Gliclazide tablets are and what they are used for

What you need to know before you take Gliclazide tablets

How to take Gliclazide tablets

Possible side effects

How to store Gliclazide tablets

Contents of the pack and other information

medicines to treat asthma or used during

labour (intravenous salbutamol, ritodrine and

terbutaline),

medicines to treat breast disorders, heavy

menstrual bleeding and endometriosis (danazol),

St John's Wort -Hypericum perforatum- preparations.

Blood glucose disturbance (low blood sugar and high

blood sugar) can occur when a medicine belonging to

a class of antibiotics called fluoroquinolones is taken at

the same time as Gliclazide tablets, especially in

elderly patients.

Gliclazide tablets may increase the effects of medicines

which reduce blood clotting (e.g. warfarin).

Consult your doctor before you start taking another

medicinal product. If you go into hospital tell the

medical staff you are taking Gliclazide tablets.

Gliclazide tablets with food, drink and alcohol

Gliclazide tablets can be taken with food and

non-alcoholic drinks. Drinking alcohol is not

recommended as it can alter the control of your

diabetes in an unpredictable manner.

Pregnancy and breast-feeding

Gliclazide tablets are not recommended for use during

pregnancy. If you are pregnant, think you may be

pregnant or are planning to have a baby, ask your

doctor for advice before taking this medicine. You must

not take Gliclazide tablets while you are breast-feeding.

Driving and using machines

Provided your blood glucose levels are satisfactorily

controlled on Gliclazide tablets, your ability to drive or

use machines should not be affected. However, if your

blood glucose levels become too low, this could

adversely affect your concentration, and therefore your

ability to perform these tasks.

Ask your doctor whether you can drive a car if you:

have frequent episodes of low blood sugar

(hypoglycaemia),

have few or no warning signals of low blood sugar

(hypoglycaemia).

Gliclazide tablets contain Lactose

If you have been told by your doctor that you have an

intolerance to some sugars, contact your doctor before

taking this medicinal product.

3. How to take Gliclazide tablets

Dose

Always take this medicine exactly as your doctor or

pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Change in external factors (e.g. weight reduction,

change in life style, stress) or improvements in the

blood sugar control may require changed gliclazide

doses.

The recommended dose is from one to eight tablets.

This depends on the response to treatment. When the

total daily dose exceeds four tablets, it should be divided

into two equal doses taken morning and evening.

Gliclazide tablets are for oral use. Take your tablet(s)

with a glass of water before a meal.

If a combination therapy of Gliclazide tablets with

metformin, an alpha glucosidase inhibitor, a

thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, a

GLP-1 receptor agonist or insulin is initiated your doctor

will determine the proper dose of each medicine

individually for you. If you notice that your blood sugar

levels are high although you are taking the medicine

as prescribed, you should contact your doctor or

pharmacist.

If you take more Gliclazide tablets than you should

If you take too many tablets, contact your doctor or the

nearest hospital Accident & Emergency department

immediately. The signs of overdose are those of low

blood sugar (hypoglycaemia) described in Section 2.

The symptoms can be helped by taking sugar (4 to 6

lumps) or sugary drinks straight away, followed by a

substantial snack or meal. If the patient is unconscious,

immediately inform a doctor and call the emergency

services.

If you forget to take Gliclazide tablets

It is important to take your medicine every day as

regular treatment works better. However, if you forget

to take a dose of Gliclazide tablets, take the next dose

at the usual time. Do not take a double dose to make

up for a forgotten dose.

If you stop taking Gliclazide tablets

As the treatment for diabetes is usually life long, you

should discuss with your doctor before stopping this

medicinal product. Stopping could cause high blood

sugar (hyperglycaemia) which increases the risk of

developing complications of diabetes.

If you have any further questions on the use of this

medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines this medicine can cause side effects,

although not everybody gets them.

Low blood sugar (Hypoglycaemia)

The most commonly observed side effect is low blood

sugar (hypoglycaemia). For symptoms and signs see

Section ‘Warnings and Precautions’.

If left untreated these symptoms could progress to

drowsiness, loss of consciousness or possibly coma. If

an episode of low blood sugar is severe or prolonged,

even if it is temporarily controlled by eating sugar, you

should seek immediate medical attention.

Other side effects

Digestive disorders: Abdominal pain, nausea,

vomiting, indigestion, diarrhoea and constipation.

These effects are reduced when Gliclazide tablets

are taken with a meal as recommended.

Skin disorders: Skin reactions such as rash, redness,

itching, hives, angioedema (rapid swelling of tissues

such as eyelids, face, lips, mouth, tongue or throat

that may result in breathing difficulty) have been

reported. The rash may progress to widespread

blistering or peeling of the skin. Exceptionally, signs

of severe hypersensitivity reactions (DRESS) have

been reported: initially as flu-like symptoms and a

rash on the face then an extended rash with a high

temperature.

Blood disorders: Decrease in the number of cells in

the blood (e.g. platelets, red and white blood cells)

which may cause paleness, prolonged bleeding,

bruising, sore throat and fever. These symptoms

usually stop when the treatment is discontinued.

Liver disorders: There have been isolated reports of

abnormal liver function which can cause yellow skin

and eyes. If you get this, see your doctor

immediately. The symptoms generally disappear if

the drug is stopped. Your doctor will decide whether

to stop your treatment.

Eye disorders: Your vision may be affected for a

short time, especially at the start of treatment. This

effect is due to changes in blood sugar levels.

As for other sulfonylureas, the following adverse events

have been observed: cases of severe changes in the

number of blood cells and allergic inflammation of the

wall of blood vessels, reduction in blood sodium

(hyponatraemia), symptoms of liver impairment (e.g.

jaundice) which in most cases disappeared after

withdrawal of the sulfonylurea, but may lead to life

threatening liver failure in isolated cases.

Reporting of side effects

If you get any side effects, talk to your doctor,

pharmacist or nurse. This includes any possible side

effect not listed in this leaflet.

You can also report side effects directly via the Yellow

Card Scheme at:

www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store Gliclazide tablets

Keep this medicine out of the sight and reach of

children.

Do not use this medicine after the expiry date which is

stated on the carton and the blister strip after EXP. The

expiry date refers to the last day of that month.

Store in the original package.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures

will help protect the environment.

6. Contents of the pack and other information

What Gliclazide tablets contain

The active substance is gliclazide.

Each tablet of Gliclazide 40 mg contains 40mg of

gliclazide.

The other ingredients are: lactose monohydrate, maize

starch, pregelatinised maize starch, talc, magnesium

stearate.

What Gliclazide tablets look like and contents of the

pack

Gliclazide 40mg tablets are white to off-white, circular,

flat, beveled-edged, uncoated tablets with "40" on one

side and plain on the reverse side.

The tablets are packed into foil blisters of PVC/PVDC

blisters lidded with aluminium foil and come in cartons

of pack sizes of 20, 28, 56, 60, 84, 100 tablets (not all

pack sizes may be marketed).

Marketing Authorisation Holder:

Lucis Pharma Limited,

Aston Chase,

14 Aston Magna,

Moreton-in-Marsh

GL56 9QQ, UK

Manufacturer:

Saneca Pharmaceuticals a.s

Nitrianska 100

920 27 Hlohovec

Slovak Republic

This leaflet was last revised in January 2018

V4RFC16118

1. What Gliclazide tablets are and what

they are used for

Gliclazide tablets contain the active substance

gliclazide, one of a group of medicines called

sulfonylureas. It is an oral hypoglycaemic

medicine (blood sugar lowering drug). Gliclazide

tablets are used to keep blood sugar at the

correct level in adults with non-insulin dependent

diabetes when it is not controlled by diet,

physical exercise and weight loss alone.

2. What you need to know before you

take Gliclazide tablets

Do not take Gliclazide tablets:

If you are allergic to gliclazide or any of the

other ingredients of this medicine (listed

in section 6), to other medicines of the same

group (sulfonylureas), to other related

medicines (hypoglycaemic sulfonamides),

If you have insulin-dependent diabetes (type 1),

If you have ketone bodies and sugar in your

urine (this may mean you have

keto-acidosis), a diabetic pre-coma or coma,

If you have severe kidney or liver disease,

If you are taking miconazole (a treatment for

fungal infections) (see Other medicines and

Gliclazide tablets),

If you are breast-feeding (see Pregnancy and

breast-feeding).

Children and adolescents

Gliclazide tablets are not recommended for use

in children.

Warnings and precautions

Talk to your doctor before taking Gliclazide

tablets. You should observe the treatment plan

prescribed by your doctor to achieve proper

blood sugar levels. This means, apart from

regular tablet intake, you observe the dietary

regimen, have physical exercise and, where

necessary, reduce weight.

During gliclazide treatment regular monitoring of

your blood (and possibly urine) sugar level and

also your glycated haemoglobin (HbA1c) is

necessary.

In the first few weeks of treatment the risk of

having reduced blood sugar levels (hypo-

glyceamia) may be increased. So particularly

close medical monitoring is necessary.

Low blood sugar (Hypoglycaemia) may occur:

if you take meals irregularly or skip meals

altogether, if you are fasting,

if you are malnourished,

if you change your diet,

if you increase your physical activity and

carbohydrate intake does not match this

increase,

if you drink alcohol, especially in combination

with skipped meals,

if you take other medicines or natural

remedies at the same time,

if you take too high doses of gliclazide,

if you suffer from particular hormone-induced

disorders (functional disorders of the thyroid

gland, of the pituitary gland or adrenal cortex),

if your kidney function or liver function is

severely decreased.

If you have low blood sugar you may have the

following symptoms: headache, intense hunger,

nausea, vomiting, weariness, sleep disorders,

restlessness, aggressiveness, poor concentration,

reduced alertness and reaction time, depression,

confusion, speech or visual disorders, tremor,

sensory disturbances, dizziness, and helplessness.

The following signs and symptoms may also

occur: sweating, clammy skin, anxiety, fast or

irregular heart beat, high blood pressure,

sudden strong pain in the chest that may

radiate into nearby areas (angina pectoris).

If blood sugar levels continue to drop you may

suffer from considerable confusion (delirium),

develop convulsions, lose self-control, your

breathing may be shallow and your heart beat

slowed down, you may become unconscious.

In most cases the symptoms of low blood sugar

vanish very quickly when you consume some

form of sugar, e.g. glucose tablets, sugar cubes,

sweet juice, sweetened tea. You should therefore

always carry some form of sugar with you

(glucose tablets, sugar cubes). Remember that

artificial sweeteners are not effective.

Please contact your doctor or the nearest

hospital if taking sugar does not help or if the

symptoms recur.

Symptoms of low blood sugar may be absent,

less obvious or develop very slowly or you are

not aware in time that your blood sugar level has

dropped. This may happen if you are an elderly

patient taking certain medicines (e.g. those acting

on the central nervous system and beta blockers).

If you are in stress-situations (e.g. accidents,

surgical operations, fever etc.) your doctor may

temporarily switch you to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia)

may occur when gliclazide has not yet sufficiently

reduced the blood sugar, when you have not

complied with the treatment plan, if you take St

John's Wort (Hypericum perforatum) preparations

(see Other medicines and Gliclazide tablets),

or in special stress situations. These may include

thirst, frequent urination, dry mouth, dry itchy

skin, skin infections and reduced performance.

If these symptoms occur, you must contact your

doctor or pharmacist.

While taking Gliclazide tablets you should:

follow a regular diet: it is important to eat

regular meals, including breakfast and never

to miss or delay a meal,

take your medicine regularly

(see How to take Gliclazide tablets),

check your blood glucose regularly as

recommended by your doctor.

Blood glucose disturbances (low blood sugar

and high blood sugar) can occur when

gliclazide is prescribed at the same time as

medicines belonging to a class of antibiotics

called fluoroquinolones, especially in elderly

patients. In this case, your doctor will remind

you the importance of monitoring your blood

glucose.

If you have a family history of or know you have

the hereditary condition glucose-6-phosphate

dehydrogenase (G6PD) deficiency (abnormality

of red blood cells), contact your doctor before

taking this medicinal product.

Other medicines and Gliclazide tablets

Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other

medicines.

The blood sugar lowering effect of gliclazide

may be strengthened and signs of low blood

sugar levels may occur when one of the

following medicines is taken:

other medicines used to treat high blood

sugar (oral antidiabetics, GLP-1 receptor

inhibitors or insulin),

antibiotics (e.g. sulfonamides, clarithromycin),

medicines to treat high blood pressure or

heart failure (beta blockers, ACE-inhibitors

such as captopril or enalapril),

medicines to treat fungal infections

(miconazole, fluconazole),

medicines to treat ulcers in the stomach or

duodenum (H2 receptor antagonists),

medicines to treat depression (monoamine

oxidase inhibitors),

painkillers or anti-rheumatics

(phenylbutazone, ibuprofen),

medicines containing alcohol.

The blood glucose lowering effect of gliclazide

may be weakened and raised blood sugar

levels may occur when one of the following

medicines is taken:

medicines to treat disorders of the central

nervous system (chlorpromazine),

medicines reducing inflammation

(corticosteroids),

medicines to treat asthma or used during

labour (intravenous salbutamol, ritodrine and

terbutaline),

medicines to treat breast disorders, heavy

menstrual bleeding and endometriosis (danazol),

St John's Wort -Hypericum perforatum- preparations.

Blood glucose disturbance (low blood sugar and high

blood sugar) can occur when a medicine belonging to

a class of antibiotics called fluoroquinolones is taken at

the same time as Gliclazide tablets, especially in

elderly patients.

Gliclazide tablets may increase the effects of medicines

which reduce blood clotting (e.g. warfarin).

Consult your doctor before you start taking another

medicinal product. If you go into hospital tell the

medical staff you are taking Gliclazide tablets.

Gliclazide tablets with food, drink and alcohol

Gliclazide tablets can be taken with food and

non-alcoholic drinks. Drinking alcohol is not

recommended as it can alter the control of your

diabetes in an unpredictable manner.

Pregnancy and breast-feeding

Gliclazide tablets are not recommended for use during

pregnancy. If you are pregnant, think you may be

pregnant or are planning to have a baby, ask your

doctor for advice before taking this medicine. You must

not take Gliclazide tablets while you are breast-feeding.

Driving and using machines

Provided your blood glucose levels are satisfactorily

controlled on Gliclazide tablets, your ability to drive or

use machines should not be affected. However, if your

blood glucose levels become too low, this could

adversely affect your concentration, and therefore your

ability to perform these tasks.

Ask your doctor whether you can drive a car if you:

have frequent episodes of low blood sugar

(hypoglycaemia),

have few or no warning signals of low blood sugar

(hypoglycaemia).

Gliclazide tablets contain Lactose

If you have been told by your doctor that you have an

intolerance to some sugars, contact your doctor before

taking this medicinal product.

3. How to take Gliclazide tablets

Dose

Always take this medicine exactly as your doctor or

pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Change in external factors (e.g. weight reduction,

change in life style, stress) or improvements in the

blood sugar control may require changed gliclazide

doses.

The recommended dose is from one to eight tablets.

This depends on the response to treatment. When the

total daily dose exceeds four tablets, it should be divided

into two equal doses taken morning and evening.

Gliclazide tablets are for oral use. Take your tablet(s)

with a glass of water before a meal.

If a combination therapy of Gliclazide tablets with

metformin, an alpha glucosidase inhibitor, a

thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, a

GLP-1 receptor agonist or insulin is initiated your doctor

will determine the proper dose of each medicine

individually for you. If you notice that your blood sugar

levels are high although you are taking the medicine

as prescribed, you should contact your doctor or

pharmacist.

If you take more Gliclazide tablets than you should

If you take too many tablets, contact your doctor or the

nearest hospital Accident & Emergency department

immediately. The signs of overdose are those of low

blood sugar (hypoglycaemia) described in Section 2.

The symptoms can be helped by taking sugar (4 to 6

lumps) or sugary drinks straight away, followed by a

substantial snack or meal. If the patient is unconscious,

immediately inform a doctor and call the emergency

services.

If you forget to take Gliclazide tablets

It is important to take your medicine every day as

regular treatment works better. However, if you forget

to take a dose of Gliclazide tablets, take the next dose

at the usual time. Do not take a double dose to make

up for a forgotten dose.

If you stop taking Gliclazide tablets

As the treatment for diabetes is usually life long, you

should discuss with your doctor before stopping this

medicinal product. Stopping could cause high blood

sugar (hyperglycaemia) which increases the risk of

developing complications of diabetes.

If you have any further questions on the use of this

medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines this medicine can cause side effects,

although not everybody gets them.

Low blood sugar (Hypoglycaemia)

The most commonly observed side effect is low blood

sugar (hypoglycaemia). For symptoms and signs see

Section ‘Warnings and Precautions’.

If left untreated these symptoms could progress to

drowsiness, loss of consciousness or possibly coma. If

an episode of low blood sugar is severe or prolonged,

even if it is temporarily controlled by eating sugar, you

should seek immediate medical attention.

Other side effects

Digestive disorders: Abdominal pain, nausea,

vomiting, indigestion, diarrhoea and constipation.

These effects are reduced when Gliclazide tablets

are taken with a meal as recommended.

Skin disorders: Skin reactions such as rash, redness,

itching, hives, angioedema (rapid swelling of tissues

such as eyelids, face, lips, mouth, tongue or throat

that may result in breathing difficulty) have been

reported. The rash may progress to widespread

blistering or peeling of the skin. Exceptionally, signs

of severe hypersensitivity reactions (DRESS) have

been reported: initially as flu-like symptoms and a

rash on the face then an extended rash with a high

temperature.

Blood disorders: Decrease in the number of cells in

the blood (e.g. platelets, red and white blood cells)

which may cause paleness, prolonged bleeding,

bruising, sore throat and fever. These symptoms

usually stop when the treatment is discontinued.

Liver disorders: There have been isolated reports of

abnormal liver function which can cause yellow skin

and eyes. If you get this, see your doctor

immediately. The symptoms generally disappear if

the drug is stopped. Your doctor will decide whether

to stop your treatment.

Eye disorders: Your vision may be affected for a

short time, especially at the start of treatment. This

effect is due to changes in blood sugar levels.

As for other sulfonylureas, the following adverse events

have been observed: cases of severe changes in the

number of blood cells and allergic inflammation of the

wall of blood vessels, reduction in blood sodium

(hyponatraemia), symptoms of liver impairment (e.g.

jaundice) which in most cases disappeared after

withdrawal of the sulfonylurea, but may lead to life

threatening liver failure in isolated cases.

Reporting of side effects

If you get any side effects, talk to your doctor,

pharmacist or nurse. This includes any possible side

effect not listed in this leaflet.

You can also report side effects directly via the Yellow

Card Scheme at:

www.mhra.gov.uk/yellowcard or search for MHRA

Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more

information on the safety of this medicine.

5. How to store Gliclazide tablets

Keep this medicine out of the sight and reach of

children.

Do not use this medicine after the expiry date which is

stated on the carton and the blister strip after EXP. The

expiry date refers to the last day of that month.

Store in the original package.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures

will help protect the environment.

6. Contents of the pack and other information

What Gliclazide tablets contain

The active substance is gliclazide.

Each tablet of Gliclazide 40 mg contains 40mg of

gliclazide.

The other ingredients are: lactose monohydrate, maize

starch, pregelatinised maize starch, talc, magnesium

stearate.

What Gliclazide tablets look like and contents of the

pack

Gliclazide 40mg tablets are white to off-white, circular,

flat, beveled-edged, uncoated tablets with "40" on one

side and plain on the reverse side.

The tablets are packed into foil blisters of PVC/PVDC

blisters lidded with aluminium foil and come in cartons

of pack sizes of 20, 28, 56, 60, 84, 100 tablets (not all

pack sizes may be marketed).

Marketing Authorisation Holder:

Lucis Pharma Limited,

Aston Chase,

14 Aston Magna,

Moreton-in-Marsh

GL56 9QQ, UK

Manufacturer:

Saneca Pharmaceuticals a.s

Nitrianska 100

920 27 Hlohovec

Slovak Republic

This leaflet was last revised in January 2018

V4RFC16118

Read the complete document

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Gliclazide 40mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 40 mg of Gliclazide.

Excipient with known effect: Also Contains Lactose Monohydrate Ph. Eur 55

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Tablet

White to off-white, circular, flat, bevelled edged, uncoated tablets with “40” on one

side, plain on reverse.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Non insulin dependent diabetes (type 2) in adults when dietary measures,

physical exercise and weight loss alone are not sufficient to control blood

glucose.

4.2

Posology and method of administration

Posology

Initial dose: The total daily dose may vary from 40 to 320 mg taken orally.

The dose should be adjusted according to the individual patient’s response,

commencing with 40-80 mg daily (1 – 2 tablets) and increasing until adequate

control is achieved. A single dose should not exceed 160 mg (4 tablets). When

higher doses are required, Gliclazide Tablets should be taken twice daily and

according to the main meals of the day.

In obese patients or those not showing adequate response to Gliclazide Tablets

alone, additional therapy may be required.

Switching from another oral antidiabetic agent to Gliclazide 40 mg:

Gliclazide 40 mg can be used to replace other oral antidiabetic agents.

The dosage and the half-life of the previous antidiabetic agent should be taken

into account when switching to Gliclazide 40 mg.

A transitional period is not generally necessary. A starting dose of 40-80 mg

(1 to 2 tablets) should be used and this should be adjusted to suit the patient's

blood glucose response, as described above.

When switching from a hypoglycaemic sulfonylurea with a prolonged half-

life, a treatment free period of a few days may be necessary to avoid an

additive effect of the two products, which might cause hypoglycaemia.

Combination treatment with other antidiabetic agents:

Gliclazide 40 mg can be given in combination with biguanides, alpha

glucosidase inhibitors or insulin.

In patients not adequately controlled with Gliclazide 40 mg, concomitant

insulin therapy can be initiated under close medical supervision.

Special Populations

Elderly

Gliclazide 40 mg should be prescribed using the same dosing regimen

recommended for patients under 65 years of age.

Renal impairment

In patients with mild to moderate renal insufficiency, the same dosing regimen

can be used as in patients with normal renal function with careful patient

monitoring. These data have been confirmed in clinical trials.

Patients at risk of hypoglycaemia

Undernourished or malnourished,

Severe or poorly compensated endocrine disorders (hypopituitarism,

hypothyroidism, adrenocorticotrophic insufficiency),

Withdrawal of prolonged and/or high dose corticosteroid therapy,

Severe vascular disease (severe coronary heart disease, severe carotid

impairment, diffuse vascular disease).

It is recommended that the minimum daily starting dose of 40-80 mg is used.

Paediatric population

The safety and efficacy of Gliclazide 40 mg in children and adolescents have

not been established. No data are available.

4.3

Contraindications

This medicine is contra-indicated in case of:

Hypersensitivity to gliclazide or to any of the excipients listed in section 6.1,

other sulfonylureas, sulfonamides Type 1 diabetes,

Diabetic pre-coma and coma, diabetic keto-acidosis,

Severe renal or hepatic insufficiency: in these cases the use of insulin is

recommended,

Lactation (see section 4.6),

Treatment with Miconazole (see section “Interactions with other medicinal

products and other forms of Interaction”).

4.4

Special warnings and precautions for use

Hypoglycaemia:

This treatment should be prescribed only if the patient is likely to have a

regular food intake (including breakfast). It is important to have a regular

carbohydrate intake due to the increased risk of hypoglycaemia if a meal is

taken late, if an inadequate amount of food is consumed or if the food is low in

carbohydrate. Hypoglycaemia is more likely to occur during low calorie diets,

following prolonged or strenuous exercise, alcohol intake or if a combination

of hypoglycaemic agents is being used.

Hypoglycaemia may occur following administration of sulfonylureas (see

section 4.8). Some cases may be severe and prolonged. Hospitalisation may be

necessary and glucose administration may need to be continued for several

days.

Careful selection of patients, of the dose used, and clear patient directions are

necessary to reduce the risk of hypoglycaemic episodes.

Factors which increase the risk of hypoglycaemia:

patient refuses or (particularly in elderly subjects) is unable to co-operate,

malnutrition, irregular mealtimes, skipping meals, periods of fasting or

dietary changes,

imbalance between physical exercise and carbohydrate intake,

renal insufficiency,

severe hepatic insufficiency,

overdose of Gliclazide Tablets,

certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal

insufficiency,

concomitant administration of certain other medicines (see Interactions).

Renal and hepatic insufficiency:

The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered

in patients with hepatic insufficiency or severe renal failure. A hypoglycaemic

episode occurring in these patients may be prolonged, so appropriate

management should be initiated.

Patient information:

The risks of hypoglycaemia, together with its symptoms (see section 4.8),

treatment, and conditions that predispose to its development, should be

explained to the patient and to family members.

The patient should be informed of the importance of following dietary advice,

of taking regular exercise, and of regular monitoring of blood glucose levels.

Poor blood glucose control:

Blood glucose control in a patient receiving antidiabetic treatment may be

affected by any of the following: St. John's Wort (Hypericum perforatum)

preparations (see section 4.5), fever, trauma, infection or surgical intervention.

In some cases, it may be necessary to administer insulin.

The hypoglycaemic efficacy of any oral antidiabetic agent, including

gliclazide, is attenuated over time in many patients: this may be due to

progression in the severity of the diabetes, or to a reduced response to

treatment. This phenomenon is known as secondary failure which is distinct

from primary failure, when an active substance is ineffective as first-line

treatment. Adequate dose adjustment and dietary compliance should be

considered before classifying the patient as secondary failure.

Dysglycaemia:

Disturbances in blood glucose, including hypoglycaemia and hyperglycaemia

have been reported, in diabetic patients receiving concomitant treatment with

fluoroquinolones, especially in elderly patients. Indeed, careful monitoring of

blood glucose is recommended in all patients receiving at the same time

Gliclazide 40 mg and a fluoroquinolone.

Laboratory tests:

Measurement of glycated haemoglobin levels (or fasting venous plasma

glucose) is recommended in assessing blood glucose control. Blood glucose

self-monitoring may also be useful.

This medicinal product contains Lactose Monohydrate. Patients with rare

hereditary problems of galactose intolerance, the Lapp lactase deficiency or

glucose-galactose malabsorption should not take this medicine.

Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead

to haemolytic anaemia. Since gliclazide belongs to the class of sulfonylurea

agents, caution should be used in patients with G6PD-deficiency and a non-

sulfonylurea alternative should be considered.

4.5

Interaction with other medicinal products and other forms of interaction

The following products are likely to increase the risk of hypoglycaemia

Contra-indicated combination:

Miconazole (systemic route, oromucosal gel): increases the hypoglycaemic

effect with possible onset of hypoglycaemic symptoms, or even coma.

Combinations which are not recommended:

Phenylbutazone (systemic route): increases the hypoglycaemic effect of

sulfonylureas (displaces their binding to plasma proteins and/or reduces their

elimination).

It is preferable to use a different anti-inflammatory agent, or else to warn the

patient and emphasise the importance of self-monitoring.

Where necessary, adjust the dose during and after treatment with the anti-

inflammatory agent.

Alcohol: increases the hypoglycaemic reaction (by inhibiting compensatory

reactions) that can lead to the onset of hypoglycaemic coma. Avoid alcohol or

medicines containing alcohol.

Combinations requiring precautions for use

Potentiation of the blood glucose lowering effect and thus, in some instances,

hypoglycaemia may occur when one of the following drugs is taken, other

antidiabetic agents (insulins, acarbose, metformin, thiazolidinediones,

dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists), beta-blockers,

fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril),

H2-receptor antagonists, MAOIs, sulfonamides, clarithromycin and

nonsteroidal anti-inflammatory agents.

The following products may cause an increase in blood glucose levels

Combination which is not recommended:

Danazol: diabetogenic effect of danazol.

If the use of this active substance cannot be avoided, warn the patient and

emphasise the importance of urine and blood glucose monitoring. It may be

necessary to adjust the dose of the antidiabetic agent during and after

treatment with danazol.

Combinations requiring precautions during use

Chlorpromazine (neuroleptic agent): high doses >100 mg per day of

chlorpromazine) increase blood glucose levels (reduced insulin release).

Warn the patient and emphasise the importance of blood glucose monitoring.

It may be necessary to adjust the dose of the antidiabetic active substance

during and after treatment with the neuroleptic agent.

Glucocorticoids (systemic and local route: intra-articular, cutaneous and

rectal preparations) and tetracosactrin: increase in blood glucose levels with

possible ketosis (reduced tolerance to carbohydrates due to glucocorticoids).

Warn the patient and emphasise the importance of blood glucose monitoring,

particularly at the start of treatment. It may be necessary to adjust the dose of

the antidiabetic active substance during and after treatment with

glucocorticoids.

Ritodrine, salbutamol, terbutaline: (I.V.)

Increased blood glucose levels due to beta-2 agonist effects. Emphasise the

importance of monitoring blood glucose levels. If necessary, switch to insulin.

Saint John's Wort (Hypericum perforatum) preparations:

Gliclazide exposure is decreased by Saint John's Wort-Hypericum perforatum.

Emphasise the importance of blood glucose levels monitoring.

The following products may cause dysglycaemia

Combinations requiring precautions during use

Fluoroquinolones: in case of a concomitant use of Gliclazide 40 mg and a

fluoroquinolone, the patient should be warned of the risk of dysglycaemia, and

the importance of blood glucose monitoring should be emphasised.

Combination which must be taken into account

Anticoagulant therapy (e.g. Warfarin): Sulfonylureas may lead to

potentiation of anticoagulation during concurrent treatment. Adjustment of the

anticoagulant may be necessary.

4.6

Fertility, pregnancy and lactation

Pregnancy:

There is no or limited amount of data (less than 300 pregnancy outcomes)

from the use of gliclazide in pregnant women, even though there are few data

with other sulfonylureas.

Studies in animals have shown reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of Gliclazide

during pregnancy.

Control of diabetes should be obtained before the time of conception to reduce

the risk of congenital abnormalities linked to uncontrolled diabetes.

Oral hypoglycaemic agents are not suitable; insulin is the drug of first choice

for treatment of diabetes during pregnancy. It is recommended that oral

hypoglycaemic therapy is changed to insulin before a pregnancy is attempted,

or as soon as pregnancy is discovered.

Breast-feeding:

It is unknown whether gliclazide or its metabolites are excreted in human

milk. Given the risk of neonatal hypoglycaemia, the product is therefore

contra-indicated in breast-feeding mothers. A risk to the newborns/infants

cannot be excluded.

Fertility:

No effect on fertility or reproductive performance was noted in male and

female rats (see section 5.3).

4.7

Effects on ability to drive and use machines

Gliclazide 40 mg has no or negligible influence on the ability to drive and use

machines. However, patients should be informed that their concentration may

be affected if their diabetes is not satisfactorily controlled, especially at the

beginning of treatment (see special warnings and precautions).

4.8

Undesirable effects

Based on the experience with gliclazide the following undesirable effects have

been reported.

The most frequent adverse reaction with gliclazide is hypoglycaemia.

As for other sulfonylureas, treatment with gliclazide 40mg tablets can cause

hypoglycaemia, if mealtimes are irregular and, in particular, if meals are

skipped. Possible symptoms of hypoglycaemia are: headache, intense hunger,

nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor

concentration, reduced awareness and slowed reactions, depression, confusion,

visual and speech disorders, aphasia, tremor, paresis, sensory disorders,

dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions,

shallow respiration, bradycardia, drowsiness and loss of consciousness,

possibly resulting in coma and lethal outcome.

In addition, signs of adrenergic counter-regulation may be observed: sweating,

clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris

and cardiac arrhythmia.

Usually, symptoms disappear after intake of carbohydrates (sugar). However,

artificial sweeteners have no effect. Experience with other sulfonylureas

shows that hypoglycaemia can recur even when measures prove effective

initially.

If a hypoglycaemic episode is severe or prolonged, and even if it is

temporarily controlled by intake of sugar, immediate medical treatment or

even hospitalisation is required.

Gastrointestinal disturbances, including abdominal pain, nausea, vomiting

dyspepsia, diarrhoea, and constipation have been reported: if these should

occur they can be avoided or minimised if gliclazide is taken with breakfast.

The following undesirable effects have been more rarely reported:

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, angioedema,

erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson

syndrome and toxic epidermal necrolysis), and exceptionally, drug rash with

eosinophilia and systemic symptoms (DRESS).

Blood and lymphatic system disorders: changes in haematology are rare.

They may include anaemia, leucopenia, thrombocytopenia, granulocytopenia.

These are in general reversible upon discontinuation of medication.

Hepato-biliary disorders: raised hepatic enzyme levels (AST, ALT, alkaline

phosphatase), hepatitis (isolated reports). Discontinue treatment if cholestatic

jaundice appears.

These symptoms usually disappear after discontinuation of treatment.

Eye disorders: Transient visual disturbances may occur especially on

initiation of treatment, due to changes in blood glucose levels.

Class attribution effects: As for other sulfonylureas, the following adverse

events have been observed: cases of erythrocytopenia, agranulocytosis,

haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatremia, elevated

liver enzyme levels and even impairment of liver function (e.g. with

cholestasis and jaundice) and hepatitis which regressed after withdrawal of the

sulfonylurea or led to life-threatening liver failure in isolated cases.

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 Website:

www.mhra.gov.uk/yellowcard.

4.9

Overdose

The symptoms to be expected of overdose would be hypoglycaemia. Moderate

symptoms of hypoglycaemia, without any loss of consciousness or

neurological signs, must be corrected by carbohydrate intake, dose adjustment

and/or change of diet. Strict monitoring should be continued until the doctor is

sure that the patient is out of danger.

Severe hypoglycaemic reactions, with coma, convulsions or other neurological

disorders are possible and must be treated as a medical emergency, requiring

immediate hospitalisation.

If hypoglycaemic coma is diagnosed or suspected, the patient should be given

a rapid I.V. injection of 50 mL of concentrated glucose solution (20 to 30 %).

This should be followed by continuous infusion of a more dilute glucose

solution (10 %) at a rate that will maintain blood glucose levels above 1 g/L.

Patients should be monitored closely and, depending on the patient's condition

after this time, the doctor will decide if further monitoring is necessary.

Dialysis is of no benefit to patients due to the strong binding of gliclazide to

proteins.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: sulfonamides, urea derivatives. ATC code: A10B

Mechanism of action

Gliclazide is a hypoglycaemic sulfonylurea differing from other related

compounds by an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces blood glucose levels by stimulating insulin secretion from

-cells of the islets of Langerhans.

Increase in postprandial insulin and C-peptide secretion persists after two

years of treatment.

In addition to these metabolic properties, gliclazide has haemovascular

properties.

Clinical efficacy and safety

Effects on insulin release:

In type 2 diabetics, gliclazide restores the first peak of insulin secretion in

response to glucose and increases the second phase of insulin secretion. A

significant increase in insulin response is seen in response to stimulation

induced by a meal or glucose.

Haemovascular properties:

Gliclazide decreases microthrombosis by two mechanisms which may be

involved in complications of diabetes:

A partial inhibition of platelet aggregation and adhesion, with a decrease in

the markers of platelet activation (beta thromboglobulin, thromboxane B

An action on the vascular endothelium fibrinolytic activity with an increase

in tPA activity.

5.2

Pharmacokinetic properties

Absorption

Plasma levels increase reaching maximal concentrations between 2 and 6

hours.

Gliclazide is well absorbed. Food intake does not affect the rate or degree of

absorption.

Distribution

Plasma protein binding is approximately 95%. The volume of distribution is

around 19 litres.

Biotransformation

Read the complete document

PAR Gliclazide 40mg Tablets

PL 30306/0631

1

Public Assessment Report

UKPAR

Gliclazide 40mg Tablets

(gliclazide)

UK Licence Number: PL 30306/0631

Actavis Group PTC ehf.

PAR Gliclazide 40mg Tablets

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LAY SUMMARY

Gliclazide 40mg Tablets

(gliclazide, tablets, 40 mg)

This is a summary of the Public Assessment Report (PAR) for Gliclazide 40mg Tablets (PL

30306/0631). It explains how Gliclazide 40mg Tablets were assessed and their authorisation

recommended, as well as their conditions of use. It is not intended to provide practical advice on how to

use Gliclazide 40mg Tablets.

The product will be referred to as Gliclazide Tablets throughout the remainder of this public assessment

report (PAR).

For practical information about using Gliclazide Tablets, patients should read the package leaflet or

contact their doctor or pharmacist.

What are Gliclazide Tablets

and what are they used for?

Gliclazide Tablets are a ‘hybrid generic medicine’. This means that it is similar to a reference medicine

containing the same active substance but is available at a lower strength (40 mg).

The reference medicine for this product is Diamicron 80 mg Tablets (Servier Laboratories Ltd).

Gliclazide Tablets are used in the treatment of diabetes mellitus when diet alone fails to lower blood

glucose (sugar). They are not for use in children or in patients with diabetes requiring insulin.

How do Gliclazide Tablets work?

The active ingredient in this medicine is called gliclazide and is one of a group of medicines called

sulfonylureas that are used to lower the blood sugar level.

How are Gliclazide Tablets used?

The pharmaceutical form of this medicine is a tablet. The route of administration of this medicine is oral

(by mouth).

The patient must always take this medicine exactly as their doctor has told them. The patient must check

with their doctor or pharmacist if they are not sure.

This medicine should be taken with a glass of water before meals.

Doses:

Adults and the elderly

The starting dose is usually 40-80mg once daily and may be increased to a total daily dose of 40-320mg.

Do not take more than the maximum of 160mg as single dose. For doses of 320mg this will be split over

the day.

If a combination therapy of Gliclazide Tablets with metformin, an alpha glucosidase inhibitor, a

thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, a GLP-1 receptor agonist or insulin is initiated the

patient’s doctor will determine the proper dose of each medicine individually for them.

If the patient notices that their blood sugar levels are high although they are taking the medicine as

prescribed, the patient should contact their doctor or pharmacist.

PAR Gliclazide 40mg Tablets

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This medicine is

not

recommended for use in children.

Please read section 3 of the package leaflet for detailed information on dosing recommendations, the

route of administration, and the duration of treatment.

This medicine can only be obtained with a prescription.

What benefits of Gliclazide Tablets have been shown in studies?

Because Gliclazide Tablets are a lower strength hybrid application of Diamicron 80 mg Tablets (Servier

Laboratories Ltd), clinical studies have been provided for Gliclazide Tablets to show efficacy for the

lower strength of Gliclazide Tablets compared with the reference product Diamicron 80 mg Tablets

(Servier Laboratories Ltd). Studies in patients have been limited to tests to determine that Gliclazide

Tablets are bioequivalent to Diamicron 80 mg Tablets (Servier Laboratories Ltd). Two medicines are

bioequivalent when they produce the same levels of the active substance in the body.

What are the possible side effects of this medicine?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

For the full list of all side effects reported with this medicine, see section 4 of the package leaflet

available on the MHRA website.

For the full list of restrictions, see the package leaflet.

Why was this medicine approved?

The MHRA decided that this medicine’s benefits are greater than its risks and recommended that it be

approved for use.

What measures are being taken to ensure the safe and effective use of Gliclazide Tablets?

A risk management plan (RMP) has been developed to ensure that Gliclazide Tablets are used as safely

as possible. Based on this plan, safety information has been included in the Summary of Product

Characteristics and the package leaflet for Gliclazide Tablets including the appropriate precautions to be

followed by healthcare professionals and patients.

Known side effects are continuously monitored. Furthermore new safety signals reported by

patients/healthcare professionals will be monitored/reviewed continuously.

Other information about this medicine

The MHRA agreed to grant a marketing Authorisation for Gliclazide Tablets on 15 March 2016.

The full PAR for this medicine follows this summary.

For more information about treatment with this medicine, read the package leaflet, or contact your

doctor or pharmacist.

This summary was last updated in May 2016.

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TABLE OF CONTENTS

Introduction

Page 5

Quality aspects

Page 6

Non-clinical aspects

Page 7

Clinical aspects

Page 8

User consultation

Page 10

Overall conclusion, benefit/risk assessment and

recommendation

Page 10

PAR Gliclazide 40mg Tablets

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I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products

Regulatory Agency (MHRA) granted Actavis Group PTC ehf, a marketing authorisation for the

medicinal product Gliclazide Tablets (PL 30306/0631). The product is a prescription-only medicine

(POM) indicated for non-insulin dependent diabetes mellitus.

This application was submitted under Article 10(3) of Directive 2001/83/EC, as amended, as a hybrid

application, cross-referring to Diamicron 80 mg Tablets which was originally licenced on 21 December

1979 to Servier Laboratories Ltd, UK (PL 00093/0024).

Gliclazide is a hypoglycaemic sulfonylurea antidiabetic active substance differing from other related

compounds by an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of

Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of

treatment.

In addition to these metabolic properties, gliclazide has haemovascular properties.

One bioequivalence study was submitted to support this application comparing the applicant’s test

product Gliclazide Tablets (Actavis Group PTC ehf) with the reference product Diamicron 80 mg

Tablets (Servier Laboratories Ltd) under fed conditions. The applicant has stated that the bioequivalence

study was conducted in accordance with the clinical research guidelines established by the Basic

Principles defined in the Indian Council of Medical Research (ICMR) guidelines for biomedical research

on human subjects, the current Helsinki Declaration (Brazil, 2013), GCP and applicable regulatory

requirements and the ethical considerations in the protocol were adhered to.

With the exception of the bioequivalence study, no new non-clinical or clinical data were submitted,

which is acceptable given that this application was based on the product being shown to be bioequivalent

to an originator product that has been in clinical use for over 10 years.

No new or unexpected safety concerns arose during the review of information provided by the

Marketing Authorisation Holder and it was, therefore, judged that the benefits of taking Gliclazide

Tablets outweigh the risks and a Marketing Authorisation was granted.

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II

QUALITY ASPECTS

II.1

Introduction

Each tablet contains 40mg gliclazide.

Other ingredients consist of the pharmaceutical excipients

microcrystalline cellulose, pregelatinised

starch, maize starch, stearic acid and magnesium stearate. The product is packed into polyvinyl chloride

(PVC)/aluminium blisters and is available in pack sizes of 20, 28, 56, 60, 84 and 100 tablets. Not all

pack sizes may be marketed. Satisfactory specifications and Certificates of Analysis have been provided

for all packaging components.

II.2.

Drug Substance

INN:

Gliclazide

Chemical name:

1-(Hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-[(4-methylphenyl)sulfonyl]urea.

Structural formula:

Molecular formula:

Molecular mass:

323.4

Appearance:

A white or almost white powder.

Solubility:

Practically insoluble in water, freely soluble in methylene chloride, sparingly

soluble in acetone, slightly soluble in ethanol (96 per cent).

Gliclazide is the subject of a European Pharmacopoeia monograph.

All aspects of the manufacture and control of the active substance, gliclazide, are covered by the

European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of Suitability.

II.3.

Medicinal Product

Pharmaceutical Development

The objective of the development programme was to formulate safe, efficacious, stable tablets

containing 40 mg gliclazide per tablet that were comparable in performance to the reference product

Diamicron 80 mg Tablets (Servier Laboratories Ltd). A satisfactory account of the pharmaceutical

development has been provided.

Comparable

in-vitro

dissolution and impurity profiles have been provided for this product and the

reference product Diamicron 80 mg Tablets (Servier Laboratories Ltd).

All excipients comply with their respective European Pharmacopoeia monographs. Satisfactory

Certificates of Analysis have been provided for all excipients. Suitable batch analysis data have been

provided for each excipient.

None of the excipients contain materials of animal or human origin.

No genetically modified organisms (GMO) have been used in the preparation of this product.

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Manufacture of the product

A satisfactory batch formula has been provided for the manufacture of the product, along with an

appropriate account of the manufacturing process. The manufacturing process has been validated at

commercial-scale batch size and shown satisfactory results. The marketing authorisation holder has also

committed to perform process validation on future commercial-scale batches.

Finished Product Specification

The finished product specification proposed is acceptable. Test methods have been described that have

been adequately validated. Batch data have been provided that comply with the release specifications.

Certificates of Analysis have been provided for all working standards used.

Stability of the Product

Finished product stability studies were performed in accordance with current guidelines on batches of

finished product in the packaging proposed for marketing. The data from these studies support a

shelf-life of 18 months with no special storage conditions.

Suitable post approval stability commitments have been provided to continue stability testing on batches

of finished product.

II.4

Discussion on chemical, pharmaceutical and biological aspects

There are no objections to the approval of this application from a pharmaceutical viewpoint.

III

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of gliclazide are well-known, no

new non-clinical studies are required and none have been provided. An overview based on the literature

review is, thus, appropriate.

The MAH’s non-clinical expert report has been written by an appropriately qualified person and is

satisfactory, providing an appropriate review of the relevant non-clinical pharmacology,

pharmacokinetics and toxicology.

III.2

Pharmacology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

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III.3

Pharmacokinetics

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.4

Toxicology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.5

Ecotoxicity/environmental risk assessment (ERA)

Since Gliclazide Tablets are intended for generic substitution, this will not lead to an increased exposure

to the environment. An environmental risk assessment is therefore not deemed necessary.

III.6

Discussion on the non-clinical aspects

No new non-clinical studies were conducted or necessary for this type of application.

There are no objections to the approval of this application from a non-clinical viewpoint.

IV

CLINICAL ASPECTS

IV.1

Introduction

The clinical pharmacology of gliclazide is well-known. With the exception of data from the

bioequivalence study detailed below, no new pharmacodynamics or pharmacokinetic data are provided

or are required for this application.

No new efficacy or safety studies have been performed and none are required for this type of

application. A comprehensive review of the published literature has been provided by the applicant,

citing the well-established clinical pharmacology, efficacy and safety of gliclazide.

Based on the data provided, Gliclazide Tablets can be considered bioequivalent to Diamicron 80 mg

Tablets (Servier Laboratories Ltd).

IV.2

Pharmacokinetics

In support of this application, the applicant submitted the following bioequivalence study:

STUDY

An open label, randomised, two-period, two-treatment, two-sequence, single dose, crossover study

to compare the pharmacokinetics of the applicant’s test product

Gliclazide Tablets (Actavis

Group PTC ehf) versus the reference product,

Diamicron 80 mg Tablets (Servier Laboratories

Ltd), in healthy adult subjects under fed conditions.

After an overnight fast of 10 hours the subjects were administered a single dose (80 mg) of either the test

(2 x 40 mg tablets) or the reference product (1x 80 mg tablet) with 240 mL of water under fed conditions

(30 minutes after a high calorie, high fat breakfast). Blood samples were collected for plasma levels

before dosing and up to and including 60 hours after each administration. The washout period between

the treatment phases was 11 days. The pharmacokinetic results are presented below:

PAR Gliclazide 40mg Tablets

PL 30306/0631

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Summary statistics for pharmacokinetic parameters for gliclazide are shown below:

area under the plasma concentration-time curve from zero to t hours

maximum plasma concentration

Conclusion

The 90% confidence intervals of the test/reference ratio for AUC, and C

values for gliclazide lie

within the acceptable limits of 80.00% to 125.00%, in line with the ‘Guideline on the Investigation of

Bioequivalence

(CPMP/EWP/QWP/1401/98 Rev 1/Corr**). Thus, the data support the claim that the

applicant’s 40 mg test product (administered at a dose of 2 x 40 mg tablets) is bioequivalent to the

reference product Diamicron 80 mg Tablets, Servier Laboratories Ltd (administered at a dose of 1 x 80

mg tablet).

IV.3

Pharmacodynamics

No new pharmacodynamic data were submitted and none were required for an application of this type.

IV.4

Clinical efficacy

No new efficacy data were submitted and none were required for an application of this type.

IV.5

Clinical safety

No new safety data were submitted and none were required for this application.

IV.6

Risk Management Plan (RMP)

The marketing authorisation holder (MAH) has submitted a risk management plan (RMP), in accordance

with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities

and interventions designed to identify, characterise, prevent or minimise risks relating to gliclazide.

A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are

listed below:

PAR Gliclazide 40mg Tablets

PL 30306/0631

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Summary table of safety concerns:

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

IV.7

Discussion on the clinical aspects

There are no objections to the approval of this application from a clinical viewpoint

.

The grant of a marketing authorisation is recommended for this application.

V

User consultation

The package leaflet has been evaluated via a user consultation study, in accordance with the

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of

user testing the PIL was English.

The results show that the package leaflet meets the criteria for readability, as set out in the

Guideline on

the readability of the label and package leaflet of medicinal products for human use

VI

Overall conclusion, benefit/risk assessment and recommendation

The quality of the product is acceptable, and no new non-clinical or clinical safety concerns have been

identified. Extensive clinical experience with gliclazide is considered to have demonstrated the

therapeutic value of the compound. The benefit-risk is, therefore, considered to be positive.

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Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) and Patient

Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for Gliclazide Tablets is presented below:

PAR Gliclazide 40mg Tablets

PL 30306/0631

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