Gliclazide 40mg tablets

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Gliclazide
Available from:
DE Pharmaceuticals
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:
Authorization number:
; PL 43461/0010

296x210 Leaflet Reel Fed Bi Fold Profile (BST)

Dimensions:

Component:

Date Sent:

Technologist:

Technically Approved

Pharmacode:

JDE No.:

Gliclazide Tablets 40mg x 28’s (UK)

296x210 (Reel Fed)

50965118

Leaflet for Blisters

4266

R.Wrey

18/02/19

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

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Date received:

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Dimensions:

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Supplier:

Gliclazide 40mg 28 Tables PIL - UK

Black

Profile

BBBA4382

R.Wrey

01/04/19

05/04/19

R.Wrey

296 x 210

Accord Barnstaple

02

page 4

page 1

50965118

Gliclazide 40mg Tablets

Continued top of next column

Continued over page

BBBA4382

Continued top of next column

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, pharmacist or nurse.

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, pharmacist or nurse. This includes

any possible side effects not listed in this

leaflet. See section 4.

What is in this leaflet

1

What Gliclazide tablets are and what

they are used for

2

What you need to know before you

take Gliclazide tablets

3

How to take Gliclazide tablets

4

Possible side effects

5

How to store Gliclazide tablets

6

Contents of the pack and other

information

1

What Gliclazide tablets are and what

they are used for

Gliclazide belongs to a group of medicines called

sulfonylureas that are used to lower the blood

sugar level.

Gliclazide tablets are used in the treatment of

diabetes mellitus when diet, physical exercise

and weight loss alone fails to lower blood

glucose (sugar). They are not for use in children

or in patients with diabetes requiring insulin.

2

What you need to know before you

take Gliclazide tablets

Do not take Gliclazide tablets and tell

your doctor 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)

have insulin-dependent diabetes (type 1)

have ketone bodies and sugar in your urine

(this may mean you have keto-acidosis), a

diabetic pre-coma and coma

have severe kidney or liver disease

are taking miconazole (a treatment for fungal

infections) (see Other medicines and Gliclazide

tablets)

are breast-feeding (see Pregnancy and breast-

feeding).

Warnings and precautions

Talk to your doctor or pharmacist 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 regime, 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

(hypoglycaemia) may be increased. So

particularly close medical monitoring is

necessary.

Low blood sugar (hypoglycaemia) may occur:

if you have 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

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 effects not listed in this leaflet. You can also

report side effects directly via the Yellow Card

Scheme website: 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.

This medicine does not require any special

storage conditions. Do not use this medicine

after the expiry date stated on the carton. The

expiry date refers to the last day of that month.

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

contains 40mg of gliclazide.

The other ingredients are microcrystalline

cellulose, pregelatinised starch, maize starch,

stearic acid, magnesium stearate.

What Gliclazide tablets look like and

contents of the pack

Gliclazide tablets are white, circular, flat,

bevelled-edge uncoated tablet plain on one face

and the identifying letters “GU” on the reverse.

Pack size 28.

Marketing Authorisation Holder

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

Manufacturer

Accord, Barnstaple, EX32 8NS, UK

This leaflet was last revised in April 2019

If you would like a

leaflet with larger text,

please contact

01271 385257.

Accord Healthcare Ltd, North Harrow, HA1 4HF, UK

296x210 Leaflet Reel Fed Bi Fold Profile (BST)

Dimensions:

Component:

Date Sent:

Technologist:

Technically Approved

Pharmacode:

JDE No.:

Gliclazide Tablets 40mg x 28’s (UK)

296x210 (Reel Fed)

50965118

Leaflet for Blisters

4266

R.Wrey

18/02/19

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

Proof Round

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Technical

Approval

Non Printing Colours

Colours

Date sent:

Date received:

Item no:

Originator:

Origination Date:

Revision Date:

Revised By:

Dimensions:

Min Body Text Size:

Supplier:

Gliclazide 40mg 28 Tables PIL - UK

Black

Profile

BBBA4382

R.Wrey

01/04/19

05/04/19

R.Wrey

296 x 210

Accord Barnstaple

02

page 2

page 3

Continued top of next column

Continued top of next column

Continued top of next column

Continued over page

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 heartbeat, 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 heartbeat

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 prescribed by your doctor or in especially

stressful situations. These may include thirst,

frequent urination, dry mouth, dry itchy skin,

skin infections and reduced performance.

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 section 3

‘How to take Gliclazide tablets’)

check your blood glucose regularly as

recommended by your doctor.

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)

painkiller or antirheumatics (phenylbutazone,

ibuprofen)

medicines containing alcohol.

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.

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).

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 alcohol

Drinking alcohol is not recommended as it can

alter the control of your diabetes.

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).

3

How to take Gliclazide tablets

Always take this medicine exactly as your doctor

or pharmacist has told you. Check with your

doctor or pharmacist if you are not sure.

These tablets should be taken with a glass of

water before meals.

Recommended 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, your doctor will determine the

proper dose of each medicine individually for

you. lf you notice that your blood sugar levels

are high although you are taking the medicine

as prescribed, you should contact your doctor or

pharmacist.

Use in children

Not recommended.

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

Take it as soon as you remember, unless it is

nearly time for your next dose. Then carry on as

before. 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, pharmacist or

nurse.

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.

296x210 Leaflet Reel Fed Bi Fold Profile (BST)

Dimensions:

Component:

Date Sent:

Technologist:

Technically Approved

Pharmacode:

JDE No.:

Gliclazide Tablets 40mg x 28’s (UK)

296x210 (Reel Fed)

50965118

Leaflet for Blisters

4266

R.Wrey

18/02/19

* Please note that only Artwork Studio is permitted to make changes to the above artwork.

No changes are permitted by any 3rd party other than added notes and mark ups for required changes.

approved for print/date

Proof Round

UK-Eire-Artwork-Support@Actavis.com

Technical

Approval

Non Printing Colours

Colours

Date sent:

Date received:

Item no:

Originator:

Origination Date:

Revision Date:

Revised By:

Dimensions:

Min Body Text Size:

Supplier:

Gliclazide 40mg 28 Tables PIL - UK

Black

Profile

BBBA4382

R.Wrey

01/04/19

05/04/19

R.Wrey

296 x 210

Accord Barnstaple

02

page 4

page 1

50965118

Gliclazide 40mg Tablets

Continued top of next column

Continued over page

BBBA4382

Continued top of next column

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, pharmacist or nurse.

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, pharmacist or nurse. This includes

any possible side effects not listed in this

leaflet. See section 4.

What is in this leaflet

1

What Gliclazide tablets are and what

they are used for

2

What you need to know before you

take Gliclazide tablets

3

How to take Gliclazide tablets

4

Possible side effects

5

How to store Gliclazide tablets

6

Contents of the pack and other

information

1

What Gliclazide tablets are and what

they are used for

Gliclazide belongs to a group of medicines called

sulfonylureas that are used to lower the blood

sugar level.

Gliclazide tablets are used in the treatment of

diabetes mellitus when diet, physical exercise

and weight loss alone fails to lower blood

glucose (sugar). They are not for use in children

or in patients with diabetes requiring insulin.

2

What you need to know before you

take Gliclazide tablets

Do not take Gliclazide tablets and tell

your doctor 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)

have insulin-dependent diabetes (type 1)

have ketone bodies and sugar in your urine

(this may mean you have keto-acidosis), a

diabetic pre-coma and coma

have severe kidney or liver disease

are taking miconazole (a treatment for fungal

infections) (see Other medicines and Gliclazide

tablets)

are breast-feeding (see Pregnancy and breast-

feeding).

Warnings and precautions

Talk to your doctor or pharmacist 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 regime, 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

(hypoglycaemia) may be increased. So

particularly close medical monitoring is

necessary.

Low blood sugar (hypoglycaemia) may occur:

if you have 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

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 effects not listed in this leaflet. You can also

report side effects directly via the Yellow Card

Scheme website: 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.

This medicine does not require any special

storage conditions. Do not use this medicine

after the expiry date stated on the carton. The

expiry date refers to the last day of that month.

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

contains 40mg of gliclazide.

The other ingredients are microcrystalline

cellulose, pregelatinised starch, maize starch,

stearic acid, magnesium stearate.

What Gliclazide tablets look like and

contents of the pack

Gliclazide tablets are white, circular, flat,

bevelled-edge uncoated tablet plain on one face

and the identifying letters “GU” on the reverse.

Pack size 28.

Marketing Authorisation Holder

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

Manufacturer

Accord, Barnstaple, EX32 8NS, UK

This leaflet was last revised in April 2019

If you would like a

leaflet with larger text,

please contact

01271 385257.

Accord Healthcare Ltd, North Harrow, HA1 4HF, UK

Object 1

Gliclazide 40mg Tablets

Summary of Product Characteristics Updated 17-May-2019 | Accord-UK Ltd

1. Name of the medicinal product

2. Qualitative and quantitative composition

3. Pharmaceutical form

4. Clinical particulars

4.1 Therapeutic indications

4.2 Posology and method of administration

4.3 Contraindications

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Fertility, pregnancy and lactation

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

4.9 Overdose

5. Pharmacological properties

5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

6. Pharmaceutical particulars

6.1 List of excipients

6.2 Incompatibilities

6.3 Shelf life

6.4 Special precautions for storage

6.5 Nature and contents of container

6.6 Special precautions for disposal and other handling

7. Marketing authorisation holder

8. Marketing authorisation number(s)

9. Date of first authorisation/renewal of the authorisation

10. Date of revision of the text

1. Name of the medicinal product

Gliclazide 40mg Tablets

2. Qualitative and quantitative composition

Each tablet contains 40mg gliclazide

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Tablet

White, circular, flat, bevelled-edge uncoated tablet plain on one face and the identifying letters “GU” on

the reverse

4. Clinical particulars

4.1 Therapeutic indications

Non insulin dependent diabetes mellitus (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

Adults

The total daily dose may vary from 40-320mg. The dose should be adjusted according to the individual's

response, commencing with 40-80mg (1 - 2 tablets) daily and increasing until adequate control is

achieved. A single dose should not exceed 160mg. When higher doses are required, gliclazide 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 alone, additional therapy may be

required.

Switching from another oral antidiabetic agent to Gliclazide 40mg Tablets:

Gliclazide 40mg Tablets 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 40mg Tablets.

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 40mg Tablets can be given in combination with biguanides, alpha glucosidase inhibitors or

insulin.

In patients not adequately controlled with Gliclazide 40mg Tablets, concomitant insulin therapy can be

initiated under close medical supervision.

Special Populations

Elderly

Gliclazide 40mg Tablets should be prescribed using the same dosing regimen recommended for patients

under 65 years of age.

Clinical experience in the elderly to date shows that gliclazide is effective and well tolerated. Care should

be exercised however, when prescribing sulfonylureas in the elderly due to a possible age-related

increased risk of hypoglycaemia.

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 40mg Tablets in children and adolescents have not been established.

No data are available.

Method of administration

For oral use.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, other

sulfonylureas or sulfonamides

Type I diabetes

Diabetic pre-coma and coma, diabetic keto-acidosis

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

Treatment with miconazole (see section 4.5)

Lactation (see section 4.6).

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

certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency

concomitant administration of certain other medicines (see section 4.5).

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 40mg Tablets 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.

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

Contraindicated 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, for example:

Other antidiabetic agents (insulins, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4

inhibitors, GLP-1 receptor agonists), beta-blockers, fluconazole, angiotensin converting enzyme

inhibitors (captopril, enalapril), H

-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 40mg Tablets 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 not known whether gliclazide or its metabolites are excreted in breast milk. Given the risk of neonatal

hypoglycaemia, the product is 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 has no known 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 section 4.4).

4.8 Undesirable effects

Based on the experience with gliclazide, the following undesirable effects have to be mentioned.

Hypoglycaemia

The most frequent adverse reaction with gliclazide is hypoglycaemia.

As for other sulfonylureas, treatment with Gliclazide 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 are 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

gliclazide.

Hepatobiliary 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 national reporting system Yellow Card Scheme,

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple

App Store.

4.9 Overdose

An overdose of sulfonylureas may cause 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

Pharmacotherapeuticgroup: sulfonamides, urea derivatives .

ATC code: A10BB09

Mechanism of action

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.

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

Gliclazide is mainly metabolised in the liver and excreted in the urine; less than 1% of the dose is

excreted unchanged in the urine. No active metabolites have been detected in plasma.

Elimination

The elimination half-life of gliclazide is between 10 and 12 hours.

Linearity/non-linearity

The relationship between the dose administered between 40 and 400mg and the mean plasma

concentrations is linear.

Special populations

Elderly

No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.

5.3 Preclinical safety data

Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose

toxicity and genotoxicity. Long term carcinogenicity studies have not been done. No teratogenic changes

have been shown in animal studies, but lower fetal body weight was observed in animals receiving doses

9.4 fold higher than the maximum recommended dose in humans.

Fertility and reproductive performance were unaffected after gliclazide administration in animal studies.

6. Pharmaceutical particulars

6.1 List of excipients

Microcrystalline cellulose,

Pregelatinised starch

Maize starch

Stearic acid

Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

6.5 Nature and contents of container

Blister packs of PVC with Aluminium foil containing 20, 28, 56, 60 84, 100 tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Accord Healthcare Limited

Sage House

319 Pinner Road

North Harrow

Middlesex

HA1 4HF

United Kingdom

8. Marketing authorisation number(s)

PL 20075/0687

9. Date of first authorisation/renewal of the authorisation

15/03/2016

10. Date of revision of the text

10/05/2019

Company Contact Details

Accord-UK Ltd

Address

Whiddon Valley, Barnstaple, Devon, EX32 8NS, UK

Telephone

+44 (0)1271 385 200

Medical Information Direct Line

+44 (0)1271 385 257

www.accord-healthcare.co.uk

+44 (0)1271 346 106

Medical Information e-mail

[email

protected]

PAR Gliclazide 40mg Tablets

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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.

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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

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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:

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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.

PAR Gliclazide 40mg Tablets

PL 30306/0631

11

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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