Allopurinol 300 mg tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Allopurinol
Available from:
Accord Healthcare Ireland Ltd.
ATC code:
M04AA; M04AA01
INN (International Name):
Allopurinol
Dosage:
300 milligram(s)
Pharmaceutical form:
Tablet
Therapeutic area:
Preparations inhibiting uric acid production; allopurinol
Authorization status:
Not marketed
Authorization number:
PA2315/219/002
Authorization date:
2019-07-19

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

1. What Allopurinol is and what it is used for

2. What you need to know before you take Allopurinol

3. How to take Allopurinol

4. Possible side effects

5. How to store Allopurinol

6. Contents of the pack and other information

1.

What Allopurinol is and what it is

used for

Allopurinol contains the active substance allopurinol.

This medicine belongs to a group of medicines called

enzyme inhibitors, which control the speed at which

certain chemical changes occur in your body.

Allopurinol is used to treat conditions where too much

uric acid is produced by your body such as: gout;

certain types of kidney disease and kidney stones;

cancer and some enzyme disorders which lead to the

build-up of too much uric acid.

2.

What you need to know before

you take Allopurinol

Do not take Allopurinol:

if you are allergic to allopurinol or any of the other

ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking

Allopurinol if

you are suffering, or have you suffered, from liver or

kidney disease

you are taking medicines (diuretics and/or a medicine

called ACE inhibitors) for heart disease or high blood

pressure

you are experiencing an acute attack of gout

you are of Han Chinese, African or Indian origin

you have thyroid problems.

Take special care with Allopurinol

if you have kidney stones.The kidney stones will

become smaller and may have a small chance of

entering and blocking your urinary tract

Serious skin rashes (Hypersensitivity syndrome,

Stevens- Johnson syndrome, toxic epidermal

necrolysis) have been reported in patients taking

allopurinol. Frequently, the rash can involve ulcers of

the mouth, throat, nose, genitals and conjunctivitis

(red and swollen eyes). These serious skin rashes

are often preceded by influenza-like symptoms fever,

headache, body ache (flu-like symptoms). The rash

may progress to widespread blistering and peeling of

the skin. If you develop a rash or these skin

symptoms, stop taking allopurinol and contact your

doctor immediately

if you have cancer or Lesch-Nyhan syndrome the

amount of uric acid may increase in your urine. To

prevent this, you need to assure to drink sufficiently

to dilute your urine.

Children and adolescents

Use in children is rarely indicated, except in some

types of cancer (especially leukaemia) and certain

enzyme disorders such as Lesch-Nyhan syndrome.

Other medicines and Allopurinol

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

medicines used to reduce your immune response

(immunosuppressants) e.g. 6-mercaptopurine,

azathioprine and cyclosporin

adenine arabinoside (vidarabine), used to treat

herpes or chickenpox

other medicines to treat gout, such as probenecid

acetylsalicylic acid (or related medicines called

salicylates)

chlorpropamide, used to treat diabetes

medicines which thin the blood (anticoagulants),

such as warfarin

medicines used for fits (epilepsy), phenytoin

theophylline, used for breathing problems

antibiotics (ampicillin or amoxicillin)

medicines used for the treatment of cancer

didanosine, used to treat HIV infection

medicines for heart problems or high blood pressure

such as ACE inhibitors or water tablets (diuretics)

aluminium hydroxide, as it may reduce the effect of

allopurinol. There should be an interval of at least

3 hours between taking both medicines

cytotoxic medicines (e.g. cyclophosphamide,

doxorubicin, bleomycin, procarbazine, alkyl

halogenides), as blood dyscrasias occur more

frequently when cytotoxic medicines and allopurinol

are taken at the same time. Blood count monitoring

should therefore be performed at regular intervals.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you might

be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this

medicine.

Allopurinol is excreted in the human breast milk.

Allopurinol during breastfeeding is not recommended.

Driving and using machines

Allopurinol may make some people drowsy or have

problems with their coordination. Do not drive or

operate machinery until you know how it affects you.

Allopurinol contains lactose

This medicine contains lactose (a type of sugar). If you

have been told by your doctor that you have an

intolerance to some sugars, contact your doctor before

taking this medicine.

3.

How to take Allopurinol

Always take this medicine exactly as your doctor has

told you. Check with your doctor if you are not sure.

The amount of Allopurinol that people can take can be

very different. Your doctor will decide on a dose of

Allopurinol that is right for you.

The usual starting dose is in the range 100 to 300

mg daily, which may be taken as a single dose.

The dose may be increased up to 900 mg daily,

depending on the severity of your condition.

If you are taking a daily dose higher than 300 mg, your

doctor may tell you to divide the total dose into smaller

doses spaced evenly throughout the day to reduce the

risk of gastrointestinal side effects.

If you are an older person or if you have reduced liver

or kidney function, your doctor may prescribe a lower

dose or to take it at longer intervals. If you have

dialysis two or three times a week, your doctor may

prescribe a dose of 300 or 400 mg which is to be taken

straight after your dialysis.

Use in children and adolescents

Children and adolescents under 15 years: 10 to 20

mg/kg bodyweight/day up to a maximum of 400 mg

daily in three divided doses. Use in children is rarely

indicated, except in malignant conditions (especially

leukaemia) and certain enzyme disorders such as

Lesch-Nyhan syndrome.

Method of administration

Allopurinol is for oral use.

The tablets should be taken with a glass of water to

make swallowing easier.

You should take your tablets after a meal to reduce the

risk of side effects such as nausea (feeling

sick) and vomiting.

If you take more Allopurinol than you should

If you take too many tablets or someone else takes

your medicine by mistake, tell your doctor at once or

go to the hospital straight away. Take the medicine

pack with you. Signs of an overdose may include

nausea, vomiting, diarrhoea and dizziness.

If you forget to take Allopurinol

If you forget to take a dose, take another one as soon

as you remember. However, if it is nearly time for the

next dose, skip the missed dose. Do not take a double

dose to make up for the forgotten.

If you stop taking Allopurinol

Do not stop taking your Allopurinol unless your doctor

tells you to.

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.

Hypersensitivity

Uncommon (may affect up to 1 in 100 people)

Check with your doctor immediately if you experience

any of the following:

a reaction of any kind such as flaking skin,

boils or sore lips and mouth

or very rarely, sudden wheeziness,

fluttering or tightness in the chest;

collapse

Rare (may affect up to 1 in 1000 people)

fever and chills, headache, aching muscles (flu-like

symptoms) and generally feeling unwell

serious hypersensitivity reactions involving fever, skin

rash, joint pain, abnormalities in blood and liver

function tests (these may be signs of a multi-organ

sensitivity disorder)

bleeding in the lips, eyes, mouth, nose or genitals

any changes to your skin, for example; ulcers of the

mouth, throat, nose, genitals and conjunctivitis (red

and swollen eyes), widespread blisters or peeling

Very Rare (may affect up to 1 in 10000 people)

Serious allergic reaction which causes swelling of the

face or throat

Serious potentially life-threatening allergic reaction

These symptoms may mean that you are allergic to

Allopurinol. Do not take any more tablets unless your

doctor tells you to do so.

Other side effects

Common (may affect up to 1 in 10 people)

skin rash

increased level of thyroid stimulating hormone in the

blood

Uncommon (may affect up to 1 in 100 people)

feeling sick (nausea) or being sick (vomiting)

abnormal liver tests

Rare (may affect up to 1 in 1000 people)

Liver problems such as liver inflammation

Very rare (may affect up to 1 in 10000 people)

high temperature

blood in your urine (haematuria)

high levels of cholesterol in your blood

(hyperlipidaemia)

a general feeling of being unwell or feeling weak

weakness, numbness, unsteadiness on your feet,

feeling unable to move muscles (paralysis) or loss of

consciousness

headache, dizziness, drowsiness or disturbance of

vision

chest pain (angina), high blood pressure or a slow

pulse

retention of fluid leading to swelling (oedema)

particularly of the ankles

abnormal glucose metabolism (diabetes). Your doctor

may wish to measure the level of sugar in your blood

to help to decide if this is happening

occasionally Allopurinol tablets may affect your blood.

Tell your doctor as soon as you can if you notice that

you are bruising more easily than usual, or if you

develop a sore throat or other signs of an infection.

These effects usually occur in people with liver or

kidney problems. Tell your doctor as soon as possible

Allopurinol may affect the lymph nodes

male infertility, impotence

enlargement of the breasts, in men as well as women

a change in your normal bowel habit

change in taste perception

cataracts

hair loss or discolouration

depression

lack of voluntary coordination of muscle

movements (ataxia)

sensation of tingling, tickling, pricking or

burning of skin (paraesthesia)

Reporting of side effects

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

pharmacist.

This includes any possible side effects not listed

in this leaflet. You can also report side effects directly via

the national reporting system (see contact details below).

By reporting side effects you can help provide more

information on the safety of this medicine.

Ireland

HPRA Pharmacovigilance Earlsfort Terrace,

IRL - Dublin 2;

Tel: +353 1 6764971;

Fax: +353 1 6762517.

Website: www.hpra.ie;

E-mail: medsafety@hpra.ie

Malta

ADR Reporting

Website: www.medicinesauthority.gov.mt//adrportal

5. How to store Allopurinol

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 blister and the carton. The expiry date

refers to the last day of that month.

Store below 30

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 Allopurinol contains

The active substance(s) is allopurinol

Allopurinol 100 mg: Each tablet contains 100 mg

Allopurinol.

Allopurinol 300 mg: Each tablet contains 300 mg

Allopurinol.

The other ingredients are:

Lactose monohydrate, crospovidone Type B, maize

starch, povidone K 30 and magnesium stearate.

What Allopurinol looks like and contents of the pack

Allopurinol 100 mg is White to off white, round,

biconvex, uncoated tablet with inscription "AW" on one

side and plain on the other side having approximate

diameter of 8.0 mm.

Allopurinol 300 mg is White to off white, round,

biconvex with beveled edge uncoated tablet with

inscription “AX” on one side and plain on the other side

having approximate diameter of 11.2 mm.

PVC-ALU blister containing 25, 28, 30, 50, 60, 90 and

100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare Ireland Limited

Euro House

Euro Business Park

Little Island

Cork T45 K857

Ireland

Manufacturer

Accord Healthcare Limited, Sage house, 319 Pinner

road, Harrow, Middlesex, HA1 4HF,

United Kingdom

Accord Healthcare Polska Sp. z o.o,

ul. Taśmowa 7,

Warszawa, Polska, 02-677, Poland

LABORATORI FUNDACIÓ DAU

C/ C, 12-14 Pol. Ind. Zona Franca,

Barcelona, 08040, Spain

This medicinal product is authorised in the

Member States of the EEA under the following

names:

Name of

Name of medicinal product

Member State

Austria

Allopurinol Accord 100 mg, 300 mg

tabletten

Denmark

Allopurinol Accord 100 mg, 300 mg

tabletter

Estonia

Allopurinol Accord

Finland

Allopurinol Accord

Germany

Allopurinol Accord 100 mg, 300 mg

Tabletten

Lithuania

Allopurinol Accord 100 mg, 300 mg

tabletės

Latvia

Allopurinol Accord 100 mg, 300 mg

tabletes

Netherlands

Allopurinol Accord 100 mg, 300 mg

tabletten

Sweden

Allopurinol Accord 100 mg, 300 mg

tabletter

Ireland

Allopurinol 100 mg, 300 mg tablet

Malta

Allopurinol 100 mg, 300 mg tablet

Bulgaria

Allopurinol Accord 100 mg tablet

Czech Republic

Allospes

Hungary

Allopurinol Accord 100 mg, 300 mg

tabletta

Poland

Allospes

Slovenia

Allopurinol Accord 100mg,300mg

filmsko obložene tablete

Romania

Allospes 100mg,300mg comprimate

Slovak Republic

Allospes 100 mg, 300 mg tablety

Cyprus

Allopurinol Accord 100 mg tablet

Italy

Allopurinolo Accord

Spain

Allopurinol Accord 100 mg, 300 mg

comprimidos

This leaflet was last revised in April 2019.

Artwork No.

Customer

Description

Market

Language

Size

Min. Font Size

Version No.

Date

Accord

Allopurinol 100 mg & 300 mg tablets

IE-MT

English

170 x 550 mm PIL

1 (Page 1 of 2)

28~05~19 (ALLOPUR-100-300 mg(ACC-IE-MT)-PIL)

Colours Used

Pantone Black

Keyline

Prepared By

Regulatory Affairs

Checked By

Regulatory Affairs

Approved By

Quality Assurance

Package leaflet: Information for the patient

Allopurinol 100 mg tablets

Allopurinol 300 mg tablets

allopurinol

Front Side

DUMMY

92640

DUMMY

92640

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

1. What Allopurinol is and what it is used for

2. What you need to know before you take Allopurinol

3. How to take Allopurinol

4. Possible side effects

5. How to store Allopurinol

6. Contents of the pack and other information

1. What Allopurinol is and what it is

used for

Allopurinol contains the active substance allopurinol.

This medicine belongs to a group of medicines called

enzyme inhibitors, which control the speed at which

certain chemical changes occur in your body.

Allopurinol is used to treat conditions where too much

uric acid is produced by your body such as: gout;

certain types of kidney disease and kidney stones;

cancer and some enzyme disorders which lead to the

build-up of too much uric acid.

2. What you need to know before

you take Allopurinol

Do not take Allopurinol:

if you are allergic to allopurinol or any of the other

ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before taking

Allopurinol if

you are suffering, or have you suffered, from liver or

kidney disease

you are taking medicines (diuretics and/or a medicine

called ACE inhibitors) for heart disease or high blood

pressure

you are experiencing an acute attack of gout

you are of Han Chinese, African or Indian origin

you have thyroid problems.

Take special care with Allopurinol

if you have kidney stones.The kidney stones will

become smaller and may have a small chance of

entering and blocking your urinary tract

Serious skin rashes (Hypersensitivity syndrome,

Stevens- Johnson syndrome, toxic epidermal

necrolysis) have been reported in patients taking

allopurinol. Frequently, the rash can involve ulcers of

the mouth, throat, nose, genitals and conjunctivitis

(red and swollen eyes). These serious skin rashes

are often preceded by influenza-like symptoms fever,

headache, body ache (flu-like symptoms). The rash

may progress to widespread blistering and peeling of

the skin. If you develop a rash or these skin

symptoms, stop taking allopurinol and contact your

doctor immediately

if you have cancer or Lesch-Nyhan syndrome the

amount of uric acid may increase in your urine. To

prevent this, you need to assure to drink sufficiently

to dilute your urine.

Children and adolescents

Use in children is rarely indicated, except in some

types of cancer (especially leukaemia) and certain

enzyme disorders such as Lesch-Nyhan syndrome.

Other medicines and Allopurinol

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

medicines used to reduce your immune response

(immunosuppressants) e.g. 6-mercaptopurine,

azathioprine and cyclosporin

adenine arabinoside (vidarabine), used to treat

herpes or chickenpox

other medicines to treat gout, such as probenecid

acetylsalicylic acid (or related medicines called

salicylates)

chlorpropamide, used to treat diabetes

medicines which thin the blood (anticoagulants),

such as warfarin

medicines used for fits (epilepsy), phenytoin

theophylline, used for breathing problems

antibiotics (ampicillin or amoxicillin)

medicines used for the treatment of cancer

didanosine, used to treat HIV infection

medicines for heart problems or high blood pressure

such as ACE inhibitors or water tablets (diuretics).

aluminium hydroxide, as it may reduce the effect of

allopurinol. There should be an interval of at least 3

hours between taking both medicines.

cytotoxic medicines (e.g. cyclophosphamide,

doxorubicin, bleomycin, procarbazine, alkyl

halogenides), as blood dyscrasias occur more

frequently when cytotoxic medicines and allopurinol

are taken at the same time. Blood count monitoring

should therefore be performed at regular intervals.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you might

be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this

medicine.

Allopurinol is excreted in the human breast milk.

Allopurinol during breastfeeding is not recommended.

Driving and using machines

Allopurinol may make some people drowsy or have

problems with their coordination. Do not drive or

operate machinery until you know how it affects you.

Allopurinol contains lactose

This medicine contains lactose (a type of sugar). If you

have been told by your doctor that you have an

intolerance to some sugars, contact your doctor before

taking this medicine.

3. How to take Allopurinol

Always take this medicine exactly as your doctor has

told you. Check with your doctor if you are not sure.

The amount of Allopurinol that people can take can be

very different. Your doctor will decide on a dose of

Allopurinol that is right for you.

The usual starting dose is in the range 100 to 300 mg

daily, which may be taken as a single dose The dose

may be increased up to 900 mg daily, depending on

the severity of your condition.

If you are taking a daily dose higher than 300 mg, your

doctor may tell you to divide the total dose into smaller

doses spaced evenly throughout the day to reduce the

risk of gastrointestinal side effects.

If you are an older person or if you have reduced liver

or kidney function, your doctor may prescribe a lower

dose or to take it at longer intervals. If you have

dialysis two or three times a week, your doctor may

prescribe a dose of 300 or 400 mg which is to be taken

straight after your dialysis.

Use in children and adolescents

Children and adolescents under 15 years: 10 to 20

mg/kg bodyweight/day up to a maximum of 400 mg

daily in three divided doses. Use in children is rarely

indicated, except in malignant conditions (especially

leukaemia) and certain enzyme disorders such as

Lesch-Nyhan syndrome.

Method of administration

Allopurinol is for oral use.

The tablets should be taken with a glass of water to

make swallowing easier.

You should take your tablets after a meal to reduce the

risk of side effects such as nausea (feeling

sick) and vomiting.

If you take more Allopurinol than you should

If you take too many tablets or someone else takes

your medicine by mistake, tell your doctor at once or

go to the hospital straight away. Take the medicine

pack with you. Signs of an overdose may include

nausea, vomiting, diarrhoea and dizziness.

If you forget to take Allopurinol

If you forget to take a dose, take another one as soon

as you remember. However, if it is nearly time for the

next dose, skip the missed dose. Do not take a double

dose to make up for the forgotten.

If you stop taking Allopurinol

Do not stop taking your Allopurinol unless your doctor

tells you to.

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.

Hypersensitivity

Uncommon (may affect up to 1 in 100 people)

Check with your doctor immediately if you experience

any of the following:

a reaction of any kind such as flaking skin,

boils or sore lips and mouth

or very rarely, sudden wheeziness,

fluttering or tightness in the chest;

collapse

Rare (may affect up to 1 in 1000 people)

fever and chills, headache, aching muscles (flu-like

symptoms) and generally feeling unwell

serious hypersensitivity reactions involving fever, skin

rash, joint pain, abnormalities in blood and liver

function tests (these may be signs of a multi-organ

sensitivity disorder).

bleeding in the lips, eyes, mouth, nose or genitals.

any changes to your skin, for example; ulcers of the

mouth, throat, nose, genitals and conjunctivitis (red

and swollen eyes), widespread blisters or peeling.

Very Rare (may affect up to 1 in 10000 people)

Serious allergic reaction which causes swelling of the

face or throat

Serious potentially life-threatening allergic reaction

These symptoms may mean that you are allergic to

Allopurinol. Do not take any more tablets unless your

doctor tells you to do so.

Other side effects

Common (may affect up to 1 in 10 people)

skin rash

increased level of thyroid stimulating hormone in the

blood

Uncommon (may affect up to 1 in 100 people)

feeling sick (nausea) or being sick (vomiting)

abnormal liver tests

Rare (may affect up to 1 in 1000 people)

Liver problems such as liver inflammation.

Very rare (may affect up to 1 in 10000 people)

high temperature

blood in your urine (haematuria)

high levels of cholesterol in your blood

(hyperlipidaemia)

a general feeling of being unwell or feeling weak

weakness, numbness, unsteadiness on your feet,

feeling unable to move muscles (paralysis) or loss of

consciousness

headache, dizziness, drowsiness or disturbance of

vision

chest pain (angina), high blood pressure or a slow

pulse

retention of fluid leading to swelling (oedema)

particularly of the ankles

abnormal glucose metabolism (diabetes). Your doctor

may wish to measure the level of sugar in your blood

to help to decide if this is happening.

occasionally Allopurinol tablets may affect your blood.

Tell your doctor as soon as you can if you notice that

you are bruising more easily than usual, or if you

develop a sore throat or other signs of an infection.

These effects usually occur in people with liver or

kidney problems. Tell your doctor as soon as

possible.

Allopurinol may affect the lymph nodes

male infertility, impotence

enlargement of the breasts, in men as well as women

a change in your normal bowel habit

change in taste perception

cataracts

hair loss or discolouration

depression

lack of voluntary coordination of muscle

movements (ataxia)

sensation of tingling, tickling, pricking or

burning of skin (paraesthesia)

Reporting of side effects

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

pharmacist.

This includes any possible side effects not listed

in this leaflet. You can also report side effects directly via

the national reporting system (see contact details below).

By reporting side effects you can help provide more

information on the safety of this medicine.

Ireland

HPRA Pharmacovigilance Earlsfort Terrace,

IRL - Dublin 2;

Tel: +353 1 6764971;

Fax: +353 1 6762517.

Website: www.hpra.ie;

E-mail: medsafety@hpra.ie

Malta

ADR Reporting

Website: www.medicinesauthority.gov.mt//adrportal

5.

How to store Allopurinol

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 blister and the carton. The expiry date

refers to the last day of that month.

Store below 30

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 Allopurinol contains

The active substance(s) is allopurinol

Allopurinol 100 mg: Each tablet contains 100 mg

Allopurinol.

Allopurinol 300 mg: Each tablet contains 300 mg

Allopurinol.

The other ingredients are:

Lactose monohydrate, crospovidone Type B, maize

starch, povidone K 30 and magnesium stearate.

What Allopurinol looks like and contents of the pack

Allopurinol 100 mg is White to off white, round,

biconvex, uncoated tablet with inscription "AW" on one

side and plain on the other side having approximate

diameter of 8.0 mm.

Allopurinol 300 mg is White to off white, round,

biconvex with beveled edge uncoated tablet with

inscription “AX” on one side and plain on the other side

having approximate diameter of 11.2 mm.

PVC-ALU blister containing 25, 28, 30, 50, 60, 90 and

100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare Ireland Limited

Euro House

Euro Business Park

Little Island

Cork T45 K857

Ireland

Manufacturer

Accord Healthcare Limited, Sage house, 319 Pinner

road, Harrow, Middlesex, HA1 4HF,

United Kingdom

Accord Healthcare Polska Sp. z o.o,

ul. Taśmowa 7,

Warszawa, Polska, 02-677, Poland

LABORATORI FUNDACIÓ DAU

C/ C, 12-14 Pol. Ind. Zona Franca,

Barcelona, 08040, Spain

This medicinal product is authorised in the

Member States of the EEA under the following

names:

Name of

Name of medicinal product

Member State

Austria

Allopurinol Accord 100 mg, 300 mg

tabletten

Denmark

Allopurinol Accord 100 mg, 300 mg

tabletter

Estonia

Allopurinol Accord

Finland

Allopurinol Accord

Germany

Allopurinol Accord 100 mg, 300 mg

Tabletten

Lithuania

Allopurinol Accord 100 mg, 300 mg

tabletės

Latvia

Allopurinol Accord 100 mg, 300 mg

tabletes

Netherlands

Allopurinol Accord 100 mg, 300 mg

tabletten

Sweden

Allopurinol Accord 100 mg, 300 mg

tabletter

Ireland

Allopurinol 100 mg, 300 mg tablet

Malta

Allopurinol 100 mg, 300 mg tablet

Bulgaria

Allopurinol Accord 100 mg tablet

Czech Republic

Allospes

Hungary

Allopurinol Accord 100 mg, 300 mg

tabletta

Poland

Allospes

Slovenia

Allopurinol Accord 100mg,300mg

filmsko obložene tablete

Romania

Allospes 100mg,300mg comprimate

Slovak Republic

Allospes 100 mg, 300 mg tablety

Cyprus

Allopurinol Accord 100 mg tablet

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This leaflet was last revised in April 2019.

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Accord

Allopurinol 100 mg & 300 mg tablets

IE-MT

English

170 x 550 mm PIL

1 (Page 2 of 2)

28~05~19 (ALLOPUR-100-300 mg(ACC-IE-MT)-PIL)

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Pantone Black

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Allopurinol 300 mg tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 300 mg Allopurinol.

Excipients with known effect:

Each 300 mg tablet contains 99 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White to off white, round, biconvex with beveled edge uncoated tablet with inscription "AX" on one side and plain on the other

side having approximate diameter of 11.2 mm.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Allopurinol is indicated for reducing urate/uric acid formation in conditions where urate/uric acid deposition has already

occurred (e.g. gouty arthritis, skin tophi, nephrolithiasis) or is a predictable clinical risk (e.g. treatment of malignancy potentially

leading to acute uric acid nephropathy).

The main clinical conditions where urate/uric acid deposition may occur are:

-Idiopathic gout;

-Uric acid lithiasis;

-Acute uric acid nephropathy;

-Neoplastic disease and myeloproliferative disease with high cell turnover rates, in which high urate levels occur either

spontaneously, or after cytotoxic therapy;

-Certain enzyme disorders which lead to overproduction of urate, for example:

-Hypoxanthine-guanine phosphoribosyltransferase, including Lesch-Nyhan syndrome;

-Glucose-6-phosphatase including glycogen storage disease;

-Phosphoribosylpyrophosphate synthetase;

-Phosphoribosylpyrophosphate amidotransferase;

-Adenine phosphoribosyltransferase;

Allopurinol is indicated for the management of 2, 8-dihydroxyadenine (2, 8-DHA) renal stones related to deficient activity of

adenine phosphoribosyltranferase.

Allopurinol is indicated for the management of recurrent mixed calcium oxalate renal stones in the presence of hyperuricosuria,

when fluid, dietary and similar measures have failed.

Children and adolescents

-Secondary hyperuricaemia of differing origin

-Uric acid nephropathy during treatment of leukaemia

-Hereditary enzyme deficiency disorders, Lesch-Nyhan syndrome (partial or total hypoxanthin-guanin phosphoribosyl

transferase deficiency) and adenine phosophoribosyl transferase deficiency.

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4.2 Posology and method of administration

Posology

Adults

Allopurinol should be introduced at low dose e.g. 100 mg/day to reduce the risk of adverse reactions and increased only if the

serum urate response is unsatisfactory. Extra caution should be exercised if renal function is poor (see section 4.2 Renal

impairment). The following dosage schedules are suggested:

100 to 200 mg daily in mild conditions;

300 to 600 mg daily in moderately severe conditions;

700 to 900 mg daily in severe conditions.

To reduce gastrointestinal undesirable effects, doses higher than 300 mg should be given in divided doses not exceeding 300

mg at any time. If dosage on a mg/kg bodyweight basis is required, 2 to 10 mg/kg bodyweight/day should be used.

Monitoring Advice

The dose should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate

intervals.

Special populations

Elderly

In the absence of specific data, the lowest dose which produces satisfactory urate reduction should be used. Particular

attention should be paid to advice in "section 4.2 Renal impairment" and section 4.4.

Renal impairment

Since allopurinol and its metabolites are excreted by the kidney, impaired renal function may lead to retention of the

allopurinol and/or its metabolites with consequent prolongation of plasma half-lives. The following schedule may serve as

guidance for adults:

Creatinine clearance (normal value 60 to 120 ml/min)

Dosage at reduced renal function

>20 ml/min

normal dose

10 to 20 ml/min

100 to 200 mg per day

<10 ml/min

100 mg/day or longer dose intervals

If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma

oxipurinol levels below 100 μmol/litre (15.2 mg/litre).

Allopurinol and its metabolites are removed by renal dialysis. If dialysis is required two to three times a week consideration

should be given to an alternative dosage schedule of 300-400 mg allopurinol immediately after each dialysis with none in the

interim.

Hepatic impairment

Reduced doses should be used in patients with hepatic impairment. Periodic liver function tests are recommended during the

early stages of therapy.

Treatment of high urate turnover conditions, e.g. neoplasia, Lesch-Nyhan syndrome

Dosage of allopurinol should be at the lower end of the recommended dosage schedule.

If urate nephropathy or other pathology has compromised renal function, the advice given in section 4.2 Renal impairment

should be followed.

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These steps may reduce the risk of xanthine and/or oxipurinol deposition complicating the clinical situation. See also section

4.5 and section 4.8.

Paediatric population

Children and adolescents under 15 years: 10 to 20 mg/kg bodyweight/day up to a maximum of 400 mg daily in three divided

doses. Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders

such as Lesch-Nyhan syndrome.

Method of administration

Allopurinol is for oral use.

The tablets are recommended to be taken orally after a meal to increase gastro-intestinal tolerability

Should the daily dosage exceed 300 mg divided dose regime may be appropriate (see posology).

4.3 Contraindications

Hypersensitivity tothe active substance(s) or to any of the excipients listed in section 6.1

4.4 Special warnings and precautions for use

Hypersensitivity syndrome, Stevens - Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN):

Allopurinol hypersensitivity reactions can manifest in many different ways, including maculopapular exanthema,

hypersensitivity syndrome (also known as DRESS) and Stevens - Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN).

These reactions are clinical diagnoses, and their clinical presentations remain the basis for decision making. If such reactions

occur at any time during treatment, allopurinol should be withdrawn immediately. Rechallenge should not be undertaken in

patients with hypersensitivity syndrome and SJS/TEN. Corticosteroids may be beneficial in overcoming hypersensitivity skin

reactions. (See section 4.8 Adverse Reactions – Immune system disorders and Skin and subcutaneous tissue disorders).

HLA-B*5801 allele:

The HLA-B*5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity

syndrome and SJS/TEN. The frequency of the HLA-B*5801 allele varies widely between ethnic populations: up to 20% in Han

Chinese population, 8-15% in the Thai, about 12% in the Korean population and 1-2% in individuals of Japanese or European

origin. Screening for HLA-B*5801 should be considered before starting treatment with allopurinol in patient subgroups where

the prevalence of this allele is known to be high. Chronic kidney disease may increase the risk in these patients additionally. In

case that no HLA-B*5801 genotyping is available for patients with Han Chinese, Thai or Korean descent the benefits should be

thoroughly assessed and considered outweigh the possible higher risks before starting therapy. The use of genotyping has not

been established in other patient populations. If the patient is a known carrier of HLA-B*5801 (especially in those who are from

Han Chinese, Thai or Korean descent), allopurinol should not be started unless there are no other reasonable therapeutic

options and the benefits are thought to exceed risks. Extra vigilance for signs of hypersensitivity syndrome or SJS/TEN is

required and the patient should be informed of the need to stop treatment immediately at the first appearance of symptoms.

SJS/TEN can still occur in patients who are found to be negative for HLA-B*5801 irrespective of their ethnic origin.

Renal or hepatic impairment:

Reduced doses should be used in patients with hepatic or renal impairment. Patients under treatment for hypertension or

cardiac insufficiency, for example with diuretics or ACE inhibitors, may have some concomitant impairment of renal function

and allopurinol should be used with care in this group.

It is advisable to correct existing hyperuricaemia and/or hyperuricosuria with Allopurinol before starting cytotoxic therapy. It is

important to ensure adequate hydration to maintain optimum diuresis and to attempt alkalinisation of urine to increase

solubility of urinary urate/uric acid.

Chronic renal insufficiency and concomitant diuretic use, in particular thiazides, has been associated with an increased risk of

allopurinol induced SJS/TEN, and other serious hypersensitivity reactions.

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Asymptomatic hyperuricaemia:

Asymptomatic hyperuricaemia per se is generally not considered an indication for use of allopurinol. Fluid and dietary

modification with management of the underlying cause may correct the condition.

Acute gouty attacks:

Allopurinol treatment should not be started until an acute attack of gout has completely subsided, as further attacks may be

precipitated.

In the early stages of treatment with allopurinol, an acute attack of gouty arthritis may be precipitated. Therefore it is advisable

to give prophylaxis with a suitable anti-inflammatory medicinal product or colchicine for at least one month. The literature

should be consulted for details of appropriate dosage and precautions and warnings.

If acute attacks develop in patients receiving allopurinol, treatment should continue at the same dose while the acute attack is

treated with a suitable anti-inflammatory medicinal products.

Xanthine deposition:

In conditions where the rate of urate formation is greatly increased (e.g. malignant disease and its treatment, Lesch-Nyhan

Syndrome) the absolute concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the

urinary tract. This risk may be minimised by adequate hydration to achieve optimal urine dilution.

Impaction of uric acid renal stones:

Adequate therapy with allopurinol will lead to dissolution of large uric acid renal pelvic stones, with the remote possibility of

impaction in the ureter.

Thyroid disorders:

Increased TSH values (>5.5 μIU/mL) were observed in patients on long-term treatment with allopurinol (5.8%) in a long term

open label extension study. Caution is required when Allopurinol is used in patients with alteration of thyroid function.

Lactose:

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

should not take this medicinal product.

4.5 Interaction with other medicinal products and other forms of interactions

6-mercaptopurine and azathioprine:

Azathioprine is metabolised to 6-mercaptopurine which is inactivated by the action of xanthine oxidase. When

6-mercaptopurine or azathioprine is given concurrently with allopurinol, only one-quarter of the usual dose of

6-mercaptopurine or azathioprine should be given because inhibition of xanthine oxidase will prolong their activity.

Vidarabine (Adenine Arabinoside):

Evidence suggests that the plasma half-life of vidarabine is increased in the presence of allopurinol. When the two medicinal

products are used concomitantly extra vigilance is necessary, to recognise enhanced toxic effects.

Salicylates and uricosuric medicinal products:

Oxipurinol, the metabolite of allopurinol and itself therapeutically active, is excreted by the kidney in a similar way to urate.

Hence, medicinal products with uricosuric activity such as probenecid or large doses of salicylate may accelerate the excretion

of oxipurinol. This may decrease the therapeutic activity of allopurinol, but the significance needs to be assessed in each case.

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Chlorpropamide:

If allopurinol is given concomitantly with chlorpropamide when renal function is poor, there may be an increased risk of

prolonged hypoglycaemic activity because allopurinol and chlorpropamide may compete for excretion in the renal tubule.

Coumarin anticoagulants:

There have been rare reports of increased effect of warfarin and other coumarin anticoagulants when co-administered with

allopurinol, therefore, all patients receiving anticoagulants must be carefully monitored.

Phenytoin:

Allopurinol may inhibit hepatic oxidation of phenytoin but the clinical significance has not been demonstrated.

Theophylline:

Inhibition of the metabolism of theophylline has been reported. The mechanism of the interaction may be explained by

xanthine oxidase being involved in the biotransformation of theophylline in man. Theophylline levels should be monitored in

patients starting or increasing allopurinol therapy.

Ampicillin/Amoxicillin:

An increase in the frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently

with allopurinol compared to patients who are not receiving both medicinal products. The cause of the reported association

has not been established. However, it is recommended that in patients receiving allopurinol an alternative to ampicillin or

amoxicillin is used where available.

Cytostatics:

With administration of allopurinol and cytotoxic medicinal products (e.g. cyclophosphamide, doxorubicin, bleomycin,

procarbazine, alkyl halogenides), blood dyscrasias occur more frequently than when these active substances are administered

alone. Blood count monitoring should therefore be performed at regular intervals.

Cyclosporin:

Reports suggest that the plasma concentration of cyclosporin may be increased during concomitant treatment with allopurinol.

The possibility of enhanced cyclosporin toxicity should be considered if the medicinal products are co-administered.

Didanosine:

In healthy volunteers and HIV patients receiving didanosine, plasma didanosine Cmax and AUC values were approximately

doubled with concomitant allopurinol treatment (300 mg daily) without affecting terminal half-life. Therefore, dose reductions

of didanosine may be required when used concomitantly with allopurinol.

Diuretics:

An interaction between allopurinol and furosemide that results in increased serum urate and plasma oxipurinol concentrations

has been reported.

An increased risk of hypersensitivity has been reported when allopurinol is given with diuretics, in particular thiazides,

especially in renal impairment.

Angiotensin-converting-enzyme (ACE) inhibitors:

An increased risk of hypersensitivity has been reported when allopurinol is given with ACE inhibitors especially in renal

impairment.

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Aluminium hydroxide

If aluminium hydroxide is taken concomitantly, allopurinol may have an attenuated effect. There should be an interval of at

least 3 hours between taking both medicinal products.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is insufficient evidence of safety of allopurinol in human pregnancy. Animal reproductive toxicity studies have shown

conflicting results (see section 5.3).

Allopurinol should be used in pregnancy only when there is no safer alternative and when the disease itself carries risks for the

mother or unborn child.

Breastfeeding

Allopurinol and its metabolite oxipurinol is excreted in the human breast milk. Allopurinol during breastfeeding is not

recommended.

4.7 Effects on ability to drive and use machines

Since adverse reactions such as somnolence, vertigo and ataxia have been reported in patients receiving allopurinol, patients

should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain

that allopurinol does not adversely affect performance.

4.8 Undesirable effects

For this medicinal product there is no modern clinical documentation which can be used as support for determining the

frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also

when given in combination with other medicinal products.

The frequency categories assigned to the adverse drug reactions below are estimates: for most reactions, suitable data for

calculating incidence are not available. Adverse drug reactions identified through post-marketing surveillance were considered

to be rare or very rare. The following convention has been used for the classification of frequency:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Adverse reactions in association with allopurinol are common, uncommon, rare in the overall treated population and mostly of

a minor nature. The incidence is higher in the presence of renal and/or hepatic disorder.

System Organ Class

Frequency

Adverse reactions

Infections and infestations

Very rare

Furuncle

Blood and lymphatic system disorders

Very rare

Agranulocytosis

Granulocytosis

Aplastic anaemia

Thrombocytopenia

Leukopenia

Leukocytosis

Eosinophilia

Pure red cell aplasia

Immune system disorders

Uncommon

Hypersensitivity

Very rare

Angioimmunoblastic T-cell lymphoma

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Anaphylactic reaction

Metabolism and nutrition disorders

Very rare

Diabetes mellitus

Hyperlipidaemia

Psychiatric disorders

Very rare

Depression

Nervous system disorders

Very rare

Coma

Paralysis

Ataxia

Neuropathy peripheral

Paraesthesia

Somnolence

Headache

Dysgeusia

Eye disorders

Very rare

Cataract

Visual impairment

Maculopathy

Ear and labyrinth disorders

Very rare

Vertigo

Cardiac disorders

Very rare

Angina pectoris

Bradycardia

Vascular disorders

Very rare

Hypertension

Gastrointestinal disorders

Uncommon

Vomiting

Nausea

Diarrhoea

Very rare

Haematemesis

Steatorrhoea

Stomatitis

Change of bowel habit

Hepatobiliary disorders

Uncommon

Liver function test abnormal

Rare

Hepatitis (including hepatic necrosis and

granulomatous hepatitis)

Skin and subcutaneous tissue disorders

Common

Rash

Rare

Stevens-Johnson syndrome/toxic epidermal necrolysis

Very rare

Angioedema

Drug eruption

Alopecia

Hair colour changes

Musculoskeletal and connective tissue disorders

Very rare

Muscle pain

Renal and urinary disorders

Rare

Urolithiasis

Very rare

Haematuria

Azotaemia

Reproductive system and breast disorders

Very rare

Infertility male

Erectile dysfunction

Gynaecomastia

General disorders and administration site conditions

Very rare

Oedema

Malaise

Asthenia

Pyrexia

Investigations hormone increased

Common

Blood thyroid stimulating

1. Very rare reports have been received of thrombocytopenia, agranulocytosis and aplastic anaemia, particularly in individuals

with impaired renal and/or hepatic function, reinforcing the need for particular care in this group of patients.

2. A delayed multi-organ hypersensitivity disorder (known as hypersensitivity syndrome or DRESS) with fever, rashes, vasculitis,

lymphadenopathy, pseudo lymphoma, arthralgia, leucopenia, eosinophilia hepato-splenomegaly, abnormal liver function tests,

and vanishing bile duct syndrome (destruction and disappearance of the intrahepatic bile ducts) occurring in various

combinations. Other organs may also be affected (e.g. liver, lungs, kidneys, pancreas, myocardium, and colon). If such reactions

do occur, it may be at any time during treatment, allopurinol should be withdrawn immediately and permanently. Rechallenge

should not be undertaken in patients with hypersensitivity syndrome and SJS/TEN. Corticosteroids may be beneficial in

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overcoming hypersensitivity skin reactions. When generalised hypersensitivity reactions have occurred, renal and/or hepatic

disorder has usually been present particularly when the outcome has been fatal.

3. Angioimmunoblastic T-cell lymphoma has been described very rarely following biopsy of a generalized lymphadenopathy. It

appears to be reversible on withdrawal of allopurinol.

4. In early clinical studies, nausea and vomiting were reported. Further reports suggest that this reaction is not a significant

problem and can be avoided by taking allopurinol after meals.

5. Hepatic dysfunction has been reported without overt evidence of more generalised hypersensitivity.

6. Skin reactions are the most common reactions and may occur at any time during treatment. They may be pruritic,

maculopapular, sometimes scaly, sometimes purpuric and rarely exfoliative, such as Stevens-Johnson syndrome and toxic

epidermal necrolysis (SJS/TEN). Allopurinol should be withdrawn IMMEDIATELY should such reactions occur. The highest risk

for SJS and TEN, or other serious hypersensitivity reactions, is within the first weeks of treatment. The best results in managing

such reactions come from early diagnosis and immediate discontinuation of any suspect drug. After recovery from mild

reactions, allopurinol may, if desired, be re-introduced at a small dose (e.g. 50 mg/day) and gradually increased. The

HLA-B*5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity syndrome

and SJS/TEN. The use of genotyping as a screening tool to make decisions about treatment with allopurinol has not been

established. If the rash reoccurs, allopurinol should be permanently withdrawn as more severe hypersensitivity reactions may

occur (see section 4.8 Immune system disorders). If SJS/TEN, or other serious hypersensitivity reactions cannot be ruled out,

allopurinol should not be reintroduced due to the potential for a severe or even fatal reaction. The clinical diagnosis of SJS/TEN,

or other serious hypersensitivity reactions remain the basis for decision making.

7. Angioedema has been reported to occur with and without signs and symptoms of a more generalised allopurinol

hypersensitivity reaction.

8. Fever has been reported to occur with and without signs and symptoms of a more generalised allopurinol hypersensitivity

reaction (see section 4.8 Immune system disorders).

9. The occurrence of increased thyroid stimulating hormone (TSH) in the relevant studies did not report any impact on free T4

levels or had TSH levels indicative of subclinical hypothyroidism.

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6767836;

Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

Symptoms and Signs:

Ingestion of up to 22.5g allopurinol without adverse effect has been reported. Symptoms and signs including nausea, vomiting,

diarrhoea and dizziness have been reported in a patient who ingested 20g allopurinol. Recovery followed general supportive

measures.

Management:

Massive absorption of allopurinol may lead to considerable inhibition of xanthine oxidase activity, which should have no

untoward effects unless affecting concomitant medication especially with 6-mercaptopurine and/or azathioprine. Adequate

hydration to maintain optimum diuresis facilitates excretion of allopurinol and its metabolites. If considered necessary

haemodialysis may be used.

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5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antigout preparations; Preparations inhibiting uric acid production

ATC code: M04AA01

Mechanism of action

Allopurinol is a xanthine-oxidase inhibitor. Allopurinol and its main metabolite oxipurinol lower the level of uric acid in plasma

and urine by inhibition of xanthine oxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to

uric acid.

Pharmacodynamic effects

In addition to the inhibition of purine catabolism, in some but not all hyperuricaemic patients, de novo purine biosynthesis is

depressed via feedback inhibition of hypoxanthine-guanine hosphoribosyltransferase. Other metabolites of allopurinol include

allopurinol-riboside and xipurinol-7-riboside.

5.2 Pharmacokinetic properties

Absorption

Allopurinol is active when given orally and is rapidly absorbed from the upper gastrointestinal tract. Studies have detected

allopurinol in the blood 30-60 minutes after dosing. Estimates of bioavailability vary from 67% to 90%. Peak plasma levels of

allopurinol generally occur approximately 1.5 hours after oral administration of Allopurinol, but fall rapidly and are barely

detectable after 6 hours. Peak plasma levels of oxipurinol generally occur 3-5 hours after oral administration of Allopurinol and

are much more sustained.

Distribution

Allopurinol is negligibly bound by plasma proteins and therefore variations in protein binding are not thought to significantly

alter clearance. The apparent volume of distribution of allopurinol is approximately 1.6 litre/kg which suggests relatively

extensive uptake by tissues. Tissue concentrations of allopurinol have not been reported in humans, but it is likely that

allopurinol and oxipurinol will be present in the highest concentrations in the liver and intestinal mucosa where xanthine

oxidase activity is high.

Biotransformation

The main metabolite of Allopurinol is oxipurinol. Other metabolites of allopurinol include allopurinol-riboside and

oxipurinol-7-riboside.

Elimination

Approximately 20% of the ingested allopurinol is excreted in the faeces. Elimination of allopurinol is mainly by metabolic

conversion to oxipurinol by xanthine oxidase and aldehyde oxidase, with less than 10% of the unchanged allopurinol excreted

in the urine. Allopurinol has a plasma half-life of about 0.5 to 1.5 hours.

Oxipurinol is a less potent inhibitor of xanthine oxidase than allopurinol, but the plasma half-life of oxipurinol is far more

prolonged. Estimates range from 13 to 30 hours in man. Therefore effective inhibition of xanthine oxidase is maintained over a

24 hour period with a single daily dose of Allopurinol. Patients with normal renal function will gradually accumulate oxipurinol

until a steady-state plasma oxipurinol concentration is reached. Such patients, taking 300 mg of allopurinol per day will

generally have plasma oxipurinol concentrations of 5-10mg/litre.

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Oxipurinol is eliminated unchanged in the urine but has a long elimination half-life because it undergoes tubular reabsorption.

Reported values for the elimination half-life range from 13.6 hours to 29 hours. The large discrepancies in these values may be

accounted for by variations in study design and/or creatinine clearance in the patients.

Pharmacokinetics in patients with renal impairment

Allopurinol and oxipurinol clearance is greatly reduced in patients with poor renal function resulting in higher plasma levels in

chronic therapy. Patients with renal clearance values were between 10 and 20 ml/min, showed plasma oxipurinol

concentrations of approximately 30 mg/litre after prolonged treatment with 300 mg allopurinol per day. This is approximately

the concentration which would be achieved by doses of 600 mg/day in those with normal renal function. A reduction in the

dose of Allopurinol is therefore required in patients with renal impairment.

Pharmacokinetics in elderly patients

The kinetics of the allopurinol are not likely to be altered other than due to deterioration in renal function (see section 5.2

Pharmacokinetics in patients with renal impairment).

5.3 Preclinical safety data

In animal experiments, long-term application of high doses of allopurinol resulted in formation of xanthin precipitates

(urolithiasis), which led to morphological changes in uriniferous organs.

Mutagenicity:

Cytogenetic studies show that allopurinol does not induce chromosome aberrations in human blood cells in vitro at

concentrations up to 100 μg/ml and in vivo at doses up to 600 mg/day for a mean period of 40 months.

Allopurinol does not produce nitroso compounds in vitro or affect lymphocyte transformation in vitro.

Evidence from biochemical and other cytological investigations strongly suggests that allopurinol has no deleterious effects on

DNA at any stage of the cell cycle and is not mutagenic.

Carcinogenicity:

No evidence of carcinogenicity has been found in mice and rats treated with allopurinol for up to 2 years.

Reproductive toxictiyy:

One study in mice receiving intraperitoneal doses of 50 or 100mg/kg on days 10 or 13 of gestation resulted in foetal

abnormalities, however in a similar study in rats at 120 mg/kg on day 12 of gestation, no abnormalities were observed.

Extensive studies of high oral doses of allopurinol in mice up to 100 mg/kg/day, rats up to 200 mg/kg/day and rabbits up to

150 mg/kg/day, during days 8 to 16 of the gestation, produced no teratogenic effects.

An in vitro study using foetal mouse salivary glands in culture to detect embryotoxicity indicated that allopurinol would not be

expected to cause embryotoxicity without also causing maternal toxicity.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate

Crospovidone Type B

Maize starch

Povidone K 30

Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

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6.4 Special precautions for storage

Store below 30°C.

6.5 Nature and contents of container

PVC-ALU blister containing 25, 28, 30, 50, 60, 90 and 100 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Accord Healthcare Ireland Ltd.

Euro House

Euro Business Park

Little Island

Cork T45 K857

Ireland

8 MARKETING AUTHORISATION NUMBER

PA2315/219/002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 19

July 2019

10 DATE OF REVISION OF THE TEXT

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