Consumer medicine information

Zyloprim

Allopurinol

BRAND INFORMATION

Brand name

Zyloprim

Active ingredient

Allopurinol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Zyloprim.

SUMMARY CMI

ZYLOPRIM

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ZYLOPRIM?

ZYLOPRIM contains the active ingredient allopurinol. ZYLOPRIM is used to treat:

  • gouty arthritis or gout
  • kidney stones
  • rare conditions where high levels of uric acid occur in the blood (for example, Lesch-Nyhan syndrome).

For more information, see Section 1. Why am I using ZYLOPRIM? in the full CMI.

2. What should I know before I use ZYLOPRIM?

Do not use if you have ever had an allergic reaction to ZYLOPRIM or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use ZYLOPRIM? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ZYLOPRIM and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ZYLOPRIM?

  • Swallow the tablets whole with a full glass of water.
  • The usual adult dose range is: 100 - 200 mg per day for mild conditions, 300 - 600 mg per day for moderately severe conditions, 700 - 900 mg per day for severe conditions.
  • People over 65 years of age, and those with kidney and/or liver problems should be started on the lowest dose possible to control uric acid production.
  • Children under 15 years of age usually take 100 - 400 mg per day.

More instructions can be found in Section 4. How do I use ZYLOPRIM? in the full CMI.

5. What should I know while using ZYLOPRIM?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ZYLOPRIM
  • Drink at least two litres (8 - 10 glasses) of fluid each day
  • Tell your doctor if you have an acute attack of gout while you are taking ZYLOPRIM
  • Tell your doctor immediately. If you become pregnant or plan to breastfeed while taking this medicine.
Things you should not do
  • Do not use this medicine to treat any other complaints unless your doctor tells you to
  • Do not stop using this medicine or lower the dosage without checking with your doctor
  • Do not give this medicine to anyone else, even if they have the same condition as you.
Driving or using machines
  • ZYLOPRIM may cause dizziness, drowsiness, lack of co-ordination in some people. Make sure you know how you are affected by this medicine before you drive or use machinery.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep ZYLOPRIM in a cool dry place where the temperature will stay below 25°C.

For more information, see Section 5. What should I know while using ZYLOPRIM? in the full CMI.

6. Are there any side effects?

Stomach upsets, including nausea, vomiting, dizziness, drowsiness, headache, change in taste sensation, sleeplessness, hair loss. Serious side effects: changes in vision, tingling or numbness of the hands or feet, a change in the amount of urine passed, yellowing of the skin and eyes (jaundice), generally feeling of being unwell or depressed frequent infections such as fever, severe chills, sore throat or mouth ulcers, bleeding or bruising more easily angina or palpitations, swelling of the hands, ankles or legs. Very serious side effects: asthma, wheezing or shortness of breath, swelling of the face, lips, tongue or throat which may cause difficulty in breathing, sudden or severe itching, skin, rash or hives, other skin problems, fainting, seizures or fits, pain or tightness in the chest.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ZYLOPRIM

Active ingredient(s): allopurinol

Consumer Medicine Information (CMI)

This leaflet provides important information about using ZYLOPRIM. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ZYLOPRIM.

Where to find information in this leaflet:

1. Why am I using ZYLOPRIM?
2. What should I know before I use ZYLOPRIM?
3. What if I am taking other medicines?
4. How do I use ZYLOPRIM?
5. What should I know while using ZYLOPRIM?
6. Are there any side effects?
7. Product details

1. Why am I using ZYLOPRIM?

ZYLOPRIM contains the active ingredient allopurinol.

ZYLOPRIM is used to treat:

  • gouty arthritis or gout
  • kidney stones
  • rare conditions where high levels of uric acid occur in the blood (for example, Lesch-Nyhan syndrome).

It belongs to a group of medicines called anti-uricaemic agents.

This medicine works by reducing the production of uric acid in the body, therefore helping to prevent the formation of deposits of uric acid crystals. Deposits of uric acid crystals in the body can cause a variety of medical problems.

High levels of uric acid may cause gout attacks or kidney stones. Allopurinol is used to prevent gout attacks, not to treat them once they occur.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

Use in children

There is not enough information to recommend the use of this medicine for children.

2. What should I know before I use ZYLOPRIM?

Warnings

Do not use ZYLOPRIM if:

  • You are allergic to allopurinol, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • You or a member of your immediate family has been diagnosed with haemochromatosis (a disease involving too much iron in the body) and you are taking iron salts.

Check with your doctor if you:

  • had or have any other medical conditions including:
    - kidney problems, including kidney stones
    - liver problems
    - high blood pressure
    - heart problems
    - conditions where the levels of uric acid are abnormally high
    - cancer or tumours
    - thyroid problems.
    - diabetes
    - epilepsy

Tell your doctor if you are currently having an attack of gout.

Treatment with allopurinol should not be started until the attack has stopped, otherwise more attacks may occur.

(However, if an attack of gout occurs when a person is already taking allopurinol, it can be continued).

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Allopurinol passes into breast milk and may affect your baby. Your doctor can discuss with you the risks and benefits involved.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with ZYLOPRIM and affect how it works.

  • some medicines used to treat high blood pressure or heart problems
  • thiazide diuretics (a certain type of water tablet)
  • mercaptopurine, azathioprine or cyclosporin - medicines used to suppress the immune system
  • aspirin and other medicines known as salicylates
  • probenicid, a medicine used to treat gout or hyperuricaemia (high levels of uric acid in the blood).
  • warfarin and other coumarin type anticoagulant medicines, used to help prevent blood clots
  • chlorpropamide, a medicine used to treat diabetes
  • phenytoin, a medicine used to treat epilepsy
  • certain antibiotics such as ampicillin and amoxycillin
  • theophylline, a medicine used to treat asthma
  • aluminium hydroxide, a medicine used to treat the symptoms of too much stomach acid
  • adenine arabinoside ('Vidarabine'), an anti-viral medicine
  • medicines used for cancer (e.g. cyclophosphamide, doxorubicin)
  • didanosine, used to treat HIV infection.

Other medicines not listed above may also interact with allopurinol.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ZYLOPRIM.

4. How do I use ZYLOPRIM?

How much to take / use

  • Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines
  • Follow the instructions provided and use ZYLOPRIM until your doctor tells you to stop.
  • The usual adult dose range is:
    - 100 - 200 mg per day for mild conditions
    - 300 - 600 mg per day for moderately severe conditions
    - 700 - 900 mg per day for severe conditions.
  • People over 65 years of age, and those with kidney and/or liver problems should be started on the lowest dose possible to control uric acid production.
  • Children under 15 years of age usually take 100 - 400 mg per day.

How to take ZYLOPRIM

Swallow the tablets whole with a full glass of water.

When to take / use ZYLOPRIM

  • ZYLOPRIM should be used immediately after food, as this will lessen the chance of a stomach upset.
  • Take your medicine at the same time each day.
    Taking your medicine at the same time each day will have the best effect. It will also help you remember when to take it.
  • ZYLOPRIM is usually taken once daily. However, if your dose is more than 300 mg, your doctor may advise you to take your medicine twice a day. Then, it should be taken morning and night, after breakfast and dinner.

How to long to take ZYLOPRIM

Continue taking ZYLOPRIM for as long as your doctor tells you.

ZYLOPRIM helps to control your condition but does not cure it. It is important to keep taking ZYLOPRIM even if you feel well.

Make sure you have enough to last over weekends and holidays.

If you forget to use ZYLOPRIM

ZYLOPRIM should be used regularly at the same time each day.

If it is less than 4 hours to your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed.

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you use too much ZYLOPRIM

If you think that you have used too much ZYLOPRIM, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

  • nausea
  • vomiting
  • diarrhoea
  • dizziness.

5. What should I know while using ZYLOPRIM?

Things you should do

You should drink at least two litres (8 - 10 glasses) of fluid each day.

This will assist in reducing the uric acid levels in your body and prevent kidney stones from forming.

Tell your doctor if you have an acute attack of gout while you are taking ZYLOPRIM.

Your doctor may prescribe a medicine to relieve the acute attack. You can continue taking allopurinol.

If you are about to start any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Remind any doctor, dentist or pharmacist you visit that you are using ZYLOPRIM.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this ZYLOPRIM.

If you become pregnant or plan to breastfeed while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you should not do

  • Do not take ZYLOPRIM to treat any other complaints unless your doctor tells you to.
  • Do not give ZYLOPRIM to anyone else, even if they have the same condition as you
  • Do not stop taking ZYLOPRIM or lower the dosage without checking with your doctor.
  • Do not take ZYLOPRIM to treat an acute attack of gout.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ZYLOPRIM affects you.

ZYLOPRIM may cause (dizziness, drowsiness, lack of co-ordination etc.) in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your medicine in its original packaging until it is time to take it.
  • Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • stomach upsets, including nausea, vomiting or diarrhoea
  • dizziness, drowsiness or unsteadiness when walking
  • change in bowel habits
  • headache
  • change in taste sensation
  • sleeplessness
  • hair loss or change in hair colour
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • changes in vision
  • tingling or numbness of the hands or feet
  • a change in the amount of urine passed, going to the toilet more often or a burning feeling while passing urine
  • blood in your urine
  • yellowing of the skin and eyes (jaundice)
  • generally feeling of being unwell or depressed
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily
  • angina or palpitations
  • swelling of the hands, ankles or legs.

The below list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips, tongue or throat which may cause difficulty in breathing
  • sudden or severe itching, skin
  • rash or hives, other skin problems
  • fainting, seizures or fits
  • pain or tightness in the chest.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What ZYLOPRIM contains

Active ingredient
(main ingredient)		allopurinol
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • maize starch
  • povidone
  • sodium starch glycollate type A
  • sunset yellow FCF
  • stearic acid
Potential allergensContains sugars as lactose

Do not take this medicine if you are allergic to any of these ingredients.

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

What ZYLOPRIM looks like

ZYLOPRIM 100 mg tablets:

White, to off-white, colored round, biconvex uncoated tablets with 'AL' & '100' separated by breakline on one side and plain on the other side.

Bottle (HDPE white opaque bottle with screw cap) of 200's tablets. (Aust R 269649).

ZYLOPRIM 300 mg tablets:

Peach colored, round, biconvex uncoated tablets coded with 'AL' & '300' separated by breakline on one side and plain on other side.

Blister Pack (Clear PVDC/PVC/Aluminium silver foil) of 60's tablets. (Aust R 269645).

* Not all strengths, pack types and/or pack sizes may be available.

Who distributes ZYLOPRIM

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne, 3121 Australia
www.arrotex.com.au

This leaflet was prepared in March 2025.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Zyloprim

Active ingredient

Allopurinol

Schedule

S4

 

1 Name of Medicine

Allopurinol.

2 Qualitative and Quantitative Composition

Each allopurinol tablet contains allopurinol as the active ingredient.

Excipients with known effect.

Lactose monohydrate.
For a full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Zyloprim 100 mg tablets.

White to off white, coloured round biconvex, uncoated tablets with 'AL' and '100' separated by breakline on one side and plain on other side.

Zyloprim 300 mg tablets.

Peach coloured, round, biconvex, uncoated tablets with 'AL' and '300' separated by breakline on one side and plain on other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Main clinical manifestations of urate/uric acid deposition. These are gouty arthritis, skin tophi and/or renal involvement through crystal deposition or stone formation. Such clinical manifestations may occur in: 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 and involve:
hypoxanthine guanine phosphoribosyltransferase including Lesch-Nyhan syndrome;
glucose-6-phosphatase including glycogen storage disease;
phosphoribosylpyrophosphate synthetase;
phosphoribosylpyrophosphate amidotransferase.
Allopurinol is indicated for the management of 2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient activity of adenine phosphoribosyl transferase.
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.

4.2 Dose and Method of Administration

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

Dose frequency.

Allopurinol may be taken orally once a day after a meal. It is well tolerated, especially after food. Should the daily dosage exceed 300 mg and gastrointestinal intolerance be manifested, a divided dose regimen may be appropriate.

Adults.

2 to 10 mg/kg bodyweight/day or 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.

Children under 15 years.

10 to 20 mg/kg bodyweight/day or 100 to 400 mg daily. Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.

Use in the elderly.

In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used. Particular attention should be paid to the dosage advice in renal disorder and precautions.

Renal impairment.

Since allopurinol and its metabolites are excreted by the kidney, impaired renal function may lead to retention of the drug and/or its metabolites with consequent prolongation of plasma half-lives. In the presence of impaired renal function, serious consideration should be given to initiating treatment with a maximum dose of 100 mg/day and increasing it only if the serum and/or urinary urate response is unsatisfactory. In severe renal insufficiency, it may be advisable to use less than 100 mg/day or to use single doses of 100 mg at longer intervals than one day. Alternative schedules based on creatinine clearances are unsatisfactory because of the imprecision of low clearance values.
If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma oxipurinol levels below 100 micromol/L (15.2 microgram/mL).

Renal dialysis.

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 allopurinol 300 to 400 mg immediately after each dialysis with none in the interim.

Dosage in 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).

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. Dosage of allopurinol should be in the lower range.
If urate nephropathy or other pathology has compromised renal function, the advice given in renal impairment (see above) should be followed.
These steps may reduce the risk of xanthine and/or oxipurinol deposition complicating the clinical situation. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

4.3 Contraindications

Allopurinol should not be administered to individuals known to be hypersensitive to allopurinol or to any other components of the formulation (see Section 2 Qualitative and Quantitative Composition; Section 3 Pharmaceutical Form).
Allopurinol should not be given concomitantly with iron salts to patients with idiopathic haemochromatosis, nor should it be given to the immediate relatives of such patients.
Allopurinol is contraindicated in children with the exception of those with hyperuricemia secondary to malignancy or with Lesch-Nyhan syndrome, because safety and efficacy have not been established in other conditions.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs.
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 these patients.
Asymptomatic hyperuricaemia per se is not an indication for the use of allopurinol. Fluid and dietary modifications with management of the underlying cause may correct the condition. If other clinical conditions suggest a need for allopurinol it must be introduced at low dosage (50 to 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 Dose and Method of Administration).
Allopurinol must be withdrawn immediately and permanently at the first signs of intolerance.

Dermatological effects.

Allopurinol should be discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction. In some instances a skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial, and purpuric lesions as well as Stevens-Johnson syndrome (erythema multiforme exudativum), drug rash with eosinophilia and systemic symptoms (DRESS), Lyell's disease, generalised vasculitis, irreversible hepatotoxicity, and on rare occasions death. DRESS is also referred to as drug-induced hypersensitivity syndrome (DIHS) and Lyell's disease is also referred to as toxic epidermal necrolysis.

Hypersensitivity effects.

The occurrence of hypersensitivity reactions to allopurinol may be increased in patients with decreased renal function receiving thiazides and allopurinol concurrently. For this reason, in this clinical setting, such combinations should be administered with caution and patients should be observed closely.

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, as with uricosuric agents, an acute attack of gouty arthritis may be precipitated. Therefore it is advisable to give prophylaxis with a suitable anti-inflammatory agent or colchicine (0.5 mg three times a day) for at least one month.
If acute attacks develop in patients receiving allopurinol, treatment should continue at the same dosage while the acute attack is treated with a suitable anti-inflammatory agent.

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 thyroid stimulating hormone (TSH) values were observed in patients on long-term treatment with allopurinol in a long-term open label extension study. Caution is required when allopurinol is used in patients with alteration of thyroid function.

Haematological effects.

Bone marrow depression has been reported in patients receiving allopurinol, most of whom received concomitant drugs with the potential for causing this reaction. This has occurred as early as six weeks to as long as six years after the initiation of therapy of allopurinol. Rarely a patient may develop varying degrees of bone marrow depression, affecting one or more cell lines, while receiving allopurinol alone.

Haemochromatosis.

Allopurinol's primary action in treating gout is to inhibit the enzyme, xanthine oxidase. Xanthine oxidase may be involved in the reduction and clearance of hepatically stored iron. Some rodent studies have found increased iron storage in animals treated with allopurinol, whilst others have not. A study in 28 healthy volunteers found no change in hepatic iron storage with allopurinol treatment. There are no human studies which have investigated the safety of administering allopurinol to patients with haemochromatosis. Administration of allopurinol to patients with abnormal iron storage, including haemochromatosis, should be undertaken with caution.

Instructions to patients.

Wherever possible a high fluid intake sufficient to yield a daily urinary output of 2 L and the maintenance of a neutral or alkaline urine are desirable in hyperuricaemic patients whether or not they are on allopurinol therapy. Allopurinol is better tolerated if taken after meals.

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 population, 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 the 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 to 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.

Use in hepatic impairment.

A few cases of reversible clinical hepatotoxicity have been noted in patients taking allopurinol, and in some patients asymptomatic rises in serum alkaline phosphatase or serum transaminase have been observed. If anorexia, weight loss, or pruritus develop in patients on allopurinol, evaluation of liver function should be part of their diagnostic workup. In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy.
Reduced doses should be used in patients with hepatic impairment.

Use in renal impairment.

Some patients with pre-existing renal disease or poor urate clearance have shown a rise in serum urea during administration of allopurinol. Although the mechanism responsible for this has not been established, patients with impaired renal function should be carefully observed during the early stages of allopurinol administration and dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist. 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 these patients.
Renal failure in association with administration of allopurinol has been observed among patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions such as multiple myeloma and congestive myocardial disease were present among those patients whose renal dysfunction increased after allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy and rarely with hypersensitivity reactions associated with allopurinol. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis. A dose reduction will be required in patients with renal impairment (see Section 4.2 Dose and Method of Administration).
Patients with chronic renal impairment and concomitant diuretic use, in particular thiazides, may be at increased risk of developing hypersensitivity reactions including SJS/TEN associated with allopurinol. Extra vigilance for the signs of hypersensitivity syndrome or SJS/TEN is required and the patient should be informed of the need to stop treatment immediately and permanently at the first appearance of symptoms.

Use in the elderly.

In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Paediatric use.

Allopurinol is contraindicated in children with the exception of those with hyperuricemia secondary to malignancy or with Lesch-Nyhan syndrome, because safety and efficacy have not been established in other conditions.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

6-Mercaptopurine and azathioprine.

Allopurinol inhibits the oxidative metabolism of azathioprine and mercaptopurine by 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 and increase the possibility of toxic effect. All patients receiving this combination must be carefully monitored. The risk of overdosage is also increased when allopurinol is being given concomitantly with mercaptopurine or azathioprine.

Adenine arabinoside.

Evidence suggests that the plasma half-life of adenine arabinoside is increased in the presence of allopurinol. When the two products are used concomitantly extra vigilance is necessary, to recognise enhanced toxic effects.

Salicylates and uricosuric agents.

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

Didanosine.

Plasma didanosine levels were increased with concomitant allopurinol treatment. Therefore co-administration is not recommended. If concomitant use is unavoidable a dose reduction of didanosine may be required and patients should be closely monitored.

Chlorpropamide and other cytotoxic agents.

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

Coumarin anticoagulants.

Patients may need careful monitoring, as there have been reports of an increased response to oral anticoagulants.

Phenytoin.

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

Theophylline and other xanthines.

Experimental studies of the effect of allopurinol on theophylline metabolism have produced contradictory findings. Inhibition of the metabolism of theophylline has been reported. 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 drugs. 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 cytostatics (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.

Ciclosporin.

Reports suggest that the plasma concentration of ciclosporin may be increased during concomitant treatment with allopurinol. The possibility of enhanced ciclosporin toxicity should be considered if the drugs are co-administered.

Angiotensin-converting-enzyme (ACE) inhibitors.

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

Diuretics.

Thiazide diuretics may increase the risk of serous allopurinol toxicity, including hypersensitivity reactions and the combination should be monitored, especially if renal function is compromised.

Antacids.

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 medicines.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Reproduction studies in rabbits and rats using dosages up to 20 times the usual human dosage have not revealed any evidence of impaired fertility. Only rarely has infertility in human males and impotence occurred during allopurinol therapy, however a causal relationship to the drug has not been established.
(Category B2)
There is inadequate evidence of safety of allopurinol in human pregnancy, although it has been in wide use for many years without apparent ill consequence.
One study in mice receiving a high intraperitoneal dose on days 10 to 13 of pregnancy resulted in foetal abnormalities but extensive studies of high oral doses in mice, rats and rabbits during days 8 to 16 produced none.
Use in pregnancy only when there is no safe alternative and when the disease itself carries risks for the mother or child.
 Reports indicate that allopurinol and its metabolite, oxipurinol, are excreted in human breast milk. Concentrations of 1.5 mg/L allopurinol and 53.7 mg/L oxipurinol have been demonstrated in breast milk from a woman taking allopurinol 300 mg/day. There are, however, no data concerning the effects of allopurinol, or its metabolism, on the breast-fed child. 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 where alertness is mandatory until they are reasonably certain that allopurinol does not adversely affect performance.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions are usually reversed by the reduction of dosage or complete withdrawal of allopurinol. Taking allopurinol after meals may minimise gastrointestinal disturbances. Where hypersensitivity reactions occur, allopurinol should be withdrawn immediately. Corticosteroids may be beneficial in overcoming such reactions.
Adverse reactions in association with allopurinol are 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.

Dermatological.

These 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). 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. Allopurinol should be withdrawn immediately should such reactions occur. After recovery from mild reactions, allopurinol may, if desired, be reintroduced at a small dose (e.g. 50 mg/day) and gradually increased. If the rash recurs, allopurinol should be permanently withdrawn as more severe hypersensitivity reactions may occur. If SJS/TEN, or other serious hypersensitivity reactions cannot be ruled out, do not re-introduce allopurinol due to the potential for a severe or even fatal reaction. The clinical diagnosis of SJS/TEN remains the basis for decision making. If such reactions occur at any time during treatment, allopurinol should be withdrawn immediately and permanently.
Lichenoid drug reaction has been identified as an undesirable effect with a 'not known' frequency.

Generalised hypersensitivity.

Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia resembling Stevens-Johnson and/or Lyell's disease (toxic epidermal necrolysis) occur rarely. Drug rash with eosinophilia and systemic symptoms (DRESS) (drug-induced hypersensitivity syndrome (DIHS)) also occurs rarely.
Associated vasculitis and tissue response may be manifested in various ways including hepatitis, interstitial nephritis and, very rarely, epilepsy. If such reactions do occur, it may be at any time during treatment. Allopurinol should be withdrawn immediately and permanently.
Corticosteroids may be beneficial in 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.
Very rarely acute anaphylactic shock has been reported.

Angioimmunoblastic lymphadenopathy.

Angioimmunoblastic lymphadenopathy has been described rarely following biopsy of a generalised lymphadenopathy. It appears to be reversible on withdrawal of allopurinol.

Hepatic function.

Rare reports of hepatic dysfunction ranging from asymptomatic rises in liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis) have been reported without overt evidence of more generalised hypersensitivity. Granulomatous hepatitis appears to be reversible on withdrawal of allopurinol.

Gastrointestinal.

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. Recurrent haematemesis has been reported as an extremely rare event as has steatorrhoea.

Haematological.

Bone marrow depression has been reported in patients receiving additional medications during allopurinol therapy. However, rarely has a patient receiving allopurinol alone, acquired one or more of their cell lines to be affected by bone marrow depression. There have been occasional reports of transient reduction in the numbers of circulating formed elements of the blood, usually in association with renal and/or hepatic disorder. Adverse effects such as leukocytosis, leukopenia, eosinophilia, thrombocytopenia, aplastic anaemia, agranulocytosis and granulocytopenia, have occurred very rarely. The clinical significance has yet to be demonstrated.

Other.

The following complaints have been reported occasionally: fever, general malaise, asthenia, headache, vertigo, ataxia, somnolence, dysgeusia, coma, depression, paralysis, paraesthesia, neuropathy, visual disorder, cataract, macular changes, taste perversion, stomatitis, changed bowel habit, infertility, impotence, nocturnal emission, diabetes mellitus, hyperlipidaemia, furunculosis, alopecia, discoloured hair, angina, hypertension, bradycardia, oedema, pyrexia, uraemia, haematuria, azotaemia, angioedema and gynaecomastia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Accidental or deliberate ingestion of up to 5 g of allopurinol or very rarely 20 g, has been reported.

Symptoms.

These include nausea, vomiting, diarrhoea and dizziness.

Treatment.

Recovery followed general supportive measures.
Massive absorption of allopurinol may lead to considerable inhibition of xanthine oxidase activity, which should have no untoward effects unless 6-mercaptopurine and/or azathioprine is being taken concomitantly. Adequate hydration to maintain optimum diuresis facilitates excretion of allopurinol and its metabolites. If considered necessary, haemodialysis may be used.
Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Allopurinol inhibits xanthine oxidase, the enzyme which catalyses the conversion of hypoxanthine to xanthine, and of xanthine to urate/uric acid. See Figure 1.
Allopurinol decreases urate formation in two ways:
1. The inhibition of xanthine oxidase reduces the amount of hypoxanthine and xanthine converted to urate/uric acid.
2. This action makes more hypoxanthine and xanthine available for reutilisation in the purine metabolic cycle, which in turn, by a feedback mechanism, decreases overall de novo purine formation.
Since allopurinol decreases urate formation, it reduces urate/uric acid concentrations in both body fluids and urine. In contrast, the uricosuric agents which increase urate/uric acid excretion via the kidney will reduce the urate concentration in body fluids, but increase urate/uric acid concentration in urine. Reduction of the urate concentrations in body fluids by allopurinol permits mobilisation and dissolution of urate deposits anywhere in the body, the commonest sites being those in the skin, bones, joints and kidney interstitial tissue.
Therapeutic effects therefore include: the resolution of skin tophi and the healing of urate sinuses; eventual reduction in the frequency of attacks of acute gouty arthritis, improvement in joint mobility; reduction of the urate load to be excreted via the kidney; prevention and treatment of acute uric acid nephropathy; and, in the long-term, reduced risk of renal impairment by urate/uric acid and prevention and dissolution of uric acid renal stones.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Allopurinol is approximately 90% absorbed from the gastrointestinal tract.

Distribution.

Allopurinol is uniformly distributed in total tissue water with the exclusion of the brain, where concentrations of the drugs are approximately 50% those of other tissues. Within muscle, small amounts of allopurinol and oxypurinol crystals have been found. Allopurinol and oxypurinol are not bound to plasma proteins. Allopurinol and oxypurinol are distributed into breast milk.

Metabolism.

Allopurinol is rapidly converted in the body to the pharmacologically active principal metabolite oxypurinol and other metabolites including allopurinol riboside and oxypurinol-7-riboside. Peak plasma levels generally occur at 1.5 hours and 4.5 hours for allopurinol and oxypurinol respectively. Oxypurinol is also an inhibitor of xanthine oxidase.

Excretion.

The renal clearance of hypoxanthine and xanthine is at least 10 times greater than that of uric acid. The increased xanthine and hypoxanthine in the urine have not been accompanied by problems of nephrolithiasis.
Approximately 20% of the ingested allopurinol is excreted in the faeces. Because of its rapid oxidation to oxypurinol and a renal clearance rate approximately that of glomerular filtration rate, allopurinol has a plasma half-life of about 1 to 2 hours. Little allopurinol is found in the urine 6 hours after administration. Allopurinol and oxypurinol are mainly excreted in the urine. Oxypurinol, however, has a longer plasma half-life (approximately 15.0 hours) and therefore effective xanthine oxidase inhibition is maintained over a 24 hour period with single daily doses of allopurinol. Whereas allopurinol is cleared essentially by glomerular filtration, oxypurinol is reabsorbed in the kidney tubules in a manner similar to the reabsorption of uric acid.

5.3 Preclinical Safety Data

Genotoxicity/ carcinogenicity.

No data is available on whether or not allopurinol has mutagenic or carcinogenic effects within humans or animals. Cytogenetic studies show that allopurinol does not induce chromosome aberrations in human blood cells in vitro at concentrations up to 100 microgram/mL and in vivo at doses up to 600 mg/day for mean period of 40 months.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet contains the following inactive ingredients: lactose monohydrate, maize starch, povidone, sodium starch glycollate type A, sunset yellow FCF, stearic acid.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Zyloprim 100 mg tablets.

Bottle (HDPE white opaque bottle with screw cap) of 200 tablets (AUST R 269649).

Zyloprim 300 mg tablets.

Blister pack (Clear PVDC/PVC/Aluminium silver foil) of 60 tablets (AUST R 269645).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Allopurinol is a white or off-white, almost odourless powder. It is very slightly soluble in water and in alcohol, and is practically insoluble in chloroform and in ether. It dissolves in dilute solutions of alkali hydroxides.

Chemical structure.


Chemical name: 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one.
Molecular formula: C5H4N4O.
Molecular weight: 136.1.

CAS number.

315-30-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes