Consumer medicine information

Allmercap

Mercaptopurine monohydrate

BRAND INFORMATION

Brand name

Allmercap

Active ingredient

Mercaptopurine monohydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Allmercap.

SUMMARY CMI

ALLMERCAP®

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 ALLMERCAP®?

ALLMERCAP® contains mercaptopurine monohydrate as the active ingredient. ALLMERCAP® is used solely or in combination with other medicines to treat acute leukaemia, a cancer of certain blood cells.

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

2. What should I know before I take ALLMERCAP®?

Do not use if you have ever had an allergic reaction to mercaptopurine monohydrate or any of the oral liquid suspension ingredients listed at the end of this CMI.

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

For more information, see Section 2. What should I know before I take ALLMERCAP®? in the full CMI.

3. What if I am taking other medicines?

Some medicines may be affected by ALLMERCAP® or may affect how well 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 take ALLMERCAP®

  • ALLMERCAP® is taken in the evening as an oral liquid suspension.
  • Your doctor will decide what dose and for how long you will be taking ALLMERCAP® depending on factors such as your age and weight, pre-existing medical condition, whether you are taking any other medications, and your response to treatment.

More instructions can be found in Section 4. How do I take ALLMERCAP®? in the full CMI.

5. What should I know while taking ALLMERCAP®?

Things you must do
  • Tell your doctor if, for any reason, you have not taken your medicine exactly as directed.
  • Tell any other specialist, doctor, dentist or pharmacist that you are on ALLMERCAP®.
  • Tell your doctor if you become pregnant, are trying to become pregnant or trying to father a child.
  • Use a sunscreen with a high SPF and protective clothing and limit exposure to sunlight and UV light.
Things you must not do
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use ALLMERCAP® to treat any other complaints unless your doctor says to.
Driving or using machines
  • Be careful driving or operating machinery until you know how ALLMERCAP® affects you.
Looking after your medicine
  • Keep it in a cool, dry place, protected from light, where the temperature stays below 25°C.
  • Do not leave it in a car, on window sills, near a sink or in the bathroom.
  • Keep it where children cannot reach it.

For more information, see Section 5. What should I know while taking ALLMERCAP®? in the full CMI.

6. Are there any side effects?

If you get any of the following side effects, tell your doctor immediately or go to Accident and Emergency at your nearest hospital: wheezing, swelling of the lips/mouth, difficulty in breathing, lumpy rash (hives), fainting, sudden abdominal pain with nausea and vomiting.

Tell your doctor if you notice any of the following: nausea and vomiting, diarrhoea, fever, severe chills, sore throat or mouth ulcers, bruising or bleeding more easily than normal, loss of appetite and/or weight loss, jaundice, tiredness, headache, shortness of breath, dizziness, looking pale, painful/swollen joints, skin rash, hair loss, skin nodules.

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

ALLMERCAP®

Active ingredient(s): mercaptopurine monohydrate

Consumer Medicine Information (CMI)

This leaflet answers some common questions about ALLMERCAP®. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking ALLMERCAP® against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

Where to find information in this leaflet:

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

1. Why am I using ALLMERCAP®?

ALLMERCAP® contains mercaptopurine monohydrate as the active ingredient. It belongs to a group of medicines called cytotoxics (also called chemotherapy).

ALLMERCAP® is used alone or in combination with other medicines to treat acute leukaemia, a cancer of certain blood cells.

It works by interfering with the growth of cancer cells.

Ask your doctor if you have any questions about why ALLMERCAP® has been prescribed for you.

2. What should I know before I take ALLMERCAP®?

Warnings

When you must not take it

Do not take ALLMERCAP® if you have ever had an allergic reaction to:

  • Mercaptopurine monohydrate
  • any of the oral liquid suspension ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty in breathing; swelling of the face, lips, tongue or any other parts of the body; rash, itching or hives on the skin.

Always check the ingredients to make sure you can use this medicine.

Do not receive the yellow fever vaccine whilst you are taking ALLMERCAP®.

Do not take ALLMERCAP® after the expiry date printed on the bottle.

If you take it after the expiry (EXP) date has passed, it may not work as well.

Do not take it if the packaging is torn or shows signs of tampering.

ALLMERCAP® contains aspartame (E951), hydroxybenzoates and sorbates.

Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

Low blood sugar has sometimes been seen in children, mainly in children under the age of six or with a low body mass index. Common symptoms of low blood sugar include, but are not limited to, fast heart rate, shaking, sweating, hunger, confusion and loss of consciousness. Talk to your child's doctor if this happens.

Check with your doctor if you:

  • are allergic to any other medicines or any other foods, dyes or preservatives.
  • have received the yellow fever vaccine.

Tell your doctor if you have or have had any of the following conditions:

  • have recently received or are receiving radiotherapy or chemotherapy
  • have recently been vaccinated or are planning to be vaccinated
  • have chickenpox, shingles or hepatitis B (a liver disease caused by a virus)
  • have kidney or liver disease
  • have a condition where your body produces too little of a natural chemical called thiopurine methyltransferase (TPMT).
  • have inflammatory bowel disease – some patients with inflammatory bowel disease who have received mercaptopurine monohydrate have developed a rare and aggressive type of cancer called Hepatosplenic T-cell Lymphoma
  • have an inherited mutation in the NUDT15 gene (a gene which is involved in the break down of Allmercap in the body) – you may have a higher risk of infections and hair loss and your doctor may give you a lower dose.
  • have Lesch-Nyhan Syndrome, a rare inherited condition where there is a deficiency of the hypoxanthine-guanine-phosphoribosyltransferase enzyme.

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.

Do not take ALLMERCAP® if you are planning to become pregnant or father a child unless you and your doctor have discussed the risks and benefits involved.

As with all cytotoxic drugs, ALLMERCAP® may harm eggs and sperm. Reliable contraceptive methods must be taken to avoid pregnancy whilst you or your partner is taking this medicine.

Do not take ALLMERCAP® if you are pregnant unless you and your doctor have discussed the risks and benefits involved.

It may affect your developing baby if you take it during pregnancy.

Do not take this medicine whilst breast feeding.

It is not recommended for use while breast feeding as it is found in breast milk.

3. What if I am taking other medicines?

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

Some medicines may be affected by ALLMERCAP® or may affect how well it works. You may need to take different amounts of your medicine or you may need to take different medicines. These include:

  • allopurinol, oxipurinol and/or thiopurinol
  • methotrexate
  • infliximab
  • medicines to treat or prevent blood clots e.g. warfarin
  • 6-thioguanine
  • aminosalicylate derivatives such as olsalazine, mesalazine or sulphasalazine
  • vaccinations with 'live' organism vaccines
  • Other medicines used to suppress the body's immune defence system agents
  • ribavirin
  • anti-epileptic medicines such as phenytoin. Blood levels of anti-epileptic medicines may need to be monitored and doses adjusted if necessary.
  • febuxostat

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

4. How do I take ALLMERCAP®?

How much to take

Take ALLMERCAP® exactly as directed by your doctor.

Your doctor will decide what dose and for how long you will be taking ALLMERCAP®. This depends on factors such as:

  • your age and weight
  • any pre-existing conditions such as kidney or liver disease
  • your response to the treatment
  • other medicines taken in combination with ALLMERCAP®.

For children the usual dose is 2.5 mg/kg bodyweight/day, but your dose will be carefully adjusted by your doctor depending on your condition. Your doctor may change the dose and frequency of your medicine as your condition changes. Your doctor may order regular blood cell count, liver function and urine tests while you are taking ALLMERCAP® in order to monitor your condition and to change your dose if necessary.

When to take ALLMERCAP®

It is important to take ALLMERCAP® in the evening to make the medicine more effective.

How to take it

You can take your medicine with food or on an empty stomach but the choice of method should be consistent from day to day. You should take your medicine at least 1 hour before or 2 hours after having milk or dairy products.

Your pack of ALLMERCAP® contains a bottle of medicine, a cap, a bottle adaptor and two dosing syringes (a purple 1 mL syringe and an orange 5 mL syringe). Always use the syringes provided to take your medicine. The syringes provided must only be used with ALLMERCAP®.

It is important that you use the correct dosing syringe for your medicine. Your doctor or pharmacist will advise which syringe to use depending on the dose that has been prescribed.

The smaller 1 mL syringe (purple), marked from 0.1 mL to 1 mL, is for measuring doses of less than or equal to 1 mL. You should use this one if the total amount you have to take is less than or equal to 1 mL (each graduation of 0.1 mL contains 2 mg of mercaptopurine monohydrate).

The larger 5 mL syringe (orange), marked 1 mL to 5 mL, is for measuring doses of more than 1 mL. You should use this one if the total amount you have to take is more than 1 mL (each graduation of 0.2 mL contains 4 mg of mercaptopurine monohydrate).

If you are a parent or care giver administering the medicine, wash your hands before and after administering a dose. Wipe up spillages immediately. To decrease the risk of exposure disposable gloves should be used when handling ALLMERCAP®.

If ALLMERCAP® comes into contact with skin, eyes or nose, it should be washed immediately and thoroughly with soap and water.

When you use the medicine follow the instructions below:

  1. Put on disposable hand gloves before handling ALLMERCAP®.
  2. Shake the bottle vigorously for at least 30 seconds to ensure the medicine is well mixed (figure 1).
  3. Remove the bottle cap (figure 2) and push the adaptor firmly into the top of the bottle and leave in place for future doses (figure 3).
  4. Push the tip of the dosing syringe into the hole in the adaptor (figure 4). Your doctor or pharmacist will advise you of the correct syringe to use, either the 1 mL (purple syringe) or the 5 mL (orange syringe) in order to give the correct dose.
  5. Turn the bottle upside down (figure 5).
  6. Pull the plunger of the syringe back so that the medicine is drawn from the bottle into the syringe. Pull the plunger back to the point on the scale that corresponds to the dose prescribed (figure 5). If you are not sure about how much medicine to draw into the syringe, always ask your doctor or nurse for advice.
  7. Turn the bottle back the right way up and carefully remove the syringe from the adaptor, holding it by the barrel rather than the plunger.
  8. Gently put the tip of the syringe into your mouth and to the inside of your cheek.
  9. Slowly and gently push the plunger down to gently squirt the medicine into the inside of your cheek and swallow it. DO NOT forcefully push down the plunger, or squirt the medicine to the back of your mouth or throat, as you may choke.
  10. Remove the syringe from your mouth.
  11. Swallow the dose of oral liquid suspension then drink some water, making sure no medicine is left in your mouth.
  12. Put the cap back on the bottle with the adaptor left in place. Ensure that the cap is tightly closed.
  13. Wash the syringe with warm ‘soapy’ water and rinse well. Hold the syringe under water and move the plunger up and down several times to make sure the inside of the syringe is clean. Let the syringe dry completely before you use that syringe again for dosing. Store the syringe in a hygienic place with the medicine.

Repeat the above for each dose as instructed by your doctor or pharmacist.

Like all cytotoxic drugs, ALLMERCAP® is irritant to the eyes and skin. To prevent irritation it is important to wash your hands immediately after handling the oral liquid suspension, to avoid contact with the eyes.

How long to take it

Your doctor will tell you how long to take ALLMERCAP® for. Do not stop taking it or change the dose without first checking with your doctor.

If you forget to take ALLMERCAP®

Tell your doctor if, for any reason, you have not taken your medicine exactly as directed.

Otherwise, your doctor may think that it was not working as it should and change your treatment unnecessarily.

Do not take a double dose to make up for the one you have missed. Visit your doctor regularly so they can check your progress and make sure your medicine is working.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (in Australia telephone 131126, in New Zealand telephone 0800 764 766, in Hong Kong telephone your doctor or the nearest hospital) for advice, if you think you or anyone else may have taken too much ALLMERCAP®, even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

5. What should I know while taking ALLMERCAP®?

Things you must do

Tell any other specialist, doctor, dentist or pharmacist that you are on ALLMERCAP®, especially if you are about to be started on any new medicines, immunisations, vaccinations or radiotherapy.

Tell your doctor if you become pregnant, are trying to become pregnant or trying to father a child.

Use a sunscreen with a high SPF and protective clothing and limit exposure to sunlight and UV light.

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Do not use ALLMERCAP® to treat any other complaints unless your doctor says to.

Things to be careful of

Do not have any vaccinations without your doctor's approval.

ALLMERCAP® can lower the number of white blood cells and platelets in your blood. This means that you have an increased chance of getting an infection or bleeding. The risk of viral, fungal and bacterial infections is increased and the infections may be more serious.

Driving or using machines

Be careful driving or operating machinery until you know how ALLMERCAP® affects you.

Looking after your medicine

Storage

Keep it in a cool, dry place, protected from light, where the temperature stays 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.

When to discard your medicine

After first opening of the bottle, discard any unused contents after 8 weeks (56 days). Write the date of first opening on the bottle to help you remember.

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
Gut and digestion:
  • nausea and vomiting
  • diarrhoea
Signs of infections such as:
  • fever
  • severe chills
  • sore throat
  • mouth ulcers
Signs of unusual bleeding such as:
  • bruising
  • bleeding more easily than normal
Appetite:
  • loss of appetite and/or weight loss
Signs of liver problems such as:
  • jaundice, a yellowing of the whites of the eyes or the skin
Blood and lymphatic system disorders:
  • production of bone marrow cells may be reduced. You may notice an increase in infections. Your doctor will do regular blood tests
  • symptoms of anaemia (reduced blood cells) include tiredness, headache, shortness of breath, dizziness, looking pale
Joints:
  • painful, swollen joints
Skin and hair:
  • skin rash
  • hair loss
  • skin nodules (erythema nodosum)
Reproduction:
  • in men, sperm production may be reduced
Tell your doctor if you notice any of the following these less serious side effects.

Serious side effects

Serious side effectsWhat to do
Signs of an allergic reaction such as:
  • wheezing
  • swelling of the lips/mouth
  • difficulty breathing
  • lumpy rash (hives)
  • fainting
  • sudden abdominal pain with nausea and vomiting.
Signs of liver problems:
  • jaundice - yellowing of the whites of the eyes or the skin
  • fever or chills
  • light brown urine
Cancer related:
  • as with all cytotoxic medicines, there is an increased risk of some cancers
  • as with all cytotoxic medicines, there is an increased risk of damage to the genes in some cells.
In Children:
  • Low blood sugar (hypoglycaemia) - the frequency is unknown.
If you get any of these serious side effects, tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

Tell your doctor if you notice anything else that is making you feel unwell.

Other side effects not listed above may also 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 (in Australia) or https://nzphvc.otago.ac.nz/consumer-reporting/ (in New Zealand). In Hong Kong telephone your doctor or the nearest hospital. By reporting side effects, you can help provide more information on the safety of this medicine.

7. Product details

Ingredients

Active ingredient
(main ingredient)		One mL of suspension contains 20 mg of mercaptopurine monohydrate.
Other ingredients
(inactive ingredients)		xanthan gum
aspartame (E951)
concentrated raspberry juice
sodium methylhydroxybenzoate (E219)
sodium ethylhydroxybenzoate (E215)
potassium sorbate (E202)
sodium hydroxide
purified water.

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

What ALLMERCAP® looks like

ALLMERCAP® is a pink to brown oral liquid suspension. It comes in bottles of 100 mL capped with a child-resistant closure. Each pack contains one bottle, a bottle adaptor and two dosing syringes (a purple syringe graduated to 1 mL and an orange syringe graduated to 5 mL). Your doctor or pharmacist will advise which syringe to use depending on the dose that has been prescribed.

Australian Registration Number: AUST R 213881

Who distributes ALLMERCAP®

Sponsor

In Australia:

Link Medical Products Pty Ltd
5 Apollo Street
Warriewood NSW 2012
Australia
Ph: 1800 181 060
linkhealthcare.com.au

In New Zealand:

Link Pharmaceuticals Ltd
Suite 38, Level 8
139 Quay Street
Auckland 1010
New Zealand
Ph: +64 (9) 358 7146

This leaflet was updated in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Allmercap

Active ingredient

Mercaptopurine monohydrate

Schedule

S4

 

1 Name of Medicine

Mercaptopurine monohydrate.

2 Qualitative and Quantitative Composition

Allmercap oral liquid suspension contains 20 mg/mL mercaptopurine monohydrate.

Excipients with known effect.

Hydroxybenzoates, sorbates, and aspartame.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Allmercap is a pink/brown oral liquid suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Allmercap oral liquid suspension is indicated for: treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients.

4.2 Dose and Method of Administration

Dosage (dose and interval).

Allmercap is only indicated for use in children. For children the usual dose is 2.5 mg/kg bodyweight/day, but the dose and duration of administration depend on the nature and dosage of other cytotoxic agents given in conjunction with mercaptopurine. The dosage should be carefully adjusted to suit the individual patient.
Mercaptopurine has been used in various combination therapy schedules for acute leukaemia and the literature should be consulted for details.
When allopurinol and mercaptopurine are administered concomitantly it is essential that only a quarter of the usual dose of mercaptopurine is given since allopurinol decreases the rate of catabolism of mercaptopurine.
Mercaptopurine is metabolised by the polymorphic Thiopurine Methyl Transferase (TPMT) enzyme. Patients with little or no inherited TPMT activity are at increased risk for severe toxicity from conventional doses of mercaptopurine and generally require substantial dose reduction. TPMT genotyping or phenotyping can be used to identify patients with absent or reduced TPMT activity. TPMT testing cannot substitute for haematological monitoring in patients receiving mercaptopurine. The optimal starting dose for homozygous deficient patients has not been established (see Section 4.4 Special Warnings and Precautions for Use).

Method of administration.

Allmercap may be taken with food or on an empty stomach, but patients should standardise the method of administration. The dose should not be taken at the same time as milk or dairy products (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Allmercap should be taken at least 1 hour before or 2 hours after milk or dairy products.

Renal or hepatic impairment.

Consideration should be given to reducing the dosage in patients with impaired hepatic or renal function.

Patients with NUDT15 variant.

Patients with inherited mutated NUDT15 gene are at increased risk for severe mercaptopurine toxicity, (see Section 4.4 Special Warnings and Precautions for Use). These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes (see Section 4.4 Special Warnings and Precautions for Use). Genotypic testing of NUDT15 variants may be considered before initiating mercaptopurine therapy. In any case, close monitoring of blood counts is necessary.

4.3 Contraindications

Hypersensitivity to any component of the preparation.
Concomitant use with yellow fever vaccine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
In view of the seriousness of the indications there are no other absolute contraindications.

4.4 Special Warnings and Precautions for Use

Mercaptopurine monohydrate is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
Co-administration of ribavirin and mercaptopurine is not advised. Ribavirin may reduce efficacy and increase toxicity of mercaptopurine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The handling of Allmercap oral liquid suspension should follow standard guidelines for the handling and disposal of cytotoxic drugs.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised if either partner is receiving Allmercap oral liquid suspension.

Immunosuppression.

Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.

Cytotoxic and haematological monitoring.

Since mercaptopurine is strongly myelosuppressive, full blood counts must be monitored daily during remission induction. Patients must be carefully monitored during therapy.
Treatment with mercaptopurine causes bone marrow suppression leading to leucopenia and thrombocytopenia, and less frequently anaemia. Full blood counts must be taken daily during remission induction and careful monitoring of haematological parameters should be conducted during maintenance therapy. The mercaptopurine oral suspension and tablet are not bioequivalent with respect to peak plasma concentration, and therefore intensified haematological monitoring of the patient is advised on switching formulations.
The leucocyte and platelet counts continue to fall after treatment is stopped, so at the first sign of abnormally large fall in the counts, treatment should be interrupted immediately.
Bone marrow suppression is reversible if mercaptopurine is withdrawn early enough.
During remission induction in acute myelogenous leukaemia the patient may frequently have to survive a period of relative bone marrow aplasia and it is important that adequate supportive facilities are available.
The dosage of mercaptopurine may need to be reduced when this agent is combined with other drugs whose primary or secondary toxicity is myelosuppression (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effect of concomitant drugs on mercaptopurine, Myelosuppressive agents).

Hepatotoxicity.

Mercaptopurine is hepatotoxic and liver function tests should be monitored weekly during treatment. More frequent monitoring may be advisable in those with pre-existing liver disease or receiving other potentially hepatotoxic therapy. The patient should be instructed to discontinue mercaptopurine immediately if jaundice becomes apparent.

Renal toxicity.

During remission induction when rapid cell lysis is occurring, uric acid levels in blood and urine should be monitored as hyperuricaemia and/or hyperuricosuria may develop, with the risk of uric acid nephropathy.

Renal and/or hepatic impairment.

Caution is advised during the administration of mercaptopurine in patients with renal impairment and/or hepatic impairment. Consideration should be given to reducing the dosage in these patients and haematological response should be carefully monitored (see Section 4.2 Dose and Method of Administration).

TPMT testing.

There are individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) who may be unusually sensitive to the myelosuppressive effect of mercaptopurine and prone to developing rapid bone marrow depression following the initiation of treatment with mercaptopurine. There have been fatal cases of myelosuppression in patients with low or absent TPMT activity treated with thiopurines. This problem could be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulfasalazine. Also a possible association between decreased TPMT activity and secondary leukaemias and myelodysplasia has been reported in individuals receiving mercaptopurine in combination with other cytotoxics (see Section 4.8 Adverse Effects (Undesirable Effects)).
Some laboratories offer testing for TPMT deficiency, although these tests have not been shown to identify all patients at risk of severe toxicity. Therefore, close monitoring of blood counts is still necessary.
Cross resistance usually exists between mercaptopurine and tioguanine (Lanvis).

Hypersensitivity.

Patients suspected to have previously presented with a hypersensitivity reaction to mercaptopurine monohydrate should not be advised to use its pro-drug azathioprine, unless the patient has been confirmed as hypersensitive to mercaptopurine monohydrate with allergological tests, and has tested negative for azathioprine. As azathioprine is a pro-drug of mercaptopurine monohydrate, patients with a previous history of hypersensitivity to azathioprine must be assessed for hypersensitivity to mercaptopurine monohydrate prior to initiating treatment.

Carcinogenesis and mutagenesis.

Mercaptopurine in common with other anti-metabolites is potentially mutagenic and chromosome damage has been reported in rats and humans.
Increases in chromosomal aberrations were observed in the peripheral lymphocytes of leukaemic patients and in a hypernephroma patient who received an unstated dose of mercaptopurine and in patients with chronic renal disease treated at doses of 0.4-1.0 mg/kg/day.
In view of its action on cellular deoxyribonucleic acid (DNA), mercaptopurine is potentially carcinogenic and consideration should be given to the theoretical risk of carcinogenesis with this treatment. Three cases have been documented of the occurrence of acute nonlymphatic leukaemia in patients who received mercaptopurine for non-neoplastic disorders. A single case has been reported where a patient was treated for pyoderma gangrenosum with mercaptopurine monohydrate and later developed acute nonlymphatic leukaemia.
A patient with Hodgkin's disease treated with mercaptopurine and multiple additional cytotoxic agents developed acute myelogenous leukaemia.
Twelve and a half years after mercaptopurine treatment for myasthenia gravis, a female patient developed chronic myeloid leukaemia.
Reports of hepatosplenic T-cell lymphoma in the inflammatory bowel disease population (this is an unregistered indication) have been received when azathioprine (the prodrug to mercaptopurine) or mercaptopurine is used either with or without concomitant treatment with anti-TNF alpha antibody. This rare type of T cell lymphoma has an aggressive disease course and is usually fatal (see Section 4.8 Adverse Effects (Undesirable Effects)).

Carcinogenicity.

Patients receiving immunosuppressive therapy, including mercaptopurine, are at an increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ. The increased risk appears to be related to the degree and duration of immunosuppression. It has been reported that discontinuation of immunosuppression may provide partial regression of the lymphoproliferative disorder.
A treatment regimen containing multiple immunosuppressants (including thiopurines) should therefore be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities. A combination of multiple immunosuppressants, given concomitantly increases the risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders.

Infections.

Patients treated with mercaptopurine alone or in combination with other immunosuppressive agents, including corticosteroids, have shown increased susceptibility to viral, fungal and bacterial infections, including severe or atypical infection, and viral reactivation. The infectious disease and complications may be more severe in these patients than in non-treated patients.
Prior exposure to or infection with varicella zoster virus should be taken into consideration prior to starting treatment. Local guidelines may be considered, including prophylactic therapy if necessary. Serologic testing prior to starting treatment should be considered with respect to hepatitis B. Local guidelines may be considered, including prophylactic therapy for cases which have been confirmed positive by serologic testing. Cases of neutropenic sepsis have been reported in patients receiving mercaptopurine for ALL.

Macrophage activation syndrome.

Allmercap is only indicated for treatment of ALL in paediatric patients.
Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD) (unlicensed indication), and there could potentially be an increased susceptibility for developing the condition with the use of mercaptopurine. If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible, and treatment with mercaptopurine should be discontinued. Physicians should be attentive to symptoms of infection such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS.

Lesch-Nyhan syndrome.

Limited evidence suggests that neither mercaptopurine monohydrate nor its pro-drug azathioprine are effective in patients with hypoxanthine-guanine-phosphoribosyltransferase deficiency (Lesch-Nyhan syndrome). The use of mercaptopurine monohydrate or azathioprine is not recommended in these patients.

UV exposure.

Patients treated with mercaptopurine monohydrate are more sensitive to the sun. Exposure to sunlight and UV light should be limited, and patients should be advised to wear protective clothing and to use a sunscreen with a high protection factor.

Patients with NUDT15 variant.

Patients with inherited mutated NUDT15 gene are at increased risk for severe mercaptopurine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy. They generally require dose reduction, particularly those being NUDT15 variant homozygotes (see Section 4.2 Dose and Method of Administration). In any case, close monitoring of blood counts is necessary.

Hypoglycaemia.

Cases of symptomatic hypoglycaemia have been reported in children with ALL receiving 6 mercaptopurine (see Section 4.8 Adverse Effects (Undesirable Effects)). The majority of reported cases were in children under the age of six or with a low body mass index.

Use in the elderly.

Allmercap is only indicated for use in children.

Paediatric use.

Allmercap is only indicated for use in children.

Effects on laboratory tests.

See Section 4.4, Cytotoxic and haematological monitoring.

Excipients.

This medicinal product contains aspartame (E951), a source of phenylalanine. May be harmful for people with phenylketonuria. Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age.
It also contains sodium methyl parahydroxybenzoate and sodium ethyl parahydroxybenzoate which may case allergic reaction (possibly delayed).
This medicine contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. Long term use increase the risk of dental caries and it is essential that adequate dental hygiene is maintained.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant administration of yellow fever vaccine is contraindicated, due to the risk of fatal disease in immunocompromised patients. Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Effect of concomitant drugs on mercaptopurine.

Ribavirin.

Ribavirin inhibits the enzyme, inosine monophosphate dehydrogenase (IMPDH), leading to a lower production of the active 6-thioguanine nucleotides. Severe myelosuppression has been reported following concomitant administration of a pro-drug of mercaptopurine and ribavirin; therefore, concomitant administration of ribavirin and mercaptopurine is not advised (see Section 4.4 Special Warnings and Precautions for Use).

Myelosuppressive agents.

When mercaptopurine is combined with other myelosuppressive agents, caution should be used; dose reductions may be needed based on haematological monitoring (see Section 4.4 Special Warnings and Precautions for Use).

Allopurinol/oxipurinol/thiopurinol and other xanthine oxidase inhibitors.

Xanthine oxidase activity is inhibited by allopurinol, oxipurinol and thiopurinol, which results in reduced conversion of biologically active 6-thioinosinic acid to biologically inactive 6-thiouric acid.
When allopurinol, oxipurinol and/or thiopurinol and mercaptopurine are administered concomitantly it is essential that only a 25% of the usual dose of mercaptopurine is given (see Section 4.2 Dose and Method of Administration) since allopurinol decreases the rate of catabolism of mercaptopurine.
Other xanthine oxidase inhibitors, such as febuxostat, may decrease the metabolism of mercaptopurine monohydrate. Concomitant administration is not recommended as data are insufficient to determine an adequate dose reduction.

Aminosalicylates.

There is in vitro and in vivo evidence that aminosalicylate derivatives (e.g. olsalazine, mesalazine or sulphasalazine) inhibit the TPMT enzyme. Therefore, lower doses of mercaptopurine may need to be considered when administered concomitantly with aminosalicylate derivatives (see Section 4.4 Special Warnings and Precautions for Use).
Following unregulated consumption of salicylates, sulphonamides or undefined tranquillisers by patients receiving mercaptopurine therapy, a slower onset of pancytopenia has been documented.

Methotrexate.

Methotrexate may increase mercaptopurine monohydrate AUC. Therefore, when mercaptopurine monohydrate is administered concomitantly with high dose methotrexate, the dose should be adjusted to maintain a suitable white blood cell count.

Infliximab.

Interactions have been observed between azathioprine, a pro-drug of mercaptopurine monohydrate, and infliximab. Patients receiving ongoing azathioprine experienced transient increases in 6-TGN (6-thioguanine nucleotide, an active metabolite of azathioprine) levels and decreases in the mean leukocyte count in the initial weeks following infliximab infusion, which returned to previous levels after 3 months.

Effect of mercaptopurine on other drugs.

Anticoagulants.

Inhibition of the anticoagulant effect of warfarin and acenocoumarol has been reported when coadministered with mercaptopurine; therefore, higher doses of the anticoagulant may be needed. It is recommended that coagulation tests are closely monitored when anticoagulants are concurrently administered with mercaptopurine.

Anti-epileptic medicines.

Cytotoxic agents may decrease the intestinal absorption of phenytoin. Careful monitoring of the phenytoin serum levels is recommended. It is possible that the levels of other anti-epileptic medicinal products may also be altered. Serum antiepileptic levels should be closely monitored during treatment with mercaptopurine monohydrate, making dose adjustments as necessary.

Other forms of interaction.

The administration of mercaptopurine with food may decrease systemic exposure slightly but this is unlikely to be of clinical significance. Therefore, Allmercap may be taken with food or on an empty stomach, but patients should standardise the method of administration. The dose should not be taken with milk or dairy products since they contain xanthine oxidase, an enzyme which metabolises mercaptopurine and might therefore lead to reduced plasma concentrations of mercaptopurine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy (Category D), Maternal exposure and Paternal exposure.
(Category D)
Substantial transplacental and transamniotic transmission of mercaptopurine and its metabolites from the mother to the foetus have been shown to occur.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised if either partner is receiving Allmercap oral liquid suspension.
Mercaptopurine has been shown to be embryotoxic in rats at doses that are not toxic to the mother. It has also been proven to be embryolethal when administered at higher doses in the first half of the gestation period. The potential risk for humans is largely unknown.

Maternal exposure.

Normal offspring have been born after mercaptopurine therapy administered as a single chemotherapy agent during human pregnancy, particularly when given prior to conception or after the first trimester.
Abortions and prematurity have been reported after maternal exposure. Multiple congenital abnormalities have been reported following maternal mercaptopurine treatment in combination with other chemotherapy agents.
Mercaptopurine causes embryolethality and severe teratogenic effects in mice, rats, hamsters and rabbits at doses that are non-toxic to the mother. In all species, the degree of embryotoxicity and type of malformations is dependent on the dose and the stage of gestation at the time of administration.

Paternal exposure.

Congenital abnormalities and spontaneous abortions have been reported after paternal exposure to mercaptopurine.
A leukaemia patient treated with mercaptopurine 100 mg/day (plus splenic irradiation) throughout pregnancy gave birth to a normal, premature baby. A second baby, born to the same mother who was treated as before, together with busulfan 4 mg/day, had multiple severe abnormalities, including corneal opacities, microphthalmia, cleft palate and hypoplasia of the thyroid and ovaries. The use of mercaptopurine should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case the potential hazard to the foetus must be balanced against the expected benefit to the mother.
Transient profound oligospermia was observed in a young man who received mercaptopurine 150 mg/day plus prednisone 80 mg/day for acute leukaemia. Two years after cessation of the chemotherapy he had a normal sperm count and fathered a normal child.
 Mercaptopurine has been detected in the breast milk of renal transplant patients receiving immunosuppressive therapy with azathioprine, a pro-drug of mercaptopurine and thus mothers receiving mercaptopurine should not breastfeed.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

The following convention has been utilised for the classification of undesirable effects: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10,000 and < 1/1000), very rare (< 1/10,000).

Infections and infestations.

Uncommon: Bacterial and viral infections, infections associated with neutropenia.

Neoplasms benign, malignant and unspecified (including cysts and polyps).

Rare: neoplasms including lymphoproliferative disorders, skin cancers (melanomas and nonmelanomas), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ.
Very rare: secondary leukaemia and myelodysplasia.
Frequency unknown: Hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease (an unlicensed indication) when used in combination with or without concomitant anti-TNF alpha antibody has been reported (see Section 4.4 Special Warnings and Precautions for Use).

Blood and lymphatic system disorders.

Very common: bone marrow suppression; leucopenia and thrombocytopenia. The main side effect of treatment with mercaptopurine is bone marrow suppression leading to leucopenia and thrombocytopenia.
Common: anaemia.

Immune system disorders.

Hypersensitivity reactions with the following manifestations have been reported.
Uncommon: arthralgia; skin rash; drug fever.
Rare: facial oedema.

Metabolism and nutrition disorders.

Common: anorexia.
Frequency unknown: hypoglycaemia.

Gastrointestinal disorders.

Common: nausea; vomiting; pancreatitis in the IBD population (an unlicensed indication), stomatitis and diarrhoea.
Uncommon: pancreatitis (in the licensed indication), oral ulceration.
Rare: intestinal ulceration.

Hepatobiliary disorders.

Common: biliary stasis; hepatotoxicity.
Uncommon: hepatic necrosis.
Frequency unknown: Portal hypertension*, nodular regenerative hyperplasia*, sinusoidal obstruction syndrome*.
* In patients with inflammatory bowel disease (IBD), and unlicensed indication.
Mercaptopurine is hepatotoxic in animals and humans. The histological findings in humans have shown hepatic necrosis and biliary stasis.
The incidence of hepatotoxicity varies considerably and can occur with any dose, but more frequently when the recommended dose of 2.5 mg/kg bodyweight daily is exceeded.
Monitoring of liver function tests may allow early detection of liver toxicity. This is usually reversible if mercaptopurine therapy is stopped soon enough. However, irreversible liver damage leading to a fatal outcome has occurred.

Skin and subcutaneous tissue disorders.

Rare: alopecia.
Frequency unknown: photosensitivity reaction; erythema nodosum.

Reproductive system and breast disorders.

Rare: transient oligospermia.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Symptoms.

Gastrointestinal effects, including nausea, vomiting, diarrhoea and anorexia may be early symptoms of overdosage having occurred. The principal toxic effect is on the bone marrow and haematological toxicity is likely to be more profound with chronic overdosage than with a single ingestion of mercaptopurine.
The risk of overdosage is also increased when allopurinol is being given concomitantly with mercaptopurine. Liver dysfunction and gastroenteritis may also occur.

Treatment.

As there is no known antidote, blood counts should be closely monitored and general supportive measures, together with appropriate blood transfusion, instituted if necessary. Active measures (such as the use of activated charcoal) may not be effective in the event of mercaptopurine overdose unless the procedure can be undertaken within 60 minutes of ingestion.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Mercaptopurine is an analogue of adenine, one of the bases required for nucleic acid biosynthesis, and of the purine base hypoxanthine. Hence mercaptopurine acts as an antimetabolite and interferes with the synthesis of nucleic acids in proliferating cells. Its metabolites are also pharmacologically active.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption of an oral tablet dose of mercaptopurine is incomplete and variable averaging about 50% of the administered dose. The half-life of mercaptopurine in the circulation is of the order of 90 minutes. It is extensively metabolised and excreted via the kidneys and the active metabolites have a longer half-life than the parent drug. Mercaptopurine has pKa's of 7.7 and 11.
In a study of healthy adult volunteers given a single dose of Allmercap oral liquid suspension, the mean Cmax was found to be 86.6 nanogram/mL at 45 minutes. The mean AUC0-t was found to be 121.6 nanogram/mL.h.
Comparison of the oral tablet and oral suspension shows the AUC to be 14% (90%CI 8, 21) and Cmax to be 39% (90%CI 22, 58) higher with the oral suspension.

5.3 Preclinical Safety Data

Genotoxicity.

Mercaptopurine in common with other anti-metabolites is potentially mutagenic and chromosome damage has been reported in rats and humans.

Carcinogenicity.

Given its genotoxic potential, mercaptopurine is potentially carcinogenic. See Section 4.4, Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Xanthan gum, aspartame, Rubus idaeus (raspberry juice), sodium methyl hydroxybenzoate, sodium ethyl hydroxybenzoate, potassium sorbate, sodium hydroxide, and purified water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

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. Protect from light.
A shelf life of 56 days is proposed after first opening the bottle, when stored below 25°C.

6.5 Nature and Contents of Container

100 mL Type III coloured glass bottle with a tamper evident child resistant closure (HDPE with expanded polyethylene liner). The product is supplied with a bottle adaptor and 2 oral syringes (graduated to 1 mL and 5 mL).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements for cytotoxic drugs.

6.7 Physicochemical Properties

Mercaptopurine monohydrate is odourless or practically odourless, yellow crystalline powder, with a solubility of 0.26 mg/mL in water at 37°C.
The chemical name of mercaptopurine monohydrate is 1,7-dihydro-6H-purine-6-thione hydrate.
Relative molecular mass: 170.2.
Molecular formula: C5H4N4S.H2O.

Chemical structure.


CAS number.

6112-76-1 (monohydrate).

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes