Allmercap

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Mercaptopurine 20 mg/mL
Available from:
Link Pharmaceuticals Ltd
INN (International Name):
Mercaptopurine 20 mg/mL
Dosage:
20 mg/mL
Pharmaceutical form:
Oral suspension
Composition:
Active: Mercaptopurine 20 mg/mL Excipient: Aspartame Potassium sorbate Purified water Raspberry flavour - concentrated juice (nova) Sodium ethyl hydroxybenzoate Sodium hydroxide Sodium methyl hydroxybenzoate Xanthan gum
Prescription type:
Prescription
Manufactured by:
Fermion Oy
Therapeutic indications:
Allmercap is indicated for the treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients.
Product summary:
Package - Contents - Shelf Life: Bottle, glass, Amber glass bottle with a tamper evident child resistant closure (component) - 100 mL - 15 months from date of manufacture stored at or below 25°C protect from light 56 days opened stored at or below 25°C - Combination pack, Bottle + syringe adapter + 1 mL and 5 mL oral dosing syringes - 100 mL - 15 months from date of manufacture stored at or below 25°C protect from light 56 days opened stored at or below 25°C - Syringe, plastic, Graduated 1 mL oral dosing syringe - 1 mL -   - Syringe, plastic, Graduated 5 mL oral dosing syringe - 5 mL -   - Unknown, Syringe adapter for use wtih an oral dosing syringe, original cap replacement - 1 pieces -  
Authorization number:
TT50-9990
Authorization date:
2016-06-08

Read the complete document

ALLMERCAP CMI

Page 1

ALLMERCAP

®

mercaptopurine monohydrate 20 mg/mL oral liquid suspension

Consumer Medicine Information (CMI)

What is in this leaflet

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.

What ALLMERCAP® is used for

ALLMERCAP

contains mercaptopurine monohydrate as the active ingredient. It belongs to a group of

medicines called cytotoxics (also called chemotherapy).

ALLMERCAP

is used solely 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.

Your doctor may have prescribed it for another purpose. This medicine is only available with a doctor's

prescription.

There is no evidence that it is addictive.

Before you take it

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.

Do not receive the yellow fever vaccine whilst you are taking

ALLMERCAP

®

.

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.

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.

ALLMERCAP CMI

Page 2

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.

Before you start to take it

Tell your doctor if you are allergic to any other medicines or any other foods, dyes or preservatives.

Tell your doctor if you have received the yellow fever vaccine.

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

you have recently received or are receiving radiotherapy or chemotherapy

you have recently been vaccinated or are planning to be vaccinated

chickenpox, shingles or hepatitis B (a liver disease caused by a virus)

kidney or liver disease

a condition where your body produces too little of a natural chemical called thiopurine

methyltransferase (TPMT).

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

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.

Lesch-Nyhan Syndrome, a rare inherited condition where there is a deficiency of the

hypoxanthine-guanine-phosphoribosyltransferase enzyme.

If you have not told your doctor about any of the above, tell them before you start taking

ALLMERCAP

®

.

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

phenytoin

febuxostat

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking

this medicine.

How to take it

How much to take

Take ALLMERCAP

®

exactly as directed by your doctor.

ALLMERCAP CMI

Page 3

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.

How to take it

It is important to take ALLMERCAP

in the evening to make the medicine more effective.

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

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)

ALLMERCAP CMI

Page 4

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.

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.

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.

While you are taking it

Things you must do

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

ALLMERCAP CMI

Page 5

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.

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

Be careful driving or operating machinery until you know how ALLMERCAP

®

affects you.

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.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are taking ALLMERCAP

®

All medicines can cause some side effects. Sometimes they are serious, most of the time they are not.

You may need medical treatment if you get some of the side effects.

The following side effects have been reported with ALLMERCAP

®

production of bone marrow cells may be reduced. You may notice an increase in infections. Your

doctor will do regular blood tests, but you should tell them at once if you notice any signs of fever or

infection or any unexpected bruising, bleeding or signs of blood in your urine

increased risk of liver disease or damage

in men, sperm production may be reduced

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.

Tell your doctor if you notice any of the following:

nausea and vomiting

diarrhoea

infections such as fever, severe chills, sore throat or mouth ulcers

bruising or bleeding more easily than normal

loss of appetite and/or weight loss

jaundice, a yellowing of the whites of the eyes or the skin

a condition in which there is a decreased number of red blood cells, called anaemia. Symptoms

include tiredness, headaches, shortness of breath, dizziness and looking pale.

painful, swollen joints

skin rash

hair loss.

If you get any of the following side effects, tell your doctor immediately or go to Accident and

ALLMERCAP CMI

Page 6

Emergency at your nearest hospital:

wheezing

swelling of the lips/mouth

difficulty in breathing

hayfever

lumpy rash (hives)

fainting

sudden abdominal pain with nausea and vomiting.

Tell your doctor if you notice anything else that is making you feel unwell, even if you think the

problems are not connected with this medicine and are not referred to in this leaflet.

Other side effects not listed above may also occur in some people.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After taking it

Storage

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.

Heat and dampness can affect some medicines.

Keep it where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to

dispose of medicines no longer required. These measures will help to protect the environment.

Product description

What it 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.

Ingredients

Active ingredient:

One mL of suspension contains 20 mg of mercaptopurine monohydrate.

Inactive ingredients:

xanthan gum

aspartame (E951)

concentrated raspberry juice

sodium methylhydroxybenzoate (E219)

sodium ethylhydroxybenzoate (E215)

potassium sorbate (E202)

sodium hydroxide

ALLMERCAP CMI

Page 7

purified water.

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 32, Level 26, PwC Tower

188 Quay Street

Auckland 1010

New Zealand

In Hong Kong:

Unit 16, Floor 12

Corporation Square

8 Lam Lok Street

Kowloon Bay

Hong Kong

Australian Registration Number: AUST R 213881

This leaflet was prepared in January 2021.

Read the complete document

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 1 of 11

1 PRODUCT NAME

ALLMERCAP 20mg/mL oral suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

ALLMERCAP oral suspension contains 20 mg/mL mercaptopurine monohydrate.

The chemical name of mercaptopurine monohydrate is 1,7-dihydro-6H-purine-6-thione hydrate.

Relative molecular mass: 170.2

Molecular formula is C

CAS No.: 6112-76-1 (monohydrate)

Chemical structure is:

Mercaptopurine is odourless or practically odourless, yellow crystalline powder, with a solubility of

0.26 mg/mL in water at 37°C.

For the full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

ALLMERCAP is a pink/brown oral liquid suspension.

4 CLINICAL PARTICULARS

4.1

Therapeutic indications

ALLMERCAP oral suspension is indicated for:

Treatment of Acute Lymphoblastic Leukaemia (ALL) in paediatric patients.

4.2

Dose and method of administration

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

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 2 of 11

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). 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 4.4). These patients generally require dose reduction; particularly those being NUDT15

variant homozygotes (see 4.4). 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

Precautions

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).

The handling of ALLMERCAP oral 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 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

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 3 of 11

remission induction and careful monitoring of haematological parameters should be conducted

during maintenance therapy. The mecaptopurine 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 Interaction with

other medicines and other forms of interactions).

Heptatoxicity

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 sulphasalazine. 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

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).

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 4 of 11

Hypersensitivity

Patients suspected to have previously presented with a hypersensitivity reaction to mercaptopurine

monohydrates 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, mutagenesis, impairment of fertility

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.

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 Undesirable effects).

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

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 5 of 11

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.

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.

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). The frequency of NUDT15 c.415C>T has an ethnic variability of approximately 10 % in East

Asians, 4 % in Hispanics, 0.2 % in Europeans and 0 % in Africans. In any case, close monitoring of

blood counts is necessary.

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 cause 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.

ALLMERCAP® NEW ZEALAND DATA SHEET

ALLMERCAP Data Sheet

11 February 2021

Page 6 of 11

4.5

Interaction with other medicines and other forms of interaction

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).

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).

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 PRECAUTIONS).

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

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Inhibition of the anticoagulant effect of warfarin and acenocoumarol has been reported when co-

administered 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

Use In Pregnancy

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 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.

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.

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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.

Use in Lactation

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 breast feed.

4.7

Effects on ability to drive and use machines

No studies on the effect on the ability to drive and use machines have been performed. A

detrimental effect on these activities cannot be predicted from the pharmacology of the active

substance.

4.8

Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are

asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

Adverse 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 non-

melanomas), 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).

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

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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

Reproductive system and breast disorders

Rare: transient oligospermia.

4.9

Overdose

For advice on the management of overdose please contact the National Poisons Centre on 0800

POISON (0800 764766).

Contact the Poisons Information Centre on telephone 0800 764 766 for advice on management of

overdose.

Symptoms

Gastro-intestinal 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.

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5 PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

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.

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 suspension, the mean

Cmax was found to be 86.6 ng/mL at 45 minutes. The mean AUC0-t was found to be 121.6 ng/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

Mercaptopurine in common with other anti-metabolites is potentially mutagenic and chromosome

damage has been reported in rats and humans.

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.

6 PHARMACEUTICAL PARTICULARS

6.1

List of excipients

ALLMERCAP oral suspension also contains the following inactive ingredients: xanthan gum,

aspartame, rubus idaeus (raspberry juice), sodium methyl hydroxybenzoate, sodium ethyl

hydroxybenzoate, potassium sorbate, sodium hydroxide, and purified water.

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

12 months.

56 days after first opening.

6.4

Special precautions for storage

Store below 25°C. Protect from light.

6.5

Nature and contents of container <and special equipment for use, administration or

implantation>

ALLMERCAP is a pink/brown oral liquid suspension in a 100 mL amber glass bottle with a tamper

evident child resistant closure. 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 <and other handling>

Safe handling

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