Consumer medicine information

Lanvis

Tioguanine

BRAND INFORMATION

Brand name

Lanvis

Active ingredient

Tioguanine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lanvis.

What is in this leaflet

This leaflet answers some common questions about LANVIS. 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 giving you this medicine 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 LANVIS is used for

LANVIS contains tioguanine as the active ingredient. It belongs to a group of medicines called cytotoxics.

LANVIS is used solely or in combination with other medicines to treat certain types of blood disorders (leukaemia).

LANVIS acts by inhibiting the growth of cancer cells.

Ask your doctor if you have any questions about why LANVIS 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 LANVIS if you have ever had an allergic reaction to:

  • tioguanine
  • any of the tablet 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 take it if:

  • you have severe liver or kidney disease
  • you have leucopenia, a lack of white blood cells
  • you have anaemia, a lack of red blood cells
  • you have fever and chills caused by a virus (viraemia)
  • the expiry date (EXP) printed on the pack has passed
  • the packaging is torn or shows signs of tampering.

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 or have had any of the following conditions:

  • you have recently been vaccinated or are planning to be vaccinated
  • kidney or liver disease
  • blood disorders
  • Lesch-Nyhan Syndrome
  • NUDT15 variant (mutated NUDT15 gene)
  • a condition where your body produces too little of a natural chemical called thiopurine methyltransferase (TPMT).

Tell your doctor if you are planning to become pregnant or intending to father a child. As with all cytotoxic drugs, LANVIS may harm eggs and sperm. You or your partner should take adequate contraceptive precautions while you are taking this medicine.

Do not take LANVIS if you are pregnant or breast feeding unless you and your doctor have discussed the risks and benefits involved.

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

Taking other medicines

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

Some medicines may be affected by LANVIS 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:

  • busulphan
  • allopurinol
  • aminosalicylate derivatives e.g. olsalazine,mesalazine or sulphasalazine
  • vaccinations with ‘live’ organism vaccines.

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 LANVIS exactly as directed by your doctor. Your doctor will decide what dose and for how long you will be taking LANVIS. This depends on factors such as your weight, any pre-existing conditions and your response to the treatment. Your doctor may change the dose and frequency of your medicine as your condition changes.

Your doctor may order regular blood cell count and liver function tests while you are taking LANVIS in order to monitor your condition and to change your dose if necessary.

How long to take it for

Your doctor will tell you how long to take LANVIS for.

Do not stop taking LANVIS or change the dose without first checking with your doctor.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have taken too much LANVIS, 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 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 LANVIS, 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.

Patients taking LANVIS are more sensitive to the sun. Limit your exposure to sunlight and UV light. Wear protective clothing and use a sunscreen with a high SPF.

Things you must not do

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

Do not use LANVIS 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 LANVIS affects you.

Do not have any vaccinations without your doctor’s approval. Wait until at least 3 months after chemotherapy treatment has been completed before receiving a vaccine and only after consultation with your doctor.

LANVIS 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. Your doctor will monitor your blood count while you are undergoing chemotherapy.

Side effects

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

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.

Tell your doctor if you notice any of the following:

  • nausea and vomiting
  • diarrhoea
  • jaundice (yellowing of the whites of the eyes or skin)
  • weight gain due to fluid retention
  • swelling due to build-up of fluid around the stomach
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal
  • blood in the urine
  • lowered resistance to disease (immunosuppression)

Tell your doctor immediately if you notice any of the following allergic-type symptoms:

  • wheezing, swelling of the lips or mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting.

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 your tablets in the bottle until it is time to take them. If you take the medicine out of the bottle it may not keep as well.

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.

Product description

What it looks like

LANVIS tablets are white to off-white, round, biconvex, scored and imprinted ‘T40’on one side and plain on the other.

Available in bottles of 25 tablets.

Ingredients

Active ingredient:

Each tablet contains 40 mg of tioguanine.

Inactive ingredients:

  • acacia
  • lactose monohydrate
  • magnesium stearate
  • starch-potato
  • stearic acid

LANVIS tablets do not contain sucrose, tartrazine or any other azo dyes.

Sponsor

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Phone: +61 2 8436 8300
Web: www.aspenpharma.com.au

Australian Registration Number: AUST R 11110

This leaflet was revised in March 2022

Published by MIMS June 2022

BRAND INFORMATION

Brand name

Lanvis

Active ingredient

Tioguanine

Schedule

S4

 

1 Name of Medicine

Tioguanine.

2 Qualitative and Quantitative Composition

Each scored tablet contains 40 mg of tioguanine and the excipients lactose monohydrate, potato starch, acacia, stearic acid and magnesium stearate.

3 Pharmaceutical Form

Tablets, uncoated.

4 Clinical Particulars

4.1 Therapeutic Indications

Acute myeloblastic leukaemia. Less commonly, chronic granulocytic (myelocytic, myeloid, myelogenous) leukaemia. Although superior results are generally obtained with busulfan (Myleran) in the treatment of chronic granulocytic leukaemia. Lanvis may be useful during blast crises or periods of thrombocytopenia induced by busulfan or other therapy. A degree of cross resistance exists between Lanvis (tioguanine) and Puri-Nethol (mercaptopurine) and generally it is not to be expected that patients who no longer respond to mercaptopurine will respond to tioguanine or vice versa. Unlike mercaptopurine the detoxification of Lanvis is not dependent on xanthine oxidase, hence therapy with Lanvis is not affected by the xanthine oxidase inhibitor, allopurinol (Zyloprim).
Recent evidence suggests that Lanvis is particularly useful in concurrent or sequelist combination with other antineoplastic drugs, e.g. cytosine arabinoside. Not effective for the treatment of chronic lymphocytic leukaemia or solid tumours. The aim of therapy is to achieve normal appearance of the bone marrow and peripheral blood. It is recognised, however, that in treating acute leukaemia, one may not always be able to achieve complete remissions and must be satisfied with partial improvement.

4.2 Dose and Method of Administration

The dosage and duration of administration of Lanvis must be carefully adjusted for each patient to obtain optimum benefit without toxic effects. Therapy should be initiated in a specialised unit with full facilities for supportive therapy. Lanvis is usually administered in accordance with a protocol, in combination with other drugs. The following comments are for general guidance. The usual initial dose is approximately 2 to 2.5 mg/kg bodyweight/day, orally. It is usually calculated to the nearest multiple of 20 mg. The total daily dose may be given at one time. Some regimens, however, demand 12 hourly dosage.
Although the effect usually occurs slowly over a period of two to four weeks, there may occasionally be a rapid fall in leucocyte count within one or two weeks. This may occur in some adults with acute leukaemia and high total leucocyte counts, as well as certain adults with chronic granulocytic leukaemia. For this reason it is important to observe such patients closely. Daily blood counts are necessary during intensive therapy with multi-drug protocols.
Lanvis is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
Lanvis may be continued in the usual dosage when allopurinol is used concomitantly to inhibit uric acid formation. Smaller doses may be advisable in patients with impaired renal or hepatic function.

Dosing for TPMT-deficient patients.

Patients with inherited little or no thiopurine S-methyltransferase (TPMT) activity are at increased risk for severe tioguanine toxicity from conventional doses of tioguanine and generally require substantial dose reduction. The optimal starting dose for homozygous deficient patients has not been established (see Section 4.4 Special Warnings and Precautions for Use, Monitoring).
Most patients with heterozygous TPMT deficiency can tolerate recommended tioguanine doses, but some may require dose reduction. Genotypic and phenotypic tests of TPMT are available (see Section 4.4 Special Warnings and Precautions for Use, Monitoring). Consideration should be given to reducing the dosage in patients with impaired hepatic function.

Patients with NUDT15 variant.

Patients with inherited mutated NUDT15 gene are at increased risk for severe thiopurine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy and generally require substantial dose reduction. Patients of Asian ethnicity are particularly at risk, due to the increased frequency of the mutation in this population. The optimal starting dose for heterozygous or homozygous deficient patients has not been established.
Genotypic and phenotypic testing of NUDT15 variants should be considered before initiating thiopurine therapy in all patients (including paediatric patients) to reduce the risk of thiopurine-related severe leukocytopenia and alopecia, especially in Asian populations (see Section 5.2).

4.3 Contraindications

Hypersensitivity to any component of the preparation.
Although success may be obtained after six or more induction courses, therapy should be reviewed if remission is not achieved after two or three attempts at induction. It should not be used during viraemic states, marrow aplasia, severe anaemia, leucopenia or in bleeding states, severe liver dysfunction, renal failure or intolerance to the drug. Some of these conditions may be corrected by appropriate therapy and this allows for therapy to proceed.

4.4 Special Warnings and Precautions for Use

Lanvis is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.
In all cases, patients in remission should not receive live organism vaccines until at least 3 months after their chemotherapy treatment has been completed.

Hepatic effects.

Lanvis is not recommended for maintenance therapy or similar long-term continuous treatments due to the high risk of liver toxicity associated with vascular endothelial damage (see Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects)). This liver toxicity has been observed in a high proportion of children receiving Lanvis as part of maintenance therapy for acute lymphoblastic leukaemia and in other conditions associated with continuous use of Lanvis. This liver toxicity is particularly prevalent in males. Liver toxicity usually presents as the clinical syndrome of hepatic veno-occlusive disease (hyperbilirubinaemia, tender hepatomegaly, weight gain due to fluid retention and ascites) or with signs of portal hypertension (splenomegaly, thrombocytopenia and oesophageal varices). Histopathological features associated with this toxicity include hepatoportal sclerosis, nodular regenerative hyperplasia, peliosis hepatis and periportal fibrosis.
Lanvis therapy should be discontinued in patients with evidence of liver toxicity as reversal of signs and symptoms of liver toxicity have been reported upon withdrawal.

Haematological effects.

Treatment with Lanvis causes bone marrow suppression leading to leucopenia and thrombocytopenia (see Hepatic effects). Anaemia has been reported less frequently.
Bone marrow suppression is readily reversible if Lanvis is withdrawn early enough.

Monitoring.

Patients must be carefully monitored during therapy including blood cell counts and weekly liver function tests. Early indications of liver toxicity are signs associated with portal hypertension such as thrombocytopenia out of proportion with neutropenia and splenomegaly. Elevations of liver enzymes have also been reported in association with liver toxicity but do not always occur.
Since 6-tioguanine is strongly myelosuppressive full blood counts must be carried out frequently.
During remission induction, patients must be carefully monitored during therapy.
It may be advisable to perform liver function tests more frequently in patients with known pre-existing liver disease or in patients who are receiving tioguanine and other hepatoxic drugs.
It is advisable to start with smaller doses in patients with liver disease, since most of the ingested drug is metabolised in the liver. The same considerations apply to renal disease because of the primarily renal excretion of the metabolites. Frequent blood counts should be undertaken during therapy, and caution must be exercised to avoid toxicity, the chief manifestation of which is depression of the bone marrow, resulting in leucopenia and eventually thrombocytopenia and bleeding.
Since the drug may have a delayed and prolonged action, it is important to withdraw the medication temporarily at the first sign of abnormally large fall in the white blood cell count or of abnormal depression of the bone marrow. Blood counts should be made at least once weekly during maintenance therapy and daily during remission induction. Supportive therapy may be required, e.g. barrier nursing, antibiotics, antiemetics, glucocorticoids for capillary fragility, platelets and blood transfusions as appropriate.
Patients on myelosuppressive chemotherapy are particularly susceptible to a variety of infections.
During remission induction, particularly when rapid cell lysis is occurring, adequate precautions should be taken to avoid hyperuricaemia and/or hyperuricosuria and the risk of uric acid nephropathy (see Section 4.8 Adverse Effects (Undesirable Effects)).

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 Lanvis and prone to developing rapid bone marrow depression following the initiation of treatment with Lanvis. 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.
Patients should be tested for TPMT activity before starting Lanvis. TPMT testing cannot substitute for complete blood count monitoring in patients receiving Lanvis. TPMT genotyping can be used to identify patients with absent or reduced TPMT activity. Patients with low or absent TPMT activity (homozygous for non-functional alleles) are at an increased risk of developing severe, life-threatening myelotoxicity from Lanvis if conventional doses are given. Alternative therapies may be considered for patients who have low or absent TPMT activity. Lanvis should be administered with caution to patients having one non-functional allele (heterozygous) who are at risk for reduced TPMT activity that may lead to toxicity if conventional doses are given. Dosage reduction is recommended in patients with reduced TPMT activity.
TPMT testing is widely available through pathology laboratories and genetic testing services.

NUDT15 mutation.

Patients with inherited mutated NUDT15 gene are at increased risk for severe thiopurine toxicity, such as early leukopenia and alopecia, from conventional doses of thiopurine therapy and generally require substantial dose reduction. Patients of Asian ethnicity are particularly at risk, due to the increased frequency of the mutation in this population. The optimal starting dose for heterozygous or homozygous deficient patients has not been established. Genotypic and phenotypic testing of NUDT15 variants should be considered before initiating thiopurine therapy in all patients (including paediatric patients) to reduce the risk of thiopurine-related severe leukocytopenia and alopecia, especially in Asian populations (see Section 5.2).
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.
Patients on myelosuppressive chemotherapy are particularly susceptible to a variety of infections.
Patients treated with thioguanine in combination with other immunosuppressive or chemotherapeutic agents, have shown increased susceptibility to viral, fungal, and bacterial infections, including severe or atypical infection. The infectious disease and complications may be more severe in these patients than in non-treated patients.
If the patient is infected during treatment appropriate measures should be taken, which may include antiviral therapy and supportive care.
During remission induction, particularly when rapid cell lysis is occurring, adequate precautions should be taken to avoid hyperuricaemia and/or hyperuricosuria and the risk of uric acid nephropathy (see Section 4.8 Adverse Effects (Undesirable Effects)).

Monitoring.

Since 6-thioguanine is strongly myelosuppressive full blood counts must be carried out frequently during remission induction. Patients must be carefully monitored during therapy.
The leucocyte and platelet counts continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in these counts, treatment should be temporarily discontinued.

Lesch-Nyhan syndrome.

Since the enzyme hypoxanthine guanine phosphoribosyl transferase is responsible for the conversion of Lanvis to its active metabolite, it is possible that patients deficient in this enzyme, such as those suffering from Lesch-Nyhan syndrome, may be resistant to the drug. Resistance to azathioprine (Imuran), which has one of the same active metabolites as Lanvis, has been demonstrated in two children with Lesch-Nyhan syndrome.

UV exposure.

Patients treated with 6-tioguanine are more sensitive to the sun. Exposure to sunlight and UV light should be limited, and patients should be recommended to wear protective clothing and to use a sunscreen with a high protection factor.

Carcinogenicity, mutagenicity and impairment of fertility.

In view of its action on DNA, Lanvis is potentially mutagenic and carcinogenic.

Use in elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The combination of busulfan and Lanvis has resulted in the development of nodular regenerative hyperplasia, portal hypertension and oesophageal varices.
The concomitant use of allopurinol to inhibit uric acid formation does not necessitate reduction of dosage of Lanvis.
As there is in vitro evidence that aminosalicylate derivatives (e.g. olsalazine, mesalazine or sulfasalazine) inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent Lanvis therapy (see Section 4.4 Special Warnings and Precautions for Use).
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Section 4.4 Special Warnings and Precautions for Use).
During concomitant administration of other myelotoxic substances or radiation therapy, the risk of myelosuppression is increased.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
Lanvis is a potent teratogen in animals, and its exhibition in pregnancy has been associated with fetal chromosome abnormality. The benefits and risks must therefore be weighed before use in pregnancy. Whenever possible, use of the drug should be deferred until after the first trimester of pregnancy.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Lanvis.
There have been isolated cases where men who have received combinations of cytotoxic agents including Lanvis, have fathered children with congenital abnormalities.
 There are no reports documenting the presence of Lanvis or its metabolites in maternal milk. It is suggested that mothers receiving Lanvis 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 frequency of undesirable effects: Very common ≥ 1/10 (≥ 10%), common ≥ 1/100 and < 1/10 (≥ 1% and < 10%), uncommon ≥ 1/1000 and < 1/100 (≥ 0.1% and < 1%), rare ≥ 1/10,000 and < 1/1000 (≥ 0.01% and < 0.1%), very rare < 1/10,000 (< 0.01%).

Blood and lymphatic system disorders.

Very common: bone marrow failure (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal disorders.

Common: stomatitis, gastrointestinal disorder including nausea and vomiting (requiring treatment or withholding of the drug) and diarrhoea.
Rare: necrotising colitis and perforation.

Hepatobiliary disorders.

Very common: liver toxicity associated with vascular endothelial damage when Lanvis is used in maintenance or similar long-term continuous therapy which is not recommended (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).
This usually presents as the clinical syndrome of veno-occlusive liver disease (hyperbilirubinaemia, tender hepatomegaly, weight gain due to fluid retention and ascites) or signs and symptoms of portal hypertension (splenomegaly, varices thrombocytopenia and oesophageal). Elevation of liver transaminases, blood alkaline phosphatase and gamma glutamyl transferase and jaundice may also occur.
Histopathological features associated with this toxicity include portal fibrosis, nodular regenerative hyperplasia, peliosis hepatis and periportal fibrosis.
Common: liver toxicity during short-term cyclical therapy presenting as veno-occlusive liver disease.
Reversal of signs and symptoms of this liver toxicity has been reported upon withdrawal of short-term or long-term continuous therapy.
Rare: hepatic necrosis has been reported in a few cases including patients receiving combination chemotherapy, oral contraceptives, high dose Lanvis and alcohol.
Other adverse reactions that have been reported include transient treatment-related megaloblastic marrow changes, development of immunosuppressive states and agranulocytosis (with consequent liability to infection requiring adequate barrier nursing and appropriate antibiotics), and thrombocytopenia requiring haemostatic measures.

Renal and urinary disorders.

Common: hyperuricaemia and/or hyperuricosuria and urate nephropathy (see Section 4.4 Special Warnings and Precautions for Use).

Postmarketing data.

Skin and subcutaneous tissue disorders.

Frequency not known: photosensitivity.
Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring if 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

Signs.

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 Lanvis.

Treatment.

As there is no known antidote the blood picture should be closely monitored and general supportive measures, together with appropriate blood transfusion instituted if necessary. Further management should be as clinically indicated. For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Tioguanine, a derivative of mercaptopurine, is an antagonist to purine metabolism, but its precise mechanism of antineoplastic activity has not been determined. Its tumour inhibitory effects may be due to incorporation into DNA and RNA; feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversion.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

No data available.

Distribution.

No data available.

Metabolism.

No data available.

Excretion.

No data available.

Biotransformation.

NUDT15 R139C (NUDT15 c.415C > T) variant.

Recent studies indicate that a strong association exists between the NUDT15 variant NUDT15 c.415C > T [p.Arg139Cys] (also known as NUDT15 R139C [rs116855232]), which is thought to lead to a loss of function of the NUDT15 enzyme, and thiopurine mediated toxicity such as leukopenia and alopecia. Patients who are NUDT15 variant homozygotes (NUDT15 T risk alleles) are at an excessive risk of thiopurine toxicity compared with the C homozygotes.
Reduced thiopurine doses for patients who carry the NUDT15 variants may decrease their risk of toxicity. Therefore, genotypic analysis determining NUDT15 genotype should be determined for all patients, including paediatric patients, prior to initiating thiopurine treatment (see Section 4.2). The prescribing physician is advised to establish whether dose reduction is required based on patient response to treatment as well as their genetic profile.
Patients with variants in both the NUDT15 and TPMT enzymes are significantly less tolerant of thiopurines than those with risk alleles in only one of these two genes.
The precise mechanism of NUDT15-associated thiopurine-related toxicity is not understood.

5.3 Preclinical Safety Data

Genotoxicity and carcinogenicity.

See Section 4.4 Special Warnings and Precautions for Use, Carcinogenicity, mutagenicity and impairment of fertility.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet contains tioguanine 40 mg as the active ingredient plus the inactive ingredients: lactose monohydrate, potato starch, acacia, magnesium stearate and stearic acid.

6.2 Incompatibilities

No data available.

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. Store in a dry place.

6.5 Nature and Contents of Container

Tablets 40 mg (white to off-white, round, biconvex scored and marked 'T40' on one side and plain on the other).
Supplied in an amber glass bottle with a HDPE/PP child resistant cap containing 25 tablets.

6.6 Special Precautions for Disposal

No data available.

6.7 Physicochemical Properties

Tioguanine is a pale yellow, crystalline powder. Practically insoluble in water and ethanol (96%). It dissolves in dilute solutions of alkali hydroxides.
Tioguanine, known chemically as 2-amino-1,7-dihydro-6H-purine-6-thione, is an analogue of the nucleic acid constituent guanine, and is closely related structurally and functionally to Puri-Nethol (mercaptopurine). Its structural formula is:

Chemical structure.


CAS number.

The CAS registry number is 154-42-7.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription only medicine).

Summary Table of Changes