Drugs List

Therapeutic Indications

Uses

Leukaemia

Administration

Plasma levels may be reduced following emesis or intake of food.

Whilst the tablets are scored, they should only be broken to ease swallowing not to administer specific doses. If tablets are broken, use appropriate personal protective equipment to avoid skin contamination or inhalation of the drug.

Contraindications

Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Inherited NUDT15 gene mutation
Inherited thiopurine methyltransferase deficiency
Dehydration
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hyperuricaemia
Lactose intolerance
Lesch-Nyhan syndrome
Renal impairment
Uric acid nephropathy

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 3 months after treatment
Not recommended for maintenance therapy
Maintain adequate hydration of patient prior / during treatment
Male: Greater risk of developing hepatotoxicity
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor blood counts regularly
Monitor liver function tests weekly
Monitor patients for signs of tumour lysis syndrome
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider treatments to prevent hyperuricaemia
Discontinue immediately following signs of acute hepatotoxicity
Potentially mutagenic and carcinogenic
Discontinue immediately if any severe fall in blood counts occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Male & female: Ensure adequate contraception during treatment
Advise patient on appropriate sun protection methods

Early indications of liver toxicity include portal hypertension (thrombocytopenia out of proportion to neutropenia or splenomegaly). Toxicity can also present as hepatic veno-occlusive disease (hyperbilirubinaemia, tender hepatomegaly, weight gain due to fluid retention and ascites). Elevations of liver enzymes do not always occur.

Close monitoring is advised in patients with inherited TPMT deficiency as they are prone to developing rapid bone marrow suppression. This risk is further increased by co-administration of drugs that inhibit TPMT (e.g. aminosalicylates). Whilst laboratory tests are available to identify TPMT deficiency, there is potential that the tests will fail to identify some at risk patients. Patients may require substantial dose reductions however at the time of writing there are no standard recommendations for dose modifications. Most patients with heterozygous TPMT deficiency are able to tolerate standard doses.

During remission induction there is a higher risk of myelosuppression and tumour lysis syndrome (particularly during rapid cell lysis). During this period, monitor full blood counts frequently and ensure adequate precautions to avoid hyperuricaemia, hyperuricosuria and uric acid nephropathy. Patients with acute myelogenous leukaemia may frequently experience periods of relative bone marrow aplasia during remission induction. It is important that adequate supportive facilities are available for these patients.

Resistance to tioguanine may occur in patients with Lesch-Nyhan syndrome due to a deficiency in the enzyme responsible for converting tioguanine to its active metabolite.

Dose reduction may be necessary in patients with inherited mutated NUDT15 gene due to an increased risk of severe tioguanine toxicity. Genotypic testing of NUDT15 variants may be considered before initiating tioguanine therapy.

Pregnancy and Lactation

Pregnancy

Tioguanine is contraindicated during pregnancy.

The manufacturer advises tioguanine should be avoided 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. The effect of concurrent therapies must also be considered.

Lactation

Tioguanine is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking tioguanine.

It is unknown whether tioguanine or its metabolites are excreted in human breast milk. The effect of concurrent therapies must also be considered.

Side Effects

Anaemia
Ascites
Bone marrow depression
Gamma glutamyl transferase (GGT) increased
Gastrointestinal intolerance
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatomegaly
Hepatoportal sclerosis
Hepatotoxicity
Hyperbilirubinaemia
Hyperuricaemia
Hyperuricosuria
Increase in alkaline phosphatase
Increased susceptibility to infection
Increases in hepatic enzymes
Intestinal necrosis
Jaundice
Leucopenia
Nephropathy
Nodular regenerative hyperplasia
Oesophageal varices
Peliosis hepatis
Periportal fibrosis
Photosensitivity
Portal hypertension
Splenomegaly
Stomatitis
Thrombocytopenia
Weight gain (fluid retention)

Presentation

Oral formulations of tioguanine.

Drugs List

Therapeutic Indications

Uses

Leukaemia

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

The exact dose and duration of administration will depend on the nature and dosage of other cytotoxic drugs given in conjunction with tioguanine.

Tioguanine may be used at various stages during treatment in short-term cycles. It is not recommended for use during maintenance therapy or similar long-term continuous treatments due to the high risk of hepatotoxicity.

Adults

Children

Administration

Plasma levels may be reduced following emesis or intake of food.

Whilst the tablets are scored, they should only be broken to ease swallowing not to administer specific doses. If tablets are broken, use appropriate personal protective equipment to avoid skin contamination or inhalation of the drug.

Contraindications

Breastfeeding
Galactosaemia
Pregnancy

Precautions and Warnings

Inherited NUDT15 gene mutation
Inherited thiopurine methyltransferase deficiency
Dehydration
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hyperuricaemia
Lactose intolerance
Lesch-Nyhan syndrome
Renal impairment
Uric acid nephropathy

Administration of live vaccines is not recommended
Live virus vaccine should not be given for 3 months after treatment
Not recommended for maintenance therapy
Maintain adequate hydration of patient prior / during treatment
Male: Greater risk of developing hepatotoxicity
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor blood counts regularly
Monitor liver function tests weekly
Monitor patients for signs of tumour lysis syndrome
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider treatments to prevent hyperuricaemia
Discontinue immediately following signs of acute hepatotoxicity
Potentially mutagenic and carcinogenic
Discontinue immediately if any severe fall in blood counts occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Male & female: Ensure adequate contraception during treatment
Advise patient on appropriate sun protection methods

Early indications of liver toxicity include portal hypertension (thrombocytopenia out of proportion to neutropenia or splenomegaly). Toxicity can also present as hepatic veno-occlusive disease (hyperbilirubinaemia, tender hepatomegaly, weight gain due to fluid retention and ascites). Elevations of liver enzymes do not always occur.

Close monitoring is advised in patients with inherited TPMT deficiency as they are prone to developing rapid bone marrow suppression. This risk is further increased by co-administration of drugs that inhibit TPMT (e.g. aminosalicylates). Whilst laboratory tests are available to identify TPMT deficiency, there is potential that the tests will fail to identify some at risk patients. Patients may require substantial dose reductions however at the time of writing there are no standard recommendations for dose modifications. Most patients with heterozygous TPMT deficiency are able to tolerate standard doses.

During remission induction there is a higher risk of myelosuppression and tumour lysis syndrome (particularly during rapid cell lysis). During this period, monitor full blood counts frequently and ensure adequate precautions to avoid hyperuricaemia, hyperuricosuria and uric acid nephropathy. Patients with acute myelogenous leukaemia may frequently experience periods of relative bone marrow aplasia during remission induction. It is important that adequate supportive facilities are available for these patients.

Resistance to tioguanine may occur in patients with Lesch-Nyhan syndrome due to a deficiency in the enzyme responsible for converting tioguanine to its active metabolite.

Dose reduction may be necessary in patients with inherited mutated NUDT15 gene due to an increased risk of severe tioguanine toxicity. Genotypic testing of NUDT15 variants may be considered before initiating tioguanine therapy.

Pregnancy and Lactation

Pregnancy

Tioguanine is contraindicated during pregnancy.

The manufacturer advises tioguanine should be avoided 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. The effect of concurrent therapies must also be considered.

Lactation

Tioguanine is contraindicated during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking tioguanine.

It is unknown whether tioguanine or its metabolites are excreted in human breast milk. The effect of concurrent therapies must also be considered.

Side Effects

Anaemia
Ascites
Bone marrow depression
Gamma glutamyl transferase (GGT) increased
Gastrointestinal intolerance
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatomegaly
Hepatoportal sclerosis
Hepatotoxicity
Hyperbilirubinaemia
Hyperuricaemia
Hyperuricosuria
Increase in alkaline phosphatase
Increased susceptibility to infection
Increases in hepatic enzymes
Intestinal necrosis
Jaundice
Leucopenia
Nephropathy
Nodular regenerative hyperplasia
Oesophageal varices
Peliosis hepatis
Periportal fibrosis
Photosensitivity
Portal hypertension
Splenomegaly
Stomatitis
Thrombocytopenia
Weight gain (fluid retention)

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2021

Reference Sources

Summary of Product Characteristics: Tioguanine 40mg Tablets. Aspen. Revised November 2017.

NICE Evidence Services Available at: www.nice.org.uk
Last accessed: 05 March 2021