Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic
Leukaemia - acute myeloid
Leukaemia - acute promyelocytic

Unlicensed Uses

Crohn's disease - maintenance of remission
Severe Crohn's disease
Ulcerative colitis: induction of remission
Ulcerative colitis: maintenance of remission

Administration

Administration of daily dose should be in the evening as this may lower the risk of relapse.

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Inherited thiopurine methyltransferase deficiency
Dehydration
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Lactose intolerance
Phenylketonuria
Renal impairment - creatinine clearance below 50ml/minute

Administration of live vaccines is not recommended
Some formulations contain aspartame - caution in phenylketonuria
Not all available brands are licensed for all indications
Not all formulations are licensed for all uses
Treatment to be initiated and supervised by a specialist
Oral solution contains sucrose and hydroxybenzoates
Some formulations contain lactose
Some formulations contain sucrose
Different formulations are not bioequivalent
Monitor closely if switching between tablet formulation and oral solution
Accidental contact of soln with skin/mucous membranes-rinse well with water
Avoid contact with mucous membranes
Avoid contact with skin or eyes
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Take at the same time in respect to food as absorption may be affected
Monitor haematological parameters before and during treatment
Elderly: Monitor renal function and consider dose modification
Monitor for presence of hepatitis B markers
Monitor for signs of Macrophage Activation Syndrome (MAS)
Monitor liver function tests weekly
Monitor patients for signs of tumour lysis syndrome
Monitor patients receiving concurrent anticoagulants
Monitor renal function regularly
Monitor uric acid levels
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider treatments to prevent hyperuricaemia
Potentially mutagenic and carcinogenic
Risk of developing opportunistic infections
Discontinue at first signs of jaundice
Discontinue if Macrophage Activation Syndrome is suspected
Discontinue immediately if any severe fall in blood counts occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Reduce dose to 25% of normal when given with allopurinol
Advise patient to avoid dairy products 1 hour before and 2 hours after dose
Male & female: Contraception required during & for 3 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Advise patient to use SPF 50+ sunscreen and lip balm during treatment

Individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) may be unusually sensitive to the myelosuppressive effect of tioguanine and prone to developing rapid bone marrow depression following initiation of treatment with tioguanine. This problem could be exacerbated by co-administration with drugs that inhibit TPMT.

Individuals with inherited mutated NUDT15 gene are at increased risk of severe 6-mercaptopurine toxicity. Patients with NUDT15 variant generally require dose reduction of mercaptopurine, particularly individuals that are NUDT15 homozygotes.

During remission induction in acute myelogenous leukaemia the patient may frequently experience a period of relative bone marrow aplasia and it is important that adequate supportive facilities are available.

Adequate precautions should be taken to avoid hyperuricaemia, hyperuricosuria and uric acid nephropathy during remission induction, especially when rapid cell lysis is occurring.

Macrophage Activation Syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions. If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible. Physicians should be attentive to the symptoms of infection as this is a known trigger for MAS.

Pregnancy and Lactation

Pregnancy

Mercaptopurine is contraindicated during pregnancy.

The manufacturers recommend avoiding mercaptopurine during pregnancy.

Mercaptopurine is an active metabolite of azathioprine. Mercaptopurine is potentially carcinogenic and mutagenic; prematurity and malformation have been reported, although there are also reports of normal outcomes when the mother has taken mercaptopurine during pregnancy.

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

Mercaptopurine is contraindicated during breastfeeding.

The manufacturers recommend avoiding mercaptopurine during breastfeeding.

Mercaptopurine has been detected in the breast milk of patients receiving immunosuppressive therapy with azathioprine, a pro-drug of mercaptopurine.

Due to the molecular weight of mercaptopurine excretion into the breast milk is to be expected. There is some evidence of the risk to the infant but in consideration of the known side effects extreme caution would be advised. If administered the infants complete blood count and liver function should be closely monitored. Infants with the rare deficiency of thiopurine-methyltransferase (TPMT) could be sensitive to maternal long-term therapy while being breastfed.

The effect of concurrent therapies must also be considered.

Side Effects

Alopecia
Anaemia
Anorexia
Arthralgia
Biliary stasis
Bone marrow depression
Diarrhoea
Drug fever
Facial oedema
Gastro-intestinal ulceration
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatotoxicity
Hyperuricaemia
Hyperuricosuria
Hypoglycaemia
Jaundice
Kaposi's Sarcoma
Leucopenia
Lymphoproliferative disorders
Malignant melanoma
Mouth ulcers
Myelodysplastic syndrome
Nausea
Neoplasms
Nodular regenerative hyperplasia
Non Kaposi's sarcoma
Non melanoma skin cancer
Oligospermia (reversible)
Opportunistic infections
Pancreatitis
Photosensitivity
Portal hypertension
Rash
Secondary leukaemia
Stomatitis
Thrombocytopenia
Uterine carcinoma
Vomiting

Presentation

Oral formulations of mercaptopurine.

Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic
Leukaemia - acute myeloid
Leukaemia - acute promyelocytic

Unlicensed Uses

Crohn's disease - maintenance of remission
Severe Crohn's disease
Ulcerative colitis: induction of remission
Ulcerative colitis: maintenance of remission

Dosage

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

Doses may vary significantly if this agent is used as monotherapy or different combinations.

When using this agent, specialist literature, national guidelines, cancer networks protocols and Trust chemotherapy protocols should be consulted.

Adults

Children

Administration

Administration of daily dose should be in the evening as this may lower the risk of relapse.

Contraindications

Breastfeeding
Pregnancy

Precautions and Warnings

Inherited thiopurine methyltransferase deficiency
Dehydration
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Lactose intolerance
Phenylketonuria
Renal impairment - creatinine clearance below 50ml/minute

Administration of live vaccines is not recommended
Some formulations contain aspartame - caution in phenylketonuria
Not all available brands are licensed for all indications
Not all formulations are licensed for all uses
Treatment to be initiated and supervised by a specialist
Oral solution contains sucrose and hydroxybenzoates
Some formulations contain lactose
Some formulations contain sucrose
Different formulations are not bioequivalent
Monitor closely if switching between tablet formulation and oral solution
Accidental contact of soln with skin/mucous membranes-rinse well with water
Avoid contact with mucous membranes
Avoid contact with skin or eyes
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Take at the same time in respect to food as absorption may be affected
Monitor haematological parameters before and during treatment
Elderly: Monitor renal function and consider dose modification
Monitor for presence of hepatitis B markers
Monitor for signs of Macrophage Activation Syndrome (MAS)
Monitor liver function tests weekly
Monitor patients for signs of tumour lysis syndrome
Monitor patients receiving concurrent anticoagulants
Monitor renal function regularly
Monitor uric acid levels
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider treatments to prevent hyperuricaemia
Potentially mutagenic and carcinogenic
Risk of developing opportunistic infections
Discontinue at first signs of jaundice
Discontinue if Macrophage Activation Syndrome is suspected
Discontinue immediately if any severe fall in blood counts occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Reduce dose to 25% of normal when given with allopurinol
Advise patient to avoid dairy products 1 hour before and 2 hours after dose
Male & female: Contraception required during & for 3 months after treatment
Advise patient to avoid exposure to sunlight and UV rays during treatment
Advise patient to use SPF 50+ sunscreen and lip balm during treatment

Individuals with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) may be unusually sensitive to the myelosuppressive effect of tioguanine and prone to developing rapid bone marrow depression following initiation of treatment with tioguanine. This problem could be exacerbated by co-administration with drugs that inhibit TPMT.

Individuals with inherited mutated NUDT15 gene are at increased risk of severe 6-mercaptopurine toxicity. Patients with NUDT15 variant generally require dose reduction of mercaptopurine, particularly individuals that are NUDT15 homozygotes.

During remission induction in acute myelogenous leukaemia the patient may frequently experience a period of relative bone marrow aplasia and it is important that adequate supportive facilities are available.

Adequate precautions should be taken to avoid hyperuricaemia, hyperuricosuria and uric acid nephropathy during remission induction, especially when rapid cell lysis is occurring.

Macrophage Activation Syndrome (MAS) is a known, life-threatening disorder that may develop in patients with autoimmune conditions. If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible. Physicians should be attentive to the symptoms of infection as this is a known trigger for MAS.

Pregnancy and Lactation

Pregnancy

Mercaptopurine is contraindicated during pregnancy.

The manufacturers recommend avoiding mercaptopurine during pregnancy.

Mercaptopurine is an active metabolite of azathioprine. Mercaptopurine is potentially carcinogenic and mutagenic; prematurity and malformation have been reported, although there are also reports of normal outcomes when the mother has taken mercaptopurine during pregnancy.

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

Mercaptopurine is contraindicated during breastfeeding.

The manufacturers recommend avoiding mercaptopurine during breastfeeding.

Mercaptopurine has been detected in the breast milk of patients receiving immunosuppressive therapy with azathioprine, a pro-drug of mercaptopurine.

Due to the molecular weight of mercaptopurine excretion into the breast milk is to be expected. There is some evidence of the risk to the infant but in consideration of the known side effects extreme caution would be advised. If administered the infants complete blood count and liver function should be closely monitored. Infants with the rare deficiency of thiopurine-methyltransferase (TPMT) could be sensitive to maternal long-term therapy while being breastfed.

The effect of concurrent therapies must also be considered.

Side Effects

Alopecia
Anaemia
Anorexia
Arthralgia
Biliary stasis
Bone marrow depression
Diarrhoea
Drug fever
Facial oedema
Gastro-intestinal ulceration
Hepatic necrosis
Hepatic veno-occlusive disease
Hepatotoxicity
Hyperuricaemia
Hyperuricosuria
Hypoglycaemia
Jaundice
Kaposi's Sarcoma
Leucopenia
Lymphoproliferative disorders
Malignant melanoma
Mouth ulcers
Myelodysplastic syndrome
Nausea
Neoplasms
Nodular regenerative hyperplasia
Non Kaposi's sarcoma
Non melanoma skin cancer
Oligospermia (reversible)
Opportunistic infections
Pancreatitis
Photosensitivity
Portal hypertension
Rash
Secondary leukaemia
Stomatitis
Thrombocytopenia
Uterine carcinoma
Vomiting

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: August 2019

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Martindale: The Complete Drug Reference, 39th edition (2017) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Hanixol 50mg tablets. Fontus Health Ltd. Revised June 2019.
Summary of Product Characteristics: Mercaptopurine 50mg tablets. Aspen Europe. Revised December 2018.
Summary of Product Characteristics: Xaluprine 20mg/ml oral suspension. Nova Laboratories Ltd. Revised May 2020.

The Renal Drug Handbook. 4th edition. (2014) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

N.A.P.O.S. The Drug Database for Acute Porphyria
Available at: https://www.drugs-porphyria.org/monograph2.php?id=2975
Last accessed: 22 August 2019

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 August 2019