Chemical formula: C₅H₄N₄S Molecular mass: 152.177 g/mol PubChem compound: 667490
Mercaptopurine interacts in the following cases:
Vaccinations with other live organism vaccines are not recommended in immunocompromised individuals.
Since 6-mercaptopurine pharmacokinetics has not been formally studied in hepatic impairment, no specific dose recommendations can be given. Since there is a potential for reduced elimination of mercaptopurine, consideration should be given to reduced starting doses in patients with impaired hepatic function. Patients should be closely monitored for dose related adverse reactions.
Since 6-mercaptopurine pharmacokinetics has not been formally studied in renal impairment, no specific dose recommendations can be given. Since impaired renal function may result in slower elimination of mercaptopurine and its metabolites and therefore a greater cumulative effect, consideration should be given to reduced starting doses in patients with impaired renal function. Patients should be closely monitored for dose related adverse reactions.
As there is in vitro evidence that aminosalicylate derivatives (eg. olsalazine, mesalazine or sulfazalazine) inhibit the TPMT enzyme, which metabolises 6-mercaptopurine, they should be administered with caution to patients receiving concurrent mercaptopurine therapy.
Inhibition of the anticoagulant effect of warfarin, when given with 6-mercaptopurine, has been reported. Monitoring of the INR (International Normalised Ratio) value is recommended during concomitant administration with oral anticoagulants.
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 metabolism of 6-mercaptopurine via xanthine oxidase. Also other xanthine oxidase inhibitors, such as febuxostat, may decrease the metabolism of mercaptopurine and concomitant administration is not recommended as data are insufficient to determine an adequate dose reduction.
It is possible that the levels of anti-epileptic medicinal products may also be altered. Serum antiepileptic levels should be closely monitored during treatment with mercaptopurine, making dose adjustments as necessary.
The effect of mercaptopurine therapy on human fertility is unknown but there are reports of successful fatherhood/motherhood after receiving treatment during childhood or adolescence. Transient profound oligospermia has been reported following exposure to mercaptopurine in combination with corticosteroids.
Cytotoxic agents may decrease the intestinal absorption of phenytoin. Careful monitoring of the phenytoin serum levels is recommended.
Treatment with 6-mercaptopurine causes bone marrow suppression leading to leucopenia and thrombocytopenia and, less frequently, to anaemia. Careful monitoring of haematological parameters should be conducted 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 the counts, treatment should be interrupted immediately. Bone marrow suppression is reversible if 6-mercaptopurine is withdrawn early enough.
Patients treated with 6-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 6-mercaptopurine for ALL.
Patients with inherited mutated NUDT15 gene are at increased risk for severe 6-mercaptopurine toxicity. These patients generally require dose reduction; particularly those being NUDT15 variant homozygotes. Genotypic testing of NUDT15 variants may be considered before initiating 6-mercaptopurine therapy. In any case, close monitoring of blood counts is necessary.
Mercaptopurine should not be given to patients who are pregnant or likely to become pregnant without careful assessment of risk versus benefit.
There have been reports of premature birth and low birth weight following maternal exposure to mercaptopurinee. There have also been reports of congenital abnormalities and spontaneous abortion following either maternal or paternal exposure. Multiple congenital abnormalities have been reported following maternal 6-mercatopurine treatment in combination with other chemotherapy agents.
A more recent epidemiological report suggests that there is no increased risk of preterm births, low birth weight at term, or congenital abnormalities in women exposed to mercaptopurine during pregnancy.
It is recommended that newborns of women exposed to mercaptopurine during pregnancy are monitored for haematological and immune system disturbances.
Mercaptopurine has been identified in the colostrum and breast-milk of women receiving azathioprine treatment and thus women receiving mercaptopurine should not breast-feed.
Evidence of the teratogenicity of mercaptopurine in humans is equivocal. Both sexually active men and women should use effective methods of contraception during treatment and for at least three months after receiving the last dose. Animal studies indicate embryotoxic and embryolethal effects.
The effect of mercaptopurine therapy on human fertility is unknown but there are reports of successful fatherhood/motherhood after receiving treatment during childhood or adolescence. Transient profound oligospermia has been reported following exposure to mercaptopurine in combination with corticosteroids.
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.
The main adverse reaction of treatment with 6-mercaptopurine is bone marrow suppression leading to leucopenia and thrombocytopenia.
For mercaptopurine there is a lack of modern clinical documentation which can serve as support for accurately determining the frequency of adverse reactions.
The following events have been identified as adverse reactions. The adverse reactions are displayed by system organ class and frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000) and very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Uncommon: Bacterial and viral infections, infections associated with neutropenia
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
Unknown: Hepatosplenic T-cell lymphoma*
Very common: Bone marrow suppression; leucopenia and thrombocytopenia
Common: Anaemia
Uncommon: Arthralgia, skin rash, drug fever
Rare: Facial oedema
Common: Anorexia
Unknown: Hypoglycaemia†
Common: Stomatitis, diarrhoea, vomiting, nausea
Uncommon: Pancreatitis, oral ulceration
Very rare: Intestinal ulceration
Common: Biliary stasis, hepatotoxicity
Uncommon: Hepatic necrosis
Rare: Alopecia
Unknown: Photosensitivity reaction
Rare: Transient oligospermia
* In patients with inflammatory bowel disease (IBD), an unlicensed indication.
† In the paediatric population.
6-mercaptopurine is hepatotoxic in animals and man. The histological findings in man 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 is exceeded.
Monitoring of liver function tests may allow early detection of hepatotoxicity. This is usually reversible if 6-mercaptopurine therapy is stopped soon enough but fatal liver damage has occurred.
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