[2] Common side effects include bone marrow suppression, liver toxicity, vomiting, and loss of appetite.
Treatment is discontinued in up to 30% of patients due these effects but therapeutic drug monitoring of the biologically active metabolites, i.e. thiopurine nucleotides can help to optimize the efficacy and safety.
Clinically, most hospitals resort to on-exchange LC-MS (liquid chromatography - mass spectrometry) but the newly developed approach of porous graphitic carbon based chromatography hyphenated with mass spectrometry appears superior with respect to patient care in this respect.
[7] Symptoms of allergic reaction to mercaptopurine include rash, itching, swelling, dizziness, trouble breathing, and inflammation of the pancreas.
Toxicity of mercaptopurine can be linked to genetic polymorphisms in thiopurine S-methyltransferase (TPMT), nudix hydrolase 15 (NUDT15),[8][9] and inosine triphosphate pyrophosphatase (ITPA).
[14] The European Crohn's and Colitis Organisation (ECCO) concluded in a consensus paper in 2010 that while AZA and mercaptopurine have an FDA rating of D, new research in both animals and humans indicates that "thiopurines are safe and well tolerated during pregnancy.
"[15] Mercaptopurine causes changes to chromosomes in animals and humans, though a study in 1990[16] found, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal."
[22][23][24] Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving mercaptopurine.
[25][27] The FDA-approved drug label for mercaptopurine recommends testing for TPMT activity to identify people at risk for myelotoxicity.
[32] The collaboration was initiated by Cornelius P. Rhoads, who had run chemical weapons programs for the US Army and had been involved in the work that led to the discovery that nitrogen mustards could potentially be used as cancer drugs, and had become the director of Memorial in 1948.