L01BB02 - Mercaptopurine |
Propably not porphyrinogenic |
PNP |
Important Information
Patients on immunosuppressive therapy have an increased risk of infections. Since infections have a potential to trigger acute porphyric attacks vigilance is motivated regarding signs or symptoms of infection and/or possible symptoms of a porphyric attack.
Side effects
Infections are common in patients using immunosuppressant drugs. Since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended.
Common adverse reactions of mercaptopurine that can be confused with an acute porphyric attack are abdominal pain, nausea and vomiting. These side effects may potentially be porphyrinogenic through reduction in caloric intake.
Rationale
Mercaptopurine is not suspected to be a substrate of CYP450 enzymes and is not known to affect the activity of any CYP450 enzymes. Based on the pharmacokinetics, it is not expected to have any porphyrinogenic effects.
Chemical description
Mercaptopurine in a thiopurin
Therapeutic characteristics
Mercaptopurine is an antineoplastic agent and immunosuppressant. It is used to treat acute leukaemia, especially in children, and chronic myeloic leukaemia all stages.
It is administered orally.
Hepatic exposure
Significant
Metabolism and pharmakokinetics
Mercaptopurine is extensively metabolized in the liver by methylation and oxidation as well as by the formation of inorganic sulfates. Considerable amounts are oxidized to thiouric acid by xanthine oxidase (Martindale). It is excreted in the urine as mercaptopurine (46 %) and metabolites.
Co-administration of mercaptopurine and warfarin may result in decreased plasma concentration of warfarin, but the mechanism behind is unclear (Martin 2003). There are no reports of interactions with CYP-metabolism of other drugs (Lexi-Interact), and mercaptopurine is not listed as an inducer or an inhibitor of CYP450 enzymes (Rendic 2002 and SPC).
References
- Scientific articles
- Martin, A. L., Mehta, S. D. Diminished Anticoagulant Effects of Warfarin with Concomitant Mercaptopurine Therapy. Pharmacotherapy 2003; 23(2):260-4. #1929
- Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2): 83-448. PMID 11996015. #4568
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Mercaptopurine. Pharmaceutical Press #1932
- Government bodies
- #1302
- Drug interaction databases
- Lexi-Interact in UpToDate. Mercaptopurine: Drug interaction program. #1928
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Puri-Nethol. #1930
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