L04AX01 - Azathioprine |
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 like nausea and vomiting may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
Infections are common in patients using immunosuppressants and 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 azathioprine that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Azathioprine is exclusively or predominately metabolized by other enzymes than CYP, and is not known to affect the activity of any CYP enzymes. Based on the pharmacokinetics, azathioprine is not expected to have any porphyrinogenic effects.
Chemical description
Nitroamidazolpurine, an imidazol derivative of mercaptopurine.
Therapeutic characteristics
Azathioprine is an immunosuppressant used in the prevention of transplant rejection, and it is also used in autoimmune diseases. It is administered orally or as an intravenous injection
Metabolism and pharmakokinetics
Azathiporine is converted to 6-mercaptopurine via a non-enzymatic process, and subsequently metabolized to inactive metabolites by xanthine oxidase and thiopurine S-methyltransferase respectively, and to the active 6-thioguanin nucleotides by hypoxantin-guanin phosphoribosyltransferase.
Preclinical data
Found to accumulate porphyrins in chicken embryo model (Cochon et al 1997).
Published experience
Reports of uneventful use:
Warholm et al 2003 (tolerated in 1 patient with AIP).
Nunez et al 1987 (tolerated in 1 patient with AIP and in 1 patient with VP)
Day et al 1982 (tolerated in 1 patient with VP)
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria.
References
- Scientific articles
- Cochón AC, Aldonatti C et al, Evaluation of the porphyrinogenic risk of antineoplastics. J Appl Toxicol. 1997 May-Jun;17(3):171-7. PMID 38880326. #2334
- Day RS, Eales L, Porphyrins in renal transplantation. Nephron. 1982;30(1):22-7. PMID 7045710. #4615
- Schwab M, Klotz U, Pharmacokinetic considerations in the treatment of inflammatory bowel disease Clin Pharmacokinet. 2001;40(10):723-51 PMID 11707060. #2335
- Singh N, Infectious complications in organ transplant recipients with the use of calcineurin-inhibitor agent-based immunosuppressive regimens. Curr Opin Infect Dis. 2005 Aug;18(4):342-5. PMID 15985832. #4616
- Nunez DJ, Williams PF, Herrick AL, Evans DB, McColl KEL. Renal transplantation for chronic renal failure in acute porphyria. Nephrology Dialysis Transplantation 1987; 2(4):271-274. #2320
- Warholm C, Wilczek H. Renal transplantation in a case of acute intermittent porphyria. Journal of Clinical Pharmacology 2003; 43(10):1158-1160. #2324
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Azathioprin. Pharmaceutical Press 2009. #2337
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Imuran. #2338
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