General A gastrointestinal hypersensitivity reaction characterized by severe nausea and vomiting has been reported. These symptoms may also be accompanied by diarrhea, rash, fever, malaise, myalgias, elevations in liver enzymes, and occasionally, hypotension. Symptoms of gastrointestinal toxicity most often develop within the first several weeks of therapy with AZASAN® (azathioprine) and are reversible upon discontinuation of the drug. The reaction can recur within hours after rechallenge with a single dose of AZASAN® (azathioprine) . Laboratory Tests Complete Blood Count (CBC) Monitoring Patients on AZASAN® (azathioprine) should have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary. TPMT Testing It is recommended that consideration be given to either genotype or phenotype patients for TPMT. Phenotyping and genotyping methods are commercially available. The most common non-functional alleles associated with reduced levels of TPMT activity are TPMT*2, TPMT*3A and TPMT*3C. Patients with two non-functional alleles (homozygous) have low or absent TPMT activity and those with one non-functional allele (heterozygous) have intermediate activity. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions. TPMT testing may also be considered in patients with abnormal CBC results that do not respond to dose reduction. Early drug discontinuation in these patients is advisable. TPMT TESTING CANNOT SUBSTITUTE FOR COMPLETE BLOOD COUNT (CBC) MONITORING IN PATIENTS RECEIVING AZASAN®. See CLINICAL PHARMACOLOGY, WARNINGS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections. Carcinogenesis, Mutagenesis, Impairment of Fertility See WARNINGS section. Pregnancy Teratogenic Effects Pregnancy Category D. See WARNINGS section. Nursing Mothers The use of AZASAN® in nursing mothers is not recommended. Azathioprine or its metabolites are transferred at low levels both transplacentally and in breast milk.17, 18, 19 Because of the potential for tumorigenicity shown for azathioprine, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and efficacy of azathioprine in pediatric patients have not been established. REFERENCES 2. Weinshilboum R. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab Dispos. 2001;29:601-605. 3. McLeod HL, Siva C. The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics. Pharmacogenomics. 2002;3:89-98. 4. Anstey A, Lennard L, Mayou SC, et al. Pancytopenia related to azathioprine – an enzyme deficiency caused by a common genetic polymorphism: a review. JR Soc Med. 1992; 85:752-756. 5. Stolk JN, Beorbooms AM, de Abreu RA, et al. Reduced thiopurine methyltransferase activity and development of side effects of azathioprine treatment in patients with rheumatoid arthritis. Arthritis Rheum. 1998; 41:1858-1866. 6. Data on file, Prometheus Laboratories Inc. 7. Yates CR, Krynetski EY, Loennechen T, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med. 1997; 126:608-614. 8. Black AJ, McLeod HL, Capell HA, et al. Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann Intern Med. 1998; 129:716-718. 9. Clunie GP, Lennard L. Relevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine. Rheumatology. 2004; 43:13-18. 10. Clark JM. The mutagenicity of azathioprine in mice, Drosophila melanogaster, and Neurospora crassa. Mutat Res. 1975; 28:87-99. 11. Data on file, Prometheus Laboratories Inc. 12. Tagatz GE, Simmons RL. Pregnancy after renal transplantation. Ann Intern Med. 1975; 82:113-114. Editorial Notes. 13. Cote' CJ, Meuwissen HJ, Pickering RJ. Effects on the neonate of prednisone and azathioprine administered to the mother during pregnancy. J Pediatr. 1974; 85:324-328. 14. DeWitte DB, Buick MK, Cyran SE, et al. Neonatal pancytopenia and severe combined immunodeficiency associated with antenatal administration of azathioprine and prednisone. J Pediatr. 1984; 105:625-628. 15. Williamson RA, Karp LE. Azathioprine teratogenicity: review of the literature and case report. Obstet Gynecol. 1981; 58:247-250. 16. Tallent MB, Simmons RL, Najarian JS. Birth defects in child of male recipient of kidney transplant. JAMA. 1970; 211:1854-1855. 17. Data on file, Prometheus Laboratories Inc. 18. Saarikoski S, Seppälä M. Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus. Am J Obstet Gynecol. 1973; 115:1100-1106. 19. Coulam CB, Moyer TP, Jiang NS, et al. Breast-feeding after renal transplantation. Transplant Proc. 1982; 14: 605-609. Last reviewed on RxList: 9/14/2009
This monograph has been modified to include the generic and brand name in many instances.