azathioprine (Azanin, Imuran, Imurel)
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Introduction
Tradenames: Azanin, Imuran, Imurel.
Indications
- to prevent organ rejection after transplantation
- liver transplantation
- prevention of renal graft rejection[6]
- treatment of lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Crohn's disease, ulcerative colitis, myasthenia gravis, autoimmune thrombocytopenia, pemphigus, dermatomyositis, polymyositis, vasculitis[7]
Contraindications
- generally safer than mycophenolate & well-tolerated during pregnancy[7]
- consider an alternate agent for patients with low or deficient TPMT activity*
* see thiopurine methyltransferase in erythrocytes & TPMT gene mutation
Dosage
Tabs: 50 mg
Injection: 100 mg
Caution: dosage should be decreased 60-75% when coadministered with allopurinol.
Pharmacokinetics
- 60% oral bioavailability
- rapidly converted to an active metabolite, 6-mercaptopurine
- 6-mercaptopurine is metabolized by xanthine dehydrogenase
- inactivated by placenta[7]
elimination via liver
elimination via kidney
Monitor
- baseline
- CBC, LFTs, serum creatinine[7]
- consider thiopurine methyltransferase in erythrocytes to assess likelihood of myelosuppression
- thereafter
- CBC, LFTs, serum creatinine every 3 months
- CBC weekly until a stable dose is reached, then monthly for 1-3 months[5]
- CBC, liver function tests quarterly[5]
Adverse effects
- common (> 10%)
- not common (1-10%)
- uncommon (< 1%)
- hypotension, alopecia, aphthous stomatitis, hepatotoxicity, arthralgias, myalgias, rigors, retinopathy, dyspnea, hypersensitivity reactions
- other[3]
- dose-related bone marrow suppression
- serious infections with long term therapy
- diarrhea
- increased risk for acute pancreatitis in patients with inflammatory bowel disease[9]
Drug interactions
- xanthine dehydrogenase inhibitors allopurinol & febuxosat increase effect & toxicity of azathioprine
- coadministration of ACE inhibitors may induce severe leukopenia
- methotrexate increases serum levels of mercaptopurine
- azathioprine decreases cyclosporine levels
- azathioprine increases activity of warfarin
- drug interaction(s) of xanthine oxidase inhibitors with azathioprine
- drug interaction(s) of methotrexate with biological response modifier
- drug interaction(s) of mercaptopurine in combination with allopurinol
Laboratory
Mechanism of action
- immunosuppressive
- antagonist to purine metabolism
- may inhibit DNA & RNA synthesis
- inhibits proliferation of lymphocytes, B-cells & T-cells
More general terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 524
- ↑ 3.0 3.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 5.2 Prescriber's Letter 16(2): 2009 Rheumatoid Arthritis: The Role of DMARDs Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250210&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Deprecated Reference
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
- ↑ Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline information for azathioprine and TPMT. https://www.pharmgkb.org/guideline/PA166104933
- ↑ 9.0 9.1 Wintzell V, Svanstrom H, Olen O et al Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease: a Swedish-Danish nationwide cohort study. Lancet Child & Adolescent Health. Jan 23, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30685366 https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext