Contents

Search

azathioprine (Azanin, Imuran, Imurel)

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] - inactivated by placenta [7] - consider an alternate agent for patients with low or deficient TPMT activity* * see thiopurine methyltransferase in erythrocytes & TPMT gene mutation Dosage: 1) lupus erythematosus & rheumatoid arthritis: a) start: 1.5 mg/kg/day PO QD or divided BID. b) increase: 8-12 week intervals. c) max: 2.5 mg/kg/day 2) renal transplantation a) start 3-5 mg/kg/day PO b) maintenance 1-3 mg/kg/day PO Tabs: 50 mg Injection: 100 mg Caution: dosage should be decreased 60-75% when coadministered with allopurinol. Pharmacokinetics: 1) 60% oral bioavailability 2) rapidly converted to an active metabolite, 6-mercaptopurine 3) 6-mercaptopurine is metabolized by xanthine dehydrogenase 4) inactivated by placenta [7] 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: 1) common (> 10%) - leukopenia, secondary infection, nausea/vomiting, anorexia, anemia, fever/chills 2) not common (1-10%) - hepatitis, pancytopenia, thrombocytopenia, skin rash 3) uncommon (< 1%) - hypotension, alopecia, aphthous stomatitis, hepatotoxicity, arthralgias, myalgias, rigors, retinopathy, dyspnea, hypersensitivity reactions 4) other [3] a) dose-related bone marrow suppression b) serious infections with long term therapy c) diarrhea 5) increased risk for acute pancreatitis in patients with inflammatory bowel disease [9] Drug interactions: 1) xanthine dehydrogenase inhibitors allopurinol & febuxosat increase effect & toxicity of azathioprine 2) coadministration of ACE inhibitors may induce severe leukopenia 3) methotrexate increases serum levels of mercaptopurine 4) azathioprine decreases cyclosporine levels 5) azathioprine increases activity of warfarin Laboratory: - thiopurine methyltransferase in erythrocytes - TPMT gene mutation Mechanism of action: 1) immunosuppressive 2) antagonist to purine metabolism 3) may inhibit DNA & RNA synthesis 4) inhibits proliferation of lymphocytes, B-cells & T-cells

Interactions

drug interactions drug adverse effects of immunosuppressive agents monitor with immunosuppressive agents

General

disease-modifying antirheumatic agent (DMARD) immunosuppressive agent mercaptopurine; thiopurine

Properties

MISC-INFO: elimination route LIVER KIDNEY pregnancy-category D safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 524
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Prescriber's Letter 16(2): 2009 Rheumatoid Arthritis: The Role of DMARDs Detail-Document#: 250210 (subscription needed) http://www.prescribersletter.com
  6. Deprecated Reference
  7. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
  8. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline information for azathioprine and TPMT. https://www.pharmgkb.org/guideline/PA166104933
  9. 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: 30685366 https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30401-2/fulltext