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Azathioprine

Pronunciation

Class: Immunosuppressive Agents
VA Class: IM600
CAS Number: Azathioprine: 446-86-6
Brands: Azasan, Imuran

Warning(s)

  • Long-term immunosuppression with azathioprine increases risk of malignancy in humans.100 134 136 137 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

  • Malignancies, including posttransplant lymphoma and hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease, reported.100 136 137 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

  • Only clinicians familiar with the risks, mutagenic potential, and possible hematologic toxicity should prescribe azathioprine.100 134 136

  • Inform patients of risk of malignancy associated with azathioprine.100 136 137 (See Advice to Patients.)

Introduction

Immunosuppressive antimetabolite.100 134 136

Uses for Azathioprine

Renal Allotransplantation

Prevention of rejection of renal allografts.100 134 136

Rheumatoid Arthritis

Management of the signs and symptoms of rheumatoid arthritis.100 134 136

Crohn’s Disease

Has been used to induce and maintain remission in adults with moderate to severely or chronically active Crohn’s disease.110 111 112 113 114 117 118 119 120 122

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Has been used in the management of fistulizing Crohn’s disease.111 115 116 131 132

Has been used in children with refractory or corticosteroid-dependent Crohn’s disease.128 129 133

Carefully consider risks and benefits in patients with inflammatory bowel disease, especially in adolescents and young adults.100 136 137 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Azathioprine Dosage and Administration

General

  • Azathioprine is an antimetabolite and is handled according to guidelines for cytotoxic drugs.100 136 c Consult specialized references for procedures for proper handling and disposal of hazardous drugs.100 134 136

Administration

Administer orally or by slow IV injection or IV infusion.100 134 136

Low-dose corticosteroids and NSAIAs (including aspirin) may be continued in patients with rheumatoid arthritis.100 134 136 The manufacturers state that combined use of azathioprine and other disease modifying antirheumatic drugs (DMARDs) has not been studied and is not recommended.100 134 136

Oral Administration

Administer once or twice daily.100 134

IV Administration

When used for renal allotransplantation, the IV route may be used initially in patients unable to tolerate oral medication.136 Institute oral therapy as soon as possible (at the same dosage).136 c

Reconstitution and Dilution

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitute vial containing 100 mg of azathioprine with 10 mL of sterile water for injection.136 Reconstituted solution may be further diluted prior to administration (final volume depends on infusion time).136

Rate of Administration

Usually infused over 30–60 minutes; may be administered over 5 minutes to 8 hours.136

Dosage

Available as azathioprine and azathioprine sodium; dosage expressed as azathioprine.100 134 136

Consider determining thiopurine methyl transferase (TPMT) phenotype or genotype prior to initiation of therapy and using results to select dosage.100 136 (See Hematologic Effects and TPMT Testing under Cautions.)

If rapid fall in leukocyte count, persistent leukopenia, or other evidence of bone marrow suppression develops, temporarily discontinue or reduce dosage.100 134 136 Consider TPMT testing in patients with abnormal CBC results that persist despite dosage reduction.100 136 (See Hematologic Effects and TPMT Testing under Cautions.)

If used with allopurinol, adjustment in the treatment regimen recommended.100 134 136 (See Specific Drugs under Interactions.)

If severe, continuous rejection occurs, it is probably preferable to allow the allograft to be rejected than to increase the dosage of azathioprine to very toxic levels.c

Pediatric Patients

Crohn’s Disease
Oral

1.5–2 mg/kg daily has been used.128 129 133

Adults

Renal Allotransplantation
Oral

Initially, 3–5 mg/kg as a single daily dose beginning on the day of transplantation (and in some cases 1–3 days before transplantation).100 134 c Reduction to maintenance dosage of 1–3 mg/kg daily usually possible.100 134

IV

3–5 mg/kg as a single daily dose beginning on the day of transplantation (and in some cases 1–3 days before transplantation) until the patient is able to tolerate oral administration (usually 1–4 days).136 c

Rheumatoid Arthritis
Oral

Initially, 1 mg/kg (50–100 mg) daily in 1 or 2 doses.100 134

If initial response unsatisfactory and there are no serious adverse effects after 6–8 weeks, the daily dosage may be increased by 0.5 mg/kg.100 134 Thereafter, daily dosage may be increased, if needed, by 0.5 mg/kg every 4 weeks up to a maximum dosage of 2.5 mg/kg daily.100 134 Patients whose disease does not improve after 12 weeks of therapy are considered nonresponders.100 134

When used for maintenance dosage, use lowest effective dosage to reduce toxicities.100 134 Dosage can be reduced in increments of 0.5 mg/kg (approximately 25 mg) daily every 4 weeks while other therapy is kept constant.100 134

Optimum duration of therapy undetermined.100 134

Crohn’s Disease
Oral

2–4 mg/kg daily has been used.116 119 126 132

Prescribing Limits

Adults

Rheumatoid Arthritis
Oral

Maximum 2.5 mg/kg daily.100 134

Special Populations

Renal Impairment

Use low initial dosage in patients with renal impairment.c

Renal Allotransplantation

Lower dosage may be necessary in relatively oliguric patients, especially in those with tubular necrosis in the immediate posttransplant period.100 134 136

Cautions for Azathioprine

Contraindications

  • Known hypersensitivity to azathioprine or any ingredient in the formulation.100 134 136

  • Management of rheumatoid arthritis in pregnant women.100 134 136

  • Management of rheumatoid arthritis in patients previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan), because of prohibitive risk of neoplasia.100 134 136 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Warnings/Precautions

Warnings

Malignancies and Lymphoproliferative Disorders

Increased risk of lymphoma and other malignancies, particularly of the skin.100 134 136 137 Monitor for occurrence of malignancies.137

Risk of posttransplant lymphomas may be increased in patients receiving aggressive immunosuppressive therapy; maintain therapy at lowest effective dosage.100 136

Risk of malignancy may be increased in patients with rheumatoid arthritis, although to a lesser extent than in renal transplant patients; precise risk of malignancy associated with azathioprine unknown.100 136 Acute myelogenous leukemia and solid tumors reported in azathioprine-treated patients with rheumatoid arthritis.100 136 Patients with rheumatoid arthritis previously treated with alkylating agents (e.g., cyclophosphamide, chlorambucil, melphalan) may have a prohibitive risk of malignancy if treated with azathioprine.100 136

Hepatosplenic T-cell lymphoma, a rare, aggressive, usually fatal malignancy, reported in azathioprine-treated patients with inflammatory bowel disease.100 136 137

Hepatosplenic T-cell lymphoma mostly reported in adolescents and young adult males with Crohn’s disease or ulcerative colitis receiving a combination of immunosuppressive agents, including tumor necrosis factor (TNF) blocking agents and/or thiopurine analogs (azathioprine or mercaptopurine); however, cases also reported in patients receiving azathioprine or mercaptopurine alone.100 136 137 Carefully consider risks and benefits of these agents, especially in adolescents and young adults with Crohn’s disease or ulcerative colitis.137

Patients with certain conditions (e.g., Crohn’s disease, rheumatoid arthritis) may be at increased risk for lymphoma; may be difficult to measure added risk of TNF-blocking agents, azathioprine, and/or mercaptopurine.137

Hematologic Effects

Severe leukopenia, thrombocytopenia, anemias including macrocytic anemia, and/or pancytopenia reported.100 134 136 Delayed hematologic suppression may occur.100 134 136

When receiving usual dosages of azathioprine, patients with low or absent levels of S- methyl transferase (TPMT) activity (0.3% of the population) are at increased risk of life-threatening myelotoxicity; alternative therapy advised.100 135 136 Patients with intermediate TPMT activity (10–11% of the population) are at increased risk of hematologic toxicity; dosage reduction recommended.100 135 136

Hematologic toxicity is dose related and may be more severe in patients undergoing graft rejection.100 134 136

Perform CBC, including platelet count, weekly during the first month of therapy, twice monthly during the second and third months, then monthly thereafter; monitor more frequently if therapy changes are needed.100 134 136

If rapid decrease in leukocyte count, persistent leukopenia, or other evidence of bone marrow suppression develops, promptly reduce dosage or temporarily discontinue the drug.100 134 136

Azathioprine-induced leukopenia does not correlate with therapeutic effect; do not increase dosage intentionally to decrease leukocyte count.100 136

Infectious Complications

Increased susceptibility to infection (i.e., opportunistic infections, sepsis, life-threatening/fatal infections).100 134 136 Treat infection promptly and reduce azathioprine dosage or consider alternative therapy.100 134 136

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.100 134 136

Avoid use in pregnant women unless benefits outweigh risks.100 134 136

Avoid pregnancy during therapy.100 134 136 If patient becomes pregnant, apprise of potential fetal hazard.100 134 136

Manufacturers state that azathioprine should not be used to treat rheumatoid arthritis in pregnant women;100 134 136 some clinicians state that use in pregnancy should be limited to women with severe or life-threatening rheumatoid arthritis.109

Serious neonatal leukopenia and thrombocytopenia may be prevented by reducing azathioprine dosage at 32 weeks’ gestation; monitor prenatal growth and follow offspring long-term.109

Sensitivity Reactions

GI Hypersensitivity

Severe nausea and vomiting, sometimes accompanied by diarrhea, rash, fever, malaise, myalgias, elevations in liver enzymes, hypotension, reported.100 134 136 Develops during the first several weeks of therapy; reversible upon discontinuation; can occur after rechallenge.100 134 136

General Precautions

TPMT Testing

Genetically determined differences in TPMT activity may lead to differences in patient response and/or toxicity.100 135 136 (See Hematologic Effects under Cautions.) The most common nonfunctional alleles associated with reduced TPMT activity are TPMT*2, TPMT*3A, and TPMT*3C.100 136 Patients with 2 nonfunctional alleles (homozygous) have low or absent TPMT activity; those with 1 nonfunctional allele (heterozygous) have intermediate activity.100 136

Consider determining the TPMT genotype or phenotype prior to initiating therapy and in patients with abnormal CBC results that persist despite dose reduction.100 136 (See Hematologic Effects under Cautions and see Dosage.)

Specific Populations

Pregnancy

Category D.100 134 136 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into human milk.100 134 136 Discontinue nursing or the drug because of potential tumorigenicity.100 134 136

Pediatric Use

Safety and efficacy not established.100 134 136

Hepatosplenic T-cell lymphoma reported in adolescents receiving azathioprine for the management of inflammatory bowel disease.100 136 137 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Renal Impairment

Dosage adjustment may be needed.100 134 136

Common Adverse Effects

Hematologic, GI (nausea, vomiting).100 134 136

Interactions for Azathioprine

Drugs Affecting Myelopoiesis

Risk of severe leukopenia, especially in renal transplant recipients.100 134 136

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Potential for increased toxicity (anemia, severe leukopenia)100 134 136

Allopurinol

Allopurinol inhibits metabolic pathway catalyzed by xanthine oxidase; may increase risk of azathioprine toxicity100 134 136

Reduce azathioprine dosage to 25–33% of usual dosage; consider further dosage reduction or alternative therapy in patients with low or absent TPMT activity100 134 136

Aminosalicylates (mesalamine, olsalazine, sulfasalazine)

Aminosalicylates inhibit metabolic pathway catalyzed by TPMT; may increase risk of azathioprine toxicity100 134 136

Use concomitantly with caution100 134 136

Co-trimoxazole

Possible increased leukopenia, especially in renal transplant recipients100 134 136

Ribavirin

Ribavirin inhibits metabolic pathway catalyzed by inosine monophosphate dehydrogenase, resulting in accumulation of myelotoxic metabolite of azathioprine; severe pancytopenia reported100 136

Monitor CBC, including platelet counts, weekly for first month, twice monthly during second and third months, then monthly thereafter (or more frequently if dosage or other therapy changes needed)100 136

Warfarin

Possible reduced anticoagulant effect100 134 136

Azathioprine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak serum concentration attained within 1–2 hours.100 134 136

Onset

Following oral administration in patients with rheumatoid arthritis, therapeutic response usually occurs after 6–8 weeks.100 134 136

Distribution

Extent

Not fully characterized.c

Plasma Protein Binding

30%.100 134 136

Elimination

Metabolism

Metabolized to 6-mercaptopurine.100 134 136 6-Mercaptopurine is metabolized by 2 competing metabolic pathways or is incorporated as cytotoxic nucleotides into DNA.100 136 6-Mercaptopurine undergoes thiol methylation (catalyzed by TPMT) to an inactive metabolite.100 136 6-Mercaptopurine also undergoes oxidation (catalyzed by xanthine oxidase).100 136

Elimination Route

Excreted in urine, principally as metabolites.c

Half-life

Radiolabeled metabolites: 5 hours.100 134 136

Stability

Storage

Oral

Tablets

Controlled room temperature; protect from light.100 134

Parenteral

Powder for Injection

15–25°C; protect from light and store in carton until time of use.136 Following reconstitution, use within 24 hours.136

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5%

Sodium Chloride 0.45% or 0.9%

Actions

  • Imidazolyl derivative of 6-mercaptopurine; a purine antimetabolite.100 134 136

  • Exact mechanism(s) of immunosuppression not fully elucidated; cytotoxicity due, in part, to incorporation of cytotoxic (6-thioguanine) nucleotides into DNA.100 134 136

  • Inhibits graft rejection; little effect on established graft rejections or secondary responses.100 134 136

  • Suppresses disease manifestations and underlying pathology in animal models of autoimmune disease.100 134 136

Advice to Patients

  • Increased risk of malignancy.100 136 Potential increased risk of hepatosplenic T-cell lymphoma, especially in adolescents and young adults with inflammatory bowel disease receiving thiopurines (azathioprine or mercaptopurine) and/or TNF blocking agents; importance of advising patients and caregivers of relative risks and benefits of these and other immunosuppressive agents.100 134 136 137 Importance of patients not discontinuing therapy without consulting clinician.137

  • Importance of informing patients and caregivers of the signs and symptoms of malignancies such as hepatosplenic T-cell lymphoma (e.g., splenomegaly hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss), and importance of patients informing clinicians if such signs or symptoms occur.137

  • Importance of limiting exposure to sunlight and UV light by wearing protective clothing and using sunscreen with high protection factor.100 136

  • Necessity of routine laboratory testing (e.g., CBC).100 134 136

  • Importance of informing clinician of any evidence of infection, unusual bleeding, bruising, or other manifestation of bone marrow suppression.100 134 136

  • Importance of taking azathioprine as directed.100 134 136

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; importance of advising women to avoid pregnancy while receiving azathioprine.100 134 136

  • Importance of informing clinicians of existing or contemplated therapy, including prescription (e.g., allopurinol) or OTC drugs, as well as concomitant illnesses.100 134 136

  • Importance of informing patients of other important precautionary information.100 134 136 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Azathioprine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Azathioprine Tablets (scored)

Imuran (scored)

Prometheus

75 mg

Azasan (scored)

Salix

100 mg

Azasan (scored)

Salix

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Azathioprine Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

100 mg (of azathioprine)*

Azathioprine Sodium for injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Azasan 100MG Tablets (SALIX PHARMACEUTICALS): 30/$179.99 or 90/$526.99

Azasan 75MG Tablets (SALIX PHARMACEUTICALS): 30/$149.49 or 90/$420.87

AzaTHIOprine 50MG Tablets (ROXANE): 30/$27.99 or 90/$70.97

Imuran 50MG Tablets (PROMETHEUS): 30/$180.00 or 60/$349.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 20, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Prometheus. Imuran (azathioprine) tablets prescribing information. San Diego, CA; 2011 May.

101. Marubbio AT, Danielson B. Hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine. Gastroenterology. 1975; 69:739-43. [PubMed 1098955]

102. Weitz H, Grokel JM, Loeschke K et al. Veno-occlusive disease of the liver in patients receiving immunosuppressive therapy. Virchows Arch Pathol Anat. 1982; 395:245-56. [PubMed 7051531]

103. Katzka DA, Saul SH, Jorkasky D et al. Azathioprine and hepatic venoocclusive disease in renal transplant patients. Gastroenterology. 1986; 90:446-54. [IDIS 210427] [PubMed 3510146]

104. Read AE, Wiesner RH, LaBrecque DR et al. Hepatic veno-occlusive disease associated with renal transplantation and azathioprine. Ann Intern Med. 1986; 104:651-5. [IDIS 215747] [PubMed 3008617]

105. Eisenhauer T, Hartmann H, Rumpf KW et al. Favourable outcome of hepatic veno-occlusive disease in a renal transplant patient receiving azathioprine, treated by portacaval shunt: report of a case and review of the literature. Digestion. 1984; 30:185-90. [PubMed 6389237]

106. Saway PA, Heck LW, Bonner JR et al. Azathioprine hypersensitivity: case report and review of the literature. Am J Med. 1988; 84:960-4. [IDIS 241206] [PubMed 3284343]

107. Bergmann SM, Krane NK, Leonard G et al. Azathioprine and hypersensitivity vasculitis. Ann Intern Med. 1988; 109:83-4. [IDIS 243277] [PubMed 2967660]

108. Cunningham T, Barraclough D, Muirden K. Azathioprine-induced shock. BMJ. 1981; 283:823-4. [IDIS 138587] [PubMed 6794715]

109. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med. 2000; 160:610-9. [IDIS 444392] [PubMed 10724046]

110. Sandborn WJ. Azathioprine: state of the art in inflammatory bowel disease. Scand J Gastroenterol. 1998; 33(Suppl 225):92-9.

111. Hanauer SB, Sandborn W, and the Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn’s disease in adults: Practice Guidelines. Am J Gastroenterol. 2001; 96:635-43. [IDIS 461432] [PubMed 11280528]

112. Feagan BG. Maintenance therapy for inflammatory bowel disease. Am J Gastroenterol. 2003 Dec; 98(12 Suppl): S6-S17.

113. Podolsky DK. Inflammatory Bowel Disease. N Engl J Med. 2002; 347:417-29. [IDIS 484721] [PubMed 12167685]

114. Scribano M, Pantera C. Review article: medical treatment of moderate to severe Crohn’s disease. Aliment Pharmacol Ther. 2003; 17(Suppl. 2):23-30. [PubMed 12786609]

115. Biancone L, Tosti V, Fina D et al. Review article: maintenance treatment of Crohn’s disease. Aliment Pharmacol Ther. 2003; 17(Suppl. 2):31-37. [PubMed 12786610]

116. American Gastroenterological Association position statement on perianal Crohn’s disease. Gastroenterology. 2003; 125:1503-1507.

117. Pearson DC, May GR, Fick G et al. Azathioprine for maintenance of remission in Crohn’s disease Cochrane review). Cochrane Database Sys Rev. . 2000; 2:CD 000067.

118. Hanauer SB, Present DH. The state of the art in the management of inflammatory bowel disease. Rev Gastroenterol Disord. 2003; 3:81-92. Selby WS. Current issues in Crohn’s disease. Rev Gastroenetrol Disord. 2003; 3:81-92.

119. Summers RW, Switz DM, Sessions JT Jr et al. National Cooperative Crohn’s Disease Study: results of drug treatment. Gastroenterology. 1979; 77:847-69. [IDIS 109536] [PubMed 38176]

120. Hanauer SB. Inflammatory bowel disease. N Engl J Med. 1996; 334:841-8. [IDIS 361805] [PubMed 8596552]

121. Markowitz J, Grancher K, Mandel F et al for the Subcommittee on Immunosuppressive Use of the Pediatric IBD Collaborative Research Forum. Immunosuppressive therapy in pediatric inflammatory bowel disease: results of a survey of the North American Society for Pediatric Gastroenterology and Nutrition. Am J Gastroenterol. 1993; 88:44-8. [IDIS 308848] [PubMed 8420272]

122. Candy S, Wright J, Gerber M et al. A controlled double blind study of azathioprine in the management of Crohn’s disease. Gut. 1995; 37:674-8. [IDIS 357251] [PubMed 8549944]

123. O’Donoghue DP, Dawson AM, Powell-Tuck J et al. Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn’s disease. Lancet. 1978; 2:955-7. [PubMed 81986]

124. Rosenberg JL, Levin B, Wall AJ et al. A controlled trial of azathioprine in Crohn’s disease. Am J Dig Dis. 1975; 20:721-6. [PubMed 1098449]

125. Willoughby JM, Beckett J, Kumar PJ et al. Controlled trial of azathiorpine in Crohn’s disease. Lancet. 1971; 2:944-7. [IDIS 25690] [PubMed 4107900]

126. Bouhnik Y, Lémann M, Mary JY et al. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996; 347:215-9. [IDIS 359686] [PubMed 8551879]

127. Pearson DC, May GR, Gordon H et al. Azathioprine and 6-mercaptopurine in Crohn’s disease: a meta-analysis. Ann Intern Med. 1995; 123:132-42. [IDIS 349544] [PubMed 7778826]

128. Kirschner BS. Differences in the management of inflammatory bowel disease in children and adolescents compared to adults. Neth J Med. 1998; 53:S13-8. [PubMed 9883009]

129. Kirschner BS. Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology. 1998; 115:813-21. [IDIS 415209] [PubMed 9753482]

130. Sandborn W, Sutherland L, Pearson D et al. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2000; 2:CD 000545.

131. Rutgeerts P. Treatment of perianal fistulizing Crohn’s disease. Aliment Pharmacol Ther. 2004; 20(Suppl 4):106-10. [PubMed 15352905]

132. Dejaco C, Harrer M, Waldhoer T et al. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn’s disease. Aliment Pharmacol Ther. 2003; 18:1113-20. [PubMed 14653831]

133. Verhave M, Winter HS, Grand RJ. Azathioprine in the treatment of children with inflammatory bowel disease. J Pediatr. 1990; 117:809-14. [IDIS 274975] [PubMed 2231216]

134. Salix Pharmaceuticals. Azasan (azathioprine) tablets prescribing information. Morrisville, NC; 2005 Oct.

135. Lichtenstein. Use of laboratory testing to guide 6-mercaptopurine/asathioprine therapy. Gastroenterol. 2004; 127:1558-64.

136. Bedford Laboratories. Azathioprine sodium injection prescribing information. Bedford, OH; 2011 Jul.

137. US Food and Drug Administration. FDA drug safety communication: Safety review update on reports of hepatosplenic T-cell lymphoma in adolescents and young adults receiving tumor necrosis factor (TNF) blockers, azathioprine and/or mercaptopurine. Rockville, MD; 2011 Apr 14. From FDA website. Accessed 2011 Jul 26.

c. AHFS Drug Information 2012. McEvopy GK, ed. Azathioprine/Azathioprine Sodium. Bethesda, MD: American Society of Health-System Pharmacists; 2012: .

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 188-9.

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