Skip to Content

Azathioprine (Systemic)

Primary: IM403
Secondary: MS109; GA400

Commonly used brand name(s): Imuran.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



antirheumatic (disease-modifying)—

bowel disease (inflammatory) suppressant—

lupus erythematosus suppressant—


Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.


Transplant rejection, organ (prophylaxis)—Azathioprine is indicated as an adjunct for prevention of rejection in renal homotransplantation {01}. [It is also indicated in the prevention of rejection in cardiac, hepatic, and pancreatic transplantation{12} .]

Arthritis, rheumatoid (treatment)—Azathioprine is indicated for the management of severe, active, and erosive rheumatoid arthritis unresponsive to rest or conventional medications {01}.

[Bowel disease, inflammatory (treatment){35}{36}]1
[Cirrhosis, biliary (treatment)]1
[Dermatomyositis, systemic (treatment){39}{40}{45}]1
[Glomerulonephritis (treatment)]1
[Hepatitis, chronic active (treatment){37}]1
[Lupus erythematosus, systemic (treatment){38}{50}]1
[Myasthenia gravis (treatment){41}]1
[Myopathy, inflammatory (treatment)]1
[Nephrotic syndrome (treatment){42}]1
[Pemphigoid (treatment)]1or
[Pemphigus (treatment)]1—Azathioprine also is indicated in the treatment of other immunologic diseases including regional and ulcerative colitis, biliary cirrhosis, systemic dermatomyositis (polymyositis), glomerulonephritis, chronic active hepatitis, systemic lupus erythematosus (SLE), inflammatory myopathy, myasthenia gravis, nephrotic syndrome, pemphigus, and pemphigoid.

1 Not included in Canadian product labeling.


Physicochemical characteristics:
Molecular weight—
    277.27 {24}

Mechanism of action/Effect:

The exact mechanism of immunosuppressive action is unknown since the exact mechanism of the immune response itself is complex and not completely understood. The immunosuppressive effects of azathioprine involve a greater suppression of delayed hypersensitivity and cellular cytotoxicity tests than of antibody responses {01}. Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins; it may also interfere with cellular metabolism and inhibit mitosis.

The mechanism of action of azathioprine in rheumatoid arthritis and other immunologic diseases is unknown but may be related to immunosuppression {01}. Azathioprine has a steroid-sparing effect, which allows a reduction in steroid dose when the two are combined in chronic inflammatory diseases {01}.


Well absorbed from the gastrointestinal tract {01}.

Protein binding:

Low (30%) {01}.


Largely converted to 6-mercaptopurine {01} and 6-thioinosinic acid (active metabolites). Further metabolism—Hepatic, largely by xanthine oxidase, and in erythrocytes {01}. Proportions of metabolites vary among individual patients {01}.


Approximately 5 hours (unchanged drug and metabolites) {01}.

Onset of action:

In rheumatoid arthritis—6 to 8 weeks {01}.

In other inflammatory disorders—4 to 8 weeks {03}.

Time to peak concentration:

Serum—1 to 2 hours {01}.

Duration of action:

Immunosuppressant—Clinical effects may persist for long periods after the medication is eliminated.

    Hepatic (biliary) {01}.
    Renal (1 to 2% unchanged).
    In dialysis—Partially removable by hemodialysis {01}.

Precautions to Consider


Azathioprine has been shown to be carcinogenic in animals and may be associated with an increased risk of development of carcinomas in humans, especially skin cancer and reticulum cell tumors or lymphomas in renal transplant patients and acute myelocytic leukemia and some solid tumors in rheumatoid arthritis patients {01} {06}. The risk of neoplastic toxicity appears to be lower in rheumatoid arthritis patients than in renal transplant patients; however, there is evidence that the risk is increased with prior use of alkylating agents {01}.


Mutagenic effects have been reported in animals, and chromosomal abnormalities (reversible when azathioprine is discontinued) have been noted in humans {01}.

Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in sperm viability and sperm count in mice at doses 10 times the human therapeutic dose {01}; a reduced percentage of fertile matings occurred when animals received 5 mg per kg of body weight (mg/kg) {01}.

Adequate and well-controlled studies in humans have not been done {01}.

Azathioprine crosses the placenta {01}.

Risk-benefit must be considered, especially during the first trimester, since azathioprine affects cell kinetics and can theoretically cause mutagenicity or teratogenicity.

There have been reports of limited immunologic abnormalities (lymphopenia, diminished immunoglobulin G [IgG] and immunoglobulin M [IgM] levels, cytomegalovirus [CMV] infection, and decreased thymic shadow; pancytopenia and severe immune deficiency) and other abnormalities (preaxial polydactyly in an infant whose mother received azathioprine and prednisone; meningomyelocele, bilateral dislocated hips, and bilateral talipes equinovarus in an infant whose father received azathioprine) in infants of renal homograft recipients treated with azathioprine {01}.

Azathioprine is not recommended for use in pregnant women with rheumatoid arthritis {01}.

Teratogenic effects (including skeletal malformations and visceral abnormalities) have been reported in rabbits and mice given doses equivalent to the human dose (5 mg/kg a day) {01}.

FDA Pregnancy Category D {01}.


Azathioprine is distributed, at low concentrations, into breast milk {01} {29}. Use by nursing mothers is not recommended because of possible adverse effects (especially tumorigenicity) in the infant {01}.


Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of azathioprine in children.


Although appropriate studies on the relationship of age to the effects of azathioprine have not been performed in the geriatric population, geriatrics-specific problems are not expected to limit the usefulness of this medication in the elderly. However, elderly patients are more likely to have age-related renal function impairment, which may require reduced dosage in patients receiving azathioprine.


The bone marrow–depressant effects of azathioprine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

In addition, azathioprine rarely causes sores in the mouth and on the lips.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Allopurinol    (allopurinol-induced inhibition of xanthine oxidase–mediated metabolism may result in greatly increased azathioprine activity and toxicity {01} {25} {26} {27}; concurrent use should be avoided if possible, especially in renal transplant patients, because of the high risk of 6-mercaptopurine [azathioprine metabolite] accumulation and consequent azathioprine toxicity if the transplanted kidney is rejected {02}; if concurrent use is essential, it is recommended that azathioprine dosage be reduced to one quarter to one third of the usual dosage {01}, the patient be carefully monitored, and subsequent dosage adjustments be based on patient response and evidence of toxicity)

Angiotensin-converting enzyme inhibitors    (increased risk of anemia and leukopenia {01})

Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of azathioprine may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of azathioprine, if necessary, should be based on blood counts)

» Bone marrow depressants, other (see Appendix II ){01} or
Radiation therapy    (concurrent use with azathioprine may increase the bone marrow depressant effects of these medications and radiation therapy; dosage reduction may be required; use prior to azathioprine therapy may be associated with an increased risk of development of neoplasms {01})

» Immunosuppressants, other, such as:
Corticosteroids, glucocorticoid
Muromonab-CD3    (concurrent use with azathioprine may increase the risk of infection and development of neoplasms {01})

Vaccines, killed virus    (because normal defense mechanisms may be suppressed by azathioprine therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)

» Vaccines, live virus    (because normal defense mechanisms may be suppressed by azathioprine therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the azathioprine therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)

Warfarin    (activity of warfarin may be decreased; increased doses of warfarin may be needed {43} {44})

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Amylase and
Aspartate aminotransferase (AST [SGOT]) and
Bilirubin    (serum values may be increased in association with toxic hepatitis and biliary stasis, primarily in allograft recipients; may also be increased as part of a gastrointestinal hypersensitivity reaction {01}; uncommon in rheumatoid arthritis patients {01})

Albumin, plasma and
Hemoglobin and
Uric acid in blood and urine    (concentrations may be decreased)

Mean corpuscular volume (MCV)    (may be increased; occurs commonly, as a sign of macrocytosis)

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)

» Gout    (because of interaction with allopurinol)

» Hepatic function impairment
» Infection
» Renal function impairment    (increased risk of hematologic toxicity {01}; a lower dosage of azathioprine is recommended for patients with impaired renal function {01})

» Sensitivity to azathioprine{01}
» Xanthine oxidase deficiency, severe    (reduced metabolism may result in increased azathioprine activity and toxicity {03})

» Caution should be used also in patients who have had previous cytotoxic drug therapy and radiation therapy.

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Complete blood counts    (recommended at least weekly during the first 2 months of therapy {04}; frequency may be reduced to monthly once the patient is stabilized)

Side/Adverse Effects

Note: The risk of hematologic and neoplastic toxicity appears to be lower in rheumatoid arthritis patients {01} because of the lower doses used {14}. Bone marrow depression may be more severe in renal transplant patients whose hemografts are undergoing rejection {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
Leukopenia or infection (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination{05})—leukopenia is usually asymptomatic
megaloblastic anemia{30} (unusual tiredness or weakness)

Note: Leukopenia may be severe or delayed {01} and is dose-related {01}. It is not correlated with therapeutic effect {01}.
The incidence of infection in renal transplant patients is 30 to 60 times that in patients taking azathioprine for rheumatoid arthritis {01}.
Infections may be fatal {01}.

Incidence less frequent
Hepatitis or biliary stasis{01}{32}{33} —asymptomatic
thrombocytopenia (unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin{05})—usually asymptomatic

Note: Hepatotoxicity usually occurs within 6 months of transplantation and usually is reversible on withdrawal of azathioprine {01}. It is uncommon (incidence less than 1%) in rheumatoid arthritis patients {01}. Hepatotoxicity occurs more frequently at dosages above 2.5 mg per kg of body weight (mg/kg) per day {03}.
Thrombocytopenia may be severe or delayed {01} and is dose-related {01}.

Incidence rare
Gastrointestinal hypersensitivity reaction{01}{47}{49} (severe nausea and vomiting with diarrhea; sudden fever; joint pain; sudden unusual feeling of discomfort or illness)
hepatic veno-occlusive disease{01}{07}{08}{09}{31} (stomach pain; swelling of feet or lower legs)—potentially fatal
hypersensitivity{10} (fast heartbeat; sudden fever; muscle or joint pain; redness or blisters on skin{10}{11})
pancreatitis, hypersensitivity{01}{10}{34} (severe stomach pain with nausea and vomiting)
pneumonitis (cough; shortness of breath)
sores in mouth and on lips

Note: Symptoms of the gastrointestinal hypersensitivity reaction usually develop within the first several weeks of therapy and are reversible on withdrawal of azathioprine {01}, although they will recur within hours after the first dose on rechallenge {01} {47} {49}. Hypotension may occasionally occur {01}. Hepatic enzymes may also be elevated {01}.
Hypersensitivity reactions usually occur after at least 1 week of therapy {10} and are reversible on withdrawal {10}. The reaction may be more severe on rechallenge and can be fatal {10}.

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Loss of appetite
nausea or vomiting{01}

Incidence less frequent
Skin rash{01}

Those indicating the need for medical attention if they occur after medication is discontinued
Bone marrow depression, delayed{46} (black, tarry stools; blood in urine; cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination; pinpoint red spots on skin; unusual bleeding or bruising)


Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and/or chronic
Bleeding{01} (pinpoint red spots on skin; unusual bleeding or bruising)
leukopenia or infection{01} (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)
hepatotoxicity{01} —usually asymptomatic; however, liver function test abnormalities may occur

Treatment of overdose
There is no published literature establishing the superiority of any specific techniques to treat azathioprine overdose. Treatment of azathioprine overdose is supportive {51}.

To decrease absorption—Although there is no literature on the usefulness of techniques to decrease absorption of azathioprine, gastric emptying within 30 minutes to 1 hour of ingestion may decrease systemic absorption {51}.

To enhance elimination—Hemodialysis can be used to enhance elimination. In one study, 45% of ingested azathioprine was removed during 8 hours of hemodialysis {01}.

Monitoring—White blood cell count and liver function tests should be monitored until the values return to normal. In one case of acute ingestion of 7500 mg of azathioprine, the values returned to normal after 6 days {01}.

Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Azathioprine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to azathioprine

Pregnancy—Use not recommended because of mutagenic or teratogenic potential

Breast-feeding—Not recommended because of risk of serious side effects
Other medications, especially allopurinol or other immunosuppressants
Other medical problems, especially chickenpox, gout, hepatic function impairment, herpes zoster, infection, pancreatitis, renal function impairment, or xanthine oxidase deficiency

Proper use of this medication
» Importance of not taking more or less medication than the amount prescribed

Caution with combination therapy; taking each medication at the right time

» Checking with physician before discontinuing medication

Possible nausea or vomiting; taking after meals or at bedtime {03} to reduce stomach upset

Checking with physician if vomiting occurs shortly after dose is taken

» Proper dosing

Missed dose:
If dosing schedule is once a day—Not taking missed dose and not doubling next one

If dosing schedule is several times a day—Taking as soon as possible or doubling next dose; checking with physician if more than one dose is missed

» Proper storage

Precautions while using this medication
» Importance of close monitoring by physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding other persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with bacterial or viral infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur

Side/adverse effects
Importance of discussing possible effects, including cancer, with physician

Signs of potential side effects, especially leukopenia, infection, megaloblastic anemia, hepatitis, biliary stasis, thrombocytopenia, gastrointestinal hypersensitivity reaction, hepatic veno-occlusive disease, hypersensitivity, pancreatitis, pneumonitis, and sores in mouth and on lips

Asymptomatic side effects, including hepatotoxicity

General Dosing Information
Patients receiving azathioprine should be under supervision of a physician experienced in immunosuppressive therapy {01}.

A variety of dosage schedules and regimens of azathioprine, alone or in combination with other immunosuppressive agents, are used. The prescriber may consult the medical literature as well as the manufacturer's literature in choosing a specific dosage.

Dosage must be adjusted to meet the individual requirements of each patient, on the basis of clinical response and appearance or severity of toxicity.

Cadaveric kidneys frequently develop a tubular necrosis with delayed onset of adequate function, necessitating a reduction in azathioprine dosage. If persistent negative nitrogen balance occurs, dosage should be reduced.

Because of the delayed action of azathioprine, dosage should be reduced or the medication withdrawn at the first sign of an abnormally large or persistent decrease in leukocyte count (to less than 3000 per cubic millimeter) or platelet count (to less than 100,000 per cubic millimeter) or other evidence of bone marrow depression {01}. Therapy may be reinstituted at a lower dosage when leukocyte and platelet counts return to acceptable levels, usually after 7 to 10 days.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of azathioprine. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In patients with neutropenia who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

If an infection develops, it must be treated promptly; reduction of azathioprine dosage and/or use of other drugs may be necessary {01}.

If symptoms of toxic hepatitis or biliary stasis appear, azathioprine therapy may have to be withdrawn. Patients with existing hepatic function impairment should be monitored carefully and treated with conservative doses (some clinicians recommend an initial dose of two thirds the usual dose). If hepatic veno-occlusive disease is clinically suspected, it is recommended that azathioprine be permanently withdrawn {01}.

If signs of homograft rejection occur, a larger dose may be necessary. However, the dose should not be increased to toxic levels {01}. Other therapy should be considered if signs of homograft rejection persist.
For parenteral dosage forms
Azathioprine may be administered by intravenous push or infusion. Time for infusion is usually 30 to 60 minutes, but may range from 5 minutes to 8 hours {01}.

Gastrointestinal upset may be reduced by giving oral azathioprine in divided doses or after meals {01}.

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics and immunosuppressants may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic and immunosuppressant agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic and immunosuppressant agents. {01}

The manufacturer does not make any recommendations regarding the use of a biological containment cabinet or the wearing of disposable surgical gloves during reconstitution and dilution of azathioprine sodium for injection.

Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


Usual adult and adolescent dose
Transplant rejection, organ (prophylaxis)
Initial: Oral, 3 to 5 mg per kg of body weight {01} or 120 mg per square meter of body surface area a day, one to three days before or at the time of {01} {03} surgery, the dosage being adjusted to maintain the homograft without causing toxicity.

Maintenance: Oral, 1 to 3 mg per kg of body weight or 45 mg per square meter of body surface area a day.

Rheumatoid arthritis or
[Bowel disease, inflammatory]1 or
[Cirrhosis, biliary]1 or
[Dermatomyositis, systemic]1 or
[Glomerulonephritis]1 or
[Hepatitis, chronic active]1 or
[Lupus erythematosus, systemic]1 or
[Myopathy, inflammatory]1 or
[Myasthenia gravis]1 or
[Nephrotic syndrome]1 or
[Pemphigoid]1 or
Initial: Oral, 1 mg per kg of body weight a day, the dosage being increased in increments of 500 mcg (0.5 mg) per kg of body weight a day after six to eight weeks, then every four weeks as necessary up to a maximum dose of 2.5 mg per kg of body weight a day.

Maintenance: Oral, the dosage being reduced to the minimum effective dose in decrements of 500 mcg (0.5 mg) per kg of body weight a day every four to eight {03} weeks.

Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available

50 mg (Rx) [Imuran (scored) (lactose){01}][Generic] (scored){23}


50 mg (Rx) [Imuran (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 25 °C (59 and 77 °F), in a well-closed container {01}. Protect from light {01}.

Parenteral Dosage Forms

Note: The dosing and strengths of the dosage form available are expressed in terms of azathioprine base.


Usual adult and adolescent dose
Transplant rejection, organ (prophylaxis)
Initial: Intravenous 3 to 5 mg (base) per kg of body weight a day {01} prior to {03}, during, or soon after surgery, the dosage being adjusted to maintain the homograft without causing toxicity.

Maintenance: Intravenous, 1 to 3 mg (base) per kg of body weight a day.

Usual pediatric dose
See Usual adult and adolescent dose.

Size(s) usually available:

100 mg (base) (Rx) [Imuran (lyophilized){01}][Generic]


100 mg (base) (Rx) [Imuran (lyophilized)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 25 °C (59 and 77 °F). Protect from light {01} {19}.

Preparation of dosage form:
Azathioprine Sodium for Injection USP is reconstituted for intravenous use by adding 10 mL of sterile water for injection to the vial and swirling to dissolve {01}.

Reconstituted solutions may be further diluted for administration by intravenous infusion with 0.9% sodium chloride injection or 5% dextrose and 0.9% sodium chloride injection {01}.

Reconstituted solutions of azathioprine are stable for 24 hours at room temperature {01}. Although solutions may be stable for longer periods, because there is no preservative, use within 24 hours is recommended for reasons of sterility {01}.

Mixing with alkaline solutions, especially on warming {01}, may result in conversion to 6-mercaptopurine {01}. Conversion to mercaptopurine also occurs in the presence of sulfhydryl compounds such as cysteine, glutathione, and hydrogen sulfide {01}.

Revised: 12/03/1998

  1. Imuran package insert (Glaxo Wellcome—US), Rev 11/97, Rec 10/98.
  1. Panelist comment.
  1. Panel comment, 1989 revision.
  1. Panel comment, 1989 revision.
  1. Reviewers' responses to Hematology-Oncology Panel (1985-1990) Memorandum No. 19.
  1. Henne T, Schmahl D. Occurrence of second primary malignancies in man—a second look. Cancer Treat Rev 1985; 12: 77-94.
  1. Read AE, Wiesner RH, La Brecque DR, et al. Hepatic veno-occlusive disease associated with renal transplantation and azathioprine therapy. Ann Intern Med 1986; 104: 651-5.
  1. Fonseca V, Havard CWH. Portal hypertension secondary to azathioprine in myasthenia gravis. Postgrad Med J 1988; 64: 950-2.
  1. Lemley DE, Delacey LM, Seeff LB, et al. Azathioprine induced hepatic veno-occlusive disease in rheumatoid arthritis. Ann Rheum Dis 1989; 48: 342-6.
  1. Saway PA, Heck LW. Azathioprine hypersensitivity: case report and review of the literature. Am J Med 1988; 84: 960-4.
  1. Bergman SM, Krane NK, Leonard G, et al. Azathioprine and hypersensitivity vasculitis. Ann Intern Med 1988 Jul 1; 109: 83-4.
  1. Panel comment, 1991.
  1. Panel comment, 1991.
  1. Panel comment, 1991.
  1. Hold.
  1. Hold.
  1. Hold.
  1. Hold.
  1. Azathioprine sodium for injection package insert (Quad—US), Rev 9/87.
  1. Hold.
  1. Korman N. Pemphigus. J Am Acad Dermatol 1988; 18: 1219-38.
  1. Pugh MC, Pugh CB. Current concepts in clinical therapeutics: disease-modifying drugs for rheumatoid arthritis. Clin Pharm 1987; 6: 475-91.
  1. Azathioprine tablets package insert (Roxane—US), Rev 12/95, Rec 2/97.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1997. p. 73.
  1. Berns A, Rubenfeld S, Rymzo WT Jr, et al. Hazard of combining allopurinol and thiopurine. N Engl J Med. 1972; 286: 730-1.
  1. Zimm S, Ettinger LJ, Holcenberg JS, et al. A phase I and clinical pharmacological study of mercaptopurine administered as a prolonged intravenous infusion. Cancer Res 1985; 45: 1869-73.
  1. Zimm S, Collins JM, O'Neill D, et al. Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clin Pharmacol Ther 1983; 34: 810-7.
  1. Boyd IW. Allopurinol-azathioprine interaction. J Intern Med 1991; 229: 386.
  1. Saarikoski S, Seppala M. Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus. Am J Obstet Gynecol 1973; 115: 1100-6.
  1. Lennard L, Murphy M. Severe megaloblastic anemia associated with abnormal azathioprine metabolism. Br J Clin Pharmacol 1984; 17: 171-2.
  1. Zarday Z, Veith FJ, Gliedman ML, et al. Irreversible liver damage after azathioprine. JAMA 1972; 222: 690-1.
  1. Horsmans Y, Rahier J, Geubel AP. Reversible cholestasis with bile duct injury following azathioprine therapy: a case report. Liver 1991; 11: 89-93.
  1. Sterneck M, Wiesner R, Ascher N, et al. Azathioprine hepatotoxicity after liver transplantation. Hepatology 1991; 14: 806-10.
  1. Herskowitz LJ, Olansky S, Lang PG. Acute pancreatitis associated with long-term azathioprine therapy: occurrence in a patient with systemic lupus erythematosus. Arch Dermatol 1979; 115: 179.
  1. 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.
  1. 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(8097): 955-7.
  1. Stellon AJ, Hegarty JE, Portmann B, et al. Randomised controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis. Lancet 1985; 1(8430): 668-70.
  1. Steinberg AD. The treatment of lupus nephritis. Kidney Int 1986; 30: 769-87.
  1. Rowen AJ, Reichel J. Dermatomyositis with lung involvement, successfully treated with azathioprine. Respiration 1983; 44: 143-6.
  1. Jacobs JC. Methotrexate and azathioprine treatment of childhood dermatomyositis. Pediatrics 1977; 59: 212-8.
  1. Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology 1998; 50: 1778-83.
  1. Baker LR, Tucker B, Macdougall IC, et al. Treatment of progressive renal failure and nephrotic syndrome with azathioprine and prednisolone. Postgrad Med J 1997; 73: 647-8.
  1. Rivier G, Khamashta MA, Hughes GR. Warfarin and azathioprine: a drug interaction does exist [letter]. Am J Med 1993; 95: 342.
  1. Singleton JD, Conyers L. Warfarin and azathioprine: an important drug interaction [letter]. Am J Med 1992; 92: 217.
  1. Ng YT, Ouvrier RA, Wu T. Drug therapy in juvenile dermatomyositis: follow-up study. J Child Neurol 1998; 13: 109-12.
  1. Verhelst JA, Van den Enden E, Mathys R. Rapidly evolving azathioprine induced pancytopenia [letter]. J Rheumatol 1987; 14: 862.
  1. Cochrane D, Adamson AR, Halsey JP. Adverse reactions to azathioprine mimicking gastroenteritis [letter]. J Rheumatol 1987; 14: 1075.
  1. Kvien TK, Hoyeraal HM, Sandstad B. Azathioprine versus placebo in patients with juvenile rheumatoid arthritis: a single center double blind comparative study. J Rheumatol 1986; 13: 118-23.
  1. Assini JF, Hamilton R, Strosberg JM. Adverse reactions to azathioprine mimicking gastroenteritis. J Rheumatol 1986; 13: 1117-8.
  1. Russell AS, Bretscher PA. Immunosuppressive therapy in systemic lupus erythematosus. J Rheumatol 1987; 14 Suppl 13: 194-8.
  1. Ellenhorn MJ. Ellenhorn's medical toxicology. Baltimore, MD: Williams & Wilkins; 1997. p. 777-9.