Imuran (Azathioprine) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The principal and potentially serious toxic effects of IMURAN are hematologic and gastrointestinal. The risks of secondary infection and neoplasia are also significant (see WARNINGS). The frequency and severity of adverse reactions depend on the dose and duration of IMURAN as well as on the patient's underlying disease or concomitant therapies. The incidence of hematologic toxicities and neoplasia encountered in groups of renal homograft recipients is significantly higher than that in studies employing IMURAN for rheumatoid arthritis. The relative incidences in clinical studies are summarized below:

* Data on the rate and risk of neoplasia among persons with rheumatoid arthritis treated with azathioprine are limited. The incidence of lymphoproliferative disease in patients with RA appears to be significantly higher than that in the general population. In one completed study, the rate of lymphoproliferative disease in RA patients receiving higher than recommended doses of azathioprine (5 mg/kg per day) was 1.8 cases per 1000 patient-years of follow-up, compared with 0.8 cases per 1000 patient-years of follow-up in those not receiving azathioprine. However, the proportion of the increased risk attributable to the azathioprine dosage or to other therapies (i.e., alkylating agents) received by patients treated with azathioprine cannot be determined.
Toxicity	Renal Homograft	Rheumatoid Arthritis
Leukopenia (any degree)	>50%	28%
<2500 cells/mm3	16%	5.3%
Infections	20%	<1%
Neoplasia		*
Lymphoma	0.5%
Others	2.8%

Hematologic: Leukopenia and/or thrombocytopenia are dose-dependent and may occur late in the course of therapy with IMURAN. Dose reduction or temporary withdrawal may result in reversal of these toxicities. Infection may occur as a secondary manifestation of bone marrow suppression or leukopenia, but the incidence of infection in renal homotransplantation is 30 to 60 times that in rheumatoid arthritis. Macrocytic anemia and/or bleeding have been reported.

TPMT genotyping or phenotyping can help identify patients with low or absent TPMT activity (homozygous for non-functional alleles) who are at increased risk for severe, life-threatening myelosuppression from IMURAN. See CLINICAL PHARMACOLOGY, WARNINGS and PRECAUTIONS:Laboratory Tests. Death associated with pancytopenia has been reported in patients with absent TPMT activity receiving azathioprine. ^{6, 20}

Gastrointestinal: Nausea and vomiting may occur within the first few months of therapy with IMURAN, and occurred in approximately 12% of 676 rheumatoid arthritis patients. The frequency of gastric disturbance often can be reduced by administration of the drug in divided doses and/or after meals. However, in some patients, nausea and vomiting may be severe and may be accompanied by symptoms such as diarrhea, fever, malaise, and myalgias (see PRECAUTIONS). Vomiting with abdominal pain may occur rarely with a hypersensitivity pancreatitis. Hepatotoxicity manifest by elevation of serum alkaline phosphatase, bilirubin, and/or serum transaminases is known to occur following azathioprine use, primarily in allograft recipients. Hepatotoxicity has been uncommon (less than 1%) in rheumatoid arthritis patients. Hepatotoxicity following transplantation most often occurs within 6 months of transplantation and is generally reversible after interruption of IMURAN. A rare, but life-threatening hepatic veno-occlusive disease associated with chronic administration of azathioprine has been described in transplant patients and in one patient receiving IMURAN for panuveitis.^{21, 22, 23} Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity. If hepatic veno-occlusive disease is clinically suspected, IMURAN should be permanently withdrawn.

Others: Additional side effects of low frequency have been reported. These include skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative nitrogen balance, reversible interstitial pneumonitis and hepatosplenic T-cell lymphoma.

REPORTS OF SUSPECTED IMURAN SIDE EFFECTS / ADVERSE REACTIONS

Possible Imuran side effects / adverse reactions in 39 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2011-10-03

Patient: 39 year old female

Reactions: Pneumonia Aspiration, Drug Ineffective, Progressive Multifocal Leukoencephalopathy

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Mycophenolate Mofetil
    Indication: Polymyositis

Imuran
    Indication: Polymyositis
    Start date: 2002-11-01
    End date: 2005-02-01

Cyclosporine
    Indication: Polymyositis

Methotrexate
    Indication: Polymyositis
    Start date: 2001-12-01
    End date: 2002-11-01

Mabthera
    Indication: Polymyositis

Mabthera
    Dosage: form: infusion

Mabthera

Mabthera

Mabthera

Other drugs received by patient: Prednisone; Prednisone; Prednisone; Prednisone; Prednisone; Prednisone; Prednisone

Possible Imuran side effects / adverse reactions in 66 year old female

Reported by a physician from Japan on 2011-10-04

Patient: 66 year old female weighing 35.0 kg (77.0 pounds)

Reactions: Cytomegalovirus Infection, Pyrexia

Adverse event resulted in: hospitalization

Suspect drug(s):
Solu-Medrol
    Indication: Colitis Ulcerative
    Start date: 2011-02-12
    End date: 2011-02-14

Remicade
    Indication: Colitis Ulcerative
    Start date: 2011-02-14

Imuran
    Administration route: Oral
    Indication: Colitis Ulcerative
    Start date: 2011-01-01

Other drugs received by patient: Ganciclovir; Enteronon-R; Codeine Phosphate Hemihydrate; Thiaton; Loperamide HCL; Flurbiprofen; Asacol

Possible Imuran side effects / adverse reactions in 37 year old female

Reported by a individual with unspecified qualification from France on 2011-10-06

Patient: 37 year old female

Reactions: Pneumonia Aspiration, Drug Ineffective, Progressive Multifocal Leukoencephalopathy

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Mabthera
    Indication: Polymyositis

Methotrexate
    Indication: Polymyositis
    Start date: 2001-12-01
    End date: 2002-11-01

Mabthera

Mycophenolate Mofetil
    Indication: Polymyositis

Cyclosporine
    Indication: Polymyositis

Mabthera

Imuran
    Indication: Polymyositis
    Start date: 2002-11-01
    End date: 2005-02-01

Mabthera

Mabthera
    Dosage: form: infusion

Other drugs received by patient: Prednisone; Prednisone; Prednisone; Prednisone; Prednisone; Immune Globulin NOS; Prednisone; Prednisone