Imuran 50 Mg Tablet
Indications / Uses :As an immunosuppressant antimetabolite either alone or, more commonly, in combination with other agents (usually corticosteroids) and procedures which influence the immune response. Therapeutic effect may be evident only after weeks or months and can include a steroid-sparing effect, thereby reducing the toxicity associated with high dosage and prolonged usage of corticosteroids.
Imuran, in combination with corticosteroids and/or other immunosuppressive agents and procedures, is indicated to enhance the survival of organ transplants eg, renal, cardiac and hepatic transplants; and to reduce the corticosteroid requirements of renal transplant recipients.
Imuran is indicated for the treatment of moderate to severe inflammatory bowel disease (IBD) (Crohn’s disease or ulcerative colitis) in patients in whom corticosteroid therapy is required, in patients who cannot tolerate corticosteroid therapy or in patients whose disease is refractory to other standard 1st-line therapy.
Imuran, either alone or more usually in combination with corticosteroids and/or other drugs and procedures, has been used with clinical benefit (which may include reduction of dosage or discontinuation of corticosteroids) in a proportion of patients suffering from severe rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis and polymyositis, autoimmune chronic active hepatitis, pemphigus vulgaris, polyarteritis nodosa, autoimmune hemolytic anemia, chronic refractory idiopathic thrombocytopenic purpura and relapsing remittent multiple sclerosis.
Administration : Should be taken on an empty stomach: Take at least 1 hr before or 3 hr after food/milk.
Contraindications : Hypersensitivity to azathioprine or to any of the excipients of Imuran. Hypersensitivity to 6-MP should alert the physician to probable hypersensitivity to Imuran.
Special Precautions : Immunization using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunizations with organism vaccines are not recommended (see Interactions).
Co-administration of ribavirin and Imuran are not advised. Ribavirin may reduce efficacy and increase toxicity of Imuran (see Interactions).
Monitoring: There are potential hazards in the use of Imuran. It should be prescribed only if the patient can be adequately monitored for toxic effects throughout the duration of therapy.
Particular care should be taken to monitor hematological response and to reduce the maintenance dosage to the minimum required for clinical response.
It is suggested that during the first 8 weeks of therapy, complete blood count should be performed weekly or more frequently if high dosage is used or if severe renal and/or hepatic disorder is present. The blood count frequency may be reduced later in therapy, but it is suggested that complete blood counts are repeated monthly, or at least at intervals of not longer than 3 months.
At the 1st signs of an abnormal fall in blood counts, treatment should be interrupted immediately as leukocytes and platelets may continue to fall after treatment is stopped.
Patients receiving Imuran should be instructed to report immediately any evidence of infection, unexpected bruising or bleeding, or other manifestations of bone marrow depression. Bone marrow suppression is reversible if Imuran is withdrawn early enough.
Imuran is hepatotoxic and liver function tests should be routinely monitored during treatment. More frequent monitoring may be advisable in those with preexisting liver disease or receiving other potentially hepatotoxic therapy. The patient should be instructed to discontinue Imuran immediately if jaundice becomes apparent.
There are rare individuals with an inherited deficiency of the TPMT who may be unusually sensitive to the myelosuppressive effect of Imuran and prone to developing rapid bone marrow depression following the initiation of treatment with Imuran. This problem could be exacerbated by co-administration with drugs that inhibit TPMT eg, olsalazine, mesalazine or sulfasalazine. Also a possible association between decreased TPMT activity and secondary leukemias and myelodysplasia has been reported in individuals receiving 6-MP (the active metabolite of azathioprine) in combination with other cytotoxics (see Adverse Reactions). Some laboratories offer testing for TPMT deficiency, although these tests have not been shown to identify all patients at risk of severe toxicity. Therefore, close monitoring of blood counts is still necessary.
The dosage of Imuran may be reduced when this agent is combined with other drugs whose primary or secondary toxicity is myelosuppression (see Cytostatic/Myelosuppressive Agents under Interactions).
Renal and/or Hepatic Impairment: Caution is advised during the administration of Imuran in patients with renal and/or hepatic impairment. Consideration should be given to reducing the dosage in these patients and haematological response should be carefully monitored (see Special Patient Populations under Pharmacokinetics and Dosage & Administration).
Lesch-Nyhan Syndrome: Limited evidence suggests that Imuran is not beneficial to patients with hypoxanthine-guanine-phosphoribosyltransferase deficiency (Lesch-Nyhan syndrome). Therefore, given the abnormal metabolism in these patients, it is not prudent to recommend that these patients should receive Imuran.
Varicella Zoster Virus Infection (see Adverse Reactions): Infection with varicella zoster virus (VZV; chickenpox and herpes zoster) may become severe during the administration of immunosuppressants. Caution should be exercised especially with respect to the following.
Before starting the administration of immunosuppressants, the physician should check to see if the patient has a history of VZV. Serologic testing may be useful in determining previous exposure. Patients who have no history of exposure should avoid contact with individuals with chickenpox or herpes zoster. If the patient is exposed to VZV, special care must be taken to avoid patients developing chickenpox or herpes zoster, and passive immunization with varicella-zoster immunoglobulin (VZIG) may be considered.
If the patient is infected with VZV, appropriate measures should be taken, which may include antiviral therapy and supportive care.
Progressive Multifocal Encephalopathy (PML): PML, an opportunistic infection caused by the JC virus, has been reported in patients receiving Imuran with other immunosuppressive agents. Immunosuppressive therapy should be withheld at the 1st sign or symptom suggestive of PML and appropriate evaluation undertaken to establish a diagnosis (see Adverse Reactions).
Hepatitis B (see Adverse Reactions): Hepatitis B carriers [defined as patients positive for hepatitis B surface antigen (HBsAg) for >6 months], or patients with documented past HBV infection, who receive immunosuppressive drugs are at risk of reactivation of HBV replication, with asymptomatic increases in serum HBV, DNA and ALT levels. Local guidelines may be considered including prophylactic therapy with oral anti-HBV agents.
Effects on the Ability to Drive or Operate Machinery: There are no data on the effect of Imuran on driving performance or the ability to operate machinery. A detrimental effect on these activities cannot be predicted from the pharmacology of Imuran.
Carcinogenicity: (See Adverse Reactions.) Patients receiving immunosuppressive therapy are at an increased risk of developing non-Hodgkin’s lymphomas and other malignancies, notably skin cancers (melanoma and non melanoma), sarcomas (Kaposi’s and non-Kaposi’s) and uterine cervical cancer in situ. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. It has been reported that reduction or discontinuation of immunosuppression may be associated with partial or complete regression of non-Hodgkin’s lymphomas and Kaposi’s sarcomas.
Reports of hepatosplenic T-cell lymphoma in the IBD population have been received when Imuran is used in combination with anti-TNF agents.
Patients receiving multiple immunosuppressive agents may be at risk of over-immunosuppression, therefore such therapy should be maintained at the lowest effective level. As is usual for patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited and patients should wear protective clothing and use a sunscreen with a high protection factor.
Mutagenicity: Chromosomal abnormalities have been demonstrated in both male and female patients treated with Imuran. It is difficult to assess the role of Imuran in the development of these abnormalities. Chromosomal abnormalities, which disappear with time, have been demonstrated in lymphocytes from the offspring of patients treated with Imuran. Except in extremely rare cases, no overt physical evidence of abnormality has been observed in the offspring of patients treated with Imuran.
Imuran and long-wave ultraviolet (UV) light have been shown to have a synergistic clastogenic effect in patients treated with Imuran for a range of disorders.