Azathioprine Pharmachemie Adverse Reactions

Infections and infestations: Patients receiving Azathioprine alone or in combination with other immunosuppressants, particularly corticosteroids, have shown increased susceptibility to viral, fungal and bacterial infections, including severe or atypical infection with varicella, herpes zoster and other infectious agents.
Neoplasms benign and malignant (including cysts and polyps): The risk of developing malignancy (e.g. skin cancer, reticulum cell sarcoma, lymphomas), is increased in patients who receive immunosuppressive drugs, particularly in transplant recipients receiving aggressive treatment and such therapy should be maintained at the lowest effective levels. Evidence suggests that the risk also may be evaluated in patients with rheumatoid arthritis patients. The increase risk of neoplasia following Azathioprine therapy should be explained to patients.
There have been reports of acute myelogenous leukemia and solid tumors in patients with rheumatoid arthritis.
Blood and lymphatic system disorders: Azathioprine may be associated with a dose-related, generally reversible, depression of bone marrow function, most frequently expressed as leucopenia, but also sometimes as anaemia and thrombocytopenia and rarely as agranulocytosis, pancytopenia and aplastic anaemia.
These occur particularly in patients predisposed to myelotoxicity, such as those with TPMT deficiency and renal or hepatic insufficiency and in patients failing to reduce the dose of Azathioprine when receiving concurrent allopurinol therapy.
Reversible, dose-related increases in mean corpuscular volume and red cell haemoglobin content have occurred in association with Azathioprine therapy. Megaloblastic bone marrow changes have also been observed but severe megaloblastic anaemia and erythroid hypoplasia are rare.
Immune system disorders: Several different clinical syndromes, which appear to be idiosyncratic manifestations of hypersensitivity, have been described occasionally following administration of Azathioprine.
Clinical features include general malaise, dizziness, nausea, vomiting, diarrhoea, fever, rigors, exanthema, rash, vasculitis, myalgia, arthralgia, hypotension, renal dysfunction, hepatic dysfunction.
In many cases, rechallenge has confirmed an association with Azathioprine.
Immediate withdrawal of Azathioprine and institution of circulatory support where appropriate have led to recovery in the majority of cases.
Other marked underlying pathology has contributed to the very rare deaths reported.
Following a hypersensitivity reaction to Azathioprine, the necessity for continued administration of Azathioprine should be carefully considered on an individual basis.
Respiratory thoracic and mediastinal disorders: Reversible pneumonitis.
Gastrointestinal disorders: Nausea, vomiting, anorexia and diarrhea may occur in patients receiving large dosages of Azathioprine when first given. This appears to be relieved by administering the tablets after meals. Vomiting with abdominal pain may occur rarely with hypersensitivity pancreatitis.
Symptoms of GI toxicity must often develop within the first several weeks of Azathioprine therapy and reversible upon discontinuance of the drug. The reaction can occur within several hours after rechallenge with a single dose of the drug.
Other adverse GI effects include ulceration of the mucous membranes of the mouth, esophagitis with possible ulceration, and steatorrhea.
Hepatotoxicity and biliary stasis: Biliary stasis has been reported in less frequent and is dose-related.
Azathioprine-induced hepatotoxicity and is usually reversible on withdrawal of therapy.
Rare, but life-threatening hepatic damage associated with chronic administration of Azathioprine has been described, primarily in transplant patients. Periodic measurement, serum transaminases, alkaline phosphatase and bilirubin are indicated for early detection of hepatotoxicity. If hepatic veno-occlusive disease is clinically suspected, it is recommended that Azathioprine be permanently withdrawn.
Skin and subcutaneous tissue disorders: Hair loss has been described on a low frequency in patients receiving Azathioprine.