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Gastroenterologie Clinique Et Biologique May 2005Purine analogues are major drugs in the treatment of inflammatory bowel diseases (IBD). We present four cases of nodular regenerative hyperplasia of the liver (NRH)...
Purine analogues are major drugs in the treatment of inflammatory bowel diseases (IBD). We present four cases of nodular regenerative hyperplasia of the liver (NRH) developed in patients with IBD treated with azathioprine. All patients had either abnormal liver tests and/or low platelet count. Although biochemical and hematological abnormalities regressed after azathioprine withdrawal, the long term evolution of the hepatic lesions (and the risk to develop further complications including portal hypertension) remains to be determined. Male gender seems to be a major risk factor by providing a predisposing pharmacogenetic profile of purine analogue metabolism. Clinicians should be aware of this serious complication which may occur with any of the purine analogues (azathioprine, 6-mercaptopurine, and 6-thioguanine).
Topics: Adult; Azathioprine; Focal Nodular Hyperplasia; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Middle Aged; Risk Factors
PubMed: 15980758
DOI: 10.1016/s0399-8320(05)82136-0 -
BMJ (Clinical Research Ed.) Jul 1992To determine whether azathioprine can prevent relapse in ulcerative colitis. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine whether azathioprine can prevent relapse in ulcerative colitis.
DESIGN
One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.
SETTING
Outpatient clinics of five hospitals.
SUBJECTS
79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.
MAIN OUTCOME MEASURE
Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.
RESULTS
For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.
CONCLUSIONS
Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.
Topics: Azathioprine; Chronic Disease; Colitis, Ulcerative; Double-Blind Method; Humans; Long-Term Care; Recurrence
PubMed: 1638191
DOI: 10.1136/bmj.305.6844.20 -
Journal of the American Academy of... Nov 1993
Topics: Aged; Anaphylaxis; Azathioprine; Female; Humans; Male; Middle Aged; Pemphigoid, Bullous; Polyarteritis Nodosa
PubMed: 7901249
DOI: 10.1016/s0190-9622(08)81710-0 -
Orvosi Hetilap Feb 2006Azathioprine-associated interstitial pneumonitis. The early hypersensitivity reaction and the late bone marrow depression are well known side effects of the...
Azathioprine-associated interstitial pneumonitis. The early hypersensitivity reaction and the late bone marrow depression are well known side effects of the azathioprine; the interstitial pneumonia is a rare complication. A 40-year old male patient was treated with azathioprine due to extensive ulcerative colitis for ten years. He complained seven days of fever, cough and catarrhal signs, without the symptoms of active colitis. The opportunistic infections were ruled out. Chest X-ray, CT and lung biopsy proved the presence of interstitial inflammation. The azathioprine therapy was discontinued as the potential source of the pulmonary infiltrate. As a result of steroid therapy, as well as emergency unit care, the pulmonary infiltrates decreased gradually. Three months later his ulcerative colitis relapsed, for this an ileo-anal pouch surgery was done. In case of atypical pneumonia, without proven opportunistic infection, azathioprine-associated interstitial pneumonitis may be present, which heal after cessation of the drug.
Topics: Adult; Azathioprine; Colitis, Ulcerative; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Male; Radiography
PubMed: 16610616
DOI: No ID Found -
British Medical Journal Oct 1978Twenty-five patients taking part in a controlled trial to compare azathioprine plus prednisone with prednisone alone in the treatment of pemphigoid were followed up for... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Twenty-five patients taking part in a controlled trial to compare azathioprine plus prednisone with prednisone alone in the treatment of pemphigoid were followed up for three years. Results showed that the addition of azathioprine 2.5 mg/kg body weight daily reduced the total maintenance dose of prednisone needed by about 45%, with no increase in serious side effects or mortality. The suggestion that azathioprine might increase the risk of disseminated malignancy in elderly patients was not supported. We conclude that in future trials the combination of azathioprine with prednisone should be used as the standard treatment for comparison.
Topics: Aged; Azathioprine; Clinical Trials as Topic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Prednisone; Skin Diseases, Vesiculobullous
PubMed: 363229
DOI: 10.1136/bmj.2.6146.1190 -
Gastroenterology Feb 1986We report 3 cases of hepatic venocclusive disease occurring in renal transplant patients receiving azathioprine and combine our experience with 4 other previously...
We report 3 cases of hepatic venocclusive disease occurring in renal transplant patients receiving azathioprine and combine our experience with 4 other previously reported cases. The data suggest a clinical syndrome characterized by (a) delayed clinical onset, (b) striking male predominance, (c) presentation with jaundice followed by evidence of portal hypertension, and (d) poor prognosis. One of our patients, who is still alive 40 mo after the first onset of symptoms of liver disease, showed striking clinical improvement with discontinuation of azathioprine and subsequent deterioration on reinstitution. We suggest that azathioprine may be closely linked with the development of venocclusive disease in renal transplant patients and that the frequency of this disorder may be more common than previously reported. To attempt to prevent a fatal outcome, this group of patients should be closely monitored for the earliest signs of hepatic venocclusive disease through periodic serum bilirubin and alkaline phosphatase determinations. Patients with abnormal tests should undergo liver biopsy. If hepatic venocclusive disease is found, prompt withdrawal of azathioprine is indicated.
Topics: Adult; Azathioprine; Chemical and Drug Induced Liver Injury; Hepatic Veins; Humans; Immunosuppression Therapy; Kidney Transplantation; Liver; Liver Diseases; Male; Middle Aged
PubMed: 3510146
DOI: 10.1016/0016-5085(86)90947-9 -
Deutsche Medizinische Wochenschrift... Feb 2003
Review
Topics: Azathioprine; Bone Marrow; Drug Interactions; Drug Monitoring; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma, Non-Hodgkin; Mercaptopurine; Methyltransferases; Structure-Activity Relationship; Thioguanine
PubMed: 12594624
DOI: 10.1055/s-2003-37378 -
The Journal of Pharmacology and... Oct 1975The metabolic disposition of the methylnitroimidazole moiety of azathioprine, labeled with 14C in carbons 4 and 5 of this imidazole ring, was investigated in the dog....
The metabolic disposition of the methylnitroimidazole moiety of azathioprine, labeled with 14C in carbons 4 and 5 of this imidazole ring, was investigated in the dog. The administration of the radioactive drug (10 mg/kg p.o.) was followed, after absorption, by a rapid uptake of the radioactivity into the blood cells, with subsequent redistribution to the plasma. The total urinary excretion of 14C was 41.6% in 32 hours. Anion exchange and high-pressure liquid chromatography of the urine revealed a large number of 14C-containing metabolites. These included unmetabolized azathioprine, 1-methyl-4-nitro-5-(N-acetyl-S-cysteinyl)imidazole, 1-methyl-4-nitro-5-thioimidazole and several compounds with ultraviolet absorption spectra similar to 5-substituted amino-1-methyl-4-nitroimidazoles. The most prominent of these was a highly acidic metabolite which was found to be identical in chemical, chromatographic and spectral properties with N,N'-[5-(1-METHYL-4-NITRO)IMIDAZOLYL]CYSTINE. This metabolite as well as 1-methyl-4-nitro-5-(N-acetyl-S-cysteinyl)imidazole and 1-methyl-4-nitro-5-thioimidazole were also identified in the urine of a dog given 1-methyl-4-nitro-5-(S-glutathionyl)-imidazole (10 mg/kg i.v.) suggesting that the latter compound is an intermediate in the formation of these urinary metabolites. The profile of the methylnitroimidazole urinary metabolites in the dog was similar to that in man and different from that in the rat. A metabolic pathway for the formation of these metabolites in the dog is proposed.
Topics: Animals; Azathioprine; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Chromatography, Paper; Chromatography, Thin Layer; Dogs; Male; Spectrophotometry, Ultraviolet; Time Factors
PubMed: 1181404
DOI: No ID Found -
Yakugaku Zasshi : Journal of the... Aug 2004To clarify the effectiveness and safety of azathioprine (AZA) and 6-mercaptopurine (6MP) in the induction and maintenance of remission in ulcerative colitis (UC) by... (Meta-Analysis)
Meta-Analysis Review
To clarify the effectiveness and safety of azathioprine (AZA) and 6-mercaptopurine (6MP) in the induction and maintenance of remission in ulcerative colitis (UC) by using a systematic review of published studies. Studies were searched for from within the 1966 to March 2003 MEDLINE database, Cochrane Library 2003 issue 1, and the 1981 to March 2003 Japana Centra Revuo Medicina database. References from published studies and reviews were also obtained. Randomized, placebo-controlled trials of oral AZA or 6MP therapy in adult patients with active or quiescent UC were included. Ratios for the induction and maintenance of remission, the steroid-sparing effect, and the incidence of adverse drug reactions (ADRs) were compared and evaluated between the two study arms and expressed by the odds ratio (OR) specific for the individual studies and the meta-analytic summary for the OR. We could find no randomized controlled trial for 6MP therapy. However, four clinical trials for AZA therapy were included in this meta-analysis. For the induction of remission, the pooled OR of the response to AZA therapy compared with placebo in active UC was 1.45 (95% Confidence Interval (CI): 0.68 to 3.08). For the maintenance of remission, the pooled OR for AZA therapy was 2.26 (95% CI: 1.27 to 4.01). The number needed to treat (NNT) to prevent one recurrence was 6 patients. The pooled OR for AZA therapy's ADRs compared with placebo was 2.11 (95% CI: 0.92 to 4.84). From the viewpoint of effectiveness and safety, this meta-analysis suggests that AZA might be useful in the maintenance of remission in UC patients.
Topics: Adult; Azathioprine; Colitis, Ulcerative; Confidence Intervals; Humans; Mercaptopurine; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 15297725
DOI: 10.1248/yakushi.124.555 -
Canadian Medical Association Journal Dec 1973
Topics: Adult; Arthritis; Azathioprine; Fever; Humans; Liver Cirrhosis; Male
PubMed: 4759485
DOI: No ID Found