-
Gastroenterology Oct 2013
Topics: Azathioprine; Crohn Disease; Female; Humans; Immunosuppressive Agents; Male
PubMed: 23973853
DOI: 10.1053/j.gastro.2013.08.022 -
Archivos Argentinos de Pediatria Aug 2016Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through...
Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts. In patients with fever and severe neutropenia, early empirical antibiotic treatment should be initiated to prevent severe and disseminated infection. Two patients with this condition are reported.
Topics: Adolescent; Azathioprine; Female; Humans; Immunosuppressive Agents; Pancytopenia
PubMed: 27399027
DOI: 10.5546/aap.2016.e252 -
Inflammatory Bowel Diseases Aug 2021
Topics: Azathioprine; Drug Substitution; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mesalamine
PubMed: 33999201
DOI: 10.1093/ibd/izab102 -
Genes Apr 2019The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with...
The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Candidate genetic variants ( rs1142345, rs1800460, rs1800462, rs3957357, and deletion) were determined by polymerase chain reaction (PCR) assays and pyrosequencing. Statistical analysis was performed using linear mixed effects models for the association between the candidate variants and the pharmacological variables (azathioprine doses and metabolites). Azathioprine metabolites were measured in 257 samples (median 2 per patient, inter-quartile range IQR 1-3). Clinical efficacy at the first evaluation available resulted better in ulcerative colitis than in Crohn's disease patients (88.0% versus 52.5% responders, = 0.0003, linear mixed effect model, LME). TGN concentration and the ratio TGN/dose at the first evaluation were significantly higher in responder. rs1142345 variant (4.8% of patients) was associated with increased TGN (LME = 0.0042), TGN/dose ratio (LME < 0.0001), decreased azathioprine dose (LME = 0.0087), and MMPN (LME = 0.0011). deletion (58.1% of patients) was associated with a 18.5% decrease in TGN/dose ratio and 30% decrease in clinical efficacy. variant (12.8% of patients) showed a trend ( = 0.049, LME) for an association with decreased clinical efficacy; however, no significant effect on azathioprine pharmacokinetics could be detected. In conclusion, GSTs variants are associated with azathioprine efficacy and pharmacokinetics.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Biotransformation; Female; Gene Deletion; Glutathione Transferase; High-Throughput Nucleotide Sequencing; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Methyltransferases; Middle Aged; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Treatment Outcome; Young Adult
PubMed: 30987408
DOI: 10.3390/genes10040277 -
Journal of the American Academy of... Dec 1987
Topics: Aged; Aged, 80 and over; Azathioprine; Black People; Combined Modality Therapy; Humans; Male; Photosensitivity Disorders
PubMed: 3429721
DOI: 10.1016/s0190-9622(87)80499-1 -
British Medical Journal (Clinical... Dec 1981
Topics: Aged; Arthritis, Rheumatoid; Azathioprine; Humans; Male; Pancreatitis
PubMed: 6799065
DOI: 10.1136/bmj.283.6305.1548 -
British Medical Journal (Clinical... Sep 1981
Topics: Arthritis, Rheumatoid; Azathioprine; Female; Humans; Hypotension; Middle Aged; Shock
PubMed: 6794715
DOI: 10.1136/bmj.283.6295.823-a -
Alimentary Pharmacology & Therapeutics Apr 2003Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and...
BACKGROUND
Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and its impact on growth and surgical morbidity in children.
METHODS
This retrospective cohort study included all children treated with azathioprine and diagnosed with IBD between 1996-2001. Outcome measures included indications for azathioprine use, adverse-effects and reasons for treatment discontinuation. Height and weight at diagnosis, treatment onset and current follow-up was recorded, and Z scores for height standardised for time.
RESULTS
107 children received azathioprine at 3 mg/kg. 61% had Crohn's disease and 83% started azathioprine within 2 years of diagnosis. Only 2/107 children had to stop azathioprine because of persistent adverse effects and 16/107 required surgery. There was a trend toward better growth in a group of children with Crohn's disease following treatment with high dose azathioprine therapy (P = 0.08).
CONCLUSIONS
Azathioprine is a safe and well-tolerated maintenance therapy at 3 mg/kg for children with IBD. The prevalence of surgery and growth failure in a cohort of children with moderate to severe IBD appears less than previously reported. In children with Crohn's disease, growth velocity may be maximised by an emphasis on nutritional therapy and the use of high dose azathioprine.
Topics: Administration, Oral; Adolescent; Azathioprine; Child; Child, Preschool; Cohort Studies; Follow-Up Studies; Growth; Humans; Infant; Inflammatory Bowel Diseases; Logistic Models; Retrospective Studies
PubMed: 12656694
DOI: 10.1046/j.1365-2036.2003.01540.x -
British Medical Journal Oct 1974Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections and were treated with co-trimoxazole or another antibiotic in a controlled randomized prospective trial. The incidence of leucopenia in the group treated with co-trimoxazole (10.6%) was not significantly different from that in the group treated with other antibiotics (23.6%). Leucopenia when it occurred did so soon after transplantation at a time when the function of the renal transplant was poor in relation to the dosage of azathioprine given. In all cases the temporary withdrawal of azathioprine relieved the leucopenia despite continuation of the co-trimoxazole treatment. This study did not provide any evidence that co-trimoxazole plus azathioprine was a more potent cause of leucopenia than azathioprine alone.
Topics: Administration, Oral; Azathioprine; Cadaver; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Kidney; Kidney Transplantation; Leukopenia; Sulfamethoxazole; Transplantation, Homologous; Trimethoprim; Urinary Tract Infections
PubMed: 4609544
DOI: 10.1136/bmj.4.5935.15 -
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