Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations

Curkovic, Ivanka; Rentsch, Katharina; Frei, Pascal; Fried, Michael; Rogler, Gerhard; Kullak‐Ublick, Gerd A.; Jetter, Alexander

doi:10.1007/s00228-013-1500-1

Cited by 25 publications

(34 citation statements)

References 29 publications

(71 reference statements)

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“…Another mechanism proposed for allopurinol-thiopurine combination therapy is to inhibit the activity of TPMT by thioxanthine [115] and thus reverse the production of 6-MeMP [109]. Taken together, combined therapy with thiopurines and allopurinol reduces the risk of side effects of thiopurines and improves the likelihood of a long-term effective immunomodulator therapy in IBD [110,[116][117][118][119][120]. Thus, combined therapy in a large single-center cohort study of 109 patients with IBD showed a beneficial outcome in patients with hepatotoxicity, other adverse reactions (e.g., gastrointestinal disturbance, rash, flu-like symptoms, tremor, headache, and fatigue), an inadequate response with low 6-TGN and high 6-MeMP levels, and an adverse metabolite profile or when combined therapy was used as primary treatment because of high TPMT activity on monotherapy [107].…”

Section: Thiopurine Therapy Combined With Allopurinolmentioning

confidence: 97%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease (IBD). This review focuses on the metabolism and mode of action of thiopurines and MTX, and provides an updated overview of individualized treatment strategies in which efficacy in IBD can be increased without compromising safety. The patient-based monitoring instruments adapted into clinical practice include pretreatment thiopurine S-methyltransferase testing, thiopurine metabolite monitoring, and blood count measurements that may help guiding the dosage to improve clinical outcome. Other approaches for optimizing thiopurine therapy in IBD include combination therapy with allopurinol, 5-aminosalicylates, and/or biologics. Similar strategies are yet to be proven effective in improving the outcome of MTX therapy. Important challenges for the management of IBD in the future relate to individualized dosing of immunomodulators for maximal efficacy with minimal risk of side effects. As low-cost conventional immunomodulators still remain a mainstay in pharmacotherapy of IBD, more research remains warranted, especially to substantiate these tailored management strategies in controlled clinical trials.

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Section: Thiopurine Therapy Combined With Allopurinolmentioning

confidence: 97%

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

et al. 2015

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“…Only one case of an AHS-like syndrome has been reported in the literature to date with febuxostat [26]. There are no adequate studies on the effects of febuxostat on hypertension, kidney disease progression, or cardiovascular disease.…”

Section: Dose Adjustment and Safety Of Allopurinol In Patients With Ckdmentioning

confidence: 99%

“…Once the backbone of kidney transplant immunosuppression protocols, azathioprine is seldom used for this purpose nowadays. Moreover, recent studies have shown that the low-dose combination of azathioprine and allopurinol in patients with inflammatory bowel disease, who have an unfavorable tioguanine metabolite profile, is safe [26]. …”

Section: Allopurinol In Kidney Transplant Recipientsmentioning

confidence: 99%

Allopurinol as a Kidney-Protective, Cardioprotective, and Antihypertensive Agent: Hype or Reality?

Kanbay

Solak

Gaipov³

et al. 2014

Blood Purif

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Numerous experimental and clinical studies suggest that uric acid might have pathobiologic implications in the development and progression of hypertension, kidney disease, and coronary heart disease, among others, resulting in renewed interest in uric acid as a potential pathogenic mediator in these clinical conditions. Despite encouraging animal studies showing beneficial roles of allopurinol, clinical studies and randomized controlled trials remain scarce, and, despite available clinical evidence supporting a therapeutic role for allopurinol, multiple issues remain before routine use of allopurinol can be recommended for use in patients with hyperuricemia and hypertension, kidney disease, or coronary heart disease. These include a need for more robust clinical trial data that evaluate efficacy on hard clinical outcomes, optimal dose, duration of treatment, and the potential for serious allergic reactions. In this article we review the current available evidence describing the effects of allopurinol in hypertension, kidney disease, and coronary heart disease, highlighting unresolved issues surrounding allopurinol use for uric acid lowering in individuals without gout.

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“…In 3 open studies on IBD, allopurinol combination therapy increased thioguanine nucleotide (6-TGN) levels to greater than with monotherapy levels Khan ( Table 1 ) [44][45][46] . In UC patients, combination therapy with allopurinol gave better relapse rates than sulfasalazine and prednisone enema alone, but the results on combination therapy with mesalamine were not as promising ( Table 1 ) [47,48] .…”

Section: Allopurinolmentioning

confidence: 99%

“…Allopurinol had been tested as a combined therapy with routinely used drugs such as sulfasalazines or steroids [44][45][46][47][48]85] . In 3 open studies on IBD, allopurinol combination therapy increased thioguanine nucleotide (6-TGN) levels to greater than with monotherapy levels Khan ( Table 1 ) [44][45][46] .…”

Section: Allopurinolmentioning

confidence: 99%

Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal

2017

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The gastrointestinal tract digests and absorbs dietary nutrients, protects the body against physical and chemical damage from contents in its lumen, provides immunity against external antigens, and keeps an optimum environment for the gut microbiota. These functions cannot be performed normally in several diseases of which the following are discussed here: irritable bowel syndrome and inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Because these diseases are associated with oxidative stress, a host of antioxidant supplements are used for maintenance and recovery of the gut functions. However, the benefits of these supplements have not been established. The available 80 human trials were rated for levels of confidence and for benefits of the antioxidant supplements. For Crohn's disease, the supplements for which clear benefits occurred in at least 2 studies were allopurinol, Boswellia serrata (frankincense or shallaki), Artemesia species (wormwood), Tripterygium wilfordii (léi gōng téng), and omega-3 fatty acids. Similar beneficial supplements for ulcerative colitis were allopurinol, Matricaria chamomilla (chamomile), Curcuma longa (curcumin in turmeric), and omega-3 fatty acids. There was also a clear benefit for ulcerative colitis in 2 studies where a multiherbal Chinese medicine preparation and an Ayurvedic medicine preparation were used. For irritable bowel syndrome, there was only a marginal benefit of some of the antioxidant supplements. Thus, some antioxidant supplements may be beneficial at certain stages of specific diseases. This is consistent with the current concept that antioxidants act by inhibiting oxidative stress pathways in a tissue- and environment-specific manner and not by simply acting as scavengers.

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Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations

Abstract: Combination therapy with only 50 mg allopurinol and 50 mg azathioprine daily is sufficient, efficacious and safe in most IBD patients with inadequate thiopurine metabolite concentrations to optimize azathioprine-based IBD therapy.

Cited by 25 publications

References 29 publications

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease

Allopurinol as a Kidney-Protective, Cardioprotective, and Antihypertensive Agent: Hype or Reality?

Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal

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