Side Effects of thioguanine: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Thioguanine is an effective treatment for inflammatory bowel disease (IBD), but its use has been limited by the risk of side effects. 4 One of the main challenges in using thioguanine is that it is metabolized by the enzyme thiopurine methyltransferase (TPMT). 4 Genetic variations in the TPMT gene can lead to different levels of TPMT activity, which can affect the metabolism of thioguanine and increase the risk of side effects. 4 However, recent studies suggest that monitoring thioguanine metabolite levels and adjusting the dose of thioguanine can reduce the risk of side effects. 19 In addition, some studies have suggested that thioguanine may be a better alternative to conventional thiopurines, such as azathioprine and mercaptopurine, for certain patients. 9 7

Reasons for Side Effects

Side effects of thioguanine are largely due to its metabolism by TPMT. 4 TPMT is responsible for converting thioguanine into inactive metabolites. 4 Genetic variations in the TPMT gene can lead to different levels of TPMT activity. 4 Low TPMT activity means that thioguanine is not broken down as quickly, increasing the risk of side effects. 4

Common Side Effects

Hepatotoxicity

Hepatotoxicity is a potential side effect of thioguanine. 4 It is thought to be caused by high levels of methylated thioguanine metabolites. 4 Symptoms of hepatotoxicity include jaundice, abdominal pain, loss of appetite, and elevated liver enzymes. 4

Myelosuppression

Myelosuppression is a serious side effect of thioguanine. 4 It is caused by high levels of thioguanine nucleotides in the blood. 4 Myelosuppression can lead to low blood cell counts, increasing the risk of infections and bleeding. 4

Gastrointestinal Symptoms

Gastrointestinal symptoms are a common side effect of thioguanine. 1 These symptoms include nausea, vomiting, abdominal pain, and diarrhea. 1 They are usually mild and temporary. 1

Countermeasures for Side Effects

Hepatotoxicity

Regular monitoring of liver function tests can help detect early signs of hepatotoxicity. 4 Adjusting the dose of thioguanine or using alternative therapies may be necessary to manage hepatotoxicity. 4

Myelosuppression

Regular blood tests can help monitor for myelosuppression. 4 Adjusting the dose of thioguanine or using alternative therapies may be necessary to manage myelosuppression. 4

Gastrointestinal Symptoms

Adjusting the dose of thioguanine or using anti-emetics and antidiarrheals may be helpful to manage gastrointestinal symptoms. 1

Comparison Between Studies

Commonalities

Several studies have shown that thioguanine can be effective for IBD but has potential side effects. 4 7 1 These side effects include hepatotoxicity, myelosuppression, and gastrointestinal symptoms. 4 1 Studies have also shown that monitoring thiopurine metabolites can help manage these side effects. 19

Differences

There are variations in the severity of side effects reported in different studies. 4 1 This could be due to factors such as differences in patient populations, thioguanine dosage, and methods used to assess side effects. 4 1 Some studies have also highlighted the potential benefits of thioguanine compared to conventional thiopurines for certain patient groups. 9 7

Cautions Regarding Application in Real Life

Thioguanine is an effective treatment for IBD, but its use should be carefully considered due to the potential for serious side effects. 4 Regular monitoring of blood counts and liver function tests is essential. 4 Patients should be informed about the potential side effects and their management. 4

Limitations of Current Research

While research has improved our understanding of thioguanine's use in IBD, there are still gaps in knowledge. 4 More research is needed to better understand the long-term safety and efficacy of thioguanine. 4

Future Research Directions

Future research should focus on identifying ways to reduce the risk of side effects and to better understand the optimal use of thioguanine for different patient groups. 4 Large-scale clinical trials are also needed to further evaluate the long-term safety and efficacy of thioguanine. 4

Conclusion

Thioguanine is a valuable treatment option for IBD, but its use should be carefully considered due to the potential for side effects. 4 Monitoring thiopurine metabolites and adjusting the dose of thioguanine can help manage these side effects. 19 Further research is needed to optimize the use of thioguanine and improve its safety profile. 4

Keywords
Benefit Keywords
ALL treatment
1
Autoimmune hepatitis treatment
Corticosteroid withdrawal
Liver test normalization
2
Chemotherapy
Immunosuppression
3
Acute leukemia treatment
Autoimmune disease treatment
Graft rejection prevention
Inflammatory bowel disease treatment
4
IBD treatment
5
UC treatment
6
Remission of Crohn's disease
Remission of ulcerative colitis
7
Cancer treatment
Infection treatment
8
Effective Crohn's disease treatment
Possible alternative treatment
9
IBD treatment
10
Treat psoriasis
11
Crohn's disease treatment
12
Improved ALL treatment outcome
13
Individualized chemotherapy
14
Leukemia treatment
Reduced leucopenia
15
Reduced adverse effects
16
DNA damage prevention
Thiopurine therapy
17
Autoimmune hepatitis treatment
18
Treat inflammatory bowel diseases
19
Autoimmune hepatitis treatment
20
IBD treatment
Mercaptopurine switch
21
IBD treatment
thiopurine metabolism improvement
22
BCa treatment
Nature-inspired compounds
23
Improved IBD response
24
Improved survival
25
Eczema treatment
26
AZA/6MP efficacious
AZA/6MP safe
27
Risk Keywords
6MMP toxicity
1
Liver toxicity
Side effects
2
Carcinogenic side effects
3
Bone marrow toxicity
Hepatic toxicity
4
Hepatotoxicity
Myelotoxicity
Nodular regenerative hyperplasia
5
Myelosuppression
6
Hepatotoxicity
7
Severe side effects
8
Intolerant reactions
9
Side effects
10
Myelosuppression
11
Drug intolerance
12
Chemotherapy-related toxicity
13
Drug overdose
14
UVA-mediated photochemical damage
17
Azathioprine intolerance
18
Side-effects
19
Drug intolerance
Hepatotoxicity
Myelosuppression
Nonresponse
20
Thiopurine AE
Treatment discontinuation
21
None mentioned
23
Myelosuppression
25
AZA/6MP side effects
27
Literature analysis of 27 papers
Positive Content
26
Neutral Content
1
Negative Content
0
Article Type
1
0
0
12
27
3.

Photochemical and Photodynamical Properties of Sulfur-Substituted Nucleic Acid Bases.

Author: AshwoodBrennan, PollumMarvin, Crespo-HernándezCarlos E

Chemotherapy
Immunosuppression
Carcinogenic side effects

Sulfur-substituted nucleobases are widely used in chemotherapy and immunosuppression. This review examines the photochemical properties of these compounds and explores their potential for targeted phototherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

[Therapeutic drug monitoring of 6-thioguanine nucleotides in inflammatory bowel disease: interest and limits].

Author: JourdilNicole, FonroseXavier, BoulieuRoselyne, Stanke-LabesqueFrançoise,

Acute leukemia treatment
Autoimmune disease treatment
Graft rejection prevention
Inflammatory bowel disease treatment
Bone marrow toxicity
Hepatic toxicity

Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressant drugs that are used to prevent graft rejection and treat autoimmune disease. Their metabolism is affected by thiopurine methyl transferase (TPMT) activity, and high levels of the active metabolite, 6-thioguanine nucleotide, can cause bone marrow toxicity.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : French

6.

Thiopurine maintenance therapy for ulcerative colitis: the clinical significance of monitoring 6-thioguanine nucleotide.

Author: HanaiHiroyuki, IidaTakayuki, TakeuchiKen, AraiOsamu, WatanabeFumitoshi, AbeJinrou, MaruyamaYasuhiko, OohataAkihiko, IkeyaKentarou, KageokaMasanobu, MiwaIchita, YoshirouSatou, HosodaYoshisuke, KubotaTakahiro

UC treatment
Myelosuppression

Pharmacogenetic guidance of 6-mercaptopurine dose is necessary due to the role of thiopurine methyltransferase polymorphisms in determining therapeutic efficacy and toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

7.

Is there a role for thioguanine therapy in IBD in 2017 and beyond?

Author: TaylorKirstin M, WardMark G, BlakerPaul A, SparrowMiles P

Remission of Crohn's disease
Remission of ulcerative colitis
Hepatotoxicity

Thioguanine is an alternative thiopurine that has shown efficacy in inflammatory bowel disease. This study aims to outline the rational use of thioguanine, including safety monitoring, with particular regard to hepatotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future.

Author: BurkeMatthew P, BorlandKayla M, LitoshVladislav A

Cancer treatment
Infection treatment
Severe side effects

Nucleoside and nucleobase antimetabolites are important in treating cancer and infections. Their close resemblance to natural analogs provides potency but also incurs severe side effects, especially in chemotherapy. This review discusses current antimetabolite drugs and explores approaches to nucleobase modifications for developing novel bioactive nucleoside analogs with improved therapeutic windows.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine.

Author: BonazB, BoitardJ, MarteauP, LémannM, CoffinB, FlouriéB, BelaicheJ, CadiotG, MetmanE-H, CortotA, ColombelJ-F,

Effective Crohn's disease treatment
Possible alternative treatment
Intolerant reactions

TG is a possible alternative treatment in Crohn's disease patients, intolerant (especially for pancreatitis) or resistant to AZA/MP.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines.

Author: LooserRahel, DoulberisMichael, RosselJean-Benoit, FrancYannick, MüllerDaniel, BiedermannLuc, RoglerGerhard,

IBD treatment
Side effects

This study aimed to investigate the impact of 5-aminosalicylic acid (5-ASA) co-treatment on 6-thioguanine nucleotide (6-TGN) concentrations in patients with inflammatory bowel disease (IBD) receiving azathioprine (AZA) or 6-mercaptopurine (6-MP).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Favourable Tolerability and Drug Survival of Tioguanine Versus Methotrexate After Failure of Conventional Thiopurines in Crohn's Disease.

Author: SavelkoulE H J, MaasM H J, BourgonjeA R, CrouwelF, BiemansV B C, den BroederN, RusselM G V M, RömkensT E H, de BoerN K, DijkstraG, HoentjenF

Crohn's disease treatment
Drug intolerance

This study compared the tolerability and drug survival of methotrexate and tioguanine therapy in patients with Crohn's disease after failure of conventional thiopurines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

13.

Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia.

Author: AplencRichard, LangeBeverly

Improved ALL treatment outcome
Chemotherapy-related toxicity

This study reviewed current research on the impact of genetic variations in drug-processing genes on the treatment of pediatric acute lymphoblastic leukemia (ALL).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

[Significance of TPMT activity and TGNs level detection for individualizing 6-mercaptopurine chemotherapy].

Author: GuLong-jun, YeQi-dong, LiangAi-bin, ZhaoJin-cai, XueHui-liang, TangYao-nian, ChenJing, YeYu-chun

Individualized chemotherapy
Drug overdose

Measuring thiopurine methyltransferase (TPMT) activity before mercaptopurine (6-MP) therapy and thioguanine nucleotides (TGNs) levels during 6-MP therapy may help prevent side effects from drug overdose and individualize 6-MP chemotherapy in children with acute lymphoblastic leukemia (ALL).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

17.

Novel DNA lesions generated by the interaction between therapeutic thiopurines and UVA light.

Author: ZhangXiaohong, JeffsGraham, RenXiaolin, O'DonovanPeter, MontanerBeatriz, PerrettConal M, KarranPeter, XuYao-Zhong

DNA damage prevention
Thiopurine therapy
UVA-mediated photochemical damage

UVA radiation can cause potentially harmful side effects by damaging DNA 6-TG, which is incorporated into cellular DNA by the thiopurines, 6-thioguanine (6-TG), 6-mercaptopurine, and its prodrug azathioprine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine.

Author: de BoerNanne K H, van NieuwkerkCarin M J, Aparicio PagesM Nieves, de BoerSybrand Y, DerijksLuc J J, MulderChris J J

Autoimmune hepatitis treatment
Azathioprine intolerance

This study reports three patients with autoimmune hepatitis who could not tolerate azathioprine but tolerated 6-thioguanine 0.3 milligram per kilogram daily well. All three patients improved clinically.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases.

Author: DewitO

Treat inflammatory bowel diseases
Side-effects

Thiopurines are commonly used to treat inflammatory bowel diseases, but side effects and inefficacy can lead to withdrawal of the drug. This review discusses the rationale for measuring thiopurine metabolites to optimize thiopurine therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

Review article: opportunities to improve and expand thiopurine therapy for autoimmune hepatitis.

Author: CzajaAlbert J

Autoimmune hepatitis treatment
Drug intolerance
Hepatotoxicity
Myelosuppression
Nonresponse

Thiopurine efficacy and safety in autoimmune hepatitis can be enhanced by monitoring and manipulating metabolic pathways, individualizing dosage, and addressing drug resistance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease.

Author: CococcioniLucia, PensabeneLicia, PuotiMaria Giovanna, El-KoulySara, ChadokufaSibongile, BuckinghamRaechel, GaynorEdward, SaliakellisEfstratios, KiparissiFevronia, BorrelliOsvaldo

IBD treatment
thiopurine metabolism improvement

This study compares the efficacy and safety of split-dose thiopurine and allopurinol-thiopurine cotherapy strategies in children with inflammatory bowel disease (IBD) who failed conventional thiopurine treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

23.

Unveiling the mechanism of action of nature-inspired anti-cancer compounds using a multi-omics approach.

Author: SoaresNelson C, AliAmjad, SrinivasuluVunnam, SharafBasma M, GiddeyAlexander D, OkendoJavan, Al-HroubHamza M, SemreenMohammad H, HamadMawieh, Al-TelTaleb H

BCa treatment
Nature-inspired compounds
None mentioned

Two newly discovered nature-inspired anticancer compounds, SIMR3066 and SIMR3058, were evaluated for their mechanism of action using a multi-omics approach. The study found that both compounds disrupted several signaling pathways, including glycolysis, the Krebs cycle, and oxidative phosphorylation, in breast cancer cells. These results suggest that combining proteomics with metabolomics is a powerful tool for investigating the mechanism of action of potential anticancer drug candidates.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

24.

Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease.

Author: AnsariA, PatelN, SandersonJ, O'DonohueJ, DuleyJ A, FlorinT H J

Improved IBD response

Combining allopurinol with reduced-dose thiopurine was an effective treatment strategy for patients with inflammatory bowel disease (IBD) who experienced adverse reactions to full-dose thiopurine drugs. The combination therapy resulted in clinical remission in 78% of patients, and was particularly beneficial in avoiding non-hepatic adverse drug reactions.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine treatment.

Author: CoulthardS A, MathesonE C, HallA G, HogarthL A

Improved survival
Myelosuppression

This article discusses the genetic basis of thiopurine metabolism and its importance in treating acute lymphoblastic leukemia. Thiopurines are effective in preventing relapse but can cause severe side effects if patients have low thiopurine methyltransferase (TPMT) activity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

26.

Thiopurine metabolite levels in patients with atopic dermatitis and/or chronic hand/foot eczema treated with azathioprine.

Author: GarritsenF M, van der SchaftJ, Bruijnzeel-KoomenC A F, van SchaikR H, de GraafM, van den BroekM P H, de Bruin-WellerM S

Eczema treatment

Azathioprine is a drug that is used to treat eczema. This study discusses how azathioprine works and how its effectiveness can be improved by better understanding the drug's metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

Azathioprine: state of the art in inflammatory bowel disease.

Author: SandbornW J

AZA/6MP efficacious
AZA/6MP safe
AZA/6MP side effects

6-mercaptopurine (6MP) and azathioprine (AZA) are effective and safe for selected patients with inflammatory bowel disease (IBD), with controlled trials supporting their use in inflammatory and fistulizing Crohn's disease, steroid sparing, and remission maintenance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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