Side Effects of azathioprine: A Synthesis of Findings from 17 Studies

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Original Abstract of the Article

Major Research Findings

Azathioprine is an immunosuppressant drug used to treat autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis, and multiple sclerosis. This drug is metabolized into its active metabolite, 6-mercaptopurine. These drugs suppress the growth of immune cells by inhibiting cell growth and DNA synthesis. While the efficacy of azathioprine has been demonstrated in numerous studies, the risk of side effects also exists. Several studies indicate that azathioprine side effects are linked to genetic polymorphism, particularly in the thiopurine methyltransferase (TPMT) gene. TPMT is a crucial enzyme involved in the metabolism of azathioprine. Polymorphism in the TPMT gene can impact enzyme activity, potentially increasing the risk of side effects. The side effects of azathioprine can also be influenced by other factors such as dosage, duration of treatment, age, and overall health status. Common side effects of azathioprine include bone marrow suppression, gastrointestinal symptoms, liver damage, and pancreatitis. The side effects of azathioprine should be carefully monitored before and during treatment.

Reasons for Side Effects

The side effects of azathioprine are primarily associated with the drug's metabolism. Azathioprine is metabolized in the body into 6-mercaptopurine. While 6-mercaptopurine suppresses the growth of immune cells, it can also affect other cells, potentially leading to side effects. The metabolism of azathioprine involves an enzyme called thiopurine methyltransferase (TPMT). Polymorphism in the TPMT gene can lead to reduced enzyme activity, affecting azathioprine metabolism. TPMT activity varies due to genetic polymorphism, resulting in individual differences in drug metabolism rates. Slow metabolism can lead to azathioprine lingering in the body for longer durations, increasing the risk of side effects.

Common Side Effects

Bone Marrow Suppression

Azathioprine can cause bone marrow suppression. Bone marrow suppression is a reduction in blood cell production in the bone marrow. Bone marrow suppression from azathioprine can lead to a decrease in white blood cells, red blood cells, and platelets. A decrease in white blood cells increases the risk of infection. Red blood cell reduction can cause anemia. Platelet reduction increases the risk of bleeding. 9 , 7

Gastrointestinal Symptoms

Azathioprine can cause gastrointestinal symptoms. Gastrointestinal symptoms include nausea, vomiting, abdominal pain, and diarrhea. 4 , 1

Liver Damage

Azathioprine can cause liver damage. Liver damage refers to inflammation or dysfunction of the liver. Liver damage from azathioprine can manifest as elevated liver enzymes or jaundice. , 17

Pancreatitis

Azathioprine can cause pancreatitis. Pancreatitis is inflammation of the pancreas. Pancreatitis from azathioprine can manifest as abdominal pain, nausea, and vomiting. 10

Other Side Effects

In addition to the side effects mentioned above, azathioprine can also cause other side effects such as rash, hair loss, muscle pain, joint pain, and fatigue. , 14 , 11 , , 13 , 8 , 15

Side Effect Management

Bone Marrow Suppression Management

To manage bone marrow suppression, the azathioprine dosage may be reduced or discontinued. If bone marrow suppression progresses, treatments such as blood transfusions or bone marrow transplants may be necessary. 9

Gastrointestinal Symptom Management

Gastrointestinal symptoms can be managed through dietary changes and medication. Dietary changes focus on consuming easy-to-digest foods. Medication may include anti-nausea or anti-diarrheal drugs. 4

Liver Damage Management

Liver damage management involves reducing or discontinuing azathioprine dosage. If liver damage progresses, medication such as steroids may be necessary. 17

Pancreatitis Management

Pancreatitis management involves reducing or discontinuing azathioprine dosage. If pancreatitis progresses, medication such as digestive enzymes may be necessary. 10

Other Side Effect Management

Managing other side effects may involve reducing or discontinuing azathioprine dosage. If the side effects are severe, medication such as steroids may be necessary. , 14 , 11 , , 13 , 8 , 15

Comparison Across Studies

Commonalities Across Studies

Numerous studies have demonstrated the effectiveness of azathioprine in treating autoimmune diseases. However, it is also evident that azathioprine is a drug associated with the risk of side effects. Many studies indicate that azathioprine side effects vary depending on factors such as genetic polymorphism, dosage, treatment duration, age, and overall health status.

Differences Across Studies

The risk of azathioprine side effects can vary across studies. This variation could be attributed to factors such as the patient population in the study, azathioprine dosage used, treatment duration, and study design. For example, studies have yielded varying results regarding the relationship between TPMT gene polymorphism and azathioprine side effects. This discrepancy is believed to be due to differing frequencies of TPMT gene polymorphism in the patient populations studied.

Considerations for Real-Life Application

While azathioprine is an effective medication for treating many autoimmune diseases, it is crucial to understand that it carries the risk of side effects. If you are prescribed azathioprine, it is important to follow your doctor's instructions and undergo regular blood tests to minimize the risk of side effects. Early detection of azathioprine side effects is critical. Consult your doctor immediately if you experience any side effects.

Limitations of Current Research

Research on the side effects of azathioprine still has many unanswered questions. For instance, there may be other genetic polymorphisms besides TPMT that influence azathioprine side effects. Additionally, azathioprine side effects could be affected by factors such as age and overall health status. Further research is needed to investigate these factors.

Future Research Directions

Future research is essential to advance our understanding of azathioprine side effects. This could include studies to identify other genetic polymorphisms that contribute to azathioprine side effects, research on the development of new drugs or treatment methods to mitigate azathioprine side effects, and research to develop new methods for evaluating the risk of azathioprine side effects.

Conclusion

Azathioprine is an effective drug for treating many autoimmune diseases, but it's important to be aware of the associated risk of side effects. To minimize the risk of side effects, adhere to your doctor's instructions and undergo regular blood tests. Early detection of azathioprine side effects is crucial. Consult your doctor immediately if you experience any side effects.

Literature analysis of 17 papers
Positive Content
13
Neutral Content
3
Negative Content
1
Article Type
2
0
0
1
17
1.

Rheumatoid arthritis: treatment with azathioprine (IMURAN (R)). Clinical side-effects and laboratory abnormalities.

Author: WhisnantJ K, PelkeyJ

Treats rheumatoid arthritis
Blood count alterations
Gastrointestinal symptoms
Leucopenia

Azathioprine, an immunosuppressant, was found to be generally well-tolerated in 542 patients with rheumatoid arthritis. The most common side effects were gastrointestinal symptoms and alteration in blood counts.

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

2.

Reduced thiopurine methyltransferase activity and development of side effects of azathioprine treatment in patients with rheumatoid arthritis.

Author: StolkJ N, BoerboomsA M, de AbreuR A, de KoningD G, van BeusekomH J, MullerW H, van de PutteL B

AZA-related toxicity

Patients with rheumatoid arthritis who have inherited lower levels of thiopurine methyltransferase (TPMT) are at higher risk for severe side effects when taking azathioprine. This risk is significant for those with 'intermediate' TPMT activity, suggesting the need for TPMT measurement before treatment initiation.

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

3.

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study].

Author: HisamatsuTadakazu, MatsumotoTakayuki, WatanabeKenji, NakaseHiroshi, MotoyaSatoshi, YoshimuraNaoki, IshidaTetsuya, KatoShingo, NakagawaTomoo, EsakiMotohiro, NagahoriMasakazu, MatsuiToshiyuki, NaitoYuji, KanaiTakanori, SuzukiYasuo, NojimaMasanori, WatanabeMamoru, HibiToshifumi,

Crohn's disease treatment

Combining thiopurine with adalimumab for Crohn's disease treatment did not increase the risk of thiopurine discontinuation.

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.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

5.

TPMT and ITPA genetic variants in Lithuanian inflammatory bowel disease patients: Prevalence and azathioprine-related side effects.

Author: SteponaitieneRuta, KupcinskasJuozas, SurvilaiteSanta, VarkalaiteGreta, JonaitisLaimas, KiudelisGediminas, DenapieneGoda, ValantinasJonas, SkiecevicieneJurgita, KupcinskasLimas

IBD treatment
AZA toxicity

The study investigated the prevalence of TPMT and ITPA polymorphisms in Lithuanian IBD patients and their association with AZA-related adverse events. The study found that genetic variations in these genes can influence treatment outcomes in IBD patients.

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

6.

More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing.

Author: BroekmanMark M T J, CoenenMarieke J H, van MarrewijkCorine J, WantenGeert J A, WongDennis R, VerbeekAndre L M, KlungelOlaf H, HooymansPiet M, GuchelaarHenk-Jan, SchefferHans, DerijksLuc J J, de JongDirk J,

IBD treatment
Side effects

This study compared azathioprine (AZA) and mercaptopurine (MP) in thiopurine-naive patients with inflammatory bowel disease (IBD). The study aimed to determine the frequency of side effects and efficacy of both medications.

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.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

[Azathioprine and its side effects].

Author: MontagH

Treats autoimmune disease
Blood count changes
Gastrointestinal issues
Leukemia

Azathioprine, an immunosuppressant, has been associated with various side effects, including changes in blood count, gastrointestinal complaints, intrahepatic cholestasis, acute pancreatitis, and leukemia.

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.
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.

Language : German

11.

Side effects of azathioprine in patients with Crohn's disease.

Author: de JongDirk J, GoulletMohammed, NaberTon H J

Azathioprine may cause side effects

22% of patients discontinued azathioprine prematurely due to adverse events. Patients who discontinued azathioprine prematurely used lower doses of prednisone initially.

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

Language : English

12.

Side-effects of azathioprine treatment in rheumatoid arthritis: analysis of 10 years of experience.

Author: SpeerstraF, BoerboomsA M, van de PutteL B, van BeusekomH J, KruijsenM W, VandenbrouckeJ P

Treats rheumatoid arthritis
Increased mortality
Increased mortality from malignancy

This study investigated the long-term effects of azathioprine, a drug used to treat rheumatoid arthritis, in 91 patients. The study found that male patients had a significant excess of total mortality and mortality from malignancy compared to the general Dutch population. Female patients showed no differences from the general population.

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

14.

A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine.

Author: Zabala-FernándezWilliam, Barreiro-de AcostaManuel, EcharriAna, CarpioDaniel, LorenzoAurelio, CastroJavier, Martínez-AresDavid, PereiraSantos, Martin-GranizoIgnacio, CortonMarta, CarracedoAngel, BarrosFrancisco

IBD treatment
AZA toxicity

This study investigated the contribution of TPMT and ITPA variants to the development of AZA-related toxicity and response in patients with inflammatory bowel diseases. The study found that variants in these genes can contribute to both AZA toxicity and lack of response.

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

17.

Inflammatory bowel diseases and primary sclerosing cholangitis: hepatic and pancreatic side effects due to azathioprine.

Author: PallavicinoF, PellicanoR, ReggianiS, SimondiD, SguazziniC, BonaguraA G, CisaròF, RizzettoM, AstegianoM

IBD remission maintenance
Hepato-pancreatic side effects

The study investigates the hepato-pancreatic side-effects of azathioprine (AZA) in patients with inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC), an association found in up to 80% of PSC cases.

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

Language : English

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