Summary

The combination of azathioprine and infliximab significantly increases immunosuppression, leading to heightened risks of serious infections and certain malignancies. This combination requires careful monitoring and risk assessment, particularly for opportunistic infections and lymphoma development.

Introduction

Azathioprine is an immunosuppressive medication belonging to the antimetabolite class, commonly used to treat inflammatory bowel disease (IBD), rheumatoid arthritis, and prevent organ transplant rejection. Infliximab is a tumor necrosis factor (TNF) alpha inhibitor, a biologic medication used primarily for treating IBD, rheumatoid arthritis, psoriasis, and ankylosing spondylitis. Both medications work by suppressing the immune system through different mechanisms.

Mechanism of Interaction

Azathioprine works by interfering with DNA synthesis and cell division in rapidly dividing immune cells, particularly T and B lymphocytes. It is metabolized to 6-mercaptopurine, which inhibits purine synthesis. Infliximab binds specifically to TNF-alpha, neutralizing this key inflammatory cytokine and reducing immune system activity. When used together, these medications create additive immunosuppressive effects, significantly reducing the body's ability to fight infections and potentially increasing malignancy risk.

Risks and Symptoms

The primary risks of combining azathioprine and infliximab include: significantly increased susceptibility to serious bacterial, viral, fungal, and opportunistic infections; elevated risk of lymphoma, particularly hepatosplenic T-cell lymphoma in young males; potential for severe infections such as tuberculosis, histoplasmosis, and pneumocystis pneumonia; increased risk of skin cancers and other malignancies; possible hepatotoxicity; and bone marrow suppression leading to decreased white blood cell, red blood cell, and platelet counts.

Management and Precautions

Management of this drug combination requires: comprehensive pre-treatment screening for latent tuberculosis, hepatitis B/C, and other infections; regular monitoring of complete blood counts, liver function tests, and clinical signs of infection; patient education about infection prevention and early recognition of symptoms; prompt evaluation of any fever, unusual fatigue, or signs of infection; consideration of prophylactic treatments for certain opportunistic infections; regular skin examinations for malignancy screening; and careful risk-benefit assessment, particularly in young male patients due to lymphoma risk. Healthcare providers should maintain a low threshold for discontinuing therapy if serious infections or malignancies develop.

Azathioprine interactions with food and lifestyle

Azathioprine should be taken with food to reduce gastrointestinal side effects such as nausea and stomach upset. Alcohol consumption should be limited or avoided while taking azathioprine, as both the medication and alcohol can affect liver function, potentially increasing the risk of liver toxicity. Patients should also avoid live vaccines while on azathioprine due to its immunosuppressive effects, which can reduce the body's ability to respond to vaccines and increase infection risk. Sun exposure should be minimized and protective measures (sunscreen, protective clothing) should be used, as azathioprine increases the risk of skin cancer and photosensitivity reactions.

Infliximab interactions with food and lifestyle

Live vaccines should be avoided during Infliximab treatment and for several months after discontinuation due to increased risk of serious infections. Patients should avoid exposure to individuals with active infections when possible. Alcohol consumption should be limited or avoided, especially in patients with concurrent hepatitis B or C, as Infliximab may increase the risk of liver toxicity. Close contact with individuals who have received live vaccines (such as oral polio vaccine, nasal flu vaccine, or rotavirus vaccine) should be avoided when possible.