What medications cause immunodeficiency (immune deficiencies)?

From the Guidelines

Medications that can cause immune deficiencies include corticosteroids, immunosuppressants, chemotherapy drugs, biological agents, and long-term antibiotics, which can increase the risk of infections and require careful monitoring and management. These medications can suppress the immune system's normal function by various mechanisms, such as preventing T-cell activation, blocking inflammatory cytokines, or directly killing immune cells. According to the 2014 IDSA clinical practice guideline for vaccination of the immunocompromised host 1, patients with high-level immunosuppression, including those receiving cancer chemotherapy, solid organ transplantation, or certain biologic immune modulators, are at increased risk of infections. The guideline also notes that patients with low-level immunosuppression, including those with asymptomatic HIV infection or receiving lower doses of systemic corticosteroids, may also be at risk.

Some specific medications that can cause immune deficiencies include:

• Corticosteroids like prednisone, which can significantly impair immune responses when taken at doses above 20mg daily for more than a few weeks 1
• Immunosuppressants used in transplant medicine, such as tacrolimus, cyclosporine, and mycophenolate mofetil, which deliberately reduce immune function to prevent organ rejection
• Chemotherapy drugs like cyclophosphamide, methotrexate, and 5-fluorouracil, which destroy rapidly dividing cells, including immune cells
• Biological agents targeting specific immune pathways, such as TNF inhibitors (adalimumab, infliximab), rituximab (which depletes B cells), and JAK inhibitors (tofacitinib)
• Long-term antibiotic use, which can disrupt the microbiome and indirectly affect immune function

Patients taking these medications should be monitored for infections, maintain vaccinations (though live vaccines are often contraindicated), practice good hygiene, and promptly report fever or other infection signs to their healthcare provider. The 2016 diagnosis and treatment of leishmaniasis guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) also highlight the importance of monitoring and managing immunosuppressed patients for infections 1. Additionally, the 2012 monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients guidelines by the American College of Chest Physicians emphasize the need for careful monitoring and management of immunosuppressed patients to minimize potential harm 1.

From the FDA Drug Label

Tacrolimus can lower the ability of your immune system to fight infections. Mycophenolate mofetil can cause serious side effects: Low blood cell counts. People taking high doses of mycophenolate mofetil each day may have a decrease in blood counts, including: white blood cells, especially neutrophils. Neutrophils fight against bacterial infections. You have a higher chance of getting an infection when your white blood cell count is low.

Medications that cause immune deficiencies include:

• Tacrolimus: can lower the ability of your immune system to fight infections.
• Mycophenolate mofetil: can cause a decrease in blood counts, including white blood cells, making you more susceptible to infections. These medications can increase the risk of infections and other immune-related problems. 2, 3, 2

From the Research

Medications that Cause Immune Deficiencies

• The following medications have been identified as causing immune deficiencies:
  • Tacrolimus 4, 5, 6, 7
  • Azathioprine 4, 5, 6, 7
  • Mycophenolate mofetil 4, 5, 6, 7
  • Cyclosporine 4, 6, 7
  • Sirolimus 4, 6
  • Everolimus 4
  • Prednisone 4
  • Corticosteroids 6, 7, 8
  • Methotrexate 7
  • Rituximab 7
  • Cyclophosphamide 7
  • Eculizumab 7
  • Intravenous immunoglobulin 7
  • Subcutaneous immunoglobulin 7
  • Plasmapheresis 7

Mechanisms of Immune Deficiency

• These medications can cause immune deficiencies by:
  • Inhibiting the purine pathway and diminishing cell proliferation (mycophenolate mofetil and azathioprine) 5
  • Inhibiting lymphocyte activation by inhibiting the calcineurin pathway (tacrolimus) 5
  • Suppressing cytotoxic, phagocytic, and antigen-presenting cells involved in both the innate and adaptive immune responses (corticosteroids) 8
  • Suppressing messenger cytokines that are integral to immune function (corticosteroids) 8
  • Suppressing the hypothalamic-pituitary-adrenal (HPA) axis (corticosteroids) 8

Clinical Implications

• The use of these medications can have significant clinical implications, including:
  • Increased risk of nonmelanoma skin cancer (NMSC) in heart transplant recipients 4
  • Increased risk of infections and related morbidity or mortality (corticosteroids) 8
  • Need for monitoring of immunosuppressive agents during steroid withdrawal to ensure optimal treatment outcomes 6
  • Need for shared decision making, informed consent, risk management, and consideration of COVID-19 vaccination in patients receiving peripheral corticosteroid injections 8