What are the potential interactions between Repatha (evolocumab) and Remicade (infliximab)?

No Known Drug Interactions Between Repatha (Evolocumab) and Remicade (Infliximab)

There are no documented drug interactions between Repatha (evolocumab) and Remicade (infliximab), and these medications can be safely administered concurrently in patients requiring both treatments.

Mechanism of Action and Interaction Potential

Repatha (Evolocumab)

• Mechanism: Repatha is a PCSK9 inhibitor that binds to PCSK9 and increases the number of LDL receptors available to clear circulating LDL-cholesterol 1
• Metabolism: As a monoclonal antibody, Repatha is eliminated through proteolytic degradation pathways, not through cytochrome P450 enzymes or renal excretion
• Administration: Subcutaneous injection, either 140 mg every 2 weeks or 420 mg once monthly 1

Remicade (Infliximab)

• Mechanism: Remicade is a TNF-alpha inhibitor that binds to and neutralizes TNF-alpha, reducing inflammation 1
• Metabolism: Also eliminated through proteolytic pathways as a monoclonal antibody
• Administration: Intravenous infusion at varying doses depending on indication (typically 3-5 mg/kg) 1

Clinical Considerations

Efficacy

• No evidence suggests that either medication reduces the efficacy of the other
• Both medications can be used at their standard doses without adjustment when used together

Safety Considerations

• Immunogenicity:

  • Infliximab has known immunogenicity issues with 26-28% of patients developing antibodies against it by week 54 1
  • Concomitant immunomodulators (thiopurines or methotrexate) reduce immunogenicity risk with infliximab 1
  • No evidence suggests that evolocumab affects antibody formation against infliximab

• Infection Risk:

  • Infliximab increases risk of infections due to its immunosuppressive effects 2
  • Evolocumab does not have significant immunosuppressive properties and does not further increase infection risk when combined with infliximab

• Cardiovascular Effects:

  • Evolocumab has beneficial cardiovascular effects by reducing LDL cholesterol 3
  • TNF inhibitors like infliximab have a black box warning regarding heart failure, though this is less concerning than with some other TNF inhibitors 3
  • The combination does not appear to have additive cardiovascular risks

Practical Recommendations

Monitoring

• Infection surveillance: Continue standard monitoring for signs of infection as would be done with infliximab alone
• Lipid levels: Monitor LDL-C as normally indicated with evolocumab therapy
• Immunogenicity: Consider monitoring infliximab drug levels and antibodies, especially if efficacy wanes

Special Populations

• Inflammatory Bowel Disease: For patients with IBD requiring both medications:

  • Consider combination therapy of infliximab with a thiopurine to reduce immunogenicity and improve efficacy 1
  • This combination does not affect evolocumab use or dosing

• Cardiovascular Disease: For patients with both cardiovascular disease and inflammatory conditions:

  • The combination may be particularly beneficial as evolocumab reduces cardiovascular risk while infliximab controls inflammation
  • Monitor cardiac function in patients with pre-existing heart failure

Conclusion

The absence of documented interactions between evolocumab and infliximab in the medical literature, combined with their different mechanisms of action and metabolic pathways, suggests these medications can be safely co-administered without dose adjustments or special precautions beyond those normally required for each medication individually.