What are the contraindications to Remicade (infliximab) in patients with various medical conditions and demographics?

Contraindications to Remicade (Infliximab)

Remicade is absolutely contraindicated in patients with moderate to severe heart failure (NYHA Class III/IV) at doses >5 mg/kg, those with severe hypersensitivity reactions to infliximab, hypersensitivity to murine proteins or inactive components, and active serious infections including sepsis and active tuberculosis. 1

Absolute Contraindications

Cardiac Contraindications

• Moderate to severe heart failure (NYHA Class III/IV) at doses >5 mg/kg is an absolute contraindication 1
• A randomized trial demonstrated increased mortality and hospitalization from worsening heart failure in patients receiving infliximab 10 mg/kg 2
• Numerous postmarketing reports document worsening heart failure during therapy 2

Hypersensitivity Reactions

• Prior severe hypersensitivity reaction to any infliximab product absolutely contraindicates re-administration 1
• Known hypersensitivity to murine proteins or inactive product components 1
• Severe infusion reactions can progress to anaphylactic shock, occurring in up to 20% of patients during or within 1-2 hours of infusion 2
• For severe reactions, further infliximab is contraindicated, though other anti-TNF agents may still be considered 2

Active Infections

• Active serious infections including sepsis are absolute contraindications 2
• Anti-TNF therapy should not be started in the presence of active infection and must be discontinued if serious infection develops 2
• Active tuberculosis requires treatment delay until at least 2 months after starting TB therapy, ideally until completion 3
• Patients should not receive infliximab until active infections are adequately treated 4

Active Viral Hepatitis

• Active hepatitis B infection is an absolute contraindication 3
• Active viral hepatitis should preclude use of infliximab 2
• Hepatitis serology must be obtained before therapy initiation 3

Relative Contraindications and High-Risk Situations

Tuberculosis Risk

• All patients require mandatory TB screening with chest radiograph and tuberculin skin testing (or IGRA) before starting therapy 3
• Positive TST/IGRA, chest radiograph consistent with prior TB, or high-risk individuals require prophylactic isoniazid 5 mg/kg (maximum 300 mg) daily for 9 months before initiating infliximab 3
• Infliximab carries higher TB reactivation risk than other anti-TNF agents, with greater likelihood of extrapulmonary involvement 2
• Half of TB cases occur after three or more infusions (median 12 weeks), suggesting reactivation disease 2

Malignancy History

• Exercise caution in patients with history of malignancy 2
• Hepatosplenic T-cell lymphomas reported particularly in adolescent and young adult Crohn's disease patients receiving concomitant azathioprine or 6-mercaptopurine 2
• Insufficient data exist to definitively determine increased lymphoma or nonlymphomatous malignancy risk 2

Demyelinating Disease

• CNS demyelination disorders have been reported sporadically with TNF-alpha inhibitors 2
• Exercise caution and close monitoring in patients with history of demyelinating disease 3

Hepatitis B Carriers

• Hepatitis B carriers or patients with history of hepatitis B require monitoring for viral reactivation throughout therapy 2, 3
• While not absolute contraindications, these patients need vigilant surveillance 3

Immune-Related Hepatitis

• Infliximab is specifically contraindicated for immune-related hepatitis (as seen with immune checkpoint inhibitors) 2

Critical Pre-Treatment Requirements

Mandatory Screening

• Tuberculosis screening with chest radiograph and TST/IGRA 3
• Hepatitis B serology 3
• Assessment for active infections 4
• Consideration of endemic fungal infections for patients in or visiting endemic regions 3

Vaccination Status

• Complete all vaccinations before starting infliximab 3
• Live vaccines are absolutely contraindicated during therapy and for at least 6 months after birth in infants exposed in utero 3

Common Pitfalls to Avoid

• Do not assume prior tolerance guarantees future tolerance—delayed hypersensitivity reactions can develop after multiple infusions 4
• Do not overlook the need for TB prophylaxis completion before initiating therapy in latent TB patients 3
• Do not restart infliximab after severe infusion reactions—consider alternative anti-TNF agents instead 2
• Do not use doses >5 mg/kg in any patient with heart failure history 1
• Do not administer to patients with unresolved infections—wait until infection completely resolves 3