Summary

• Concomitant use of REMICADE with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE is not recommended due to an increased risk of infection.¹
• Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.¹
• In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines can result in clinical infections, including disseminated infections. The concurrent administration of live vaccines with REMICADE is not recommended.¹
• Fatal outcome due to disseminated Bacille Calmette-Guérin (BCG) infection has been reported in an infant who received a BCG vaccine after in utero exposure to infliximab. Infliximab is known to cross the placenta and has been detected up to 6 months following birth. At least a six month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab.¹
• Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with REMICADE.¹
• Specific drug interaction studies, including interactions with methotrexate (MTX), have not been conducted. Concomitant MTX use may decrease the incidence of anti-infliximab antibody production and increase infliximab concentrations.¹
• Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn’s disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.¹
• Upon initiation or discontinuation of REMICADE in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.¹
• Please refer to the REMICADE full Prescribing Information for further information related to this topic.

PRODUCT LABELING

WARNINGS AND PRECAUTIONS

Use with Anakinra

Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with the combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination of REMICADE and anakinra is not recommended.¹

Use with Abatacept

In clinical studies, concurrent administration of TNF-blocking agents and abatacept have been associated with an increased risk of infections including serious infections compared with TNF-blocking agents alone, without increased clinical benefit. Therefore, the combination of REMICADE and abatacept is not recommended.¹

Concurrent Administration with other Biological Therapeutics

There is insufficient information regarding the concomitant use of REMICADE with other biological therapeutics used to treat the same conditions as REMICADE. The concomitant use of REMICADE with these biologics is not recommended because of the possibility of an increased risk of infection.¹

Switching between Biological Disease-Modifying Antirheumatic Drugs (DMARDs)

Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.¹

Live Vaccines/Therapeutic Infectious Agents

In patients receiving anti-TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines can result in clinical infections, including disseminated infections. The concurrent administration of live vaccines with REMICADE is not recommended.¹

Fatal outcome due to disseminated BCG infection has been reported in an infant who received a BCG vaccine after in utero exposure to infliximab. Infliximab is known to cross the placenta and has been detected up to 6 months following birth. At least a six month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab.¹

Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with REMICADE.¹

It is recommended that all pediatric patients be brought up to date with all vaccinations prior to initiating REMICADE therapy. The interval between vaccination and initiation of REMICADE therapy should be in accordance with current vaccination guidelines.¹

DRUG INTERACTIONS

Use with Anakinra or Abatacept

An increased risk of serious infections was seen in clinical studies of other TNFα-blocking agents used in combination with anakinra or abatacept, with no added clinical benefit. Because of the nature of the adverse reactions seen with these combinations with TNF-blocker therapy, similar toxicities may also result from the combination of anakinra or abatacept with other TNFα-blocking agents. Therefore, the combination of REMICADE and anakinra or abatacept is not recommended.¹

Use with Tocilizumab

The use of tocilizumab in combination with biological DMARDs such as TNF antagonists, including REMICADE, should be avoided because of the possibility of increased immunosuppression and increased risk of infection.¹

Use with Other Biological Therapeutics

The combination of REMICADE with other biological therapeutics used to treat the same conditions as REMICADE is not recommended.¹

Methotrexate (MTX) and Other Concomitant Medications

Specific drug interaction studies, including interactions with MTX, have not been conducted. The majority of patients in rheumatoid arthritis or Crohn’s disease clinical studies received one or more concomitant medications. In rheumatoid arthritis, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. Concomitant Crohn’s disease medications were antibiotics, antivirals, corticosteroids, 6 MP/AZA and aminosalicylates. In psoriatic arthritis clinical trials, concomitant medications included MTX in approximately half of the patients as well as NSAIDs, folic acid and corticosteroids. Concomitant MTX use may decrease the incidence of anti-infliximab antibody production and increase infliximab concentrations.¹

Immunosuppressants

Patients with Crohn’s disease who received immunosuppressants tended to experience fewer infusion reactions compared to patients on no immunosuppressants. Serum infliximab concentrations appeared to be unaffected by baseline use of medications for the treatment of Crohn’s disease including corticosteroids, antibiotics (metronidazole or ciprofloxacin) and aminosalicylates.¹

Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-1, IL-6, IL-10, IFN) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as infliximab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of REMICADE in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.¹

Live Vaccines/Therapeutic Infectious Agents

It is recommended that live vaccines not be given concurrently with REMICADE. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab for at least 6 months following birth.¹

It is recommended that therapeutic infectious agents not be given concurrently with REMICADE.¹