BACKGROUND

The Food and Drug Administration (FDA) has approved Prescribing Information that does not require the use of non-polyvinyl chloride (PVC) administration equipment for REMICADE infusion. However, an infusion set with an in-line, sterile, nonpyrogenic, low-protein-binding filter (pore size of 1.2 µm or less) is required for REMICADE infusion. For more information related to the administration instructions for REMICADE or for other related REMICADE topics, please refer to the full Prescribing Information for REMICADE.

RATIONALE: Removal of Non-PVC Equipment Requirement

Restriction of the use of di-(2-ethylhexyl)phthalate (DEHP) containing PVC infusion equipment with REMICADE was required because REMICADE contains a polysorbate surfactant that has been shown to leach the plasticizer DEHP from PVC.  DEHP was found to be hepatocarcinogenic in rats and mice when administered in high oral doses.¹ Therefore, DEHP-containing PVC equipment was not recommended for use with REMICADE in order to eliminate the possible exposure of patients to DEHP.

Peroxisome proliferation is considered to be the mechanism that induces hepatocarcinoma in rodents after administration of DEHP.  Marked differences have been observed among animal species with respect to DEHP-induced peroxisome proliferation. Nonhuman primates have little or no DEHP-induced peroxisome proliferation.^1-3 Thus, while the actual carcinogenic potential of DEHP to humans is uncertain, prolonged exposure of humans to DEHP leached into blood products has not been associated with specific toxicities.⁴

The United States Environmental Protection Agency (EPA) evaluated the toxicity data for DEHP and determined a daily reference dose of DEHP.³ Based on this daily reference dose, a 50-70 kg person treated with a dose of REMICADE would receive an amount of DEHP that is approximately 50-70 times lower than the EPA’s daily reference dose.  The actual potential exposure of DEHP via REMICADE is even lower since REMICADE is not administered daily.  Based on the information presented, the requirement to use non-PVC administration equipment has been removed from the Prescribing Information for REMICADE.