Summary

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• REMICADE should be reconstituted and diluted prior to infusion by a trained medical professional using aseptic technique. The Prescribing Information recommends that the reconstituted REMICADE solution should not be diluted with any other diluent, except sterile 0.9% Sodium Chloride Injection, USP.¹
• Please refer to the DOSAGE and ADMINISTRATION/Reconstitution, Dilution, and Administration Instructions section of the full Prescribing Information for complete information on the preparation and administration of REMICADE. ¹
• REMICADE when reconstituted and further diluted with 0.45% Sodium Chloride was studied in a phase 2 pilot trial and also in a stability study and details are described below.^2-4

PRODUCT LABELING

• REMICADE (infliximab) for injection is supplied as a sterile, preservative-free, white, lyophilized powder for intravenous infusion after reconstitution and diluton.¹
• Calculate the dose, total volume of reconstituted REMICADE solution required and the number of REMICADE vials needed. More than one vial may be needed for a full dose.¹
• Reconstitute each 100 mg REMICADE vial with 10 mL of Sterile Water for Injection, USP, to obtain a concentration of 10 mg/mL, using a syringe equipped with a 21-gauge or smaller needle as follows:¹
  • Remove the flip-top from the vial and wipe the top with an alcohol swab.
  • Insert the syringe needle into the vial through the center of the rubber stopper and direct the stream of Sterile Water for Injection, USP, to the glass wall of the vial. Gently swirl the solution by rotating the vial to dissolve the lyophilized powder, which has a cake-like appearance. Avoid prolonged or vigorous agitation. DO NOT SHAKE. Foaming of the solution on reconstitution is not unusual.
  • Allow the reconstituted solution to stand for 5 minutes. Visually inspect the reconstituted solution for particulate matter and discoloration. The reconstituted solution should be colorless to light yellow and opalescent, and the solution may develop a few translucent particles as REMICADE is a protein. Do not use if the lyophilized powder has not fully dissolved or if opaque particles, discoloration, or other foreign particles are present. Do not store unused reconstituted REMICADE solution.
• Dilute the total volume of the reconstituted REMICADE solution to 250 mL^* with sterile 0.9% Sodium Chloride Injection, USP, (do not dilute with any other diluent) as follows:¹
  • Withdraw a volume from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag equal to the total volume of reconstituted REMICADE required for a dose. Slowly add the total volume of the reconstituted REMICADE solution from the vial(s) to the 250 mL infusion bottle or bag.
  • Discard any unused portion of the reconstituted REMICADE solution remaining in the vial(s).
  • Gently invert the bag to mix the solution. The resulting infusion concentration should range between 0.4 mg/mL (minimum recommended concentration) and 4 mg/mL (maximum recommended concentration) of REMICADE.

* For volumes greater than 250 mL, either use a larger infusion bag (e.g. 500 mL) or multiple 250 mL infusion bags to ensure that the concentration of the infusion solution does not exceed 4 mg/mL.

• The REMICADE infusion should begin within 3 hours of reconstitution and dilution. The infusion must be administered intravenously for at least 2 hours with an infusion set with an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 µm or less).¹
• Given that the vials do not contain antibacterial preservatives, discard any unused portion of the infusion solution (do no store for reuse).¹

No physical biochemical compatibility studies have been conducted to evaluate the co-administration of REMICADE with other agents. REMICADE should not be infused concomitantly in the same intravenous line with other agents.¹

DATA ON RECONSTITUTION/DILUTION WITH 0.45% SODIUM CHLORIDE

Phase 2 Study

In a phase 2, multicenter, randomized, double-blind, placebo-controlled pilot trial evaluating the effects of REMICADE in patients with stable class III or IV congestive heart failure, doses of REMICADE were administered at concentrations of 2.5-10 mg/mL in 0.45% sodium chloride. In this study, REMICADE was administered at a dose of either 5 mg/kg or 10 mg/kg (maximum dose 1000 mg), and patient weights ranged from 46.3-157.0 kg.⁴ REMICADE infusions were prepared under aseptic conditions using a 21-gauge (or smaller) needle to withdraw 10 mL of solution from an infusion bag of 0.45% sodium chloride. The 10 mL of 0.45% sodium chloride was then added to each vial of REMICADE. After reconstitution of the REMICADE vials, the total required amount of REMICADE solution was then withdrawn aseptically from the vials and injected into the infusion bag containing the remaining 0.45% sodium chloride.² Note that doses of REMICADE >5 mg/kg are contraindicated in patients with moderate to severe heart failure.¹

Stability Study

A study was conducted to evaluate the physical and biochemical stability of REMICADE  (100 mg) vials reconstituted with 0.45% sodium chloride to a final concentration of 10 mg/mL, as well as REMICADE vials reconstituted with 0.45% sodium chloride and further diluted with 0.45% sodium chloride to a final concentration of 2.5 mg/mL. Samples were stored at room temperature and tested for visible and subvisible particles, soluble aggregates, protein concentration, isoelectric focusing, and immunoreactivity over 24 hours.³

There was no significant change in visible particles, subvisible particles, turbidity, or soluble aggregates in either the REMICADE vials reconstituted with 0.45% sodium chloride to a concentration of 10 mg/mL or the REMICADE vials reconstituted and further diluted with 0.45% sodium chloride to a concentration of 2.5 mg/mL and stored for 24 hours at room temperature. Similarly, for both concentrations, no loss of immunoreactivity or protein concentration was observed. In summary, the findings of this study suggest that REMICADE is biochemically and physically stable for 24 hours at room temperature when reconstituted with 0.45% sodium chloride or reconstituted and further diluted with 0.45% sodium chloride to concentrations of 10 mg/mL and 2.5 mg/mL, respectively.³

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 September 2024.