INFLIXIMAB (Page 2 of 13)

2.9 Assessment for Latent and Active Tuberculosis

Prior to initiating Infliximab and periodically during therapy, patients should be evaluated for active tuberculosis and tested for latent infection [see Warnings and Precautions (5.1)].

2.10 Administration Instructions Regarding Infusion Reactions

Prior to treatment, ensure appropriate personnel and medication are available to treat reactions (e.g., hypersensitivity, other reactions) that occur during infusion and shortly after infusion. Prior to infusion with Infliximab, patients may be premedicated with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids [see Warnings and Precautions (5.7)].

For mild to moderate reactions during the infusion, consider slowing or stopping the infusion. Upon resolution of these reactions, may reinitiate at a lower infusion rate and/or with histamine-1 receptor antagonists, histamine-2 receptor antagonists, acetaminophen, and/or corticosteroids. Discontinue the infusion if the mild to moderate reactions reoccur.

Discontinue the infusion if severe hypersensitivity reactions occur during the infusion.

2.11 Reconstitution, Dilution, and Administration Instructions

Infliximab is intended for use under the guidance and supervision of a healthcare provider. The supplied lyophilized powder must be reconstituted and diluted prior to administration. The infusion solution should be prepared and administered by a trained medical professional using aseptic technique by the following procedure:

  1. Calculate the dose, total volume of reconstituted Infliximab solution required and the number of Infliximab vials needed. More than one vial may be needed for a full dose.
  2. Reconstitute each 100 mg Infliximab 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:
    • 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 infliximab 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 Infliximab solution.
  3. Dilute the total volume of the reconstituted Infliximab solution to 250 mL 1 with sterile 0.9% Sodium Chloride Injection, USP, (do not dilute with any other diluent) as follows:
    • Withdraw a volume from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag equal to the total volume of reconstituted Infliximab required for a dose. Slowly add the total volume of reconstituted Infliximab solution from the vial(s) to the 250 mL infusion bottle or bag.
    • Discard any unused portion of the reconstituted Infliximab 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 infliximab.
  4. The Infliximab 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).
  5. Given that the vials do not contain antibacterial preservatives, discard any unused portion of the infusion solution (do not store for reuse).

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


1
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.

3 DOSAGE FORMS AND STRENGTHS

For injection: 100 mg of infliximab as a white lyophilized powder in a single-dose vial for reconstitution and dilution.

4 CONTRAINDICATIONS

The use of Infliximab at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure [see Warnings and Precautions (5.5) and Adverse Reactions (6.1)].

Infliximab is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab or any of the inactive ingredients of Infliximab or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Serious Infections

Patients treated with Infliximab are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.

Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, salmonellosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.

Treatment with Infliximab should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. The risks and benefits of treatment should be considered prior to initiating therapy in patients:

  • with chronic or recurrent infection;
  • who have been exposed to tuberculosis;
  • with a history of an opportunistic infection;
  • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or
  • with underlying conditions that may predispose them to infection.

Tuberculosis

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving Infliximab, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with Infliximab during treatment for latent tuberculosis.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating Infliximab and periodically during therapy. Treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is needed prior to initiating Infliximab, even for patients previously vaccinated with Bacille Calmette-Guérin (BCG).

Anti-tuberculosis therapy should also be considered prior to initiation of Infliximab in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.

Tuberculosis should be strongly considered in patients who develop a new infection during Infliximab treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Monitoring

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Infliximab, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with Infliximab.

Infliximab should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with Infliximab should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and appropriate antimicrobial therapy should be initiated.

Invasive Fungal Infections

For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness. Appropriate empiric antifungal therapy should be considered while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections and should take into account both the risk for severe fungal infection and the risks of antifungal therapy.

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