RENFLEXIS Powder for solution for injection Ref.[11102] Active ingredients: Infliximab

2.1 Crohn’s Disease

The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adults with moderately to severely active Crohn’s disease or fistulizing Crohn’s disease. For adult patients who respond and then lose their response, consideration may be given to treatment with 10 mg/kg. Patients who do not respond by Week 14 are unlikely to respond with continued dosing and consideration should be given to discontinue RENFLEXIS in these patients.

2.2 Pediatric Crohn’s Disease

The recommended dose of RENFLEXIS for pediatric patients 6 years and older with moderately to severely active Crohn’s disease is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

2.3 Ulcerative Colitis

The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of adult patients with moderately to severely active ulcerative colitis.

2.4 Pediatric Ulcerative Colitis

The recommended dose of RENFLEXIS for pediatric patients 6 years and older with moderately to severely active ulcerative colitis is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks.

2.5 Rheumatoid Arthritis

The recommended dose of RENFLEXIS is 3 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter for the treatment of moderately to severely active rheumatoid arthritis. RENFLEXIS should be given in combination with methotrexate. For patients who have an incomplete response, consideration may be given to adjusting the dose up to 10 mg/kg or treating as often as every 4 weeks bearing in mind that risk of serious infections is increased at higher doses [see Adverse Reactions (6.1)].

2.6 Ankylosing Spondylitis

The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 6 weeks thereafter for the treatment of active ankylosing spondylitis.

2.7 Psoriatic Arthritis

The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of psoriatic arthritis. RENFLEXIS can be used with or without methotrexate.

2.8 Plaque Psoriasis

The recommended dose of RENFLEXIS is 5 mg/kg given as an intravenous induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter for the treatment of chronic severe (i.e., extensive and/or disabling) plaque psoriasis.

2.9 Monitoring to Assess Safety

Prior to initiating RENFLEXIS 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

Adverse effects during administration of infliximab products have included flu-like symptoms, headache, dyspnea, hypotension, transient fever, chills, gastrointestinal symptoms, and skin rashes. Anaphylaxis might occur at any time during RENFLEXIS infusion. Approximately 20% of patients in all clinical trials of infliximab experienced an infusion reaction compared with 10% of placebo-treated patients [see Adverse Reactions (6.1)]. Prior to infusion with RENFLEXIS, premedication may be administered at the physician’s discretion. Premedication could include antihistamines (anti-H1 +/- anti-H2), acetaminophen and/or corticosteroids.

During infusion, mild to moderate infusion reactions may improve following slowing or suspension of the infusion, and upon resolution of the reaction, reinitiation at a lower infusion rate and/or therapeutic administration of antihistamines, acetaminophen, and/or corticosteroids. For patients that do not tolerate the infusion following these interventions, RENFLEXIS should be discontinued.

During or following infusion, patients who have severe infusion-related hypersensitivity reactions should be discontinued from further RENFLEXIS treatment. The management of severe infusion reactions should be dictated by the signs and symptoms of the reaction. Appropriate personnel and medication should be available to treat anaphylaxis if it occurs.

2.11 General Considerations and Instructions for Preparation and Administration

RENFLEXIS is intended for use under the guidance and supervision of a physician. The reconstituted infusion solution should be prepared by a trained medical professional using aseptic technique by the following procedure:

1. Calculate the dose, total volume of reconstituted RENFLEXIS solution required and the number of RENFLEXIS vials needed. Each RENFLEXIS vial contains 100 mg of the infliximab-abda antibody.
2. Reconstitute each RENFLEXIS vial with 10 mL of Sterile Water for Injection, USP, 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. 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. The reconstituted solution concentration is 10 mg/mL. The solution should be colorless to light yellow and opalescent, and the solution may develop a few translucent particles as infliximab-abda is a protein. Do not use if the lyophilized cake has not fully dissolved or if opaque particles, discoloration, or other foreign particles are present.
3. Dilute the total volume of the reconstituted RENFLEXIS solution dose to 250 mL with sterile 0.9% Sodium Chloride Injection, USP, by withdrawing a volume equal to the volume of reconstituted RENFLEXIS from the 0.9% Sodium Chloride Injection, USP, 250 mL bottle or bag. Do not dilute the reconstituted RENFLEXIS solution with any other diluent. Slowly add the total volume of reconstituted RENFLEXIS solution to the 250 mL infusion bottle or bag. Gently mix. The resulting infusion concentration should range between 0.4 mg/mL and 4 mg/mL.
4. The RENFLEXIS infusion should begin within 3 hours of reconstitution and dilution. The infusion must be administered over a period of not less than 2 hours and must use an infusion set with an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 μm or less). The vials do not contain antibacterial preservatives. Therefore, any unused portion of the infusion solution should not be stored for reuse.
5. No physical biochemical compatibility studies have been conducted to evaluate the coadministration of RENFLEXIS with other agents. RENFLEXIS should not be infused concomitantly in the same intravenous line with other agents.
6. Parenteral drug products should be inspected visually before and after reconstitution for particulate matter and discoloration prior to administration, whenever solution and container permit. If visibly opaque particles, discoloration or other foreign particulates are observed, the solution should not be used.

Single doses up to 20 mg/kg of infliximab have been administered without any direct toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately.

Store unopened RENFLEXIS vials in a refrigerator at 2°C to 8°C (36°F to 46°F).

If needed, unopened RENFLEXIS vials may be stored at room temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months but not exceeding the original expiration date. Once removed from the refrigerator, RENFLEXIS cannot be returned to the refrigerator.

[For storage conditions of the reconstituted product, see Dosage and Administration (2.11)].