REMICADE® ADMINISTRATION

Before infusing REMICADE®, you should carefully read the Pretreatment Checklist and go over the questions with your patient. Then, refer to this Administration Guide for the supplies you will need, administration instructions, and important information on what to do in the event your patient experiences an infusion reaction transpose®.1

  • Prior to infusion with REMICADE®, premedication may be administered at the
    physician’s discretion

  • Premedication could include antihistamines (anti-H1 +/− anti-H2), acetaminophen, and/or corticosteroids

Suggested Supplies

Infusion supplies are listed below. These items may be ordered through your
wholesaler or distributor. Please note that vials of REMICADE® must be purchased separately.

IV ACCESS SUPPLIES

*Infusion sets should meet the Needlestick Safety and Prevention Act of 2001 requiring needle safety systems.

Reconstitution and Administration Supplies

*Infusion sets should meet the Needlestick Safety and Prevention Act of 2001 requiring needle safety systems.

Infusion reaction medications include acetaminophen, antihistamines, corticosteroids, and epinephrine.

NOTE: One additional item required for REMICADE® is a medicine storage refrigerator. Prior to reconstitution and use, vials of REMICADE® must be stored at a temperature between 2°C to 8°C (36°F to 46°F).

Provide patients or their caregivers with the Medication Guide for REMICADE®. You can obtain a printable PDF of the Medication Guide here.

NOTE: REMICADE® vials do not contain antibacterial preservatives. Therefore, the reconstituted vials should be used immediately, not re-entered or stored. The diluent to be used for reconstitution is 10 mL of Sterile Water for Injection, USP. The total dose of the reconstituted product must be further diluted to 250 mL with 0.9% Sodium Chloride Injection, USP. The infusion concentration should range between 0.4 mg/mL and 4.0 mg/mL. The REMICADE® infusion should begin within 3 hours of its preparation.1

1.Calculate the dose and number of REMICADE® vials needed. Each REMICADE® vial contains 100 mg of infliximab. Calculate the total volume of reconstituted REMICADE® solution required.

2.Reconstitute each REMICADE® vial with 10 mL of Sterile Water for Injection, USP, using a syringe equipped with a 21-gauge or smaller needle. 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 solution should be colorless to light yellow and opalescent; the solution may develop a few translucent particles, as infliximab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present.

3.Dilute the total volume of the reconstituted REMICADE® solution dose to 250 mL with 0.9% Sodium Chloride Injection, USP, by withdrawing a volume of 0.9% Sodium Chloride Injection, USP, equal to the volume of reconstituted REMICADE® from the 0.9% Sodium Chloride Injection, USP, 250-mL bottle or bag. Slowly add the total volume of reconstituted REMICADE® solution to the 250-mL infusion bottle or bag. Gently mix.

4.The infusion solution must be administered over a period of not less than 2 hours and must use an infusion set with an in-line, sterile, nonpyrogenic, low-protein-binding filter (pore size of 1.2 microns or less). Any unused portion of the infusion solution should not be stored or reused.

5.No physical biochemical compatibility studies have been conducted to evaluate the coadministration of REMICADE® with other agents. REMICADE® should not be infused concomitantly in the same intravenous line with other agents.

6.Parenteral drug products should be inspected visually 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.

Infusion reactions may occur with numerous IV medications, including REMICADE®. In clinical trials of REMICADE®, the majority of infusion reactions were mild to moderate. Most of these reactions were manageable and responded to appropriate treatment steps.1

Thorough patient assessment and screening for hypersensitivity reactions are key to helping prevent infusion-related events.

Infusion reactions with REMICADE®1

  • Defined in clinical trials as any adverse event occurring during an infusion or within 1 to 2 hours after

  • Approximately 20% of patients treated with REMICADE® in all clinical studies experienced an infusion reaction compared with 10% of placebo-treated patients

  • Serious infusion reactions occurred in <1% of patients and included anaphylaxis, convulsions, erythematous rash, and hypotension

  • Approximately 3% of patients discontinued REMICADE® because of infusion reactions, and all patients who discontinued recovered with treatment and/or discontinuation of the infusion

  • In phase 3 clinical studies, 18% of adult patients treated with REMICADE® experienced an infusion reaction compared with 5% of placebo-treated patients

In the event of a mild to moderate infusion reaction1

In the event of a severe infusion reaction1

  • The management of severe infusion reactions should be dictated by the signs and symptoms of the reaction

  • Appropriate personnel and medications should be available to treat anaphylaxis if it occurs

  • Patients who have severe infusion-related hypersensitivity reactions during or following the infusion should be discontinued from further treatment with REMICADE®

Reference: 1. REMICADE® Prescribing Information. Janssen Biotech, Inc.

 

REMICADE® is indicated for:

Crohn's Disease
  • Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease (CD) who have had an inadequate response to conventional therapy
  • Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing CD
Pediatric Crohn's Disease
  • Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active CD who have had an inadequate response to conventional therapy
Ulcerative Colitis
  • Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy
Pediatric Ulcerative Colitis
  • Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active UC who have had an inadequate response to conventional therapy
Rheumatoid Arthritis
  • Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate (MTX)
Psoriatic Arthritis
  • Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis (PsA)
Ankylosing Spondylitis
  • Reducing signs and symptoms in patients with active ankylosing spondylitis (AS)
Plaque Psoriasis
  • The treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
  • REMICADE® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician

 

SERIOUS INFECTIONS

Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®.1,2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with co-morbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with REMICADE® included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including REMICADE®. These cases have had a very aggressive disease course and have been fatal. The majority of reported REMICADE® cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn's disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including REMICADE®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

CONTRAINDICATIONS

REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating REMICADE®. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (eg, ≥5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.

NEUROLOGIC EVENTS

TNF inhibitors, including REMICADE®, have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY

Treatment with REMICADE® may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

ADVERSE REACTIONS

In clinical trials, the most common REMICADE® adverse reactions occurring in >10% of patients included infections (eg, upper respiratory, sinusitis, and pharyngitis),
infusion-related reactions, headache, and abdominal pain.

USE WITH OTHER DRUGS

Concomitant use of REMICADE® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE® is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS

Live vaccines or therapeutic infectious agents should not be given with REMICADE® due to the possibility of clinical infections, including disseminated infections.

Bring pediatric patients up to date with all vaccinations prior to initiating REMICADE®. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to REMICADE®.

For more information, please see full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion. (Requires Adobe® Reader®. Click here to download.)

References:

1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.

2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

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