Class: Disease-modifying Antirheumatic Agents
CAS Number: 170277-31-3
Brands: Remicade
Special Alerts:
CORRECTION NOTICE:
The Editors of AHFS Drug Information (AHFS DI) and AHFS DI Essentials wish to inform you of an error in the Infliximab (Systemic) monograph. The error appears under the subhead IV Administration: Rate of Administration, in Dosage and Administration: Administration. In Table 1: Rate Titration Schedule, the entry in column 1, line 4 should read: 80 mL/hour.
The originally stated infusion rate of 80 mL/minute is incorrect. The correct infusion rate is 80 mL/hour.
MEDWATCH ALERT:
[Posted 09/07/2011] ISSUE: FDA notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNFα) blockers has been updated to include the risk of infection from two bacterial pathogens, Legionella and Listeria. In addition, the Boxed Warning and Warnings and Precautions sections of the labels for all of the TNFα blockers have been revised so that they contain consistent information about the risk for serious infections and the associated disease-causing pathogens.
Patients treated with TNFα blockers are at increased risk for developing serious infections involving multiple organ systems and sites that may lead to hospitalization or death due to bacterial, mycobacterial, fungal, viral, parasitic, and other opportunistic pathogens.
BACKGROUND: The class of TNFα blockers are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis.
RECOMMENDATION: The risks and the benefits of TNFα blockers should be considered prior to initiating therapy in patients with chronic or recurrent infection and patients with underlying conditions that may predispose them to infection. See the Drug Safety Communication for a listing of recommendations for healthcare professionals and patients, as well as a data summary. For more information visit the FDA website at: and .
[Posted 04/14/2011] ISSUE: FDA continues to receive reports of a rare cancer of white blood cells (known as Hepatosplenic T-Cell Lymphoma or HSTCL, primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factors (TNF) blockers, as well as with azathioprine, and/or mercaptopurine. TNF blockers include infliximab (Remicade), etancercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).
BACKGROUND: HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.
Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.
Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.
Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.
Know that people with rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or meracaptopurine.
Read the Drug Safety Communications for other specific recommendations for Healthcare Professionals and Patients and the Data Summary for additional information. For more information visit the FDA website at: and .
REMS:
FDA approved a REMS for infliximab to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
- Serious Infections
Serious, sometimes fatal infections including tuberculosis (frequently disseminated or extrapulmonary), bacterial and viral infections, invasive fungal infections (may be disseminated), and other opportunistic infections reported.1 (See Infectious Complications under Cautions.)
Carefully consider risks and benefits prior to initiating infliximab therapy in patients with chronic or recurring infections.1
Evaluate patients for latent tuberculosis infection prior to and periodically during infliximab therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating infliximab therapy.1
Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.1 Discontinue infliximab if serious infection or sepsis occurs.1 Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.1
- Malignancy
Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.1 (See Malignancies and Lymphoproliferative Disorders under Cautions.)
Aggressive, fatal hepatosplenic T-cell lymphoma reported in patients with Crohn's disease or ulcerative colitis receiving TNF blocking agents, including infliximab.1 Most of the patients were adolescent or young adult males; all received concomitant therapy with azathioprine or mercaptopurine at or prior to diagnosis.1
Introduction
Biologic response modifier and disease-modifying antirheumatic drug (DMARD); chimeric human-murine monoclonal antibody that blocks the biologic activity of tumor necrosis factor (TNF, TNF-α).1 7 20 24
Uses for Infliximab
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Crohn’s Disease
Used to reduce signs and symptoms of Crohn’s disease and to induce and maintain clinical remission in adults and pediatric patients with moderate to severe active disease who have had an inadequate response to conventional therapies (e.g., corticosteroids, mesalamine or sulfasalazine, azathioprine or mercaptopurine).1 5 6 38 51 72 89 136 142
Used to reduce the number of draining enterocutaneous and rectovaginal fistulas and to maintain fistula closure in adults with fistulizing Crohn’s disease (designated an orphan drug by FDA for this use).1 64 94 140 141 142 143 Consider use when fistulas have not responded to appropriate anti-infective regimens (e.g., ciprofloxacin and/or metronidazole) and/or immunosuppressive therapy (e.g., azathioprine or mercaptopurine).47 65 66 70
Rheumatoid Arthritis in Adults
Used in conjunction with methotrexate to manage the signs and symptoms of rheumatoid arthritis, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with moderate to severe active rheumatoid arthritis.1 14 15 17 18 41
Ankylosing Spondylitis
Management of the signs and symptoms of active ankylosing spondylitis.1 72 108 109 117 137 138
Psoriatic Arthritis
Used to manage the signs and symptoms of active arthritis in adults with psoriatic arthritis.1 72 105 106 107 108 131
Ulcerative Colitis
Used to manage the signs and symptoms, to achieve clinical remission and mucosal healing, and to eliminate corticosteroid use in adults with moderate to severe active ulcerative colitis who have had an inadequate response to conventional therapies.1 47 72 112 113 114 147
Juvenile Arthritis
Has been used with some success in a limited number of adults and pediatric patients with juvenile arthritis†.72 103 104
Behcet’s Syndrome
Has been used in a limited number of patients with Behcet’s syndrome†.93 102 115 116 93
Infliximab Dosage and Administration
General
Premedication and Patient Monitoring
Consider administration of premedication prior to each dose to minimize risk of infusion-related reactions.47 72
Patients receiving initial infusion and patients without a history of acute infusion reactions: Oral diphenhydramine hydrochloride (25–50 mg) and acetaminophen (650 mg) can be given before the infusion.47 72
Patients with a history of acute infusion reactions: Oral or IV prednisone (40 mg) or hydrocortisone (100 mg), oral or IV diphenhydramine hydrochloride (25–50 mg), and acetaminophen (650 mg) can be given before the infusion.72 142
Monitor patients closely during and after each IV infusion.72 Measure vital signs (pulse and BP) immediately prior to infusion, during the infusion (every 30 minutes in patients without a history of acute infusion reactions and every 15 minutes in those with a history of reactions), and for 30 minutes after completion of the infusion.72
If DBP drops 15–20 mm Hg or symptoms of hypersensitivity (e.g., urticaria, shortness of breath) occur, stop the infusion immediately, evaluate manifestations, and initiate appropriate therapy.72
If the reaction is not severe and is mitigated with a regimen of oral diphenhydramine hydrochloride (25–50 mg), oral acetaminophen (650 mg), and oral or IV prednisone (40 mg), the infusion may be resumed with caution following the rate titration schedule using an initial rate of 10 mL/hour.72 (See Rate Titration Schedule Table under Dosage and Administration.)
The infusion should be discontinued and not completed if the reaction does not resolve with the regimen described above or is more severe and/or requires treatment with epinephrine.72
Concomitant Therapy for Crohn’s Disease
Corticosteroids, mesalamine, sulfasalazine, azathioprine, mercaptopurine, methotrexate, and anti-infective agents may be continued.1
Concomitant Therapy for Rheumatoid Arthritis
Intended for use concomitantly with methotrexate; only limited data available regarding the efficacy of infliximab without concomitant methotrexate.1 17 18 20 21 23 1
Corticosteroids and NSAIAs may be continued.1
Concomitant Therapy for Psoriatic Arthritis
Concomitant Therapy for Ulcerative Colitis
REMS Program
FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for infliximab.156
The program consists of a medication guide that must be provided to patients (see Advice to Patients) and a communication plan consisting of letters and an education guide targeting selected groups of clinicians.156
The goals are to inform patients about the serious risks associated with the drug and to inform clinicians about invasive fungal infections associated with use of TNF blocking agents (see Warnings/Precautions under Cautions).156
Administration
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV infusion.1
Administer with an in-line, sterile, nonpyrogenic, low-protein-binding filter with a pore diameter of ≤1.2 mcm.1
Consult manufacturer’s labeling for additional information on reconstitution, dilution, and administration of infliximab.1
Reconstitution
Reconstitute vial containing 100 mg of infliximab powder with 10 mL of sterile water for injection to provide a solution containing 10 mg/mL.1 Reconstitute the number of vials needed to provide the indicated dosage of infliximab.1
Direct diluent toward the side of the vial with a sterile syringe and a ≤21-gauge needle; swirl vial gently to ensure dissolution; do not shake or agitate vigorously (to avoid foaming).1
Allow reconstituted solution to stand for 5 minutes before dilution.1
Dilution
Remove the volume of diluent equal to the total required volume of reconstituted infliximab solution from a 250-mL bag or bottle of 0.9% sodium chloride injection.1 Slowly add reconstituted infliximab to the bag to a total volume of 250 mL; mix gently.1 Concentration of the solution for infusion should be 0.4–4 mg/mL.1
Rate of Administration
Infuse over a period of at least 2 hours.1
IV infusions may be given at a rate of 2 mL/minute or, alternatively, a rate titration schedule may be used in an attempt to prevent or ameliorate acute infusion reactions.72
A rate titration schedule can be used in patients receiving an initial infliximab dose, those without a history of acute infusion reactions, and those with a history of such reactions.72
Table 1. Rate Titration Schedule
Rate
|
Time
|
|---|
10 mL/hour
|
first 15 minutes72
|
20 mL/hour
|
next 15 minutes72
|
40 mL/hour
|
next 15 minutes72
|
80 mL/hour
|
next 15 minutes72
|
150 mL/hour
|
next 30 minutes72
|
250 mL/hour
|
next 30 minutes72
|
Dosage
Pediatric Patients
Crohn’s Disease
Management of Moderate or Severe Active Crohn’s Disease
IV
Children ≥6 years of age: 5 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 8 weeks (maintenance regimen).1 47 86 87
Adults
Crohn’s Disease
Management of Moderate or Severe Active Crohn’s Disease or Fistulizing Crohn’s Disease
IV
5 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 8 weeks (maintenance regimen).1
Consider dose of 10 mg/kg for patients who respond initially but subsequently lose response.1
Patients who do not respond by week 14 are unlikely to respond with continued administration; consider discontinuing the drug.1
Rheumatoid Arthritis
Moderate to Severe Active Rheumatoid Arthritis
IV
3 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 8 weeks (maintenance regimen).1
Increase dosage up to 10 mg/kg and/or administer as often as once every 4 weeks for patients who have an incomplete response to 3 mg/kg; consider that risk of serious infection is increased with higher dosages.1 72
Ankylosing Spondylitis
IV
5 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 6 weeks (maintenance regimen).1
Psoriatic Arthritis
IV
5 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 8 weeks (maintenance regimen).1
Ulcerative Colitis
Moderate to Severe Active Ulcerative Colitis
IV
5 mg/kg at 0, 2, and 6 weeks (induction regimen), then every 8 weeks (maintenance regimen).1
Cautions for Infliximab
Contraindications
Doses >5 mg/kg in patients with moderate or severe heart failure.1 (See Cardiovascular Effects under Cautions.)
Known hypersensitivity to infliximab, murine proteins, or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Infectious Complications
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, and other opportunistic infections) reported with infliximab or other TNF blocking agents,1 particularly in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids).1 72 118 155 The most common opportunistic infections include tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis.1 Infections frequently are disseminated.1
Do not initiate infliximab in patients with active infections, including clinically important localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic or recurring infections, patients with underlying conditions that may predispose them to infections, and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, and blastomycosis are endemic.1
Closely monitor patients during and after infliximab therapy for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).1 155
If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 155 Discontinue infliximab if serious infection or sepsis develops.1 155
Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.1 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to infliximab therapy.1 14 18 42 59 72 111 118 Also consider antimycobacterial therapy prior to infliximab therapy for individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and for individuals with a negative tuberculin skin test who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1
Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.1 Strongly consider tuberculosis in patients who develop new infections while receiving infliximab, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.1
Invasive fungal infections often not recognized in patients receiving TNF blocking agents; this has led to delays in appropriate treatment.155
Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.1 155 Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.1 155
When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.155 Whenever feasible, consult specialist in fungal infections.155
Increased incidence of serious infection observed with concomitant use of etanercept (another TNF blocking agent) and anakinra (a human interleukin-1 receptor antagonist).1 Similar toxicities expected with concomitant use of anakinra and other agents that block TNF, including infliximab.1 (See Specific Drugs under Interactions.)
Increased incidence of infection and serious infection reported with concomitant use of a TNF blocking agent and abatacept.152 (See Specific Drugs under Interactions.)
Hepatitis B Virus (HBV) Reactivation
Increased risk of reactivation of HBV infection in patients who are chronic carriers of the virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).1 Use of multiple immunosuppressive agents may contribute to HBV reactivation.1
Screen at-risk patients prior to initiation of therapy.1 Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.1 Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.1 Discontinue infliximab and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.1 Not known whether infliximab can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.1
Hepatic Effects
Severe hepatic reactions (e.g., acute liver failure, jaundice, hepatitis, cholestasis, autoimmune hepatitis) reported; some cases were fatal or needed liver transplantation.1 144 Hepatic reactions occurred between 2 weeks and >1 year following initiation of therapy; elevations of hepatic transaminase enzymes not observed prior to discovery of liver injury in many cases.1 144
Evaluate patients with signs of liver dysfunction.1 144 If jaundice and/or marked hepatic aminotransferase elevations (≥5 times the ULN) develop, discontinue infliximab and investigate hepatic abnormality.1
Malignancies and Lymphoproliferative Disorders
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.1 154 Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).1 154 Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.1 FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.154
Aggressive, fatal cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, reported in patients with Crohn's disease or ulcerative colitis receiving TNF blocking agents, including infliximab.1 Most of the patients were adolescent or young adult males; all received concomitant therapy with azathioprine or mercaptopurine at or prior to diagnosis.1 Unclear whether occurrence is related to infliximab or combination of infliximab and other immunosuppressive agents.1
In controlled studies, lymphoma was reported more frequently in patients receiving infliximab or other TNF blocking agents than in control patients.1 Patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma.1 28 30 38 42
Acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.1 154 Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.154 FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.1 154
Malignancies (mainly lung cancer or head and neck malignancies) reported in more infliximab-treated than placebo-treated patients with moderate to severe COPD†; all had been heavy smokers.1 157 Exercise caution when considering infliximab therapy in patients with moderate to severe COPD.1
In infliximab-treated psoriasis patients, nonmelanoma skin cancer reported more commonly in those who had received prior phototherapy; monitor psoriasis patients, especially those who have received prolonged prior phototherapy, for nonmelanoma skin cancer.1
Other malignancies (basal cell carcinoma, breast cancer, melanoma, colorectal cancer, rectal adenocarcinoma, squamous cell carcinoma) reported in patients receiving infliximab.1 14 17 141
In controlled clinical studies of infliximab, the rate of malignancies other than lymphoma and nonmelanoma skin cancer was increased in infliximab-treated patients compared with control patients, but the rate was similar to the expected rate in the general population.1
Role of TNF blocking agents in development of malignancies not fully determined.1 22 28 30 31 32 33 38 42 43 62 154 157
Some immune related diseases (e.g., Crohn’s disease) have been shown to increase risk of cancer independent of treatment with TNF blocking agents, while for others (e.g., juvenile idiopathic arthritis) it is unknown whether there is an increased risk of cancer.154
Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.154 Exercise caution when considering use of infliximab in patients with malignancy or a history of malignancy or when considering whether to continue therapy in patients who develop a malignancy; effect on development and course of malignancies not fully evaluated.1 22 28 30 31 32 33 34 35 38 43 44 59 62 64
Cardiovascular Effects
Associated with adverse outcomes in patients with heart failure (increased mortality and hospitalization due to worsening heart failure).1 139
Use in patients with heart failure only after consideration of other treatment options.1 If used in patients with moderate or severe heart failure, do not exceed doses of 5 mg/kg and monitor cardiac status closely.1 (See Contraindications under Cautions.)
Discontinue therapy if new or worsening symptoms of heart failure occur.1
Use in patients with heart failure (NYHA class III or IV) associated with increased mortality in patients who received infliximab 10 mg/kg and an increase in adverse cardiovascular effects (dyspnea, hypotension, angina, dizziness) in patients who received 5 or 10 mg/kg.1 Worsening heart failure (with and without identifiable precipitating factors) and new-onset heart failure (including in patients with no known pre-existing cardiovascular disease and/or who were < 50 years of age) reported.1 Not evaluated in patients with mild (NYHA class I or II) heart failure.1
Hematologic Effects
Possible leukopenia, neutropenia, thrombocytopenia, and pancytopenia, sometimes with fatal outcome.1 Use with caution in patients with a history of substantial hematologic abnormalities.1 Consider discontinuance of the drug in patients with confirmed hematologic abnormalities.1
Nervous System Effects
Optic neuritis, seizures, new onset or exacerbation of clinical manifestations and/or radiographic evidence of CNS demyelinating disorders, including multiple sclerosis, CNS manifestations of systemic vasculitis, and peripheral demyelinating disorders, including Guillain-Barré syndrome, reported rarely in patients receiving infliximab or other TNF blocking agents.1
Exercise caution when considering infliximab in patients with preexisting or recent-onset CNS demyelinating disorders.1 Consider discontinuance of the drug in patients who develop clinically important CNS adverse reactions.1
Sensitivity Reactions
Discontinue immediately for severe hypersensitivity reaction; initiate appropriate therapy.1 Drugs for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids, and/or epinephrine) should be immediately available.1 72
Acute Infusion Reactions
Acute infusion reactions consistent with hypersensitivity reactions reported within 1–2 hours after IV infusion.1 10 14 18 21 36 38 41 64 72 92 128
Signs/symptoms include urticaria, dyspnea, hypotension, fever, chills, headache, pruritus, chest pain, and/or hypertension.1 5 10 14 15 18 21 36 38 41 64 72 92 128 136 Anaphylactoid reactions (with laryngeal/pharyngeal edema and severe bronchospasm), anaphylaxis, seizures, and/or erythematous rash reported.1 36 128
Mild acute infusion reactions often controlled by slowing or discontinuing the infusion or appropriate treatment (antihistamines).1 5 10 14 18 23 28 38 42 47 72 92
Monitor patients; consider premedication; initiate infusion slowly; adjust rate or discontinue based on patient tolerance.47 72 47 72 (See Premedication and Patient Monitoring and also see Rate Titration Schedule Table under Dosage and Administration.)
Patients with antibodies to infliximab appear to be 2–3 times more likely to have an infusion reaction than patients who do not have antibodies to the drug.1
Incidence of acute infusion reactions may be lower in patients receiving concomitant therapy with immunosuppressive agents (e.g., azathioprine, mercaptopurine, methotrexate) than in those not receiving such therapy.1 47
Delayed Infusion Reactions
Delayed infusion reactions occur 3–12 days after an infusion and appear to be more common in patients retreated after a period of 2–4 years.1 10 5 40 42
Signs/symptoms include fever, rash, pruritus, urticaria, headache, sore throat, myalgia, polyarthralgia, hand and facial edema, and/or dysphagia.1 10 38 40 42 136
Delayed infusion reactions generally resolve within 1–3 days following treatment with corticosteroids, antihistamines, acetaminophen, and/or epinephrine.1 5 40
Caution when retreatment follows an extended period of time (e.g., after ≥1 year).1 10 40 42
Risk of delayed infusion reactions not increased in patients who have had an acute infusion reaction.1 40
These reactions reported most frequently in patients who have developed infliximab-specific antibodies (human antichimeric antibodies [HACA]); reactions are associated with loss of detectable infliximab serum concentrations and possible loss of efficacy.1 (See Immunologic Reactions and Antibody Formation under Cautions.)
Administration of an immunosuppressive agent (e.g., azathioprine, mercaptopurine, methotrexate) for ≥3 months prior to infliximab associated with a lower rate of development of HACA and a lower rate of infusion reactions.1 18 47 72
Delayed hypersensitivity reactions to infliximab should be reported to the manufacturer by phone at 800-457-6399.40
General Precautions
Immunologic Reactions and Antibody Formation
Possible formation of autoimmune antibodies.1 14 17 18 19 20 23 28 34 35 38 41 44 64 90 136 Lupus-like syndrome reported.1 If manifestations suggestive of lupus-like syndrome develop, discontinue infliximab.1
Antibodies to infliximab may develop.1 22 42 28 38 64 70 84 85 Antibody-positive patients more likely to experience an infusion reaction.1 10 23 70 85 (See Sensitivity Reactions under Cautions.)
Immunization
Avoid live vaccines (e.g., measles virus vaccine live, mumps virus vaccine live, rubella virus vaccine live, smallpox vaccine, typhoid vaccine live oral, varicella virus vaccine live, yellow fever vaccine).1 (See Vaccines under Interactions.)
GI Effects
Safety and efficacy data in Crohn’s disease patients with intestinal strictures is limited.4 5 38 72 88 Development or worsening of intestinal strictures and/or intestinal obstruction reported rarely in these patients.4 47 70
Use with caution in Crohn’s disease patients with intestinal strictures.47 70 72
Psoriasis
New-onset psoriasis, including pustular and palmoplantar psoriasis, reported with TNF blocking agents, including infliximab.1 154 Onset observed weeks to years following initiation of drug.154 Some patients required hospitalization.154 Most patients experienced improvement following discontinuance of the TNF blocking agent.154 FDA has concluded that there is a possible association between use of TNF blocking agents and development of psoriasis.154
Exacerbation of existing psoriasis also reported.1
Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.154
Specific Populations
Pregnancy
Category B.1
Some clinicians suggest that pregnancy be ruled out (negative pregnancy test) before initiating therapy and that an effective contraceptive be used.110
Lactation
Not known whether infliximab is distributed into milk.1 Due to potential risk in nursing infant, discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy established in children ≥6 years of age with Crohn’s disease; studied in this age group only in conjunction with conventional immunosuppressive agents.1 Safety and efficacy of long-term (>1 year) therapy not established.1
Safety and efficacy not established in children with ulcerative colitis or plaque psoriasis.1
Has been evaluated in children 4–17 years of age with juvenile arthritis† who had not responded adequately to methotrexate.1 153 Further study needed to evaluate safety and efficacy.1 72 104 153
Bring all vaccinations up to date prior to initiation of therapy in children with Crohn’s disease.1
Adverse effects reported more frequently in children than in adults with Crohn’s disease include anemia, blood in stool, leukopenia, flushing, viral infection, neutropenia, bone fracture, infection, bacterial infection, and respiratory tract allergy.1
Malignancies, some fatal, reported in children and adolescents who received TNF blocking agents.1
