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InFLIXimab

Medically reviewed by Drugs.com. Last updated on Jun 1, 2020.

Pronunciation

(in FLIKS e mab)

Index Terms

  • Avakine
  • Infliximab, Recombinant
  • Infliximab-abda
  • Infliximab-axxq
  • Infliximab-dyyb
  • Infliximab-qbtx
  • Ixifi

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Avsola: infliximab-axxq 100 mg (1 ea) [contains polysorbate 80]

Inflectra: infliximab-dyyb 100 mg (1 ea) [contains polysorbate 80]

Remicade: 100 mg (1 ea) [contains polysorbate 80]

Renflexis: infliximab-abda 100 mg (1 ea) [contains polysorbate 80]

Brand Names: U.S.

  • Avsola
  • Inflectra
  • Remicade
  • Renflexis

Pharmacologic Category

  • Antirheumatic, Disease Modifying
  • Gastrointestinal Agent, Miscellaneous
  • Immunosuppressant Agent
  • Monoclonal Antibody
  • Tumor Necrosis Factor (TNF) Blocking Agent

Pharmacology

Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha (TNFα), thereby interfering with endogenous TNFα activity. Elevated TNFα levels have been found in involved tissues/fluids of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn disease and ulcerative colitis. Biological activities of TNFα include the induction of proinflammatory cytokines (interleukins), enhancement of leukocyte migration, activation of neutrophils and eosinophils, and the induction of acute phase reactants and tissue degrading enzymes. Animal models have shown TNFα expression causes polyarthritis, and infliximab can prevent disease as well as allow diseased joints to heal.

Distribution

Within the vascular compartment; Vd: 3 to 6 L (Klotz 2007)

Onset of Action

Crohn disease: 1 to 2 weeks; Rheumatoid arthritis: 3 to 7 days

Duration of Action

Crohn disease: 8 to 48 weeks; Rheumatoid arthritis: 6 to 12 weeks

Half-Life Elimination

7 to 12 days (Klotz 2007)

Use: Labeled Indications

Ankylosing spondylitis: Treatment of adults with active ankylosing spondylitis (to reduce signs/symptoms).

Crohn disease: Treatment of adults and pediatric patients ≥6 years of age with moderately to severely active Crohn disease who have had inadequate responses to conventional therapy (to reduce signs/symptoms and induce and maintain clinical remission) or to reduce the number of draining enterocutaneous and rectovaginal fistulas and maintain fistula closure in adults.

Plaque psoriasis: Treatment of adults with chronic, severe (extensive and/or disabling) plaque psoriasis as an alternative to other systemic therapy.

Psoriatic arthritis: Treatment of adults with psoriatic arthritis (to reduce signs/symptoms of active arthritis and inhibit progression of structural damage and improve physical function).

Rheumatoid arthritis: Treatment of adults with moderately to severely active rheumatoid arthritis (with methotrexate) (to reduce signs/symptoms of active arthritis and inhibit progression of structural damage and improve physical function).

Ulcerative colitis: Treatment of adults and pediatric patients ≥6 years of age with moderately to severely active ulcerative colitis with inadequate response to conventional therapy (to reduce signs/symptoms and induce and maintain clinical remission) or to induce/maintain mucosal healing and eliminate corticosteroid use in adults.

Note: Avsola (infliximab-axxq), Inflectra (infliximab-dyyb), and Renflexis (infliximab-abda) are approved as biosimilars to Remicade (infliximab). In Canada, Avsola, Inflectra, and Renflexis are also approved as biosimilars to Remicade (infliximab).

Off Label Uses

Crohn disease (management after surgical resection)

Data from a small, randomized, double-blind, placebo-controlled trial, a prospective randomized open trial, and a meta-analysis support the use of infliximab in the management of Crohn disease after surgical resection and demonstrated infliximab lowers endoscopic recurrence and possibly histologic and clinical recurrence rates [Regueiro 2009], [Regueiro 2016], [Singh 2015], [Yoshida 2012].

Based on the American Gastroenterological Association Institute Guidelines on the Management of Crohn's Disease after Surgical Resection and American College of Gastroenterology Guidelines on the Management of Crohn's Disease in Adults, infliximab is an effective first-line agent for prophylactic therapy in patients who are higher risk for clinical recurrence.

Pustular psoriasis

In noncontrolled studies and case series/reports in a limited number of patients with pustular psoriasis, infliximab demonstrated symptomatic improvement in some patients [Kim 2014], [Smith 2013], [Sugiura 2015], [Torii 2011], [Trent 2004], [Viguier 2012].

The National Psoriasis Foundation Medical Board consensus statement recommends infliximab as a first-line treatment option for some adults with pustular psoriasis, particularly those with severe, acute generalized forms of the disease [Robinson 2012].

Pyoderma gangrenosum

Initial data suggest that infliximab may be beneficial in the treatment of refractory pyoderma gangrenosum. Larger, controlled trials are needed to fully assess the efficacy of infliximab for the treatment of pyoderma gangrenosum [Brooklyn 2006], [Ljung 2006], [Regueiro 2003].

Contraindications

Previous severe hypersensitivity (eg, anaphylaxis, hypotension, serum sickness) to infliximab, murine proteins, or any component of the formulation; doses >5 mg/kg in patients with moderate or severe heart failure (NYHA class III/IV).

Canadian labeling: Additional contraindications (not in US labeling): Severe infections (eg, sepsis, abscesses, tuberculosis, and opportunistic infections); use in patients with moderate or severe heart failure (NYHA class III/IV).

Dosing: Adult

Note: Premedication with antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen, and/or corticosteroids may be considered to prevent and/or manage infusion-related reactions. Avsola (infliximab-axxq), Inflectra (infliximab-dyyb), and Renflexis (infliximab-abda) are approved as biosimilars to Remicade (infliximab). In Canada, Avsola, Inflectra, and Renflexis are also approved as biosimilars to Remicade (infliximab).

Ankylosing spondylitis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 6 weeks thereafter.

Crohn disease: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter; dose may be increased to 10 mg/kg every 8 weeks in patients who respond but then lose their response. If no response by week 14, consider discontinuing therapy.

Crohn disease management after surgical resection (off-label use): IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter (Armuzzi 2013; Regueiro 2009; Singh 2015) or 5 mg/kg every 8 weeks (Regueiro 2016; Yoshida 2012). Note: Administer first infusion within 4 weeks after surgery in high-risk patients (Lichtenstein 2018).

Plaque psoriasis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter.

Psoriatic arthritis (with or without methotrexate): IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter.

Pustular psoriasis (off-label use): IV: 5 mg/kg at week 0, 2, and 6, followed by 5 mg/kg every 8 weeks for up to 46 weeks (Suguira 2014; Torii 2011).

Rheumatoid arthritis (in combination with methotrexate therapy): IV: 3 mg/kg at 0, 2, and 6 weeks, followed by a maintenance regimen of 3 mg/kg every 8 weeks thereafter; for patients who have incomplete responses, consider adjusting the dose up to 10 mg/kg every 8 weeks or treating as often as every 4 weeks, although consider the risk of serious infections is increased at higher doses or with more frequent administration.

Ulcerative colitis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. Doses up to 10 mg/kg were studied in clinical trials with similar efficacy observed with both doses (Rutgeerts 2005); combination therapy with a thiopurine (eg, azathioprine, mercaptopurine) has shown increased efficacy (ACG [Rubin 2019]; Panaccione 2014).

Dosage adjustment with heart failure: Weigh risk versus benefits for individual patient:

Mild heart failure (NYHA class I/II): No dosage adjustment necessary; use with caution and monitor closely for worsening of heart failure.

Moderate to severe (NYHA class III or IV): ≤5 mg/kg.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Premedication with antihistamines (H1-antagonist and/or H2-antagonist), acetaminophen and/or corticosteroids may be considered to prevent and/or manage infusion-related reactions: Renflexis (infliximab-abda) and Inflectra (infliximab-dyyb) are approved as biosimilar to Remicade. Approved uses for biosimilar agents may vary (consult product labeling).

Crohn disease: Remicade/Inflectra/Renflexis: Children ≥6 years and Adolescents: IV: Initial: 5 mg/kg/dose at 0, 2, and 6 weeks, followed by maintenance: 5 mg/kg/dose every 8 weeks thereafter. Note: If the response is incomplete, dose has been increased up to 10 mg/kg (Rufo 2012; Stephens 2003); in adult patients with Crohn disease, it has been observed that patients who do not respond by week 14 are unlikely to respond with continued dosing; consider therapy discontinuation in these patients.

Juvenile idiopathic arthritis; refractory to conventional disease-modifying drugs: Limited data available: Children ≥4 years and Adolescents: IV: Initial: 3 mg/kg at 0, 2, and 6 weeks; then 3 to 6 mg/kg/dose every 8 weeks thereafter, in combination with methotrexate during induction and maintenance (Ruperto 2010). Alternatively, some studies used 6 mg/kg/dose starting at week 14 of a methotrexate induction regimen (weeks 0 to 13); repeat dose (6 mg/kg/dose) at week 16 and 20, then every 8 weeks thereafter. Note: Trials performed with Remicade product (Ruperto 2007; Ruperto 2010; Visvanathan 2012).

Kawasaki disease, refractory to IVIG: Limited data available: Infants and Children: IV: 5 mg/kg/dose as a single infusion (AHA [McCrindle 2017]; Burns 2005; Burns 2008; Son 2011; Weiss 2004; Youn 2016)

Ulcerative colitis: Remicade: Children ≥6 years and Adolescents: IV: Initial: 5 mg/kg/dose at 0, 2, and 6 weeks, followed by maintenance: 5 mg/kg/dose every 8 weeks thereafter. Note: If the response is incomplete, dose has been increased up to 10 mg/kg (Rufo 2012; Stephens 2003)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Reconstitute vials with 10 mL SWFI to concentration of 10 mg/mL with a 21-gauge or smaller needle, directing the SWFI towards the wall of the vial. Swirl vial gently to dissolve powder; do not shake. Allow solution to stand for 5 minutes. Total dose of reconstituted product should be further diluted to 250 mL of NS injection (add reconstituted infliximab slowly and gently invert the bag to mix the solution) to a final concentration of 0.4 to 4 mg/mL. If volumes >250 mL are needed, either use a larger infusion bag (eg, 500 mL) or multiple 250 mL infusion bags to ensure that concentration of infusion solution does not exceed 4 mg/mL. Discard any unused portion of infusion solution. Do not dilute reconstituted infliximab solution with any other diluent. Infusion should begin within 3 hours of preparation (see "Storage/Stability" for additional information).

Administration

IV: The infusion should begin within 3 hours of reconstitution and dilution. Infuse over at least 2 hours, although use of shortened infusion duration (eg, 1 hour) has been utilized in patients previously tolerating at least four 2-hour infusions (Remicade Canadian product monograph; McConnell 2012; de Carvalho 2018); also refer to institution-specific protocols. Do not infuse with other agents; use in-line low protein binding filter (≤1.2 micron). Temporarily discontinue or decrease infusion rate with infusion-related reactions. Antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen and/or corticosteroids may be used to manage reactions. Infusion may be reinitiated at a lower rate upon resolution of mild to moderate symptoms.

Recommendations for treatment and prophylaxis of infusion reactions: (Note: Limited to adult patients and dosages used in Crohn disease; prospective data for other populations [pediatrics, other indications/dosing] are not available).

A protocol for the treatment of infusion reactions, as well as prophylactic therapy for repeat infusions, has been published (Mayer 2006).

Treatment of infusion reactions: Medications for the treatment of hypersensitivity reactions should be available for immediate use. For mild reactions, the rate of infusion should be decreased to 10 mL/hour. Initiate a normal saline infusion (500 to 1,000 mL/hour) and appropriate symptomatic treatment (eg, acetaminophen and diphenhydramine); monitor vital signs every 10 minutes until normal. After 20 minutes, the infusion may be increased at 15-minute intervals, as tolerated, to completion (initial increase to 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc [maximum of 125 mL/hour]). For moderate reactions, the infusion should be stopped or slowed. Initiate a normal saline infusion (500 to 1,000 mL/hour) and appropriate symptomatic treatment. Monitor vital signs every 5 minutes until normal. After 20 minutes, the infusion may be reinstituted at 10 mL/hour; then increased at 15-minute intervals, as tolerated, to completion (initial increase 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc [maximum of 125 mL/hour]). For severe reactions, the infusion should be stopped with administration of appropriate symptomatic treatment (eg, hydrocortisone/methylprednisolone, diphenhydramine and epinephrine) and frequent monitoring of vitals (consult institutional policies, if available). Re-treatment after a severe reaction should only be done if the benefits outweigh the risks and with appropriate prophylaxis. Delayed infusion reactions typically occur 1 to 7 days after an infusion. Treatment should consist of appropriate symptomatic treatment (eg, acetaminophen, antihistamine, methylprednisolone).

Prophylaxis of infusion reactions: Premedication with acetaminophen and diphenhydramine 90 minutes prior to infusion may be considered in all patients with prior infusion reactions, and in patients with severe reactions corticosteroid administration is recommended. Steroid dosing may be oral (prednisone 50 mg orally every 12 hours for 3 doses prior to infusion) or intravenous (a single dose of hydrocortisone 100 mg or methylprednisolone 20 to 40 mg administered 20 minutes prior to the infusion). On initiation of the infusion, begin with a test dose at 10 mL/hour for 15 minutes. Thereafter, the infusion may be increased at 15-minute intervals, as tolerated, to completion (initial increase 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc). A maximum rate of 125 mL/hour is recommended in patients who experienced prior mild to moderate reactions and 100 mL/hour is recommended in patients who experienced prior severe reactions. In patients with cutaneous flushing, aspirin may be considered (Becker 2004). For delayed infusion reactions, premedicate with acetaminophen and diphenhydramine 90 minutes prior to infusion. On initiation of the infusion, begin with a test dose at 10 mL/hour for 15 minutes. Thereafter, the infusion may be increased to infuse over 3 hours. Postinfusion therapy with acetaminophen for 3 days and an antihistamine for 7 days is recommended.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); may be stored at room temperature (maximum of 30°C [86°F]) for up to 6 months (not to exceed the original expiration date); do not return to refrigerated storage. The manufacturer recommends that administration of solutions diluted in NS for infusion should begin within 3 hours of reconstitution and dilution. However, a stability study of infliximab 0.4 mg/mL prepared in NS in PVC bags found no loss of biological activity when stored refrigerated at 4°C for up to 14 days (Ikeda 2012).

Avsola: Also protect from light.

Drug Interactions

Abatacept: Anti-TNF Agents may enhance the immunosuppressive effect of Abatacept. Avoid combination

Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Avoid combination

AzaTHIOprine: InFLIXimab may enhance the adverse/toxic effect of AzaTHIOprine. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. InFLIXimab may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Biologic Anti-Psoriasis Agents: InFLIXimab may enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Avoid combination

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Avoid combination

Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Thiopurine Analogs: Anti-TNF Agents may enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Monitor therapy

Tocilizumab: May enhance the immunosuppressive effect of Anti-TNF Agents. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Abdominal pain (12% to 26%), nausea (21%)

Hematologic & oncologic: Anemia (≤11%)

Hepatic: Increased serum alanine aminotransferase (<3 x ULN: 17% to 51%; ≥3 x ULN: 2% to 10%; ≥5x ULN: 1% to 4%)

Immunologic: Antibody development (10% to 52%), increased ANA titer (~50%)

Infection: Abscess (≤15%), infection (27% to 74%), serious infection (3% to 60%)

Nervous system: Headache (18%)

Respiratory: Cough (12%), pharyngitis (8% to 12%), sinusitis (14%), upper respiratory tract infection (12% to 32%)

Miscellaneous: Infusion related reaction (≤20%; severe infusion related reaction: <1%)

1% to 10%:

Cardiovascular: Bradycardia, edema, flushing (9%), hypertension (7%), hypotension, thrombophlebitis

Dermatologic: Cellulitis, diaphoresis, pruritus (7%), skin rash (10%)

Endocrine & metabolic: Dehydration

Gastrointestinal: Constipation, dyspepsia (10%), intestinal obstruction

Genitourinary: Urinary tract infection (8%)

Hematologic & oncologic: Hemolytic anemia, leukopenia (≤9%;), lymphadenopathy, malignant lymphoma, neutropenia (7%), pancytopenia, sarcoidosis, thrombocytopenia

Hepatic: Hepatitis

Hypersensitivity: Hypersensitivity reaction (≤6%), serum sickness (≤1%), type IV hypersensitivity reaction (1%)

Infection: Bacterial infection (6%), candidiasis (5%), sepsis, viral infection (8%)

Nervous system: Dizziness, fatigue (9%), pain (8%)

Neuromuscular & skeletal: Arthralgia (8%), bone fracture (7%)

Respiratory: Bronchitis (10%), lower respiratory tract infection, pleurisy, pneumonia (≤2%), pulmonary edema

Miscellaneous: Fever (7%)

<1%:

Dermatologic: Erythematous rash, urticaria

Hypersensitivity: Anaphylaxis

Infection: Cytomegalovirus disease, herpes zoster infection, nocardiosis

Nervous system: Seizure

Frequency not defined: Dermatologic: Dermal ulcer

Postmarketing:

Cardiovascular: Acute myocardial infarction, cardiac arrhythmia, cardiac failure, cerebrovascular accident, pericardial effusion, vasculitis (systemic and cutaneous), worsening of heart failure

Dermatologic: Acute generalized exanthematous pustulosis, bullous dermatitis (linear IgA) (Bryant 2016), erythema multiforme, exacerbation of psoriasis, lichenoid eruption, psoriasis (including new onset, palmoplantar, pustular), Stevens-Johnson syndrome, toxic epidermal necrolysis

Gastrointestinal: Cholestasis

Genitourinary: Malignant neoplasm of cervix

Hematologic & oncologic: Agranulocytosis, hepatosplenic T-cell lymphomas (mainly young adult or adolescent males), Hodgkin’s lymphoma, immune thrombocytopenia, leukemia, malignant melanoma, malignant neoplasm, malignant neoplasm of breast, malignant neoplasm of colon or rectum, Merkel cell carcinoma, non-Hodgkin’s lymphoma, thrombotic thrombocytopenic purpura

Hepatic: Acute hepatic failure, autoimmune hepatitis, hepatic failure, hepatic injury, hepatotoxicity (idiosyncratic), increased serum aspartate aminotransferase, jaundice, liver enzyme disorder (transient)

Hypersensitivity: Anaphylactic shock

Infection: Aspergillosis, blastomycosis, coccidioidomycosis, fungal infection, histoplasmosis, listeriosis, opportunistic infection, reactivation of HBV

Nervous system: Chronic inflammatory demyelinating polyneuropathy, demyelinating disease (peripheral), demyelinating disease of the central nervous system, Guillain-Barre syndrome, neuropathy (includes multifocal motor), transverse myelitis

Neuromuscular & skeletal: Lupus-like syndrome, multiple sclerosis

Ophthalmic: Optic neuritis, temporary vision loss

Respiratory: Bacterial pneumonia (legionnaires’ disease), bronchospasm, infection due to an organism in genus Pneumocystosis, interstitial pulmonary disease (including interstitial pneumonitis, pulmonary fibrosis), laryngeal edema, pharyngeal edema, reactivated tuberculosis, tuberculosis

ALERT: U.S. Boxed Warning

Serious infections:

Patients treated with infliximab are at an increased risk of 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 infliximab if a patient develops a serious infection or sepsis.

Reported infections include the following:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before infliximab use and during therapy. Treatment for latent infection should be initiated prior to infliximab use.

Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered in patients at risk of invasive fungal infections who develop severe systemic illness.

Bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with infliximab should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with infliximab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Malignancy:

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of reported infliximab cases have occurred in patients with Crohn disease or ulcerative colitis, and most were in adolescent and young adult males.

Warnings/Precautions

Concerns related to adverse effects:

• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.

• Cardiovascular/cerebrovascular reactions during and following infusion: Cerebrovascular accidents, MI (some fatal), hypotension, hypertension, and arrhythmias have been reported within 24 hours of infusion. Transient vision loss has also been reported during or within 2 hours of infusion. Discontinue therapy if serious reaction occurs.

• Hematologic disorders: Hematologic toxicities (eg, leukopenia, neutropenia, thrombocytopenia, pancytopenia) have been reported (may be fatal). Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias (eg, persistent fevers); discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with history of hematologic abnormalities.

• Hepatic reactions: Severe hepatic reactions (including hepatitis, jaundice, acute hepatic failure, and cholestasis) have been reported during treatment; reactions occurred between 2 weeks to >1 year after initiation of therapy and some cases were fatal or necessitated liver transplantation; discontinue with jaundice and/or marked increase in liver enzymes (≥5 times ULN).

• Hepatitis B: Reactivation of hepatitis B virus (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants (may be fatal); evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.

• Hypersensitivity or infusion reactions: Acute infusion reactions may occur. Hypersensitivity reactions, including anaphylaxis, may occur within 2 hours of infusion. Medication and equipment for management of hypersensitivity reaction should be available for immediate use. Interruptions and/or reinstitution at a slower rate may be required (consult protocols). Pretreatment may be considered, and may be warranted in all patients with prior infusion reactions. Serum sickness-like reactions have occurred; may be associated with a decreased response to treatment. The development of antibodies to infliximab may increase the risk of hypersensitivity and/or infusion reactions; concomitant use of immunosuppressants may lessen the development of anti-infliximab antibodies. The risk of infusion reactions may be increased with re-treatment after an interruption or discontinuation of prior maintenance therapy. Re-treatment in psoriasis patients should be resumed as a scheduled maintenance regimen without any induction doses; use of an induction regimen should be used cautiously for re-treatment of all other patients.

• Infections: [US Boxed Warning]: Patients receiving infliximab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised when considering use in the elderly or in patients with conditions that predispose them to infections (eg, diabetes) or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent or localized infections. Do not initiate infliximab therapy in patients with an active infection, including clinically important localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely.

• Malignancy: [US Boxed Warning]: Lymphoma and other malignancies (may be fatal) have been reported in children and adolescent patients receiving TNF-blocking agents including infliximab. Half the cases are lymphomas (Hodgkin's and non-Hodgkin's) and the other cases are varied but include malignancies not typically observed in this population. [US Boxed Warning]: Postmarketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with infliximab. Almost all patients had received concurrent or prior treatment with azathioprine or mercaptopurine at or prior to diagnosis and the majority of reported cases occurred in adolescent and young adult males with Crohn disease or ulcerative colitis. Malignancies occurred after a median of 30 months (range: 1 to 84 months) after the first dose of TNF blocker therapy; most patients were receiving concomitant immunosuppressants. The impact of infliximab on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Use caution in patients with a history of COPD, higher rates of malignancy were reported in COPD patients treated with infliximab. Psoriasis patients with a history of phototherapy had a higher incidence of nonmelanoma skin cancers. Melanoma and Merkel cell carcinoma have been reported in patients receiving TNF-blocking agents including infliximab. Perform periodic skin examinations in all patients during therapy, particularly those at increased risk for skin cancer. Women with rheumatoid arthritis had a higher incidence of invasive cervical cancer; periodic screening should be continued in women treated with infliximab.

• Tuberculosis: [US Boxed Warning]: Infliximab treatment has been associated with active tuberculosis (may be disseminated or extrapulmonary) or reactivation of latent infections. Evaluate patients for tuberculosis risk factors and latent tuberculosis infection (with a tuberculin skin test) prior to and during therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment. Most cases of reactivation have been reported within the first couple months of treatment. Caution should be exercised when considering the use in patients who have been exposed to tuberculosis.

Disease-related concerns:

• Demyelinating CNS disease: Use with caution in patients with preexisting or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease (including multiple sclerosis, systemic vasculitis, and Guillain-Barré syndrome) have been reported; consider discontinuation of therapy if patient develops significant CNS reactions.

• Heart failure: Use with caution in patients with mild heart failure (NYHA class I, II) or decreased left ventricular function; worsening and new-onset heart failure (with and without identifiable precipitating factors [eg, preexisting cardiovascular disease]) has been reported; doses >5 mg/kg are contraindicated in patients with moderate to severe heart failure (NYHA class III/IV). Monitor patients closely if doses ≤5 mg/kg are administered to patients with moderate or severe heart failure or any approved dose is administered to patients with mild heart failure and discontinue therapy with onset of new or worsening symptoms. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Seizure disorders: Use with caution in patients with a history of seizures; discontinue if significant CNS adverse reactions develop.

Special populations:

• Pediatric: Malignancies have been reported among children and adolescents receiving TNF-blocking agents. Efficacy was not established in a study to evaluate infliximab use in juvenile idiopathic arthritis (JIA).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there are no data available concerning secondary transmission of live vaccines in patients receiving therapy. A fatal outcome has been reported in an infant who received a live vaccine (BCG) after in utero exposure to infliximab. It is recommended to wait ≥6 months following birth before administering any live vaccine to infants exposed to infliximab in utero.

Monitoring Parameters

Monitor improvement of symptoms and physical function assessments. During infusion, if reaction is noted, monitor vital signs every 2 to 10 minutes, depending on reaction severity, until normal. If a serious reaction occurs (eg, cardiovascular or cerebrovascular reaction), discontinue the infusion. Active and latent TB screening prior to initiating and during therapy; signs/symptoms of infection (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; LFTs (discontinue if >5 times ULN); signs and symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).

Psoriasis patients with history of phototherapy should be monitored for nonmelanoma skin cancer. Women should be screened periodically for cervical cancer.

The American Gastroenterological Association suggests reactive therapeutic drug monitoring to guide treatment changes in adult patients treated with infliximab for active inflammatory bowel disease (Feuerstein 2017).

Reproductive Considerations

Infliximab may be used in females with rheumatic and musculoskeletal diseases who are planning a pregnancy. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).

Women with psoriasis planning a pregnancy may continue treatment with infliximab. Women with well-controlled psoriasis who wish to avoid fetal exposure can consider discontinuing infliximab 50 days prior to attempting pregnancy (Rademaker 2018).

Treatment algorithms are available for use of biologics in female patients with Crohn disease who are planning a pregnancy (Weizman 2019). Serum levels should be optimized prior to conception (Mahadevan 2019).

Infliximab is recommended for use in males with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

The American Academy of Dermatology considers tumor necrosis factor alpha (TNFα)-blocking agents for the treatment of psoriasis to be compatible for use in male patients planning to father a child (AAD-NPF [Menter 2019]).

Pregnancy Considerations

Infliximab crosses the placenta.

Infliximab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Following administration to pregnant patients with inflammatory bowel disease, cord blood and newborn concentrations of infliximab are greater than maternal serum at delivery (Julsgaard 2016; Mahadevan 2013). The mean time to infliximab clearance was 7.3 months (range: 6.2 to 8.3 months) in a study in 44 infants exposed in utero. Infliximab serum concentrations remained detectable in one infant until 12 months of age (Julsgaard 2016).

A paper describes agranulocytosis requiring treatment with granulocyte colony stimulating factor in four infants (three of which were triplets) exposed to infliximab in utero. In the singleton pregnancy, infliximab was present in the newborn serum 13 weeks after the last maternal pregnancy dose, but concentrations were not measurable in the mother. Infliximab serum concentrations were not evaluated in the triplets (Guiddir 2014). Information related to this class of medications is emerging, but based on available data, tumor necrosis factor alpha (TNFα)-blocking agents are considered to have low to moderate risk when used in pregnancy (ACOG 776 2019).

A fatal outcome has been reported in an infant who received a live vaccine (BCG) after in utero exposure to infliximab. The mother was treated with infliximab 10 mg/kg once weekly as monotherapy for steroid refractory Crohn disease. The infant was well at delivery and was not breastfed. BCG vaccination occurred at 3 months of age; the infant died at 4.5 months of age due to disseminated BCG (Cheent 2010). The risk of immunosuppression may be increased following third trimester maternal use of TNFα blocking agents; the fetus, neonate/infant should be considered immunosuppressed for 1 to 3 months following in utero exposure (AAD-NPF [Menter 2019]). Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).

Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).

Use of immune-modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 776 2019). The American Academy of Dermatology (AAD) considers TNFα-blocking agents for the treatment of psoriasis to be compatible with pregnancy (AAD-NPF [Menter 2019]).

When treatment for inflammatory bowel disease is needed in pregnant women, appropriate biologic therapy can be continued without interruption. Weight based dosing can be done using prepregnancy body weight and adjusted as needed based on disease activity and serum concentrations. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For infliximab, the final injection can be given 6 to 10 weeks prior to the estimated date of delivery, then continued 48 hours' postpartum (Mahadevan 2019).

Infliximab may be continued during the first and second trimesters of pregnancy in females with rheumatic and musculoskeletal diseases. Use should be discontinued during the third trimester in women with well-controlled disease. Newborn exposure should be considered if treatment cannot be discontinued due to active disease (ACR [Sammaritano 2020]).

Data collection to monitor pregnancy and infant outcomes following exposure to infliximab is ongoing. Health care providers are also encouraged to enroll females exposed to infliximab during pregnancy in the MotherToBaby Autoimmune Diseases Study by contacting the Organization of Teratology Information Specialists (OTIS) (877-311-8972).

Patient Education

What is this drug used for?

• It is used with methotrexate to prevent more problems in patients with moderate to very bad rheumatoid arthritis.

• It is used to treat Crohn's disease.

• It is used to treat psoriatic arthritis.

• It is used to treat plaque psoriasis.

• It is used to treat ankylosing spondylitis.

• It is used to treat ulcerative colitis.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Abdominal pain

• Diarrhea

• Loss of strength and energy

• Common cold symptoms

• Flushing

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs.

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out.

• Infusion reactions

• Skin eczema

• Excessive weight loss

• Burning or numbness feeling

• Severe headache

• Pale skin

• Swollen glands

• Night sweats

• Shortness of breath

• Vision changes

• Blindness

• Mole changes

• Skin growths

• Skin changes

• Abnormal vaginal bleeding

• Dizziness

• Passing out

• Slow heartbeat

• Fast heartbeat

• Seizures

• Extremity weakness

• Bruising

• Bleeding

• Severe loss of strength and energy

• Injection site redness or swelling

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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Frequently Asked Questions