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.
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.
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, moderate to severe, induction and maintenance of remission: Note: Combination with an immunomodulator is generally preferred (Al Hashash 2021).
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.
Plaque psoriasis: IV: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. Note: Some patients may require 10 mg/kg and/or dosing as frequently as every 4 weeks during the maintenance phase (AAD-NPF [Menter 2019]).
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.
Remsima (Canadian product): SUBQ: Initial maintenance therapy (begin 4 weeks following IV induction therapy): 120 mg once every 2 weeks. Patients receiving IV maintenance therapy and switching to SUBQ maintenance therapy: Administer first dose 8 weeks after the last IV infusion.
Missed doses:
≤7 days: Administer missed dose immediately; administer following dose as per originally planned date and thereafter on the original biweekly schedule.
≥8 days: Skip the missed dose and administer next dose as per the originally planned date and thereafter on the original biweekly schedule.
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.
There are no dosage adjustments provided in the manufacturer's labeling.
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling.
Hepatotoxicity during treatment: Jaundice and/or marked increase in liver enzymes (≥5 times ULN): Discontinue treatment.
(For additional information see "Infliximab (including biosimilars): Pediatric drug information")
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.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
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]
Generic: 100 mg (1 ea)
Yes
Remicade contains sucrose 500 mg per vial.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Auto-injector Kit, Subcutaneous:
Remsima SC: 120 mg/mL (1 ea) [contains polysorbate 80]
Solution Reconstituted, Intravenous:
Avsola: 100 mg (1 ea) [contains polysorbate 80]
Inflectra: 100 mg (1 ea) [contains polysorbate 80]
Remicade: 100 mg (1 ea) [contains polysorbate 80]
Renflexis: 100 mg (1 ea) [contains polysorbate 80]
Ixifi (infliximab-qbtx): FDA approved December 2017; anticipated availability is currently undetermined.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Avsola: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761086s000lbl.pdf#page=48
Inflectra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125544s018lbl.pdf#page=61
Ixifi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761072s006lbl.pdf#page=43
Remicade: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103772s5401lbl.pdf#page=50
Renflexis: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761054s004lbl.pdf#page=52
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.
SUBQ: Remsima (Canadian product): Allow syringe to warm to room temperature prior to use (30 minutes); do not use heat sources to warm (eg, hot water, microwave). Inject into outer area of upper arms (caregiver only), abdomen (do not use within 5 cm of belly button), or front of thighs. Rotate injection site with each dose; administer at least 3 cm away from previous injection site. Do not administer into bruised, damaged, scarred, or tender skin. Do not use damaged syringe; do not reuse or shake syringe. Administer first dose under supervision of health care provider. After proper training, patients may self-inject, or the patient's caregiver may administer.
Parenteral: The infusion should begin within 3 hours of preparation. Administer by IV infusion through an in-line, sterile, nonpyrogenic, low-protein-binding filter with pore size of ≤1.2 micrometers; do not infuse in the same IV line as other agents. Infuse over at least 2 hours; a rate titration schedule may be used to prevent acute infusion reactions. 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.
Guidelines for the treatment and prophylaxis of infusion reactions: There are no pediatric-specific guidelines available. In adults, the following 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 NS 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 infliximab 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 NS (500 to 1,000 mL/hour) and appropriate symptomatic treatment. Monitor vital signs every 5 minutes until normal. After 20 minutes, the infliximab 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. Retreatment 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, and 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 of infliximab 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-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. Note: In a trial of pediatric patients, premedication with acetaminophen (20 mg/kg; maximum single dose: 1,000 mg) and cetirizine (0.3 mg/kg if <5 years, 10 mg if ≥5 years) did not significantly impact incidence of infusion-related reactions; patients should be monitored closely (Lahdenne 2010).
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.
Guideline recommendations: Infliximab is recommended with or without an immunomodulator for induction and maintenance of remission in treatment-naïve patients with moderate to severe Crohn disease, including patients with fistulizing disease (AGA [Feuerstein 2021]). In addition, infliximab is effective for prophylactic therapy in patients following surgical resection who are at higher risk for clinical recurrence (ACG [Lichtenstein 2018]; AGA [Nguyen 2017]).
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).
Pustular psoriasis; Pyoderma gangrenosum
InFLIXimab may be confused with idaruCIZUmab, riTUXimab
Remicade may be confused with Renacidin, Rituxan
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
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
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).
Concerns related to adverse effects:
• Antibody formation: Formation of neutralizing anti-drug antibodies may occur with biologic tumor necrosis factor (TNF) inhibitors and may be associated with loss of efficacy (AAD-NPF [Menter 2019]).
• 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 (> 8 weeks) 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 (AAD-NPF [Menter 2019]).
• 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]).
• HIV: Use with caution in HIV-positive patients; TNF-α inhibitors may be appropriate in patients receiving highly active antiretroviral therapy, provided they have normal CD4 counts, no viral load, and no recent opportunistic infections (AAD-NPF [Menter 2019]).
• 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.
In an analysis of children and adolescents who had received TNF-blockers (etanercept and infliximab), the FDA identified 48 cases of malignancy. Of the 48 cases, ~50% were lymphomas (eg, Hodgkin and non-Hodgkin lymphoma). Other malignancies, such as leukemia, melanoma, Merkel cell carcinoma, and solid organ tumors, were reported; malignancies rarely seen in children (eg, leiomyosarcoma, hepatic malignancies, and renal cell carcinoma) were also observed. Of note, most of these cases (88%) were receiving other immunosuppressive medications (eg, azathioprine and methotrexate). As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma. The role of TNF-blockers in the development of malignancies in children cannot be excluded. The FDA also reviewed 147 postmarketing reports of leukemia (including acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) in patients (children and adults) using TNF blockers. Average onset time to development of leukemia was within the first 1 to 2 years of TNF-blocker initiation. Although most patients were receiving other immunosuppressive agents, the role of TNF blockers in the development of leukemia could not be excluded. The FDA concluded that there is a possible association with the development of leukemia and the use of TNF-blockers.
Reactivation of TB has been reported in pediatric patients receiving biologic response modifiers (infliximab and etanercept); prior to therapy, patients with no TB risk factors should be screened for latent TB infection (LTBI) with an age appropriate test (ie, <5 years of age: tuberculin skin test, and ≥5 years of age: IGRA [interferon gamma release assay]); if any TB risk factors are present or symptoms, both LTBI screening tests should be performed (AAP [Davies 2016])
The risk of infusion-related reactions may be increased with retreatment after an interruption or discontinuation of prior maintenance dose. A retrospective study of 57 children receiving 361 infliximab infusions reported that the rate of infusion-related reactions in children was similar to that in adults (9.7% incidence reported). Female gender, immunosuppressive use for <4 months, and prior infusion reactions were risk factors for subsequent infusion reactions in children (Crandall 2003).
None known.
Abatacept: Anti-TNF Agents may enhance the immunosuppressive effect of Abatacept. Risk X: Avoid combination
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: 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. Risk X: Avoid combination
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: 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. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination
Biologic Anti-Psoriasis Agents: InFLIXimab may enhance the immunosuppressive effect of Biologic Anti-Psoriasis Agents. Risk X: Avoid combination
Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid combination
Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Risk X: Avoid combination
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
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. Risk C: Monitor therapy
Tocilizumab: May enhance the immunosuppressive effect of Anti-TNF Agents. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Infliximab may be used in patients with rheumatic and musculoskeletal diseases who are planning to become pregnant. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).
Patients with psoriasis planning to become pregnant may continue treatment with infliximab. Patients with well-controlled psoriasis who wish to avoid fetal exposure can consider discontinuing infliximab 50 days prior to attempting to become pregnant (Rademaker 2018).
Biologics, such as infliximab, may be continued in patients with inflammatory bowel disease planning to become pregnant (Mahadevan 2019). Treatment algorithms are available for use of biologics in patients with Crohn disease who are planning to become pregnant (Weizman 2019). Serum levels should be optimized prior to conception (Mahadevan 2019).
Infliximab is recommended for use in patients 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 patients planning to father a child (AAD-NPF [Menter 2019]).
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 case report describes serum concentrations in the newborn following maternal use of infliximab during pregnancy for psoriatic arthritis. The newborn infliximab concentrations decreased from 4.46 mcg/mL at 24 days of age to 0.19 mcg/mL at 155 days of age and were undetectable at 278 days following delivery. Maternal serum concentrations were not noted (Takeuchi 2020).
Based on available data, an increased risk of major birth defects has not been observed following infliximab exposure during pregnancy (Geldhof 2020; Nielsen 2020). 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 2019).
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).
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).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of infliximab may be altered. Clearance may be decreased as pregnancy progresses leading to an increase in maternal plasma concentrations; therapeutic drug monitoring may be required in some patients (Flanagan 2020; Grišić 2020).
Use of immune-modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 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 patients, 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 patients with rheumatic and musculoskeletal diseases. Use should be discontinued during the third trimester in patients 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).
Infliximab is present in breast milk.
The potential transfer of infliximab into breast milk has been evaluated in multiple studies. Information is available from three postpartum women who were administered infliximab 5 mg/kg 1 to 24 weeks after delivery. Infliximab was detected within 12 hours and the highest milk concentrations were seen 2 to 3 days after the maternal dose (Ben-Horin 2011). In a study of 29 women, 19 had detectable breast milk concentrations with maximum concentrations occurring between 24 and 48 hours after the infusion (Matro 2018). A smaller study of three postpartum patients demonstrated breast milk concentrations can be variable within a single woman over one dosing period (Grosen 2014). Infliximab could not be detected in breast milk in some studies (Kane 2009; Stengel 2008; Vasiliauskas 2006).
In one case report, subtherapeutic infliximab concentrations were observed in a breastfed infant only exposed during breastfeeding (Fritzsche 2012). Adverse events were not observed in breastfed infants in the studies which demonstrated detectable milk concentrations and evaluated this outcome (Grosen 2014; Matro 2018).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. However, tumor necrosis factor alpha (TNFα)-blocking agents, including infliximab, are considered compatible with breastfeeding (AAD-NPF [Menter 2019]; ACOG 776 2019; ACR [Sammaritano 2020]; Mahadevan 2019).
CBC with differential (baseline); complete metabolic panel (baseline); tuberculosis (TB) screening prior to initiating and during therapy (chest Xray if TB positive); hepatitis b virus (HBV)/hepatitis C virus screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); HIV screening (baseline) (AAD-NPF [Menter 2019]); LFTs (discontinue if >5 times ULN); signs/symptoms of infection, heart failure, hypersensitivity reaction, lupus-like syndrome, malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss). 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. Monitor improvement of symptoms and physical function assessments.
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).
Inflammatory bowel disease (IBD):
Reactive therapeutic drug monitoring has been suggested to guide treatment changes in adults with active IBD.
Timing of serum sample: Draw trough <24 hours prior to next scheduled dose
Therapeutic reference range: ≥5 mcg/mL (Feuerstein 2017)
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.
Note: Pharmacokinetic data in pediatric patients (6 to 17 years) reported to be similar to adult values.
Onset of action: Crohn disease: 1 to 2 weeks; Rheumatoid arthritis: 3 to 7 days; Psoriasis: 8 to 10 weeks (AAD-NPF [Menter 2019]).
Duration of action: Crohn disease: 8 to 48 weeks; Rheumatoid arthritis: 6 to 12 weeks.
Distribution: Within the vascular compartment; Vd: 3 to 6 L (Klotz 2007); Remsima (Canadian product): Terminal phase: 7.3 to 8.8 L.
Half-life elimination: 7 to 12 days (Klotz 2007); Remsima (Canadian product): Terminal: 11.3 to 13.7 days.
Solution (reconstituted) (Avsola Intravenous)
100 mg (per each): $600.00
Solution (reconstituted) (Inflectra Intravenous)
100 mg (per each): $1,135.54
Solution (reconstituted) (inFLIXimab Intravenous)
100 mg (per each): $570.00
Solution (reconstituted) (Remicade Intravenous)
100 mg (per each): $1,401.38
Solution (reconstituted) (Renflexis Intravenous)
100 mg (per each): $904.07
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
