Drug.smallpox (vaccinia) vaccine, liveSerious - Use Alternative (1)infliximab decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tacrolimusSerious - Use Alternative (1)infliximab and tacrolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.temsirolimusSerious - Use Alternative (1)infliximab and temsirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tetanus toxoid adsorbed or fluidSerious - Use Alternative (1)infliximab decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tick-borne encephalitis vaccineSerious - Use Alternative (1)infliximab decreases effects of tick-borne encephalitis vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tisagenlecleucelSerious - Use Alternative (1)infliximab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tocilizumabSerious - Use Alternative (1)tocilizumab and infliximab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tofacitinibSerious - Use Alternative (1)infliximab, tofacitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tongkat aliSerious - Use Alternative (1)infliximab and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.trastuzumabMonitor Closely (1)trastuzumab, infliximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .trastuzumab deruxtecanMonitor Closely (1)trastuzumab deruxtecan, infliximab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .travelers diarrhea and cholera vaccine inactivatedSerious - Use Alternative (1)infliximab decreases effects of travelers diarrhea and cholera vaccine inactivated by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.typhoid polysaccharide vaccineSerious - Use Alternative (1)infliximab decreases effects of typhoid polysaccharide vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.typhoid vaccine liveSerious - Use Alternative (1)infliximab decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.ublituximabMonitor Closely (1)ublituximab and infliximab both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministeredupadacitinibContraindicated (1)infliximab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.ustekinumabSerious - Use Alternative (1)infliximab and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.valoctocogene roxaparvovecMonitor Closely (1)infliximab and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.varicella virus vaccine liveSerious - Use Alternative (1)infliximab decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.vedolizumabSerious - Use Alternative (1)vedolizumab and infliximab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid coadministration of vedolizumab with TNF blockers because of the potential for increased risk of infectionsyellow fever vaccineSerious - Use Alternative (1)infliximab decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.zoster vaccine liveSerious - Use Alternative (1)infliximab decreases effects of zoster vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.zoster vaccine recombinantMonitor Closely (1)infliximab decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant. >10% Development of antinuclear antibodies (50%) Infection (36%) Upper respiratory tract infection (32%) Abdominal pain (12%; 26% with Crohn disease) Nausea (21%) Infusion-related reaction (20%) Headache (18%) Development of antibodies to double-stranded DNA (17%) Other respiratory infection (eg, sinusitis, cough) (12-14%) Diarrhea (12%) Elevated alanine transaminase (ALT), >1 to <3 ULN (12-34%) 1-10% (Adults) Bronchitis (10%) Dyspepsia (10%) Rash (1-10%) Elevated ALT, ≥3 ULN (2-10%) Fatigue (9%) Back pain (8%) Rhinitis (8%) Urinary tract infection (8%) Arthralgia (1-8%) Fever (7%) Hypertension (7%) Pruritus (7%) Dyspnea (6%) Candidiasis (5%) Lupuslike symptoms (<5%) Elevated ALT, ≥5 ULN (<1-4%) 1-10% (Children) Leukopenia (9%) Flushing (9%) Viral infection (8%) Neutropenia (7%) Bone fracture (7%) Bacterial infection (6%) Respiratory tract allergic reaction (6%) Postmarketing Reports Adults Anaphylacticlike reactions, including anaphylactic shock, laryngeal/pharyngeal edema, severe bronchospasm, and seizure Myocardial ischemia or infarction and transient visual loss have also been rarely reported during or within 2 hours of infusion Serious infections and malignancies, including melanoma, leukemia, and Merkel cell carcinoma Neutropenia, agranulocytosis (including infants exposed in utero to infliximab), interstitial lung disease (including pulmonary fibrosis/interstitial pneumonitis and rapidly progressive disease), idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, pericardial effusion, systemic and cutaneous vasculitis, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis Peripheral demyelinating disorders (such as Guillain- Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy), new onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar), transverse myelitis, and neuropathies (additional neurologic reactions have also been observed), acute liver failure, jaundice, hepatitis, and cholestasis, serious infections, malignancies, including melanoma, Merkel cell carcinoma, and cervical cancer Children Malignancies, including hepatosplenic T-cell lymphomas Transient hepatic enzyme abnormalities, lupus-like syndromes, and the development of autoantibodies Infections (some fatal) including opportunistic infections and tuberculosis Infusion reactions Hypersensitivity reactions Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Stevens-Johnson Syndrome, toxic epidermal necrolysis, linear IgA bullous dermatosis (LABD) Acute generalized exanthematous pustulosis (AGEP), new onset and worsening psoriasis (all subtypes including pustular, primarily palmoplantar) Lichenoid reactions Black Box Warnings Serious infection risk Increased risk for developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids) Patients older than 65 years may be at greater risk Discontinue if patient develops serious infection or sepsis; reported infections include the following: (1) Active tuberculosis, including reactivation of latent disease (frequently present with disseminated or extrapulmonary disease); test for latent tuberculosis before use and during therapy; treat latent infection before use (2) Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, cryptococcosis, candidiasis, aspergillosis, salmonellosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may yield negative results in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops (3) Infections caused by other opportunistic pathogens, including bacteria (eg, Legionella, Listeria), mycobacteria (eg, Mycobacterium tuberculosis), and viruses (eg, hepatitis B virus) Malignancy Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers Manufacturer is required to report all malignancies to FDA for complete and consistent analysis Hepatosplenic T-cell lymphoma Hepatosplenic T-cell lymphoma (HSTCL) is an aggressive, rare type of T-cell lymphoma (usually fatal) Rare postmarketing cases of HSTCL are reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with infliximab Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis Most reported cases with infliximab have occurred with concomitant treatment with azathioprine or 6-mercaptopurine (6-MP), though cases have been reported in patients receiving azathioprine or 6-MP alone In the FDA Adverse Event Reporting System (AERS) database, the literature, and the HSTCL Cancer Survivors' Network, HSTCL cases have been identified in association with the following agents: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), and 6-MP (3) Contraindications Active serious infections Documented hypersensitivity Doses >5 mg/kg in patients with moderate-to-severe heart failure (NYHA Class III/IV) Cautions Patients should be closely monitored for development of signs and symptoms of infection during and after treatment Hypersensitivity reactions reported; most hypersensitivity reactions, which include anaphylaxis, urticaria, dyspnea, and/or hypotension, have occurred during or within 2 hr of infusion Caution in neurologic disorder Moderate-to-severe chronic obstructive pulmonary disease Monitor closely for signs and symptoms of demyelinating disease (eg, confusion, numbness, vision changes); consider termination of therapy if significant CNS reactions develop Risk of tuberculosis, histoplasmosis, and other opportunistic infections, as well as hepatitis B reactivation; test for HBV infection before starting infliximab; monitor HBV carriers during and several months after therapy Consider discontinuance if hematologic disorder occurs (eg, leukopenia, thrombocytopenia, neutropenia, pancytopenia) Consider discontinuance if lupuslike symptoms occur Readministration after period of no treatment resulted in higher incidence of infusion reactions than was seen with regular maintenance treatment (4% vs <1%) Consider empiric antifungal therapy for patients who develop a systemic illness on infliximab and reside or travel to regions where mycoses are endemic Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hr of initiation of infliximab infusion; cases of transient visual loss have been reported during or within 2 hr of infliximab infusion; monitor patients during infusion and if serious reaction occurs, discontinue infusion Use caution in patients with history of seizures; discontinue therapy if significant adverse reactions develop Use caution in patients with mild heart failure (NYHA Class I, II) or decreased left ventricular function; worsening and new-onset heart failure reported Before initiating therapy in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines Neurologic reactions Associated with CNS manifestation of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome Prescribers should exercise caution in considering use of therapy in patients with these neurologic disorders and should consider discontinuation of drug if these disorders develop Hepatoxicity Severe hepatic reactions (eg, acute liver failure, jaundice, hepatitis and cholestasis), have been reported in postmarketing data Severe hepatic reactions occurred between 2 weeks to more than 1 year after initiation of infliximab; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases Some fatal or necessitating liver transplantation; stop therapy in cases of jaundice and/or marked liver enzyme elevations (≥5 ULN) Malignancies Increased risk of lymphoma (including hepatosplenic T-cell lymphoma, especially if given with azathioprine or 6-MP), pneumonia, hepatotoxicity (including acute liver failure, jaundice, hepatitis, cholestasis) Increased risk of lymphoma and other cancers is reported in children and adolescents Skin cancer (eg, melanoma, Merkel cell carcinoma) is reported with TNF blockers Increased incidence of invasive cervical cancer in women reported; a causal relationship between infliximab and cervical cancer cannot be excluded; periodic screening should continue in women receiving therapy Occurrence of leukemia and new-onset psoriasis also with TNF blockers Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections reported, including patients who have previously received treatment for latent or active tuberculosis; cases of active tuberculosis have also occurred during treatment for latent tuberculosis Evaluate for tuberculosis risk factors and test for latent infection prior to initiating treatment and periodically during therapy; treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy; consider tuberculin skin test with an induration ≥5 mm is a positive test result when assessing if treatment for latent tuberculosis is needed before initiating treatment, even for patients previously vaccinated with Bacille Calmette-Guérin (BCG) Consider antitubercular therapy before initiating treatment in patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection Consult with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating antitubercular therapy is appropriate for an individual patient Consider tuberculosis if a new infection develops during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis Heart failure Worsening or new-onset congestive HF reported with TNF blockers; exercise caution when using in patients who have heart failure; consider TNF therapy in patients with HF if there are no other reasonable treatment options, and then consider only in patients with compensated HF Doses >5 mg/kg are contraindicated in patients with moderate or severe HF; 10 mg/kg-dose has been associated with an increased incidence of death and hospitalization due to worsening HF; new-onset and worsening HF, with and without