Immunosuppressants also increase risk of infection with concomitant live vaccines.tick-borne encephalitis vaccineSerious - Use Alternative (1)adalimumab 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)adalimumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tocilizumabSerious - Use Alternative (1)adalimumab and tocilizumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tongkat aliSerious - Use Alternative (1)adalimumab and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.travelers diarrhea and cholera vaccine inactivatedSerious - Use Alternative (1)adalimumab 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)adalimumab 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)adalimumab 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 adalimumab 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)adalimumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.ustekinumabSerious - Use Alternative (1)adalimumab and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.varicella virus vaccine liveSerious - Use Alternative (1)adalimumab 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 adalimumab 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)adalimumab 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)adalimumab 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)adalimumab decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant. >10% Injection site pain (12-20%) Upper respiratory tract infection (URTI) (17%) Increased creatine phosphokinase (15%) Headache (12%) Rash (12%) Sinusitis (11%) 1-10% Nausea (9%) Urinary tract infection (UTI) (8%) Abdominal pain (7%) Flulike syndrome (7%) Hyperlipidemia (7%) Back pain (6%) Hypercholesterolemia (6%) Hematuria (5%) Hypertension (5%) Increased alkaline phosphatase (5%) <1% Allergic reactions Hematologic disorder (leukopenia, thrombocytopenia, pancytopenia, aplastic anemia) Postmarketing Reports General disorders and administration site conditions: Pyrexia Hepatobiliary disorders: Liver failure, hepatitis Immune system disorders: Sarcoidosis Neoplasms benign, malignant, and unspecified (incl cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin) Nervous system disorders: Demyelinating disorders (eg, optic neuritis, Guillain-Barré syndrome), cerebrovascular accident Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism Skin reactions: Stevens-Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia, lichenoid skin reaction Vascular disorders: Systemic vasculitis, deep vein thrombosis Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis Infections: Pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, and pyelonephritis Black Box Warnings Serious infection risk Increased risk for developing serious infections resulting in hospitalization or death; patients with comorbid conditions and/or 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: Active TB, including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection before use Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, 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 Other bacterial (eg, Legionella, Listeria), mycobacterial (eg, tuberculosis), and viral (eg, hepatitis B) opportunistic pathogens Malignancy Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers Cases of acute and chronic leukemia have been reported in association with postmarketing TNF blocker use in rheumatoid arthritis (RA) and other indications; patients with RA may be at higher risk (approximately 2-fold) for leukemia than general population Manufacturers are required to report all malignancies to FDA for complete and consistent analysis Hepatosplenic T-cell lymphoma HSTCL is an aggressive, rare type of T-cell lymphoma (usually fatal) Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) reported primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers Reports have also included 1 patient being treated for psoriasis and 2 patients being treated for RA Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-MP, though cases have been reported with 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), 6-MP (3) Contraindications None Cautions Consider discontinuance if hematologic disorder occurs (thrombocytopenia, pancytopenia, aplastic anemia, leukopenia); use caution in patients with a history of significant hematologic abnormalities Coadministration with interleukin (IL)-1 blockers (eg, anakinra, ustekinumab) may lead to serious infections and neutropenia Coadministration of TNF blockers with abatacept showed increased rate of serious infections in controlled trials as compared with TNF blockers alone Treatment should not be initiated in patients with an active infection, including localized infections Risk of serious infection, including tuberculosis or hepatitis B virus; despite prophylactic treatment for TB, reactivation has occurred (see Black Box Warnings) Decreases immune response of live virus vaccines; also increases risk of infection with concomitant live virus vaccines; safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero unknown; risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants If possible, patients with JIA should be current with immunization guidelines prior to initiating adalimumab; may receive concurrent vaccinations (except for live vaccines) while taking adalimumab Autoimmunity may result in formation of autoantibodies and, rarely, development of lupuslike syndrome; if patient develops symptoms suggestive of lupus-like syndrome following treatment with adalimumab, discontinue treatment Hypersensitivity reactions (eg, anaphylaxis, angioedema) are reported rarely Worsening or new onset congestive heart failure (HF) reported with TNF blockers; exercise caution when using in patients who have HF; TNFalpha inhibitors should only be considered in patients with HF if there are no other reasonable treatment options, and then consider only in patients with compensated HF Infection and malignancy reported in elderly at higher rate; use caution Monitor closely for infection in patients undergoing surgical procedures while on therapy; not studied; consider long half-life With monotherapy, patients receiving every other week dosing may develop antibodies against this drug more frequently than those receiving weekly dosing; in patients receiving the recommended dosage of 40 mg every other week as monotherapy, the adalimumab clinical response was lower among antibody-positive patients than among antibody-negative patients; the long-term immunogenicity of adalimumab products is unknown Neurologic reactions Use of TNF blocking agents, including this medication, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome Exercise caution in considering use in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of therapy should be considered if any of these disorders develop; there is a known association between intermediate uveitis and central demyelinating disorders Malignancies Most frequently observed malignancies, other than lymphoma and non-melanoma skin cancer (NMSC), have included breast, colon, prostate, lung, and melanoma Consider risks and benefits of TNF blocker treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated NMSC or when considering continuing a TNF blocker in patients who develop a malignancy Non-melanoma skin cancer (NMSC) reported in clinical trials; examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for presence of NMSC prior to and during treatment Post-marketing cases of acute and chronic leukemia reported in association with TNF blocker use in RA and other indications Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, reported in patients treated with TNF blockers including adalimumab products; these cases have had a very aggressive disease course and have been fatal; the majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and majority were in adolescent and young adult males; almost all of the patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis; it is uncertain whether occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants; the potential risk with the combination of azathioprine or 6-mercaptopurine and this drug should be carefully considered Pregnancy Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/Mother-To-Baby HUMIRA Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn disease (CD) Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease matched comparison cohort The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant Animal studies In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with IV administration during organogenesis and later in gestation, at doses that produced exposures up to ~373 times maximum recommended human dose (MRHD) of 40 mg SC without methotrexate Clinical consideration Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity Adverse pregnancy outcomes include preterm delivery (ie, <37 weeks gestation), low birth weight (ie, <2500 g) infants, and small for gestational age at birth Fetal/neonatal adverse reaction Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab in utero owing to possible effect on infant immune system Lactation Limited data from case reports in published literature describe presence of adalimumab in human milk at infant doses of 0.1-1% of maternal serum level; there are no reports of adverse effects of adalimumab on breastfed infant and no effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Recombinant human anti-TNF-α IgG1 monoclonal antibody; blocks inflammatory activity of TNF-α; specifically binds to