of tocilizumab by receptor binding competition. Use Caution/Monitor. Coadministration of rozanolixizumab with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing rozanolixizumab and using alternative therapies.rubella vaccineSerious - Use Alternative (1)tocilizumab decreases effects of rubella vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.siponimodMonitor Closely (1)siponimod and tocilizumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.sipuleucel-TMonitor Closely (1)tocilizumab decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.sirolimusSerious - Use Alternative (1)tocilizumab and sirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.smallpox (vaccinia) vaccine, liveSerious - Use Alternative (1)tocilizumab 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)tocilizumab and tacrolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.temsirolimusSerious - Use Alternative (1)tocilizumab and temsirolimus both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tetanus toxoid adsorbed or fluidSerious - Use Alternative (1)tocilizumab decreases effects of tetanus toxoid adsorbed or fluid by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.thalidomideSerious - Use Alternative (1)tocilizumab, thalidomide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive immunosuppression; risk of serious infection.tick-borne encephalitis vaccineSerious - Use Alternative (1)tocilizumab 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)tocilizumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.tongkat aliSerious - Use Alternative (1)tocilizumab and tongkat ali both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.trastuzumabMonitor Closely (1)trastuzumab, tocilizumab. 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, tocilizumab. 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)tocilizumab 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)tocilizumab 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)tocilizumab 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 tocilizumab 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 coadministeredupadacitinibSerious - Use Alternative (1)tocilizumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.ustekinumabSerious - Use Alternative (1)tocilizumab and ustekinumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.varicella virus vaccine liveSerious - Use Alternative (1)tocilizumab decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.yellow fever vaccineSerious - Use Alternative (1)tocilizumab decreases effects of yellow fever vaccine by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.zidovudineMonitor Closely (1)tocilizumab decreases levels of zidovudine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Interaction applies to inflammatory conditions, such as rheumatoid arthritis, associated with increased levels of IL-6.zoster vaccine liveMonitor Closely (1)tocilizumab decreases effects of zoster vaccine live by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.zoster vaccine recombinantMonitor Closely (1)tocilizumab decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant. >10% SC injection site reactions (7.1-10.1%) COVID-19 EUA Constipation (13%) 1-10% Upper respiratory tract infection (6-8%) Nasopharyngitis (4-7%) Headache (3-7%) Hypertension (3-6%) ALT increased (1-6%) Bronchitis (2-4%) Rash (1-4%) Dizziness (1-3%) Mouth ulceration (1-2%) Upper abdominal pain (2-3%) Gastritis (1-2%) Oral herpes simplex (<2%) Stomatitis (<2%) Gastric ulcer (<2%) Increased weight (<2%) Total bilirubin increased (<2%) Leukopenia (<2%) Peripheral edema (<2%) Dyspnea (<2%) Cough (<2%) Conjunctivitis (<2%) COVID-19 Increased AST/ALT (10%) Constipation (9%) Urinary tract infection (5%) Hypertension (4%) Hypokalemia (4%) Anxiety (4%) Diarrhea (4%) Insomnia (4%) Neutrophil counts <1,000 cell/m3 (3.4%) Platelets counts <50,000 cells/mcL (3.2%) Nausea (3%) Postmarketing Reports Stevens-Johnson syndrome Pancreatitis Fatal anaphylaxis Drug-induced liver injury, hepatitis, hepatic failure, jaundice Rheumatoid arthritis, giant cell arteritis, and systemic sclerosis-associated interstitial lung disease Black Box Warnings Risk of serious infections Increased risk for developing serious infections that may lead to hospitalization or death Most patients who developed these infections were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids) If a serious infection develops, interrupt therapy until the infection is controlled Reported infections include Active tuberculosis, which may present with pulmonary or extrapulmonary disease Test for latent tuberculosis before tocilizumab use and during therapy; initiate treatment for latent infection prior to use Invasive fungal infections (eg, candidiasis, aspergillosis, pneumocystis); patients with invasive fungal infections may present with disseminated, rather than localized, disease Bacterial, viral and other infections due to opportunistic pathogens Carefully consider risks and benefits of treatment prior to initiating therapy in patients with chronic or recurrent infection Closely monitor signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy Contraindications Hypersensitivity Cautions May cause neutropenia, decreased platelets, elevated liver transaminases, and increased lipid parameters; monitor neutrophils, platelets, lipids, and liver function tests every 4-8 weeks Impact of treatment is unknown regarding development of malignancies, but malignancies were observed in clinical studies; treatment with immunosuppressants may increase risk of malignancies Anaphylaxis or serious hypersensitivity reactions have occurred, including fatalities, with or without concomitant arthritis therapies Impact of treatment with tocilizumab on demyelinating disorders is unknown, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA clinical studies; monitor for signs and symptoms potentially indicative of demyelinating disorders Caution if increased risk for GI perforation; gastrointestinal perforation reported, primarily as complications of diverticulitis; promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation Serious infections Do not administer in patients with an active infection, including localized infections Consider risk versus benefits before initiating in patients with chronic or recurrent infection, exposure to tuberculosis, history of serious or an opportunistic infection, have resided or traveled in areas of endemic tuberculosis or endemic mycoses, or who have underlying conditions predisposing them to infection In patients with COVID-19, testing for latent infection is not necessary prior to initiating treatment with this medication Not studied in combination with biological DMARDs (eg, TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective costimulation modulators); avoid coadministration with biological DMARDs Viral reactivation reported; cases of herpes zoster exacerbation observed in clinical studies; unknown if associated with hepatitis B reactivation; not studied COVID-19 patients Monitor for signs and symptoms of new infections during and after treatment Limited information available regarding use in patients with COVID-19 and concomitant active serious infections Consider risks and benefits of treatment in COVID-19 patients with other concurrent infections Neutropenia or thrombocytopenia (RA, GCA, SSc-ILD, COVID-19) Associated with higher incidence of neutropenia and thrombocytopenia Treatment-related reduction in platelets was not associated with serious bleeding events Not recommended to initiate treatment for RA, GCA and SSc-ILD in patients with a platelet count <100,000/mm3 Not recommended for COVID-19 in patients with an ANC <1,000/mm3 or platelets count <50,000/mm3 counts If platelet count <50,000/mm3, treatment not recommended Monitor neutrophils or platelets 4-8 weeks after initiating therapy and q3months thereafter Hepatic injury RA or GCA Serious cases of hepatic injury with IV or SC therapy; some cases have resulted in liver transplant or death; onset for cases ranged from months to years after initiating tocilizumab For RA and GCA patients, obtain a liver test panel (ALT, AST, alkaline phosphatase, and total bilirubin) before initiating therapy, every 4-8 weeks after start of therapy for the first 6 months of treatment and every 3 months thereafter Not recommended to initiate in RA or GCA patients with elevated transaminases ALT or AST greater than 1.5x ULN In patients who develop elevated ALT or AST greater than 5x ULN, discontinue therapy; for recommended modifications based upon increase in transaminases Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice; if patient is found to have abnormal liver tests (eg, ALT >3x ULN, total bilirubin >2x ULN) Interrupt treatment and establish probable cause; once liver tests normalize, restart in patients with another explanation for liver test abnormalities PJIA or SJIA A similar pattern of liver enzyme elevation is noted with in the PJIA and SJIA populations Monitor liver test panel at the time of the second administration and thereafter every 4-8 weeks for PJIA and every 2-4 weeks for SJIA COVID-19 Patients hospitalized with COVID-19 may have elevated ALT or AST levels Multiorgan failure with liver involvement has been recognized as a complication of severe COVID-19 During randomized, controlled studies, tocilizumab was associated with increased incidence of transaminase elevations When deciding to administer tocilizumab, balance potential benefit against risks of acute treatment Not recommended in patients with COVID-19 who have elevated ALT or AST >10x ULN Monitor ALT/AST when used for COVID-19 according to current standard clinical practice Drug interactions overview Vaccines Do not coadminister with live vaccines (eg, MMR, intranasal influenza) IL-6 inhibition may interfere with the normal immune response to new antigens All patients, particularly those with PJIA and SJIA, should be current with their immunizations before initiating therapy CYP450 Inhibition of IL-6 signaling in RA patients treated with tocilizumab may restore CYP450 activities to higher levels than those in the absence of tocilizumab, and thereby increases metabolism of drugs that are CYP450 substrates Exercise caution when coadministering tocilizumab with drugs that are substrates of CYP3A4 where decrease in effectiveness is undesirable, (eg, oral contraceptives, lovastatin, atorvastatin) Effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy Pregnancy Insufficient data available in pregnant women to determine whether there is a drug-associated risk for major birth defects and miscarriage Pregnancy registry Monitors pregnancy outcomes in women exposed to tocilizumab during pregnancy Register or encourage patients and pregnant women to register themselves by calling 1-877-311-8972 Fetal/neonatal adverse reactions Monoclonal antibodies (eg, tocilizumab) are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant Consider risks and benefits before administering live or live-attenuated vaccines to infants exposed in utero Lactation No data available on the presence of tocilizumab in human milk, effects of the drug on the breastfed infant, or effects of the drug on milk production Maternal immunoglobulin G (IgG) is present in human milk If tocilizumab is transferred into human milk, effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to tocilizumab are unknownPregnancy 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 Interleukin-6 receptor antagonist; IL-6 is a pleiotropic proinflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes,