other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.ofatumumab SCMonitor Closely (1)ofatumumab SC, sarilumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.phenobarbitalMonitor Closely (1)sarilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.phenytoinMonitor Closely (1)sarilumab, phenytoin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.primidoneMonitor Closely (1)sarilumab, primidone. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.quinidineMonitor Closely (1)sarilumab, quinidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.quinineMonitor Closely (1)sarilumab, quinine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.rotavirus oral vaccine, liveSerious - Use Alternative (1)sarilumab, rotavirus oral vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.rozanolixizumabMonitor Closely (1)rozanolixizumab will decrease the level or effect of sarilumab 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)sarilumab, rubella vaccine. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.sirolimusMonitor Closely (1)sarilumab, sirolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.smallpox (vaccinia) vaccine, liveSerious - Use Alternative (1)sarilumab, smallpox (vaccinia) vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.tacrolimusMonitor Closely (1)sarilumab, tacrolimus. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.theophyllineMonitor Closely (1)sarilumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.tisagenlecleucelSerious - Use Alternative (1)sarilumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.trastuzumabMonitor Closely (1)trastuzumab, sarilumab. 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, sarilumab. 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.typhoid vaccine liveSerious - Use Alternative (1)sarilumab, typhoid vaccine live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.ublituximabMonitor Closely (1)ublituximab and sarilumab 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)sarilumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.valproic acidMonitor Closely (1)sarilumab, valproic acid. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.varicella virus vaccine liveSerious - Use Alternative (1)sarilumab, varicella virus vaccine live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.yellow fever vaccineSerious - Use Alternative (1)sarilumab, yellow fever vaccine. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.zoster vaccine liveSerious - Use Alternative (1)sarilumab, zoster vaccine live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections. The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.zoster vaccine recombinantMonitor Closely (1)sarilumab decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant. >10% ALT >ULN to ≤3 x ULN (38-43%) AST >ULN to ≤3 x ULN (27-30%) 1-10% Neutropenia (7-10%) ANC <1000/mm³ (4-6%) Injection site erythema (4-5%) Injection site pruritics (4-5%) Upper respiratory tract infection (3-4%) ALT >3x to 5x ULN (3-4%) Urinary tract infection (3%) Hypertriglyceridemia (1-3%) Leukopenia (0.9-2%) AST >3x to 5x ULN (1%) ALT>5x ULN (0.7-1%) Decreased platelet counts (0.7-1%) <1% ANC <500 /mm³ (0.7%) AST>5x ULN (0.2-0.7%) Black Box Warnings Serious infections Use of sarilumab increases risk for developing serious infections that may lead to hospitalization or death Opportunistic infections reported Most patients who developed infections were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids) Avoid use in patients with active infection Closely monitor for signs and symptoms of infection during treatment; if a serious infection develops, interrupt sarilumab therapy until the infection is controlled Consider the risks and benefits of using sarilumab before initiating in patients with chronic or recurrent infection; a history of opportunistic infections, underlying conditions, in addition to RA, that may predispose them to infection, have been exposed to tuberculosis, or lived in or traveled to areas of endemic tuberculosis or endemic mycoses Reported infections include Active tuberculosis, which may present with pulmonary or extrapulmonary disease; test for latent TB before and during therapy; treatment for latent infection should be initiated before sarilumab is started; closely monitor patients for the development of signs and symptoms of TB including patients who tested negative for latent TB infection prior to initiating therapy Invasive fungal infections (eg, candidiasis, pneumocystis); patients with invasive fungal infections may present with disseminated, rather than localized, disease Bacterial, viral, and other infections due to opportunistic pathogens Contraindications Documented hypersensitivity to drug or inactive ingredients Cautions Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported (see Black Box Warnings) GI perforations reported in clinical studies, primarily as complications of diverticulitis; GI perforation risk may be increased with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids Immunosuppression may result in an increased risk of malignancies Hypersensitivity reactions reported Not recommended with active hepatic disease or hepatic impairment Laboratory abnormalities Neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities reported (see Dosage Modifications) Assess platelet count prior to initiation of therapy and monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter Assess ALT/AST levels prior to initiation of therapy and monitor ALT and AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter; when clinically indicated, consider other liver function tests such as bilirubin Assess lipid parameters approximately 4-8 weeks following initiation of therapy, then at approximately 6-month intervals; manage patients according to clinical guidelines for the management of hyperlipidemia Drug interaction overview Live virus vaccines Avoid concurrent use of live virus vaccines, owing to potentially increased risk of infections The interval between live vaccinations and initiation of sarilumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents CYP450 substrates The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, IL-1, IL-6, IL-10, TNF-alpha, IFN) during chronic inflammation Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels