been studied and vaccination with live virus vaccines is not recommended.rituximab-hyaluronidaseSerious - Use Alternative (1)rituximab-hyaluronidase, smallpox (vaccinia) vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.sarilumabSerious - 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.satralizumabSerious - Use Alternative (1)satralizumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. ive vaccines are not recommended during treatment. Administer all immunizations according to immunization guidelines. At least 4 weeks before initiating for live or live-attenuated vaccines.secukinumabContraindicated (1)secukinumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Contraindicated. Secukinumab may interfere with immune response of live vaccines and increase risk for vaccine adverse effects; prior to initiating secukinumab, complete all age appropriate immunizations.siponimodSerious - Use Alternative (1)siponimod decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Pause vaccinations beginning 1 week before initiating siponimod and for 4 weeks after stopping treatment. Coadministration with live attenuated vaccines may increase infection risk.sirolimusSerious - Use Alternative (1)sirolimus 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)tacrolimus decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.tecovirimatMonitor Closely (1)tecovirimat, smallpox (vaccinia) vaccine, live. Other (see comment). Use Caution/Monitor. Comment: No vaccine-drug interaction studies have been performed in humans. Some animal studies suggest a reduced immune response to smallpox vaccine if coadministered with tecovirimat. The clinical impact of this interaction on vaccine efficacy is unknown.temsirolimusSerious - Use Alternative (1)temsirolimus decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunosuppressants also increase risk of infection with concomitant live vaccines.teplizumabSerious - Use Alternative (1)teplizumab decreases effects of smallpox (vaccinia) vaccine, live by Other (see comment). Avoid or Use Alternate Drug. Comment: Administer all age-appropriate vaccinations before starting teplizumab. Live-attenuated vaccines are not recommended within 8 weeks before teplizumab treatment, during treatment, or up to 52 weeks after treatment.tetanus immune globulin (TIG)Monitor Closely (1)tetanus immune globulin (TIG) decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Use Caution/Monitor. Separate by 3 months.tildrakizumabSerious - Use Alternative (1)tildrakizumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Before initiating tildrakizumab therapy, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with tildrakizumab. No data are available on the response to live or inactive vaccines.tisagenlecleucelSerious - Use Alternative (1)tisagenlecleucel decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live virus vaccines is not recommended for at least 6 weeks before starting lymphodepleting chemotherapy, during CAR-T cell treatment, and until immune recovery following treatment. .tocilizumabSerious - 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.tralokinumabSerious - Use Alternative (1)tralokinumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live vaccines. Before starting tralokinumab, complete age appropriate immunizations.triamcinolone acetonide injectable suspensionSerious - Use Alternative (1)triamcinolone acetonide injectable suspension decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Corticosteroids also increase risk of infection with concomitant live vaccines.ublituximabMonitor Closely (1)ublituximab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Administer all immunizations according to immunization guidelines at least 4 weeks before initiating ublituximab for live or live-attenuated vaccines and, whenever possible, at least 2 weeks before initiating for non-live vaccines. Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion. Do not administer live or live-attenuated vaccines to infants of mothers exposed to ublituximab during pregnancy, before confirming recovery of B-cell counts as measured by CD19+ B cells.upadacitinibSerious - Use Alternative (1)upadacitinib decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.ustekinumabContraindicated (1)ustekinumab decreases effects of smallpox (vaccinia) vaccine, live by Mechanism: pharmacodynamic antagonism. Contraindicated. Prior initiating therapy, patients should receive all age-appropriate immunizations as recommended by current guidelines. Immunosuppressants also increase risk of infection with concomitant live vaccines.Serious - Use Alternative (1)ustekinumab decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Prior initiating therapy, patients should receive all age-appropriate immunizations as recommended by current guidelines. Immunosuppressants also increase risk of infection with concomitant live vaccines.vaccinia immune globulin intravenousMonitor Closely (1)vaccinia immune globulin intravenous decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Use Caution/Monitor. Defer live vaccines for 3 months after immune globulin administration.vedolizumabSerious - Use Alternative (1)vedolizumab decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of live virus vaccines while receiving vedolizumab; live vaccines may be administered concurrently with vedolizumab only if the benefits outweigh the risks.voclosporinSerious - Use Alternative (1)voclosporin decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Immunosuppressants also increase risk of infection with concomitant live vaccines. Avoid live vaccines for at least 3 months after immunosuppressants. >10% Injection site pruritus (82-92%) Injection site erythema (61-74%) Injection site pain (37-67%) Blood and lymphatic system disorders (22-59%) Lymph node pain (19-57%) Headache (32-50%) Injection site swelling (28-48%) Fatigue (34-48%) Myalgia (27-46%) Malaise (28-37%) Feeling hot (20-32%) GI disorders (23-31%) Erythema (22-24%) Rigors (12-21%) Nausea (10-19%) Diarrhea (12-16%) Decreased exercise tolerance (8-11%) Rash (6-11%) 1-10% Constipation (6%) Vomiting (3-5%) Dyspnea (3-4%) Lymphadenopathy (6-8%) Black Box Warnings Suspected cases of myocarditis and/or pericarditis have been observed in healthy adult primary vaccinees Encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), and eczema resulting in permanent sequelae or death, ocular complications, blindness, and fetal death have occurred following either primary vaccination or revaccination with smallpox vaccines This is a live vaccinia virus that can be transmitted to persons who have close contact with the recipient of the vaccine, and the risks in contacts are the same as those for the vaccinated patient The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection Risks increased with the following conditions These risks of severe adverse effects are increased with the following conditions and may result in severe disability, permanent neurologic sequelae, and/or death Cardiac disease or a history of cardiac disease Eye disease treated with topical steroids Congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications Eczema and persons with a history of eczema or other acute or chronic exfoliative skin conditions Infants aged <1 yr Pregnancy Contraindications There are very few absolute contraindications to the vaccine for those who are at high risk for smallpox The risk for experiencing serious vaccination complications must be weighed against the risks for experiencing a potentially fatal smallpox infection; see Cautions for persons who are at higher risk of experiencing serious vaccination complications Severe immune deficiency Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems Individuals with severe immunodeficiency who are not expected to benefit from the vaccine should not receive ACAM2000 These individuals may include those who are undergoing bone marrow transplantation or individuals with primary or acquired immunodeficiency who require isolation Cautions Serious complications may follow vaccination and may include myocarditis and/or pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia (vaccinia necrosum), generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson syndrome), eczema vaccinatum, blindness, and fetal death in pregnant women; these complications may rarely lead to severe disability, permanent neurological sequelae, and death Ischemic cardiac events and nonischemic, dilated cardiomyopathy have been reported following smallpox vaccination; relationship to the vaccine is unknown Accidental infection of the eye (ocular vaccinia) may result in ocular keratitis, corneal scarring, and blindness Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems, including those with leukemia, lymphoma, organ transplantation, generalized malignancy, HIV/AIDS, cellular or humoral immune deficiency, radiation therapy, or treatment with antimetabolites, alkylating agents, high-dose corticosteroids (>10 mg prednisone/day or equivalent for ≥2 weeks), or other immunomodulatory drugs; contraindicated in individuals with severe immunodeficiency (see Contraindications) Persons with eczema of any description such as, atopic dermatitis, neurodermatitis, and other eczematous conditions, regardless of severity of the condition, or persons who have a history of these conditions at any time in the past, are at higher risk of developing eczema vaccinatum Not studied in infants or children; risk of serious adverse events is higher in infants; vaccinated persons who have close contact with infants (eg, breastfeeding women), must take precautions to avoid inadvertent transmission of live vaccinia virus to infants Not studied in pregnant women; live vaccinia virus vaccines can cause fetal vaccinia and fetal death; if administered during pregnancy, the vaccinee should be apprised of the potential hazard to the fetus; pregnant women who are close contacts of vaccinees may be at increased risk because live vaccinia virus can shed and be transmitted to close contacts Contains neomycin and polymyxin B; caution with history of allergy to these components on Vaccinia immune globulin (VIG) is indicated for certain complications of vaccination live vaccinia virus smallpox vaccine; if VIG is needed or additional information is required, physicians should contact the CDC at (404) 639-3670 (M-F) or (404) 639-2888 evenings/weekends The most important measure to prevent inadvertent auto-inoculation and contact transmission from vaccinia vaccination is thorough hand washing after changing the bandage or after any other contact with the vaccination site Avoid blood and organ donation for at least 30 days following vaccination Pregnancy Pregnancy Category: D; has not been studied in pregnant women The only setting in which vaccination of pregnant women should be considered is when exposure to smallpox is considered likely Live vaccinia virus vaccines can cause fetal harm when administered to a pregnant woman; congenital infection, principally occurring during the first trimester, has been observed after vaccination with live vaccinia smallpox vaccines, although the risk may be low Generalized vaccinia of the fetus, early delivery of a stillborn infant, or a high risk of perinatal death has been reported If this vaccine is used during pregnancy, or if the vaccinee lives in the same household with or has close contact with a pregnant women, the vaccinee should be apprised of the potential hazard to the fetus Lactation Not known if excreted in breast milk, not recommended for nursing women in non-emergency situations Live vaccinia virus can be inadvertently transmitted from a lactating mother to her infant Infants are at high risk of developing serious complications from live vaccinia smallpox vaccinationPregnancy 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 Lyophilized preparation of live vaccinia virus; vaccinia virus is similar to the variola (smallpox) virus; immunity to both virus achieved with induced vaccinia virus infection by stimulating the production of neutralizing antibodies Conveys active immunity via stimulation of production of endogenously produced antibodies Pharmacokinetics Onset: Neutralizing antibodies appear 15-20 days after vaccination; appearance of neutralizing antibodies may occur 7 days following vaccination Vaccine Preparation Reconstitution Reconstitute only with diluent provided Removed vial from cold storage and bring to room temperature before reconstitution Remove