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Smallpox and Monkeypox Vaccine (Live)

Medically reviewed by Drugs.com. Last updated on Jun 9, 2023.

Index Terms

Pharmacologic Category

Pharmacology

Vaccination elicits humoral and cellular immune responses to orthopoxviruses. Smallpox and monkeypox vaccine is a live, third-generation smallpox vaccine containing Modified Vaccinia Ankara, which is replication deficient and cannot cause disease in humans or reproduce in human cells.

Use: Labeled Indications

Smallpox and monkeypox, prevention: Prevention of smallpox and monkeypox disease in adults determined to be at high risk for smallpox or monkeypox infection.

Note: Existing guidance for routine and postevent vaccination against smallpox are mostly specific to ACAM2000, a live vaccine containing replication-competent poxvirus strains. Consider the following Advisory Committee on Immunization Practices (ACIP) relevant guidance for the use of the live, replication-deficient vaccine (Jynneos) for routine vaccination of the following individuals (CDC [Petersen 2015]; CDC/ACIP [Petersen 2016]):

• Laboratory workers who directly handle cultures or animals that are contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains, or related orthopoxviruses capable of causing infections in humans (eg, monkeypox, cowpox, variola) and are immunosuppressed (eg, atopic dermatitis, HIV infection with CD4 cell counts between 50 to 199 cells/mm3, other immunocompromised state [solid organ transplantation within last 3 months, bone marrow transplant within the last 4 to 24 months, transplant recipients with active graft-versus-host disease, or current immunosuppressive therapy).

• Consideration may also be given for vaccination of health care personnel with allergy to the ACAM2000 vaccine or vaccine component who currently treat or anticipate treating patients with vaccinia virus infections or whose contact is limited to contaminated materials or administering ACAM2000 smallpox vaccine; adherence to appropriate infection prevention measures is also necessary.

For postevent smallpox vaccination, consider previous ACIP guidelines that recommend vaccination with a live, nonreplicating vaccine (eg, Jynneos) to patients exposed to smallpox virus and who are severely immunodeficient (eg, bone marrow transplant within the last 4 months, HIV with CD4 cell counts <50 cells/mm3, severe combined immunodeficiency, complete DiGeorge syndrome, other severely immunocompromised states requiring isolation). All other patients should receive postevent vaccination with a live, replication-competent vaccine (ACAM2000) (CDC [Petersen 2015]).

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Smallpox and monkeypox, prevention (primary immunization): SubQ: Two doses (0.5 mL per dose) separated by 4 weeks.

Detailed Smallpox and monkeypox vaccine dosage information

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Allow to thaw and reach room temperature before use. Do not use if particulate matter or discoloration is present (vaccine is a milky, light yellow to pale white suspension). Swirl gently for ≥30 seconds prior to use. Withdraw a 0.5 mL dose into a sterile syringe for injection.

Administration

For SubQ administration only, preferably into the upper arm. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope-related injuries, patients should be vaccinated while seated or lying down (ACIP [Ezeanolue 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Storage

Store intact vials frozen at -25°C to -15°C (-13°F to 5°F) and in the original package to protect from light. Once thawed, the vaccine is stable for 12 hours when stored at 2°C to 8°C (36°F to 46°F); do not refreeze.

Drug Interactions

Atoltivimab, Maftivimab, and Odesivimab: May diminish the therapeutic effect of Vaccines (Live). Management: Wait several months (3 to 6 months, and even as long as 11 months) after use of atoltivimab, maftivimab, and odesivimab before administering live vaccines. Consider therapy modification

Axicabtagene Ciloleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Axicabtagene Ciloleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for at least 6 weeks prior to initiation of lymphodepleting therapy, during axicabtagene ciloleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Brexucabtagene Autoleucel: May enhance the adverse/toxic effect of Vaccines (Live). Brexucabtagene Autoleucel may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live vaccines during and for 1 month after therapy with immunosuppressive doses of corticosteroids (equivalent to prednisone >2 mg/kg or 20 mg/day in persons over 10 kg for at least 2 weeks). Give live vaccines prior to therapy whenever possible. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Deflazacort: May enhance the adverse/toxic effect of Vaccines (Live). Deflazacort may diminish the therapeutic effect of Vaccines (Live). Management: Administer all vaccines according to immunization guidelines prior to initiating deflazacort. Live vaccines should be administered at least 4 to 6 weeks prior to initiating deflazacort. Consider therapy modification

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Non-US labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. US labeling states that safety and effectiveness of live vaccines administered with dimethyl fumarate has not been assessed. Monitor therapy

Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Guselkumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Immune Globulins: May diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Consider therapy modification

Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Rabies Immune Globulin (Human): May diminish the therapeutic effect of Vaccines (Live). Management: Avoid administering the measles vaccine within 4 months after administration of rabies immune globulin. Avoid administering other live vaccines within 3 months after administration of rabies immune globulin. Consider therapy modification

Risankizumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Siponimod: May enhance the adverse/toxic effect of Vaccines (Live). Siponimod may diminish the thrombocytopenic effect of Vaccines (Live). Management: Avoid administration of vaccine (live) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy and increased infection risk. Consider therapy modification

Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Tisagenlecleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, do administer a scheduled PPD skin test for at least 4-6 weeks following administration of the vaccine. Simultaneous administration of a parenteral live vaccine and PPD skin test is acceptable. Consider therapy modification

Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Monitor therapy

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination

Smallpox and monkeypox vaccine drug interactions (more detail)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Headache (35%), fatigue (30%), chills (10%)

Gastrointestinal: Nausea (17%)

Local: Pain at injection site (85%), erythema at injection site (61%), swelling at injection site (52%), induration at injection site (45%), itching at injection site (43%)

Neuromuscular & skeletal: Myalgia (43%)

1% to 10%:

Cardiovascular: Cardiac disorder (1% to 2%)

Miscellaneous: Fever (2%)

<1%: Abnormal T waves on ECG, ECG abnormality, increased ST segment on ECG, inversion T wave on ECG, palpitations, tachycardia, troponin increased in blood specimen

Smallpox and monkeypox vaccine side effects (more detail)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Ezeanolue 2017]).

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Ezeanolue 2017]).

Concurrent drug therapy issues:

• Vaccines: In order to maximize vaccination rates, the Advisory Committee on Immunization Practices (ACIP) generally recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (ACIP [Ezeanolue 2017]).

- For smallpox vaccine: May be given simultaneously with any inactive and most live vaccines. Varicella vaccine should be administered at least 4 weeks before or after smallpox vaccine, to help interpret any postvaccination rashes that may arise. Tuberculosis screening (purified protein derivative skin test) should be administered ≥1 month after smallpox vaccination, to avoid temporary false-negative test results.

Special populations:

• Altered immunocompetence: For management of postexposure to smallpox virus, vaccination with the live, nonreplicating vaccine (eg, Jynneos) is recommended in patients who are severely immunodeficient (including HIV infection with CD4 cell counts between 50 to 199 cells/mm3)(CDC/ACIP [Petersen 2015]). However, for routine immunization in applicable individuals, consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines (ACIP [Ezeanolue 2017]; IDSA [Rubin 2014]).

Dosage form specific issues:

• Gentamicin: Manufactured with gentamicin.

Other warnings/precautions:

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Ezeanolue 2017]).

Monitoring Parameters

Monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Ezeanolue 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies following vaccine administration. Maternal smallpox or monkeypox infection is associated with adverse maternal and fetal outcomes (Mbala 2017).

In general, live virus vaccines should not be used in pregnancy (ACIP [Ezeanolue 2017]). Refer to current guidelines for vaccinating pregnant females in pre-exposure and postevent settings.

Patient Education

What is this drug used for?

• It is used to prevent smallpox and monkeypox disease.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Injection site pain, redness, or swelling

• Itching

• Muscle pain

• Headache

• Nausea

• Loss of strength and energy

• Chills

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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