Pharmacology
Mechanism of Action
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.
Dosage and Administration
Dosing: Adult
Smallpox and monkeypox, prevention (primary immunization): SubQ: Two doses (0.5 mL per dose) separated by 4 weeks.
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
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
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification
Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination
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: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification
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, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. 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. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. 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
Adverse Reactions
>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
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
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.
Frequently reported side effects of this drug
- Injection site pain, redness, or swelling
- Itching
- Muscle pain
- Headache
- Nausea
- Loss of strength and energy
- Chills
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
