Drug Interactions between measles virus vaccine / rubella virus vaccine and sars-cov-2 (covid-19) nvx-cov2373 vaccine, recombinant

ADJUST DOSING INTERVAL: If multiple live, attenuated parenteral viral or bacterial vaccines are not given on the same day, but are administered within 28 days of each other, the immune response to the second live parenteral vaccine may be diminished by the immune response to the first. The exact mechanism of this interaction is unknown, but may involve competition for cellular receptors, competition for molecular substrates required for replication, and/or induction of inhibitory host proteins like interferon. Clinical data are limited and sometimes conflicting. One randomized clinical trial in Brazil was conducted in 12-month-old children (n=1769) receiving routine vaccinations. Volunteers were randomized to receive simultaneous yellow fever (YF) and measles, mumps, rubella (MMR) vaccines or to receive YF 30 days after the MMR vaccine. Subjects who received both vaccines simultaneously had lower seroconversion rates for rubella, YF, and mumps than those vaccinated 30 days apart (90% vs. 97%, 70% vs. 87%, and 62% vs. 71%, respectively). Seroconversion rates for measles were unaffected (>98% in both groups). Geometric mean titers (GMT) for rubella and YF were approximately three times higher in those who were vaccinated 30 days apart. However, a different randomized, non-inferiority trial in healthy one-year-old children in Argentina (n=738), which evaluated coadministration of MMR and YF vaccines compared to MMR followed by the YF vaccine 28 to 35 days later, or YF followed by the MMR vaccine 28 to 35 days later, reported that effective seroconversion was achieved when the two vaccines were administered concurrently. This study did note that antibody levels for rubella and YF were significantly lower following co-administration. A separate study conducted in two U.S. health maintenance organizations found that the risk for varicella vaccine failure (defined as varicella disease in a vaccinated individual) was three times higher in those who received the varicella vaccine within 28 days of the MMR vaccine, when compared to those who received the varicella vaccine more than 28 days after MMR vaccination. Clinical data are not available for all possible live vaccine combinations in all age groups.

MANAGEMENT: The U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices generally recommends that doses of live, attenuated parenteral viral or bacterial vaccines that are not administered simultaneously (using different injection sites and separate needles and syringes for injectable products not formulated as combinations) should be separated by an interval of at least 28 days. If the live vaccines involved are separated by less than 4 weeks, the second vaccine administered should not be counted and the dose should be repeated at least 4 weeks later. Oral vaccines (e.g., Ty21a typhoid vaccine and rotavirus) can be administered simultaneously with or at any interval before or after other live vaccines if indicated. The United Kingdom's Green Book recommends always separating the YF and MMR vaccines by at least 4 weeks, unless rapid protection is required in which case they advise considering an additional dose of the MMR vaccine. Additionally, the Canadian Immunization Guide recommends avoiding simultaneous administration of a first-generation smallpox vaccine with a varicella-containing vaccine; suggesting that if both are needed, the varicella-containing vaccine should be given at least 4 weeks before or after the first-generation smallpox vaccine. Current local immunization guidelines and prescribing information for individual vaccines should be consulted for specific recommendations.

MONITOR: The safety, immunogenicity, and efficacy of SARS-CoV-2 (COVID-19) vaccines when administered concurrently with other vaccines have not been adequately assessed. Data from a limited number of adult participants (n=217 Nuvaxovid; n=214 placebo) in an exploratory clinical trial sub-study showed that coadministration of dose 1 of the SARS-CoV-2 (COVID-19) NVX-CoV2373 recombinant vaccine (Nuvaxovid) and inactivated influenza vaccine on the same day resulted in a 30% lower binding antibody response to SARS-CoV-2 as assessed by an anti-spike IgG assay, with no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. However, the seroconversion rates of these participants who received both vaccines together were similar to those of participants in the main study who received Nuvaxovid alone. The clinical significance of these findings is unknown. Concomitant administration of Nuvaxovid with other vaccines has not been studied. Extensive experience with non-COVID-19 vaccines has demonstrated that immunogenicity and adverse event profiles are generally similar when vaccines are administered simultaneously compared to when they are administered alone. Studies that specifically compared coadministration of COVID-19 vaccines and seasonal influenza vaccines with separate administration of these vaccines found similar levels of immunogenicity and similar or slightly higher reactogenicity, while no specific safety concerns were identified. Taken altogether, the data suggest that COVID-19 vaccines may be coadministered with most other vaccines when necessary.

MANAGEMENT: The U.S. Centers for Disease Control and Prevention (CDC) advises that COVID-19 vaccines and other vaccines may now be administered without regard to timing, including simultaneous administration on the same day as well as coadministration within 14 days (previously, COVID-19 vaccines were recommended to be administered alone, with a minimum interval of 14 days before or after administration of any other vaccines). When deciding whether to coadminister another vaccine(s) with COVID-19 vaccines, providers should consider whether the patient is behind or at risk of becoming behind on recommended vaccines, their risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and the reactogenicity profile of the vaccines. COVID-19 vaccines should not be mixed with any other vaccine in the same syringe or vial. If multiple vaccines are administered during a single visit, each injection should be administered at a different injection site. For adolescents and adults, the deltoid muscle can be used for more than one intramuscular injection, but each injection should be separated by 1 inch or more if possible. It is also advisable to administer COVID-19 vaccines and vaccines that may be more likely to cause a local reaction (e.g., tetanus toxoid-containing and adjuvanted vaccines) in different limbs whenever possible.

MONITOR: The safety, immunogenicity, and efficacy of SARS-CoV-2 (COVID-19) vaccines when administered concurrently with other vaccines have not been adequately assessed. Data from a limited number of adult participants (n=217 Nuvaxovid; n=214 placebo) in an exploratory clinical trial sub-study showed that coadministration of dose 1 of the SARS-CoV-2 (COVID-19) NVX-CoV2373 recombinant vaccine (Nuvaxovid) and inactivated influenza vaccine on the same day resulted in a 30% lower binding antibody response to SARS-CoV-2 as assessed by an anti-spike IgG assay, with no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. However, the seroconversion rates of these participants who received both vaccines together were similar to those of participants in the main study who received Nuvaxovid alone. The clinical significance of these findings is unknown. Concomitant administration of Nuvaxovid with other vaccines has not been studied. Extensive experience with non-COVID-19 vaccines has demonstrated that immunogenicity and adverse event profiles are generally similar when vaccines are administered simultaneously compared to when they are administered alone. Studies that specifically compared coadministration of COVID-19 vaccines and seasonal influenza vaccines with separate administration of these vaccines found similar levels of immunogenicity and similar or slightly higher reactogenicity, while no specific safety concerns were identified. Taken altogether, the data suggest that COVID-19 vaccines may be coadministered with most other vaccines when necessary.

MANAGEMENT: The U.S. Centers for Disease Control and Prevention (CDC) advises that COVID-19 vaccines and other vaccines may now be administered without regard to timing, including simultaneous administration on the same day as well as coadministration within 14 days (previously, COVID-19 vaccines were recommended to be administered alone, with a minimum interval of 14 days before or after administration of any other vaccines). When deciding whether to coadminister another vaccine(s) with COVID-19 vaccines, providers should consider whether the patient is behind or at risk of becoming behind on recommended vaccines, their risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and the reactogenicity profile of the vaccines. COVID-19 vaccines should not be mixed with any other vaccine in the same syringe or vial. If multiple vaccines are administered during a single visit, each injection should be administered at a different injection site. For adolescents and adults, the deltoid muscle can be used for more than one intramuscular injection, but each injection should be separated by 1 inch or more if possible. It is also advisable to administer COVID-19 vaccines and vaccines that may be more likely to cause a local reaction (e.g., tetanus toxoid-containing and adjuvanted vaccines) in different limbs whenever possible.