Drug Interaction Report

ADJUST DOSING INTERVAL: Administration of immune globulin (Ig) preparations concurrently with, shortly before, or shortly after a live viral vaccine may interfere with the immune response to the vaccination. Ig preparations often contain significant amounts of antibodies to infectious agents that are prevalent in the general population, such as measles or varicella zoster, due to natural disease or following vaccination. The passive transfer of these antibodies close to the administration of the vaccine may prevent replication of the vaccine virus and stimulation of immunity. Likewise, vaccine virus replication and stimulation of immunity generally occurs 1 to 2 weeks after vaccination with a live, attenuated viral vaccine. Receipt of an antibody-containing Ig preparation following immunization with a live, attenuated viral vaccine during this time frame could interfere with the stimulation of immunity. In general, there appears to be minimal to no interaction between Ig preparations or blood products and the yellow fever vaccine, some live oral vaccines (rotavirus, typhoid), the live, attenuated influenza vaccine (LAIV), and the Bacille Calmette-Guerin (BCG) vaccine. This interaction may be affected by the source used to create the Ig or blood product and the vaccinations impacted may vary from country to country. Data on the immunogenicity and safety of all vaccinations with, shortly before, or shortly after the administration of all the different Ig preparations are not available.

MANAGEMENT: In general, live, attenuated viral or bacterial vaccine administration should be separated from immune globulin (Ig) preparations by either delaying the vaccine until the passive antibodies received from the Ig product have degraded (product- and dose-dependent), or delaying the Ig product until the vaccine has stimulated immunity. If rapid protection is required, vaccination should proceed, but additional dose(s) of the vaccine and/or laboratory testing to ensure vaccine efficacy may be advised. Immunization guidelines vary by country and may include exceptions to this general rule, along with other specific recommendations. According to the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, measles- and varicella-containing vaccines may be administered either 2 weeks prior to, or 3 to 11 months following the receipt of an antibody-containing Ig product, with timing dependent upon the product and dosage administered. They also recommend against delaying measles, mumps, rubella (MMR), varicella (V), or MMRV vaccination in postpartum women who received anti-Rho(D) globulin or any other blood product during the last trimester of pregnancy or at delivery, though testing for immunity to rubella and/or measles at least 3 months after vaccination may be appropriate. In addition, administration of the dengue vaccine (including pre-vaccination testing) should be delayed by 12 months in those who have received blood products or other Ig preparations. Local guidelines and prescribing information for the products involved should be consulted for further recommendations.

ADJUST DOSING INTERVAL: Administration of immune globulin (Ig) preparations concurrently with, shortly before, or shortly after a live viral vaccine may interfere with the immune response to the vaccination. Ig preparations often contain significant amounts of antibodies to infectious agents that are prevalent in the general population, such as measles or varicella zoster, due to natural disease or following vaccination. The passive transfer of these antibodies close to the administration of the vaccine may prevent replication of the vaccine virus and stimulation of immunity. Likewise, vaccine virus replication and stimulation of immunity generally occurs 1 to 2 weeks after vaccination with a live, attenuated viral vaccine. Receipt of an antibody-containing Ig preparation following immunization with a live, attenuated viral vaccine during this time frame could interfere with the stimulation of immunity. In general, there appears to be minimal to no interaction between Ig preparations or blood products and the yellow fever vaccine, some live oral vaccines (rotavirus, typhoid), the live, attenuated influenza vaccine (LAIV), and the Bacille Calmette-Guerin (BCG) vaccine. This interaction may be affected by the source used to create the Ig or blood product and the vaccinations impacted may vary from country to country. Data on the immunogenicity and safety of all vaccinations with, shortly before, or shortly after the administration of all the different Ig preparations are not available.

MANAGEMENT: In general, live, attenuated viral or bacterial vaccine administration should be separated from immune globulin (Ig) preparations by either delaying the vaccine until the passive antibodies received from the Ig product have degraded (product- and dose-dependent), or delaying the Ig product until the vaccine has stimulated immunity. If rapid protection is required, vaccination should proceed, but additional dose(s) of the vaccine and/or laboratory testing to ensure vaccine efficacy may be advised. Immunization guidelines vary by country and may include exceptions to this general rule, along with other specific recommendations. According to the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, measles- and varicella-containing vaccines may be administered either 2 weeks prior to, or 3 to 11 months following the receipt of an antibody-containing Ig product, with timing dependent upon the product and dosage administered. They also recommend against delaying measles, mumps, rubella (MMR), varicella (V), or MMRV vaccination in postpartum women who received anti-Rho(D) globulin or any other blood product during the last trimester of pregnancy or at delivery, though testing for immunity to rubella and/or measles at least 3 months after vaccination may be appropriate. In addition, administration of the dengue vaccine (including pre-vaccination testing) should be delayed by 12 months in those who have received blood products or other Ig preparations. Local guidelines and prescribing information for the products involved should be consulted for further recommendations.

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.