Drug Interactions between allogeneic processed thymus tissue and measles virus vaccine / rubella virus vaccine

GENERALLY AVOID: The administration of live, attenuated viral or bacterial vaccines or live, attenuated virus or bacteria as oncolytic immunotherapy to patients with congenital athymia who have received an allogenic thymocyte-depleted thymus tissue implant but have not yet developed sufficient immune function may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus or bacteria in the presence of inadequate immune competence. Immunizations in patients with congenital athymia have not been shown to be effective prior to the development of immune function post-implant. In addition, immunizations may trigger cytopenias prior to and in the first year after implantation. A review of culture thymus tissue implant program conducted in children with complete DiGeorge anomaly (a condition where children have congenital athymia) in the United States stated that live vaccines were only administered once patients had ceased immunosuppressive therapy(ies) and demonstrated the capacity to mount an immune response to inactivated, killed, or otherwise noninfectious vaccines. The time to development of sufficient immune function is generally 6 to 12 months after treatment with the allogenic thymocyte-depleted thymus tissue implant but may take up to 2 years in some patients.

MANAGEMENT: The administration of live attenuated vaccines or live, attenuated virus or bacteria (as oncolytic immunotherapy) to patients who have received allogenic thymocyte-depleted thymus tissue implant is not recommended. Specifically, the manufacturer recommends that live attenuated vaccines should be avoided until specific immune function criteria are met, including that they have met the criteria for inactivated vaccines and received vaccinations with inactivated agents: that the total CD4+ T cell count is greater than 200 cells/mm3, that there are more CD4+ T cells than CD8+ T cells, as well as the discontinuation of immunosuppressive therapy(ies) and immunoglobulin (IgG) replacement therapy. In addition, the manufacturer advises that no other vaccine (live or inactivated), apart from the inactivated influenza vaccine should be administered within 6 months after administration of a measles-containing vaccine, or within a 2-month period after administration of a varicella-containing vaccine. Verification of immune response is also advised, particularly with respect to varicella- and measles-containing vaccines. The product labeling should be consulted for further recommendations.

GENERALLY AVOID: The administration of live, attenuated viral or bacterial vaccines or live, attenuated virus or bacteria as oncolytic immunotherapy to patients with congenital athymia who have received an allogenic thymocyte-depleted thymus tissue implant but have not yet developed sufficient immune function may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus or bacteria in the presence of inadequate immune competence. Immunizations in patients with congenital athymia have not been shown to be effective prior to the development of immune function post-implant. In addition, immunizations may trigger cytopenias prior to and in the first year after implantation. A review of culture thymus tissue implant program conducted in children with complete DiGeorge anomaly (a condition where children have congenital athymia) in the United States stated that live vaccines were only administered once patients had ceased immunosuppressive therapy(ies) and demonstrated the capacity to mount an immune response to inactivated, killed, or otherwise noninfectious vaccines. The time to development of sufficient immune function is generally 6 to 12 months after treatment with the allogenic thymocyte-depleted thymus tissue implant but may take up to 2 years in some patients.

MANAGEMENT: The administration of live attenuated vaccines or live, attenuated virus or bacteria (as oncolytic immunotherapy) to patients who have received allogenic thymocyte-depleted thymus tissue implant is not recommended. Specifically, the manufacturer recommends that live attenuated vaccines should be avoided until specific immune function criteria are met, including that they have met the criteria for inactivated vaccines and received vaccinations with inactivated agents: that the total CD4+ T cell count is greater than 200 cells/mm3, that there are more CD4+ T cells than CD8+ T cells, as well as the discontinuation of immunosuppressive therapy(ies) and immunoglobulin (IgG) replacement therapy. In addition, the manufacturer advises that no other vaccine (live or inactivated), apart from the inactivated influenza vaccine should be administered within 6 months after administration of a measles-containing vaccine, or within a 2-month period after administration of a varicella-containing vaccine. Verification of immune response is also advised, particularly with respect to varicella- and measles-containing vaccines. The product labeling 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.