Spacing of Immunobiologics
Immune Globulin Preparations
When MMR and varicella vaccines are given with immune globulin (IG, also called immune serum globulin and immunoglobulin) preparations, antibody response can be diminished. IG preparations do not interfere with the immune response to yellow fever vaccine. The duration of inhibition of MMR and varicella vaccines is related to the dose of IG. Administration of MMR or its components and of varicella vaccines should be delayed 3-11 months after IG administration .
Table 1-2. Recommended intervals between administration of antibody-containing products and measles-containing vaccine or varicella vaccine1
| Indication |
Dose |
Recommended interval before measles or varicella vaccination |
| Tetanus (TIG) |
250 units (10 mg IgG/kg) IM 2 |
3 months |
| Hepatitis A (IG), duration of international travel |
| < 3-month stay |
0.02 mL/kg (3.3 mg IgG/kg) IM |
At least 5 months for varicella
At least 3 months for measles |
| > 3-month stay |
0.06 mL/kg (10 mg IgG/kg) IM |
At least 5 months for varicella
At least 3 months for measles |
| Hepatitis B prophylaxis (HBIG) |
0.06 mL/kg (10 mg IgG/kg) IM |
At least 3 months |
| Rabies prophylaxis (HRIG) |
20 IU/kg (22 mg IgG/kg) IM |
At least 3 months |
| Varicella prophylaxis (VZIG) |
125 units/10 kg (20-40 mg IgG/kg) IM (maximum 625 units) |
At least 5 months |
| Measles prophylaxis (IG) |
| Immunocompetent contact |
0.25 mL/kg (40 mg IgG/kg) IM |
3 - 5 months |
| Immunocompromised contact |
0.50 mL/kg (80 mg IgG/kg) IM |
6 months |
| Blood transfusion |
| Red blood cells (RBCs), washed |
10 mL/kg negligible IgG/kg) IV |
None |
| RBCs, adenine-saline added |
10 mL/kg (10 mg IgG/kg) IV |
At least 5 months for varicella
At least 3 months for measles |
| Packed RBCs (Hct 65%) 3 |
10 mL/kg (60 mg IgG/kg) IV |
At least 5 months for varicella
At least 5 months for measles |
| Plasma/platelet products |
10 mL/kg (160 mg IgG/kg) IV |
At least 5 months for varicella
At least 7 months for measles |
| Cytomegalovirus prophylaxis (CMV IGIV) |
variable |
At least 3 months |
| Respiratory syncytial virus (RSV) monoclonal antibody (Synagis) 4 |
15 mg/kg IM |
No data (or unknown) |
| RSV prophylaxis (RSV IGIV) |
750 mg/kg |
9 months |
| Intravenous immune globulin (IVIG) |
| Replacement therapy |
300-400 mg/kg IV |
8 months |
| Immune thrombocytopaenic purpura (ITP) |
400 mg/kg IV |
8 months |
| ITP |
1 gm/kg IV |
10 months |
| ITP or Kawasaki disease |
1.6 gm/kg IV - 2 gm |
11 months |
This table is adapted from the AAP Committee on Infectious Diseases. Recommended timing of routine measles immunisation for children who have recently received immune globulin preparations. Paediatrics. 1994.
1This table is not intended for determining the correct indications and dosage for the use of IG preparations. Unvaccinated people may not be fully protected against measles during the entire recommended interval, and additional doses of IG or measles vaccine may be indicated after measles exposure. Concentrations of measles antibody in an IG preparation can vary by manufacturer's lot. For example, fourfold or greater variation in the amount of measles antibody titers has been demonstrated in different IG preparations. Rates of antibody clearance after receipt of an immune globulin preparation can also vary. Recommended intervals are extrapolated from an estimated half-life of 30 days for passively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgG/kg.
2IG, immune globulin; IM, intramuscular; IV, intravenous
3Assumes a serum IgG concentration of 16 mg/mL.
4Contains only antibody to respiratory syncytial virus.
IG administration may become necessary for another indication after MMR or its individual components or varicella vaccines have been given. In such a situation, the IG may interfere with the immune response to the MMR or varicella vaccines. Vaccine virus replication and stimulation of immunity usually occur 2-3 weeks after vaccination. If the interval between administration of one of these vaccines and the subsequent administration of an IG preparation is 14 days or more, the vaccine need not be readministered. If the interval is <14 days, the vaccine should be readministered after the interval shown in Table 1-2, unless serologic testing indicates that antibodies have been produced. If administration of IG becomes necessary, MMR or its components or varicella vaccines can be administered simultaneously with IG, with the recognition that vaccine-induced immunity can be compromised. The vaccine should be administered in a body site different from that chosen for the IG injection. Vaccination should be repeated after the interval noted in Table 1-2, unless serologic testing indicates antibodies have been produced.
When IG is given with the first dose of hepatitis A vaccine (HAV), the proportion of recipients who develop protective levels of antibody is not affected, but antibody concentrations are lower. Because the final concentrations of anti-HAV are many times higher than those considered protective, this reduced immunogenicity is not expected to be clinically important. IG preparations interact minimally with other inactivated vaccines and toxoids. Therefore, other inactivated vaccines may be given simultaneously or at any time interval after or before an antibody-containing blood product is used. However, such vaccines should be administered at different sites from the IG (not from each other).
