Imogam

Rabies Antitoxins and Immunoglobulins

 
NOTE: Immediately and thoroughly cleanse all bites and scratches with soap and water. Additionally, irrigate the wounds with a virucidal agent, such as povidone-iodine solution. Consider tetanus prophylaxis and measures to control bacterial infection if medically indicated.
 
NOTE: According to U.S. federal laws, the health care provider must record in the patient's permanent record the manufacturer, lot number, administration date, and the name and address of the person administering the rabies immune globulin, human RIG.
Inform the patient, guardian, or responsible adult of the benefits and risks of the rabies immune globulin, human RIG. The action is required by the National Childhood Vaccine Injury Act of 1986.
If the rabies immune globulin, human RIG has been previously given, question the patient or guardian about any symptoms or signs of an adverse reaction.
Ensure epinephrine is available for treatment of acute anaphylactic symptoms.
Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967. Also, report an adverse event to the manufacturer of the specific agent administered.

Visually inspect parenteral products for particulate matter and discoloration prior to administration. If either particulate matter or discoloration is present, discard the vial. HyperRAB is clear or slightly opalescent, and colorless to pale yellow or light brown. HyperRAB S/D is colorless to pale yellow or pink. Kedrab is a clear to opalescent liquid.
Do not mix rabies immune globulin, human RIG with any other product in the same syringe.
Prior to administration, clean skin over the injection site with a suitable cleansing agent.
Using a sterile syringe and needle remove the appropriate dose, based on body weight, from the single dose vials. A separate, sterile syringe and needle MUST be used for each patient.
Administer rabies immune globulin, human RIG at same time as first dose of rabies vaccine or up to 7 days after first dose of rabies vaccine.
Do not administer rabies immune globulin, human RIG in the same syringe or with the same needle as the rabies vaccine.
Never administer rabies immune globulin, human RIG at the same anatomical site as the rabies vaccine.
Infiltrate as much of the dose as possible in and around any detectable bite wounds. If using HyperRAB solution (i.e., 300 International Units/mL) and additional volume is needed to infiltrate the entire wound, dilute the solution with an equal volume of 5% Dextrose Injection. DO NOT dilute with normal saline.
Inject any remaining volume intramuscularly.

Administer any excess dose not able to be injected in and around the bite wounds IM, using a separate needle, at a site distant from the rabies vaccine administration site.
When the bite site is unknown or indeterminate (undetectable), administer the full dose IM at a site distance from the rabies vaccine administration site.
The preferred injection sites are the upper arm deltoid region, or in small children, the anterolateral aspect of the thigh. Unless the exposure site is the gluteal region, avoid administration into the gluteal region, where absorbance is unpredictable.
If a large IM volume is required (i.e., more than 2 mL for pediatric patients or more than 5 mL for adults), inject the total volume in divided doses at different sites.

Although there are no clinical efficacy data supporting subcutaneous administration of rabies immune globulin, human RIG, Kedrab may be administered subcutaneously in patients for whom IM injections are contraindicated (e.g., patients with uncorrectable bleeding disorders).

anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
nephrotic syndrome / Delayed / Incidence not known

hematoma / Early / 1.0-7.0
erythema / Early / 0-5.0
edema / Delayed / 0-5.0
pyuria / Delayed / 3.0-5.0
hematuria / Delayed / 2.0-4.0
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known

malaise / Early / 50.0-50.0
headache / Early / 8.0-50.0
fever / Early / 13.0-13.0
infection / Delayed / 9.0-10.0
myalgia / Early / 0-9.0
nasal congestion / Early / 8.0-8.0
flatulence / Early / 8.0-8.0
diarrhea / Early / 8.0-8.0
abdominal pain / Early / 1.0-8.0
vomiting / Early / 7.0-7.0
fatigue / Early / 2.0-7.0
dizziness / Early / 4.0-6.0
arthralgia / Delayed / 0-6.0
insomnia / Early / 0-5.0
nausea / Early / 4.0-4.0
injection site reaction / Rapid / Incidence not known
hypoesthesia / Delayed / Incidence not known
chills / Rapid / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known

HyperRAB, HyperRAB S/D, Imogam, KEDRAB

Rx

Parenteral gamma globulin prepared from plasma of donors hyperimmunized with rabies vaccine
Used for postexposure prophylaxis, along with the rabies vaccine, for persons suspected of rabies exposure
Not indicated if more than 7 days passed since rabies vaccine administration or in patients with confirmed adequate rabies antibody titer

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer.

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around any detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer. While some product labeling states that safety and efficacy are not established in pediatric patients, the products are considered appropriate, using the weight-based recommended dosing, for postexposure prophylaxis in all children by the ACIP.

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around any detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer. While some product labeling states that safety and efficacy are not established in pediatric patients, the products are considered appropriate, using the weight-based recommended dosing, for postexposure prophylaxis in all children by the ACIP.

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer.

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around any detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer.

20 International Units/kg as a single dose as soon as possible after exposure, infiltrating as much of the dose as possible into and around any detectable bite wounds; inject any remaining volume IM. Administer rabies immune globulin, human RIG concurrently with a full course of rabies vaccine. Do not administer rabies immune globulin, human RIG to any person with a history of complete preexposure or postexposure vaccination regimen and confirmed adequate antirabies titer.

No dosage adjustments are needed.

No dosage adjustments are needed.

Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Defer immunization with measles virus vaccine, live attenuated for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the measles virus vaccine, live attenuated is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration. (Major) Defer immunization with mumps virus vaccine, live for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the mumps virus vaccine, live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration. (Major) Defer immunization with rubella virus vaccine, live for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the rubella virus vaccine, live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration. (Major) Defer immunization with varicella-zoster virus vaccine, live for at least 5 months after rabies immune globulin, human RIG administration. Do not give immune globulins for 2 months after varicella-zoster virus vaccine, live administration unless immune globulin use outweighs the benefits of vaccination. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the varicella virus vaccine live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Defer immunization with measles virus vaccine, live attenuated for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the measles virus vaccine, live attenuated is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration. (Major) Defer immunization with mumps virus vaccine, live for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the mumps virus vaccine, live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration. (Major) Defer immunization with rubella virus vaccine, live for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the rubella virus vaccine, live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration.
Rabies Vaccine: (Minor) The rabies immune globulin, human RIG may be administered concurrently with, and up to 8 days after the rabies vaccine. The RIG and the rabies vaccine must be administered via separate syringes and at different anatomical site. Avoid administering RIG if more than 7 days have elapsed since administration of the rabies vaccine as this may impair rabies vaccine-induced active immunity. Additionally, RIG doses greater than the recommended 20 International Units/kg and repeat RIG doses should also be avoided as these too may partially suppress active production of antibodies by the rabies vaccine.
Rotavirus Vaccine: (Major) Defer immunization with rotavirus pentavalent live vaccine for 4 months after rabies immune globulin, human RIG administration. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the rotavirus pentavalent live vaccine is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration.
Varicella-Zoster Virus Vaccine, Live: (Major) Defer immunization with varicella-zoster virus vaccine, live for at least 5 months after rabies immune globulin, human RIG administration. Do not give immune globulins for 2 months after varicella-zoster virus vaccine, live administration unless immune globulin use outweighs the benefits of vaccination. Antibodies in RIG may interfere with the immune response to the live virus vaccine. According to the Advisory Committee on Immunization Practices, if the varicella virus vaccine live is administered less than 4 months after receipt of RIG, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. The repeat dose and serologic tests must be performed 4 months or more after RIG administration.

HyperRAB/HyperRAB S/D/Imogam/KEDRAB/Rabies Immune Globulin (Human) Intramuscular Inj Sol: 1mL, 150IU, 300IU
HyperRAB/Rabies Immune Globulin (Human) Infiltration Inj Sol: 1mL, 300IU

20 International Units/kg, via infiltration and IM, single dose.

20 International Units/kg, via infiltration and IM, single dose.

20 International Units/kg, via infiltration and IM, single dose.

20 International Units/kg, via infiltration and IM, single dose.

20 International Units/kg, via infiltration and IM, single dose.

20 International Units/kg, via infiltration and IM, single dose.

Rabies immune globulin, human RIG is administered in conjunction with the rabies vaccine to previously unvaccinated persons who have been exposed to the rabies virus. The purpose of RIG is to provide immediate, passive immunity until vaccine-induced active immunity is developed (i.e., approximately 1 week). In previously unimmunized persons, the role of rabies immune globulin, human RIG in establishing early, passive protection against the virus is key to protecting patients against the disease.
 
When a rabies immune globulin, human RIG dose of 20 International Units/kg is given simultaneously (but at a separate site) with the first dose of rabies vaccine, concentrations of passive rabies antibody are detected 24 hours after injection in all individuals. There is minimal interference with the immune response to the initial and subsequent doses of vaccine, including booster doses. However, the vaccine-induced immune response may be suppressed if patients receive repeated or excessive rabies immune globulin, human RIG doses, or if rabies immune globulin, human RIG is administered more than 1 week after the vaccine.

Rabies immune globulin, human RIG is administered intramuscularly and infiltrated into the inoculation site. KedRAB is not bioequivalent to comparator rabies immune globulin, human RIG when coadministered with a 5-dose rabies vaccine regimen; however, pharmacokinetic differences are not expected to affect clinical outcomes.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

For Imogam, HyperRAB, and HyperRAB S/D, 20 International Units/kg produced measurable passive rabies antibody concentrations within 24 hours in all subjects. Detection of these antibodies in the serum continued throughout the 21-day study period. In another study evaluating the pharmacokinetic parameters of KedRAB and a comparator RIG product, the median time for KedRAB to achieve maximum serum concentration (Tmax) was 7 days (range 3 to 14 days) and elimination half-life was about 17.9 days after a single dose of 20 International Units/kg; maximum plasma rabies virus neutralizing antibody (RVNA) concentration after the single KedRAB dose was 0.25 IU/mL. A plot of plasma RVNA titer concentration vs. time found that in both groups, plasma RVNA declined in a biphasic manner after the absorption phase was complete. When coadministered with a 5-dose rabies vaccine regimen, the peak plasma RVNA concentrations were 71.9 IU/mL and 53.9 IU/mL, respectively; median Tmax for both groups was 14 days (range, 14 to 49 days). Half-lives for KedRAB and the comparator RIG were 48.6 hours and 52.7 hours, respectively. Administration of a single 20 International Unit/kg rabies immune globulin, human RIG dose produces minimal interference with the endogenous immune response to the rabies vaccine series.

It is not known if rabies immune globulin, human RIG can cause fetal harm when administered during pregnancy or affect reproductive capacity. Rabies immune globulin, human RIG has not been studied in pregnant women, and animal developmental or reproduction toxicity studies with rabies immune globulin, human RIG have not been conducted. Use rabies immune globulin, human RIG during pregnancy only if clearly needed. Because of the potential consequences of inadequately treated rabies exposure, pregnancy is not considered a contraindication to use of postexposure prophylaxis regimens.

Immunoglobulins, such as the rabies immune globulin, are excreted in human milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for rabies immune globulin, human RIG and any potential adverse effects on the breast-fed child from rabies immune globulin, human RIG or from the mother's underlying condition. In general, given the potential severity of the illness, postexposure regimens using rabies immune globulin, human RIG in an exposed mother should be pursued, regardless of lactation status.