Rabies Post-Exposure Prophylaxis (RPEP) of Previously Unimmunized Individuals

RPEP should be instituted immediately. This consists of rabies immune globulin (RabIg) and 4 to 5 doses of rabies vaccine that should be administered as closely as possible to the recommended schedule (see below).

Please note the importance of appropriate documentation of RPEP, including the exact location of the wound(s), as well as the exact anatomic location(s) of RabIg administration and vaccine administration and their volume/dosage and lot numbers.

Rabies immune globulin (RabIg) administration

Rabies immune globulin (RabIg) provides immediate passive antibody protection until the exposed person mounts an immune response to the rabies vaccine. These protective antibodies have a half-life of only approximately 21 days. The most effective use of RabIg is in the wound. Correctly administered at the wound site, RabIg neutralizes the virus at the wound site within a few hours. RabIg should be administered as soon as possible after exposure, typically on the same day as the first dose of rabies vaccine (day 0).

• For multiple wound sites, divide the RabIg into separate syringes and needles for each site.
• As much RabIg should be infiltrated into and around each wound as is anatomically feasible, taking care not to let any RabIg escape from the wound. If possible, the FULL dose should be infiltrated into the wound(s).
• Certain anatomical sites must be infiltrated carefully (e.g., fingers, toes) to avoid increased pressures in the tissue compartment. (See Physician Resources: “Is injecting a finger with rabies immunoglobulin dangerous?”)
• If the calculated volume of the dose of RabIg is insufficient to infiltrate all wounds, the RabIg (specifically, HyperRAB and Imogam) can be diluted according to manufacturers’ instructions in order to provide the full amount of RabIg required for thorough infiltration of all wounds.
• If the entire calculated dose of RabIg cannot be infiltrated anatomically around the wound or site of exposure, give the remainder of the dose intramuscularly (you can use the wounded limb), but reserve a limb free of RabIg, in which to give rabies vaccine. 
• Keep in mind that rabies vaccine should NEVER be injected into the gluteal region/buttocks due to the uncertainty of ensuring deposition of the entire vaccine dose well into a muscle body (as opposed to adipose tissue). Similarly, residual RabIg should NOT be administered intramuscularly in the gluteal area because of the risk of sciatic nerve injury and diminished passive protection due to unreliable absorption; however, RabIg may be infiltrated in the gluteal area if that is an exposure site.
• If the site of the wound is not identifiable (for example, some bat exposures or healed wounds), the entire dose should be administered intramuscularly. Reserve a limb free of RabIg, in which to give rabies vaccine.
• If the volume of RabIg is large, it might be necessary to use the same muscle to administer more than one injection. If this is the case, the distance separating the two injections should be between 2.5 to 5.1 cm (1 to 2 inches).
  • IMPORTANT: do NOT administer the rabies vaccine in the same anatomical area as RabIg.
  • Example: if wound site is on right hand or arm, administer vaccine into left deltoid muscle.
  • Rabies vaccine and RabIg should never be mixed in the same syringe.

As of August 2019, RabIg will be available in 2 formulations:

• 2 mL vials containing 150 IU/mL; or
• 1 mL vials containing 300 IU/mL.  

Please ensure the appropriate formula specific to the RabIg formulation being provided is used to calculate the dose required for the individual.

	For 2 mL vials containing 150 IU/mL RabIg: 20 IU/kg x (client wt in kg) ÷ 150 IU/mL = dose in mL  (dose in mL ÷ 2 mL/vial = # of vials to order) 9.09 IU/lb x (client wt in lb) ÷ 150 IU/mL = dose in mL (dose in mL÷ 2 mL/vial = # of vials to order) OR Wt (____kg) X 0.133 mL/kg =___ mL of RabIg Ex: A 70 kg adult would require 9.31 mL of RabIg: Wt (70kg) x 0.133 mL/Kg = 9.31 mL of RabIg
	For 1 mL vials containing 300 IU/mL RabIg: 20 IU/kg x (client wt in kg) ÷ 300 IU/mL = dose in mL  (dose in mL ÷ 1 mL/vial = # of vials to order ) 9.09 IU/lb x (client wt in lb) ÷ 300 IU/mL = dose in mL (dose in mL÷ 1 mL/vial = # of vials to order) OR Wt (____kg) X 0.067 mL/kg =___ mL of RabIg Ex: A 70 kg adult would require 4.69 mL of RabIg: Wt (70kg) x 0.067 mL/Kg = 4.69 mL of RabIg

Note that while the dose in mL to be administered will be different depending on which formulation of RabIg is being used, the number of vials to be dispensed will be the same.

Please use the Table below to determine how many vials are to be ordered:

PLEASE NOTE THAT THE FINAL VIAL MAY NOT NEED TO BE FULLY USED. Ensure only the total calculated dosage is administered. OPH will provide the appropriate number of vials according to the dosage calculation above. There may be some RabIg remaining in one of the vials after administration: discard the remainder of the RabIg. DO NOT EXCEED THE CALCULATED DOSE, as this might interfere with the immune response to the rabies vaccine.

If RabIg has not been administered as recommended at the initiation of the rabies vaccine series, it should be administered up to and including 7 days after vaccine initiation, but it should not be administered after that time (i.e., day 8 and beyond) since vaccine-induced antibodies begin to appear within one week. Delayed RabIg administration should still preferably be in the site(s) of the wound(s), even if partial healing has taken place.

Rabies Vaccine

In Canada, there are two active rabies vaccines that are currently approved for use. Imovax® (Sanofi Pasteur Ltd.) is prepared from rabies virus grown in human diploid cell culture (HDCV). RabAvert® (Novartis) is prepared from rabies virus grown in primary cultures of purified chick embryo cells (PCECV).

The initial rabies vaccine is administered at the same time as rabies immune globulin (RabIg), using a separate needle, syringe and injection site (preferably a separate limb). It is administered intramuscularly (IM) at a dose of 1.0 mL into the deltoid muscle. For infants and small children, the anterolateral thigh is also an acceptable injection site. The gluteal area should never be used for injections of rabies vaccine, because of variability in uptake at that site which could lead to a lower antibody response. A healthy, immunocompetent individual requires 4 doses of vaccine at the recommended vaccination schedule (see below).

Neutralizing antibodies begin developing 7 to 10 days after the initial rabies vaccine, and persist for at least 2 years.

* For infants and small children, the anterolateral thigh is an acceptable injection site.

If person is immunocompromised or on anti-malarial drugs or taking chloroquine

* For infants and small children, the anterolateral thigh is an acceptable injection site.

Missed Doses of Rabies Vaccine

Every attempt should be made to adhere to the recommended vaccination schedule. Doses should not be given sooner than the minimum time interval as lower neutralizing antibody titres may result. A dose given too soon will not count towards the series and must be replaced by a dose given at the correct interval. A delayed or missed dose should be given as soon as possible, and then the subsequent doses should have the same minimum interval between doses as in the original schedule. For example, a patient who misses the day 7 dose and presents on day 9 should have the day 7 dose administered that day and the day 14 dose given 7 days later (on day 16) and the following dose (if there is a 5^th dose) 14 days after that (on day 30).

Immunocompromised Persons

Patients who are immunocompromised, including those on corticosteroids or other immunosuppressive drugs, chloroquine, antimalarials, and those with immunosuppressive illnesses will require a 5^th dose of rabies vaccine on day 28. The ordering physician determines if the patient is considered immunocompromised and informs Ottawa Public Health.

Drug Interactions

Rabies immune globulin (RabIg) can interfere with vaccine effectiveness when given within 14 days after receiving the varicella or MMR vaccines. After receiving RabIg, administration of varicella or MMR vaccines should be postponed for 4 months.