Adverse Reaction

Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually, such reactions can be successfully managed with anti-inflammatory and antipyretic agents, such as ibuprofen or acetaminophen.

When a person with a history of serious hypersensitivity to rabies vaccine must be revaccinated, antihistamines can be administered. Epinephrine should be readily available to counteract anaphylactic reactions, and the person should be observed carefully immediately after vaccination.

Although serious systemic, anaphylactic, or neuroparalytic reactions are rare during and after the administration of rabies vaccines, such reactions pose a serious dilemma for the patient and the attending physician. A patient’s risk of acquiring rabies must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reactions for persons receiving rabies vaccines may be sought from the state or local health department or CDC.

All clinically significant adverse events occurring following administration of rabies biologics should be reported to the Vaccine Adverse Event Reporting System (VAERS), even if causal relation to vaccination is not certain. Although VAERS is subject to limitations common to passive surveillance systems, including underreporting and reporting bias, it is a valuable tool for characterizing the safety profile of vaccines and identifying risk factors for rare serious adverse reactions to vaccines. VAERS reporting forms and information are available electronically or by telephone via a 24-hour toll-free telephone number, 800-822-7967. Web-based reporting is available and providers are encouraged to report electronically to promote better timeliness and quality of safety data.

Human Diploid Cell Vaccine (HDCV)

Studies of HDCV recipients reported local reactions (e.g., pain at the injection site, redness, swelling, induration) among 60-89.5% of recipients. Most local reactions were mild and resolved spontaneously within a few days. Local pain at the injection site was the most frequently reported adverse reaction occurring in 21-77% of vaccinees. Mild systemic reactions (e.g., fever, headache, dizziness, gastrointestinal symptoms) were reported in 6.8-55.6% of recipients.

Immediate systemic hypersensitivity reactions were observed in 1.2% of recipients in one study involving boosters of HDCV one year after primary vaccination with HDCV. Immediate hypersensitivity reactions have been reported in as many as 6% of persons receiving booster vaccination with HDCV following primary rabies prophylaxis; 3% occurring within one day of receiving boosters and 3% occurring 6-14 days after boosters. Systemic allergic reactions have been associated with the presence of betapropiolactone-altered human albumin in HDCV and the development of antibodies to this allergen. No deaths resulting from these reactions have been reported.

Purified Chick Embryo Cell Vaccine (PCEC)

In studies of PCEC use, local reactions (e.g., pain at the injection site, redness, swelling, induration) were reported among 11-57% of recipients. Local pain at the injection site, the most common local reaction, was reported in 2-23% of vaccinees. Systemic reactions were less common, and have been reported in 0-31% of vaccine recipients. In one study, 7% of children administered PCEC experienced mild to moderate clinical reactions.

In another study reviewing adverse events following administration of PCEC using data from the United States Vaccine Adverse Events Reporting System (VAERS), approximately 1.1 million doses of PCEC were distributed (from 1997 to 2005) and 331 reports describing adverse events following PCEC administration were received by VAERS.

A total of 196 reported adverse events (3% serious) occurred following administration of PCEC alone, and 135 (10% serious) occurred following postexposure prophylaxis (PCEC co-administered with HRIG) or PCEC administered concomitantly with another vaccine. A total of 20 reports, three serious, were classified as anaphylaxis. One patient was found to be allergic to gelatin, a vaccine component. Among the 309 non-serious adverse events, the most frequently reported were headache, fever, myalgia, nausea, and weakness. A limitation of VAERS is that causality between vaccine administration and reported adverse events cannot be established. No deaths or rabies cases were reported following administration of PCEC.

Human Rabies Immune Globulin (HRIG)

In a clinical trial involving 16 volunteers, participants receiving HRIG alone (no vaccine) commonly reported local reactions (100% in conventional HRIG group, 75% in heat-treated HRIG group), including pain/tenderness (100% conventional HRIG, 50% heat-treated HRIG), erythema (63% conventional, 25% heat-treated), and induration (50% conventional, 31% heat-treated).

Systemic reactions were reported in 75% of participants in conventional HRIG group and 81% in heat-treated group. Headache was the most commonly reported systemic reaction (50% conventional, 69% heat-treated). Most of the reported local and systemic reactions were mild, and there were no significant differences in the frequency of adverse events between treatment groups.

Neurological Adverse Events

Rare, individual case reports of neurologic adverse events following rabies vaccination have been reported, but in none of the cases has causality been established. Five cases of neurologic illness resembling Guillain-Barré syndrome occurring after treatment with HDCV or PCEC have been identified. One case of acute neurologic syndrome involving seizure activity was reported following the administration of HDCV and human RIG. Other central and peripheral nervous system disorders have been temporally associated with HDCV vaccine.