SEE ALSO WARNINGS AND CONTRAINDICATIONS SECTIONS FOR ADDITIONAL STATEMENTS

Local reactions such as induration, swelling and reddening have been reported more often than systemic reactions. In a comparative trial in normal volunteers, Dreesen et al. (3, 24) described their experience with RabAvert compared to a HDCV rabies vaccine. Nineteen subjects received RabAvert and 20 received HDCV. The most commonly reported adverse reaction was pain at the injection site, reported in 45% of the HDCV group, and 34% of the RabAvert group. Localized lymphadenopathy was reported in about 15% of each group. The most common systemic reactions were malaise (15% RabAvert group vs. 25% HDCV group), headache (10 % RabAvert group vs. 20 % HDCV group), and dizziness (15% RabAvert group vs. 10 % HDCV group). In a recent study in the USA (4), 83 subjects received RabAvert and 82 received HDCV. Again, the most common adverse reaction was pain at the injection site in 80% in the HDCV group and 84% in the RabAvert group. The most common systemic reactions were headache (52% RabAvert group vs. 45% HDCV group), myalgia (53% RabAvert group vs. 38% HDCV group) and malaise (20% RabAvert group vs. 17% HDCV group). None of the adverse events was serious, almost all adverse events were of mild or moderate intensity. Statistically significant differences between vaccination groups were not found. Both vaccines were generally well tolerated.

Uncommonly observed adverse events include temperatures above 38°C (100°F), swollen lymph nodes, and gastrointestinal complaints. In rare cases, patients have experienced severe headache, fatigue, circulatory reactions, sweating, chills, monoarthritis and allergic reactions; transient paresthesias and one case of suspected urticaria pigmentosa have also been reported. Type III hypersensitivity reactions in pre-exposure booster immunizations have been reported with one HDCV rabies vaccine (25-27). These reactions are thought to be due to small amounts of human serum albumin (HSA) rendered allergenic by propiolactone (23, 28, 29). Human serum albumin (HSA) is present in RabAvert at concentrations less than 0.3 µg/dose. No type III hypersensitivity reactions have been observed with RabAvert (30).

Serious systemic anaphylactic reactions or neuroparalytic events have been reported in association with RabAvert administration. Against a background of 11.8 million doses distributed world-wide 10 cases of encephalitis (1 death) or meningitis, 7 cases of transient paralysis including 2 cases of Guillain-Barre Syndrome, 1 case of myelitis, 1 case of retrobulbar neuritis, and 2 cases of suspected multiple sclerosis have been temporally associated with the use of RabAvert. Also, 2 cases of anaphylactic shock have been reported. A patient's risk of developing rabies must be carefully considered, however, before deciding to discontinue immunization (see WARNINGS).

The use of corticosteroids to treat life-threatening neuroparalytic reactions may inhibit the development of immunity to rabies (see PRECAUTIONS, DRUG INTERACTIONS).

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.

Reporting of Adverse Events

Adverse events should be reported by the health care provider or patient to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Report forms and information about reporting requirements or completion of the form can be obtained from VAERS by calling the toll-free number 1-800-822-7967 (26). In the USA, such events can be reported to the Professional Services department, Chiron Corporation: phone: 1-888-CHIRON-7.

Corticosteroids, other immunosuppressive agents, antimalarials and immunosuppressive illnesses can interfere with the development of active immunity after vaccination, and may diminish the protective efficacy of the vaccine. Pre-exposure prophylaxis should be administered to such persons with the awareness that the immune response may be inadequate. Immunosuppressive agents should not be administered during post-exposure therapy unless essential for the treatment of other conditions. When rabies post-exposure prophylaxis is administered to persons receiving corticosteroids or other immunosuppressive therapy, or who are immunosuppressed, it is important that a serum sample be tested for rabies antibody to ensure that an acceptable antibody response has been induced (23).

Rabies Immuno Globulin must not be administered at more than the recommended dose, since response to active immunization may be impaired.

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