Drug Interactions between hydroxychloroquine and rabies vaccine, purified chick embryo cell

ADJUST DOSING INTERVAL: Chloroquine may reduce the antibody response to primary immunization with intradermally administered rabies vaccine. The mechanism of interaction has not been established, but may involve chloroquine-mediated impairment of macrophage antigen-processing mechanisms, which would affect recognition of antigen by T cells and, ultimately, activation of B cells and antibody production. The interaction has not been reported with rabies vaccine given intramuscularly, presumably because it provides higher and more sustained antibody titers than intradermal administration. Although rabies vaccine is not approved or marketed for intradermal use, it has been given by this route in doses of 0.1 mL as a more economical alternative, particularly in resource-poor environments and developing countries. In a study of healthy volunteers who were not previously vaccinated against rabies, 26 subjects who received chloroquine (300 mg/week beginning nine days before the first dose of vaccine and continuing until day 48) concomitantly with human diploid-cell rabies vaccine (0.1 mL intradermally on days 0, 7, and 28) had a significantly lower mean rabies-neutralizing antibody titer on each day of testing (day 28, day 49, and day 105) compared to 25 controls who received the vaccine without chloroquine. However, both groups had neutralizing antibody titers on days 49 and 105 based on CDC criteria. The blood concentrations of chloroquine and its pharmacologically active metabolite, desethylchloroquine, were negatively associated with low antibody titers. Chloroquine prophylaxis given for more than 4 weeks during the vaccination period has also been associated with poor antibody response to intradermal human diploid-cell rabies vaccine in Peace Corps volunteers and may have been responsible for one death.

MANAGEMENT: Rabies vaccine should not be administered by the intradermal route during chloroquine therapy. In patients who require chloroquine for malaria prevention and rabies vaccine for preexposure prophylaxis in preparation for travel to a rabies endemic area, intradermal administration of the vaccine may be considered only if the vaccine can be initiated early enough to allow for the entire series to be completed 30 days or more before departure. Otherwise, the intramuscular route should be used. Following intradermal administration, the rabies virus neutralizing antibody (VNAb) level should be checked 14 to 21 days after completion of the series. There are no data on the effect of chloroquine on postexposure administration of rabies vaccine. Since the intradermal route may produce a slower initial immune response, the intramuscular route is recommended. There are also no reports of interaction with hydroxychloroquine, although some manufacturers recommend the same precautions as for chloroquine.

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