Drug Interactions between proguanil and typhoid vaccine, live

ADJUST DOSING INTERVAL: The coadministration of single agent proguanil and live attenuated typhoid vaccine has been associated with diminished immunologic response to the vaccine. Proguanil possesses antibacterial activity and may be active against the vaccine strain of Salmonella typhi (Ty21a), thereby preventing a sufficient degree of multiplication to occur in order to induce a protective immune response. A significant decrease in the immune response rate was noted in a study of 30 healthy adults who received proguanil 200 mg daily with the Ty21a vaccine strain. However, in a study of 330 subjects between the ages of 4 to 16 years of age, the combination product atovaquone-proguanil (62.5-187.5 mg/day atovaquone and 25-75 mg/day proguanil depending on the body weight of the patient) did not have a significant effect on the vaccinees' immune response. Likewise, the antimalarial agents mefloquine and chloroquine, also possess antibacterial activity but have not been shown to interfere with the immunogenicity of the vaccine.

MANAGEMENT: Single agent proguanil should not be administered until at least 10 days after the last dose of live attenuated typhoid vaccine. However, the commercially available fixed combination atovaquone and proguanil can be given concurrently with this vaccine.