Drug Interaction Report

ADJUST DOSING INTERVAL: The use of live, attenuated oral typhoid vaccine with antibacterial sulfonamides or other antibiotics may result in a diminished immunologic response to the vaccine. Some antibiotics 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. Several antimalarial drugs such as chloroquine, mefloquine, and pyrimethamine-sulfadoxine also possess antibacterial activity, but concomitant administration did not significantly reduce immune response to the vaccine or compromise its efficacy in healthy adult study subjects. By contrast, concomitant administration of single agent proguanil did cause a significant decrease in the immune response rate, but the commercialized combination product atovaquone-proguanil did not have the same effect. The effects of other antimalarial agents have not been studied.

MANAGEMENT: Live, attenuated oral typhoid vaccine should not be administered during and for at least 3 days before and after treatment with antibacterial sulfonamides or other antibiotics. A longer interval should be considered following treatment with long-acting antibiotics (e.g., azithromycin). If malaria prophylaxis is needed, the same 3-day interval at the minimum should be observed between antimalarials and the vaccine. However, chloroquine, mefloquine, atovaquone-proguanil, and pyrimethamine-sulfadoxine may be given concomitantly with the vaccine. Alternatively, parenteral typhoid vaccine (typhoid Vi polysaccharide vaccine) may be considered if coadministration with antibacterial agents is required.

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.