Can caffeine interact with Levofloxacin? Sue Brennan: Caffeine and Levofloxacin—it’s possible to get an additive effect on the CNS stimulation side. Caffeine is something that perks us up mentally and because the Levofloxacin has a stimulatory effect possible, there also you can have some additive effects. Hopefully, a person isn’t taking a lot of caffeine every day, but they may have to decrease.