Drug Interactions between foscarnet and gatifloxacin

MONITOR: Limited data suggest that coadministration of foscarnet and ciprofloxacin may potentiate the risk of seizures. Both agents are individually epileptogenic and may have additive effects when combined. Specifically, foscarnet can decrease the seizure threshold by chelating ionized calcium and magnesium, while ciprofloxacin inhibits gamma-aminobutyric acid (GABA). In a published report, two patients with AIDS developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of cytomegalovirus (CMV) retinitis and disseminated Mycobacterium avium complex (MAC) infection, respectively. The first patient developed seizures both during the first and second dose of foscarnet (60 mg/kg every 8 hours) while being treated with ciprofloxacin (750 mg twice a day) and some other medications, but experienced no further seizures after discontinuation of foscarnet therapy. The second patient had been receiving foscarnet without incident until he was given ciprofloxacin and various other antimicrobial agents for MAC sepsis. Shortly thereafter, he developed seizures upon the start of a foscarnet infusion and when the infusion was restarted following a brief interruption. A study in mice also found increased seizure potential associated with the combination of foscarnet and ciprofloxacin.

MANAGEMENT: Caution is advised during coadministration of foscarnet and ciprofloxacin, particularly in elderly patients and those with renal impairment, electrolyte and metabolic abnormalities, or underlying neurologic disorders. The same precaution may be applicable during therapy with other quinolones, although clinical data are lacking.