Drug-drug interactions are a relevant issue with the fluoroquinolones, because of their extensive use, and the fact that they are often administered with other agents. Reductions in absorption of the fluoroquinolones are well recognized to occur with metal-cation containing antacids, sucralfate, iron preparations, or ranitidine. Reductions in elimination of these agents may occur with cimetidine and probenecid, which inhibit their tubular secretion.

Some fluoroquinolones interact with theophylline, phenytoin, warfarin, cyclosporin,…

….digoxin, opioids, chlorpropamide, glibenclamide, and metoprolol. This interaction can be due to inhibition of cytochrome P450 isoenzymes. Theophylline and caffeine are extensively metabolized by cytochrome P450 in the liver. However, some quinolones inhibit this activity, leading to increased theophylline levels associated with toxic reactions including tachycardia, nausea and seizures. A pharmacodynamic interaction has been demonstrated between fluoroquinolones and NSAIDs.

On the basis of clinical and pharmacological data, fluoroquinolones have been classified into three groups according to the degree of their theophylline interaction. Group I agents demonstrate a greater than 40% increase in Cmax and AUC values for theophylline (enoxacin values are 74% and 84%), and this is associated with a very high risk of inducing toxic effects. Group II agents demonstrate a 5-40% increase in theophylline levels, causing moderate side effects.

Group III agents have no significant interaction with theophylline. In fact, the mean plasma theophylline concentration following a 500mg dose of levofloxacin shows no significant change in PK values.

There is also no interaction between levofloxacin and warfarin. This was confirmed in a double blind randomized placebo-controlled study, which revealed no significant change in maximum prothrombin values, time to maximum prothrombin levels and the area under the PT-time curve.

Clarification of the interaction between levofloxacin and antacids has demonstrated that administration of magnesium and ferrous compounds is associated with a drop in absorption of levofloxacin. However, levofloxacin values were only slightly changed when administered with calcium carbonate and ranitidine. This can be overcome by staggering the administration, wherein the two drugs are taken two hours apart.

Several studies have shown that the binding of quinolones to the brain GABA receptors correlates with their epileptogenic properties. Among the quinolones tested, levofloxacin is the least likely to result in GABA receptor binding, and thus has the lowest potential for initiating CNS adverse events.

Thus, the drug interaction profile for levofloxacin favorably compares with other quinolones.

This is particularly important with medications that prolong the QT interval. In contrast, moxifloxacin and gatifloxacin have the potential to interact with medications causing QT interval prolongation, a concern with regard to cardiac adverse events. Therefore, only minor precautions need to be taken in regard to drug-drug interactions with levofloxacin.