Revisiting Oral Fluoroquinolone and Multivalent Cation Drug-Drug Interactions: Are They Still Relevant?

Abstract

Fluoroquinolones are a widely-prescribed, broad-spectrum class of antibiotics with several oral formulations notable for their high bioavailability. For certain infections, fluoroquinolones are the first line or only treatment choice. When administered orally, fluoroquinolones require proper administration to ensure adequate systemic absorption and, thereby, protect patients from treatment failure. Oral drug preparations that contain multivalent cations are well known to chelate with fluoroquinolones in the gastrointestinal tract; co-administration may lead to clinically significant decreases in oral fluoroquinolone bioavailability and an overall increase in fluoroquinolone-resistant bacteria. Based on a search and evaluation of the literature, this focused review describes oral fluoroquinolone-multivalent cation drug-drug interactions and their magnitude and offers several clinical management strategies for these potentially clinically significant interactions.

Effects of Magnesium, Calcium, and Aluminum Chelation on Fluoroquinolone Absorption Rate and Bioavailability: A Computational Study

“…The C6 fluorine substitution to the initial quinolone scaffold is now recognized as a critical pharmacophoric component, and this subclass, termed fluoroquinolones (FQs), comprise most contemporary quinolones in development and with clinical applications. Reduction in oral bioavailability due to chelation between FQs and multivalent metals is a well-established phenomenon with numerous studies disclosing disruptive interactions between quinolones and metal cations [8]. Nix et al studied the effect of aluminum and magnesium from Maalox antacid on ciprofloxacin PK.…”

“…Didanosine, an antiretroviral therapy for HIV/AIDS, is often formulated alongside dihydroxy aluminum sodium carbonate and magnesium hydroxide (in addition to sodium citrate) to lessen acid hydrolysis within the stomach. Reduction in oral bioavailability due to chelation between FQs and multivalent metals is a well-established phenomenon with numerous studies disclosing disruptive interactions between quinolones and metal cations [8]. Nix et al studied the effect of aluminum and magnesium from Maalox antacid on ciprofloxacin PK.…”

“…Reduction in oral bioavailability due to chelation between FQs and multivalent metals is a well-established phenomenon with numerous studies disclosing disruptive interactions between quinolones and metal cations [ 8 ]. Nix et al studied the effect of aluminum and magnesium from Maalox antacid on ciprofloxacin PK.…”

Multivalent cations interactions with fluoroquinolones or tetracyclines: A cross-sectional study

“…Only when given orally, drug-drug interactions (DDIs) due to chelation can occur between fluoroquinolones or tetracyclines and divalent or trivalent cation-containing compounds (DTCCs) such as iron, calcium, zinc, magnesium, and aluminum. This chelation leads to the formation of an insoluble complex compound that is poorly absorbed from the gastrointestinal tract ( D'arcy and Mcelnay, 1987 , Pitman et al, 2019 ). The mean area under the concentration–time curve of ciprofloxacin is reduced by up to 42% when co-administered with calcium, and by up to 64% when co-administered with iron preparations ( Pitman et al, 2019 ).…”

“…This chelation leads to the formation of an insoluble complex compound that is poorly absorbed from the gastrointestinal tract ( D'arcy and Mcelnay, 1987 , Pitman et al, 2019 ). The mean area under the concentration–time curve of ciprofloxacin is reduced by up to 42% when co-administered with calcium, and by up to 64% when co-administered with iron preparations ( Pitman et al, 2019 ). Another antibiotic that also can cause chelation with DTCCs but not available at our institution and might be more commonly used in pediatrics is cefdinir ( Eljaaly and Alshehri, 2020 ).…”