EBM Consult

How do aluminum containing medications reduce the absorption of levofloxacin (Levaquin)?


  • Given the broad availability of aluminum hydroxide in over-the-counter (OTC) medications (especially oral antacids), their daily or intermittent administration along with the antibiotic levofloxacin is plausible.
  • A number of factors (such as food, H2 receptor antagonists, proton pump inhibitors, etc), as well as aluminum hydroxide itself are known to increase the gastric pH (ranging from 1 to 6).
  • Levofloxacin has a carboxyl group (R-COOH) as part of its structure which can ionize, or release its H+ ion, and become negatively charged (R-COO-) when the gastric pH exceeds its pKa of 1.8 to 2.4.
  • The negatively charged carboxyl groups (R-COO-) can then interact with the positively charged aluminum ions (Al3+) resulting in "chelation".    
  • The coadministration of aluminum hydroxide and levofloxacin can reduce the intestinal absorption and thus warrants separation by at least 2 hours when being administered.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA

Last Reviewed: February 2018


  • Aluminum hydroxide Al(OH)3 is a common ingredient in many over-the-counter (OTC) oral antacid medications.   It is also used in the short-term as an oral phosphate binder in patients with hyperphosphatemia secondary to chronic kidney disease.    When using aluminum based products as an antacid, the short duration of action requires frequent administration throughout the day.  Due to its availability OTC, the route, the frequency of administration throughout the day, and the recognition that many people prefer to take all of their medications at the same time, it is plausible that the introduction of levofloxacin (Levaquin) for the treatment of a bacterial infection could be met with the presence of a tri-valent cation, such as aluminum.  The coadministration of levofloxacin and aluminum hydroxide can result in a reduction in the overall absorption and bioavailability of levofloxacin thus increasing the risk of the patient either developing bacterial drug resistance and/or treatment failure.(1)

    How does aluminum specifically interact with levofloxacin to cause a reduction in absorption or bioavailability?

    • A basic evaluation of the chemical structure of levofloxacin reveals that each levofloxacin molecule has one carboxyl group (R-COOH) as part of its structure.(2)  The important thing to note about this carboxyl group as it relates to an interaction with aluminum is its ionization state (i.e., whether it is charged or uncharged).  The carboxyl group becomes negatively charged when it releases its hydrogen (H+) ion.  This process is determined by its pKa. 
    • The pKa for carboxyl groups is approximately 1.8 to 2.4.(3)  Therefore, a pH above this pKa would result in a greater percentage of the carboxyl groups on levofloxacin being ionized (or in their negatively charged state). 
    • Depending on other medications being taken by the patient (such as antacids, H2 receptor antagonists or proton pump inhibitors) and the type of food ingested, the pH of the stomach can easily range from 1 to 6; thus, it is likely that the pKa of the carboxyl group will be exceeded.  However, even if the patient only takes the aluminum hydroxide along with the levofloxacin on an empty stomach, the aluminum hydroxide itself can interact with hydrochloric acid from the stomach to form aluminum chloride and water which can cause an increase in the gastric pH. 
    • Therefore, the magnitude of change in gastric pH (whether it is from aluminum hydroxide itself or from the combination of aluminum hydroxide and other medications) will influence the amount of ionized carboxyl groups found on levofloxacin.  Once this ionization has started to occur, the exposed and negatively charged group on levofloxacin can then bind to the positively charged aluminum (Al3+) ions that was present in the medication or supplement administered.  This final reaction is what most clinicians refer to when they say that aluminum or a cation (positively charged molecule) can "chelate" levofloxacin. 
    • The degree or significance of this interaction is, however, dependent on the time of their exposure to one another and the pH of the environment at the time.  A 2 to 4 hour separation of the aluminum containing product and the levofloxacin can avoid this interaction.  Binding or "chelation" of the levofloxacin and aluminum will result in decreased absorption or bioavailability of levofloxacin and potentially increase the risk for treatment failure of the infection.  The risk of failure to treat the infection will obviously also be influenced by the minimum inhibitory concentration (MIC) of the bacteria and the tissue being targeted.


    1. Tanaka M, Kurata T, Fujisawa C et al.  Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide.  Antimicrob Agents Chemother  1993;37:2173-8.
    2. Levofloxacin Compound Summary (CID 149096).
    3. Leiberman M, Marks AD, eds.  Mark's Basic Medical Biochemistry A Clinical Approach.  3rd Ed.  Philadelphia, PA: Lippincott Williams & Wilkins; 2009:75-91.

MESH Terms & Keywords

  • Levofloxacin, Levaquin, Fluoroquinolone, Aluminum hydroxide, ALOH, Drug Interaction