EBM Consult

How do calcium supplements decrease the absorption of ciprofloxacin (Cipro)?


  • Given the broad availability of calcium carbonate in over-the-counter (OTC) supplements, their daily or intermittent administration along with the antibiotic, ciprofloxacin (Cipro), is plausible.
  • A number of factors (such as food, H2 receptor antagonists, proton pump inhibitors, etc) as well as calcium carbonate itself are known to increase the gastric pH (ranging from 1 to 6).
  • Ciprofloxacin (Cipro) 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 calcium ions (Ca2+) resulting in "chelation".
  • The coadministration of calcium carbonate and ciprofloxacin has resulted in an average reduction in absorption (or bioavailability) by 40% 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


  • Daily use of calcium containing supplements (such as calcium carbonate) or medications are fairly common and are known to be recommended by some medical authorities.(1)  Some patients may fail to disclose their use during a review of medications at a clinic visit or upon admission to the hospital because they may not consider the supplement to be a medication.  Daily administration of calcium carbonate is usually safe and appropriate, but problems can arise when the patient develops an infection that requires the use of the antibiotic, ciprofloxacin (Cipro).  This is a very plausible situation in both the outpatient setting and hospital setting.  For patients in the outpatient setting, it is common and maybe even desirable for the patient to take all of their medications at one time.  In the hospital, administration of multiple medications simultaneously may also desirable.  Conversely, it may be that the scheduling of medication administration is simply not given enough attention in regard to avoiding combinations of drugs that should not be taken at the same time.  Regardless of the reason, the coadministration of calcium carbonate and ciprofloxacin can result in a reduction in the absorption of ciprofloxacin by an average of 40%.(2)  Absorption can be further reduced if the gastric pH is increased by other medications such as H2 receptor antagonists or proton pump inhibitors.(3)

    What does calcium do to ciprofloxacin that results in this reduction in absorption or bioavailability?

    • A basic evaluation of the chemical structure of ciprofloxacin reveals that each ciprofloxacin molecule has one carboxyl group (R-COOH) as part of its structure.(4)  The important thing to note about this carboxyl group as it relates to an interaction with calcium is its ionization state (i.e., whether it is chargedor 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 2.4.5  Therefore, a pH above this pKa would result in a greater percentage of the carboxyl groups on ciprofloxacin 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 calcium carbonate along with the ciprofloxacin on an empty stomach, the calcium carbonate itself can interact with hydrochloric acid from the stomach to form calcium chloride, carbon dioxide and water and cause an increase in the gastric pH.  Therefore, the magnitude of change in gastric pH (whether it is from calcium carbonate itself or from the combination of calcium carbonate and other medications) will influence the amount of ionized carboxyl groups found on ciprofloxacin. 
    • Once this ionization has started to occur, the exposed and negatively charged group on ciprofloxacin can then bind to the positively charged calcium (Ca++) ion that was present in the medication or supplement administered. 
    • This final reaction is what most clinicians refer to when they say that calcium or a cation (positively charged molecule) can "chelate" ciprofloxacin.  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 hour separation of the calcium containing product and the ciprofloxacin can avoid this interaction.6 Binding or "chelation" of the ciprofloxacin with calcium will result in decreased absorption or bioavailability of ciprofloxacin 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. Rose VL.  IOM recommends increased calcium intakes.  Institute of Medicine.  Am Fam Physician  1998;57:1145-6.
    2. Sahai J, Healy DP, Stotka J et al.  The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin.  Br J Clin Pharmacol  1993;35:302-4.
    3. O'Connell MB, Madden DM, Murray AM et al.  Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial.  Am J Med  2005;118:778-81.
    4. Ciprofloxacin Compound Summary (CID 17906217).  PubChem Compound.
    5. Leiberman M, Marks AD, eds.  Mark's Basic Medical Biochemistry A Clinical Approach.  3rd Ed.  Philadelphia, PA: Lippincott Williams & Wilkins; 2009:75-91.
    6. Lomaestro BM, Bailie GR.  Effect of staggered dose of calcium on the bioavailability of ciprofloxacin.  Antimicrob Agents Chemother  199135:1004-7.

MESH Terms & Keywords

  • Ciprofloxacin, Cipro, Calcium, Calcium carbonate, Ciprofloxcain Absorption, Cirpofloxacin Bioavailability