Greater Glasgow and Clyde Medicines

WARNING - Antibiotic treatment failure risk

Raising awareness of the interaction between tetracycline and fluoroquinolone antibiotics with multivalent cation-containing products (e.g. iron and calcium) to improve antimicrobial stewardship

Key messages:

  1. Concomitant oral administration of tetracycline (e.g doxycycline) and fluoroquinolone (e.g ciprofloxacin) antibiotics with multivalent cations (iron, calcium, magnesium, aluminium, zinc or sucralfate –often also contained in antacids and nutritional supplements) can result in the formation of insoluble chelation complexes in the gut.  Co-prescription orally can result in:
    • loss of antibiotic absorption and treatment failure
    • potential unnecessary escalation to broader antibiotic cover including intravenous therapy
    • development of antimicrobial resistance
  2. Serum levels of doxycycline are reduced by as much as 90% to 100% by this interaction.  Ciprofloxacin plasma levels can be reduced by over 50% by the simultaneous administration of enteral feeds and oral nutritional supplements such as Ensure®.

A recent GG&C audit of patients discharged from hospital found that 1 in 5 patients receiving a tetracycline or fluoroquinolone were co-prescribed an interacting multivalent cation-containing product at the same time and 1/3 of these patients were prescribed more than one multivalent cation-containing product.  

Action for Clinical Teams/Pharmacists:

  1. When possible, multivalent cation-containing products should be withheld/stopped in patients receiving oral tetracyclines or fluoroquinolones until the antibiotic treatment course is complete. 
  2. If the cation-containing product cannot be withheld, then an alternative antibiotic should be considered.  If necessary, contact an antimicrobial pharmacist or microbiologist for advice.
  3. If the tetracycline or fluoroquinolone and cation-containing product must be prescribed together:
    • Administration times should be spaced apart as far as possible to improve antibiotic absorption (see table below).
    • If possible, consideration should be given to reducing the dose frequency of the multivalent cation-containing product for the duration of the antibiotic course to make dose spacing more manageable.
    • In the case of oral nutritional supplements, multiple sips throughout the day should be replaced with set administration times to enable adequate spacing from oral antibiotic administration (see table below).
    • If a patient is receiving a continuous cation-containing enteral feed, administration of interacting quinolones/tetracyclines should generally be avoided unless the feeding regimen can be altered to allow adequate dose spacing. 
  4. In the case of patients receiving an antibiotic that interacts with food or dairy products, ensure this is documented in the additional comments section of the kardex.
  5. Patients discharged on a fluoroquinolone or tetracycline should be made aware of the need to avoid multivalent cation-containing products and should discuss the concomitant use of any over the counter medicines with their doctor or pharmacist.  Patients should also be reminded of food and dairy restrictions if applicable.
  6. Note, if possible patients should be made aware that H2 receptor antagonists and proton pump inhibitors do not require to be spaced apart from oral tetracycline or fluoroquinolone antibiotics.

(If viewing table on a mobile device switch to landscape)

Table: Summary of interactions and suggested actions


Co-administration with multivalent cation-containing product*:

  • Stop/withhold multivalent cation-containing product* until antibiotic course complete.
  • If concomitant administration necessary, give cation-containing product* at least 2 hours before or after antibiotic

Co-administration with dairy products:

  • Avoid concurrent administration with:

         √    milk

         √    yoghurt

         √   calcium fortified   orange juice                   

for 2 hours before or after antibiotic


Co-administration with food:

  • Avoid concurrent administration with food

for 2 hours before or after antibiotic



Potential 50-90% reduction in ciprofloxacin plasma levels. 



Potential 90% reduction in norfloxacin plasma levels.


Levofloxacin, ofloxacin, moxifloxacin

Potential 20-40% reduction in antibiotic plasma levels.  (Calcium compounds interact to a lesser extent)




Doxycycline, lymecycline, minocycline

Potential 90-100% reduction in antibiotic plasma levels.



Tetracycline, oxytetracycline

Potential 90-100% reduction in antibiotic plasma levels.

*multivalent cation-containing products include: iron, calcium, magnesium, aluminium, zinc or sucralfate  (often also contained in antacids and nutritional supplements).

For further information on interactions, refer to the BNF or Stockley's Drug Interactions available on Medicines Complete or the Summary of Product Characteristics on eMC.

For information on the safety of fluoroquinolones, click here.


Published 12/11/19. Medicines Update blogs are correct at the time of publication.