NHS Greater Glasgow & Clyde Area Drug and Therapeutics Committee
Greater Glasgow and Clyde Medicines
Medicines Update

PostScript 79 (Jan 2014) Antibiotic interactions

Antibiotic Interactions:

Quinolones and tetracyclines with metal salts and other cations

Quinolones, eg ciprofloxacin, levofloxacin, norfloxacin and ofloxacin; and tetracyclines, eg doxycycline, lymecycline and minocycline interact with products containing multivalent cations. Such products include:

 

  • aluminium or magnesium-containing antacids
  • multivitamins
  • preparations containing calcium
  • preparations containing iron
  • preparations containing zinc
  • sucralfate. 

 

 

When oral quinolones or tetracyclines are given concomitantly with such products, there is often a significant reduction in the oral absorption of the antibiotic. The interaction is caused by formation of insoluble chelation complexes in the gastrointestinal tract that inhibit antibiotic absorption. This clinically significant interaction risks rendering the antibiotic ineffective. Serum antimicrobial levels can fall below minimum inhibitory concentration so becoming sub-therapeutic (particularly against organisms such as staphylococci and Pseudomonas aeruginosa) resulting in treatment failure.  It has also been suggested that the low levels of antimicrobials which occur as a result of this interaction may contribute to the development of antimicrobial resistance.

 

A recent case involved an elderly male patient treated for an infective exacerbation of COPD with oral doxycycline. The patient’s symptoms didn’t improve within the first 24-48 hours of antibiotic therapy and escalation of empirical therapy was considered.  However, it was also noted that the patient had been receiving concomitant ferrous fumarate. The iron was withheld and symptoms improved significantly over the next 24-48 hours without the need to escalate antimicrobial therapy.

 

Whenever possible, products containing multivalent cations should be avoided in patients receiving oral quinolones or tetracyclines. If both preparations are necessary, timing of administration may help minimise the effect. The BNF recommends that:

  • Oral quinolones or tetracyclines should not be administered for at least 2 hours before or after indigestion remedies or medicines containing iron or zinc. 
  • When taking ciprofloxacin, norfloxacin and the older tetracyclines, milk and dairy products should be avoided 2 hours before and after oral drug administration. 

 

Action for Prescribers and Pharmacists

  • Be aware of the interaction between cations and quinolones / tetracycylines.
  • Consider if the interacting cation, eg iron or antacid can be stopped for the duration of the antibiotic.
  • If both products are required, ensure administration times are optimised to improve antibiotic absorption (see table below for advice from the SPCs).
  • Follow NHSGGC antimicrobial guidelines, including recording of the duration of oral antibiotics.

 

 

Antibiotic

Co-administration with products containing magnesium, aluminium, iron, zinc, calcium or sucralfate

Co-administration with food and dairy products

Ciprofloxacin

  • Potential 50-90% reduction in ciprofloxacin AUC (area under curve). 
  • Administer at least 2 hrs before or after.
  • Absorption not significantly affected by non-dairy foods. 
  • Avoid milk, yoghurt, or calcium fortified orange juice 2 hours before or after.

Norfloxacin

  • Potential 90% reduction in norfloxacin AUC.
  • Administer at least 2 hrs before or after.
  • Absorption not significantly affected by non-dairy foods. 
  • Avoid milk, yoghurt, or calcium fortified orange juice 2 hours before or after.

Levofloxacin,

ofloxacin

  • Potential 20-40% reduction in antibiotic AUC. 
  • Administer at least 2 hrs before or after.
  • Absorption not significantly affected by food or dairy products.

Doxycycline,

lymecycline, minocycline

  • Potential 90-100% reduction in antibiotic AUC.
  • Administer at least 2 hrs before or after to improve antibiotic bioavailability.
  • Absorption not significantly affected by food or dairy products.

Tetracycline,

oxytetracycline

  • Potential 90-100% reduction in antibiotic AUC.
  • Administer at least 2 hrs before or after to improve antibiotic bioavailability.

 

  • Absorption affected by food and dairy products.
  • Avoid milk, yoghurt, or calcium fortified orange juice 2 hours before or after.

 

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