Doxycycline food and OTC interactions

Since it's the time of year again when Lyme disease is a concern for patients in many parts of the United States, I thought it would be good to discuss one issue concerning doxycycline.  Doxycycline is a preferred oral agent for Lyme disease and many of its complications.  It is recommended for a variety of situations when Lyme disease is suspected or confirmed such as1:

• Single dose prophylaxis after tick bite
• Erythema migrans
• Cranial nerve palsy
• Carditis
• Lyme arthritis
• Acrodermatitis chronica atrophicans
• Co-infection with human granulocytic anaplasmosis

When ordering or verifying the typical adult dose of 100 mg orally twice daily, an alert may pop up for an interaction with several drugs including iron, calcium, magnesium, aluminum, or bismuth subsalicylate.  The proposed mechanism for this interaction is chelation in the gastrointestinal tract, compounded by the enterohepatic circulation of doxycycline.  Let's look at some of the data regarding these interactions.

Doxycycline - iron interaction

The concurrent administration of iron and tetracycline derivatives has been shown in numerous studies to reduce the levels of the tetracycline antibiotic by 50-90%.  Some investigators separated the dosing interval by giving the doxycycline up to 11 hours before the iron and a 20-45% reduced serum concentration still persisted.  This study also gave doxycycline intravenously with oral iron and found that the half-life was reduced from 16.6 to 11 hours2.  This increase in clearance is likely due to chelation during enterohepatic circulation of intravenous doxycycline.

Doxycycline - aluminum, calcium, magnesium interaction

The administration of doxycycline with any of these agents has resulted in a reduced absorption by up to 90%.  Intravenous doxycycline was also studied with aluminum antacid and the half-life decreased from 16.2 to 11.2 hours and the area under the curve (AUC) decreased by 18-44%3.  Again, this is likely attributed to binding during enterohepatic circulation.

Doxycycline - bismuth subsalicylate interaction

This interaction resulted in a reduced AUC of doxycycline by up to 51% after a multidose regimen of bismuth subsalicylate.

These interactions are particularly concerning because these agents are over-the-counter (may not be listed on patients' medication list) or may come from food sources.  Furthermore, these over-the-counter items are available in countless products falling under numerous categories including antacids, laxatives, and anti-infectives (as in bismuth subsalicylate in traveler's diarrhea or H. pylori eradication).

Take home points:

• Iron, aluminum, calcium, magnesium, and bismuth subsalicylate can significantly reduce serum concentrations of doxycycline (in many cases by more than 50%)
• Separating the dosing interval or giving the doxycycline intravenously does not uniformly negate this interaction
• These interactions can come from foods or supplements and are available in countless over-the-counter products 
• Ask the patient specifically if they take any of these products and consider discontinuing them until their doxycycline course is complete

References:

1.  Wormser GP, Dattwyler RJ, Shapiro ED, et al.  The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America.  Clin Infect Dis  2006;43:1089-134

2.  Cunha BA, Sibley CM, Ristuccia AM.  Doxycycline-review.  Ther Drug Monit  1982;4:115-135.

3.  Nguyen VX, Nix DE, Gillikin S, et al.  Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline.  Antimicrob Agents Chemother  1989;33(4):434-6.

photo by John Tann