Avoiding the Ciprofloxacin-Didanosine Interaction

1 September 1995 | Volume 123 Issue 5 | Pages 394-395

TO THE EDITOR:

Because of multiple drug allergies and the emergence of drug-resistant mycobacterial infections, the fluoroquinolones are widely used in patients with human immunodeficiency virus infection. The absorption of ciprofloxacin is dramatically reduced when it is coadministered with didanosine [1]. The interaction is caused by complexation between the magnesium and aluminum cations and the ciprofloxacin molecule, which results in the formation of a nonabsorbable complex. Standard references and the package insert for recommendations for avoiding this interaction suggest separating the dosing schedules of the agents by 2 hours [2-4]. This suggestion is clearly incorrect. Nix and colleagues [5] have shown that ciprofloxacin must be administered 2 hours before antacids or at least 6 hours after antacids to avoid this drug interaction [5].

A healthy male volunteer received ciprofloxacin, 500 mg, on four separate occasions: alone, 2 hours before receipt of two didanosine-placebo tablets (containing all the additives without the active drug), 2 hours after receipt of the didanosine-placebo tablets, and concomitantly with the didanosine-placebo tablets. Figure 1 shows that administration of ciprofloxacin 2 hours after receipt of antacids results in a reduction of its absorption to levels below the minimum inhibitory concentration for moderately sensitive microorganisms. Administration of ciprofloxacin 2 hours before antacid-containing preparations results in normal blood levels. On the basis of the results of this single volunteer study and those of the study by Nix and associates [5], fluoroquinolones should be given either 2 hours before or at least 6 hours after administration of didanosine to reduce therapeutic failures.

View larger version (16K): [in this window] [in a new window]   Figure 1. Plasma ciprofloxacin concentrations. Ciprofloxacin (500 mg) was administered alone (\#9679;); 2 hours before two didanosineantacid tablets were given; 2 hours after the didanosineantacid tablets were given; and concurrently with the didanosine-antacid tablets (\#9632;).

 

Author and Article Information

Top Author & Article Info References

Ottawa General Hospital; Ottawa, Ontario K1H 8L6; Canada

References

Top Author & Article Info References

1. Sahai J. Gallicano K, Oliveras L, Khaliq S, Hawley-Foss N, Garber G. Cations in the didanosine tablet reduce ciprofloxacin bioavailability. Clin Pharmacol Ther. 1993; 53:292-7.

2. American Hospital Formulary Service (AHFS) Drug Information. Bethesda, MD: American Society of Hospital Pharmacists; 1995:424.

3. Compendium of Pharmaceuticals and Specialties. Ottawa, Ontario: Canadian Pharmaceutical Association; 1995:1472.

4. Didanosine (Videx) package insert. Princeton, NJ: Bristol-Myers Squibb, Inc.

5. Nix DE, Watson WA, Lener ME, et al. Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. Clin Pharmacol Ther. 1989; 46:700-5.

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