Drug Interaction Report

ADJUST DOSING INTERVAL: The bioavailability of oral tetracyclines may be significantly decreased during concurrent administration with zinc-containing products. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the zinc cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In seven healthy volunteers, simultaneous oral administration of zinc sulfate 200 mg and tetracycline 500 mg resulted in a 30% to 40% reduction in tetracycline serum concentrations compared to administration of tetracycline alone. In the same study, doxycycline absorption was not significantly affected by zinc coadministration. Other studies have reported reductions of greater than 50% in tetracycline absorption in the presence of zinc salts.

MANAGEMENT: Patients receiving an oral tetracycline in combination with zinc-containing products should be advised to separate the times of administration by at least three to four hours. Doxycycline may be an appropriate alternative, since its absorption may not be significantly affected by zinc coadministration.

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GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

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