Drug Interactions between Caltrate 600 with Iron and Vitamin D and doxycycline / salicylic acid topical

ADJUST DOSING INTERVAL: Administration of a tetracycline with aluminum, calcium, or magnesium salts significantly decreases tetracycline serum concentrations. The proposed mechanism is chelation of tetracycline by the cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. The interaction has also been reported with parenteral doxycycline and oral antacids.

MANAGEMENT: The administration of tetracyclines and preparations containing aluminum, magnesium, or calcium should be separated by two to four hours. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering tetracycline antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.

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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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ADJUST DOSING INTERVAL: The bioavailability of orally administered iron may be reduced by concomitant administration of antacids or other agents with acid-neutralizing effects. The exact mechanism is unknown but may involve reduced iron solubility due to increase in gastric pH and/or reduced absorption due to complexation or precipitation of the iron. Based on existing data, sodium bicarbonate and calcium carbonate appear to have greater effects than antacids containing magnesium and aluminum hydroxides. In a study of patients with mild iron deficiency anemia, coadministration of ferrous sulfate with sodium bicarbonate 1 gram and calcium carbonate 500 mg reduced iron absorption by 50% and 67%, respectively, while 5 mL of an antacid containing magnesium and aluminum hydroxides had little effect. Another study also found no effect on iron absorption when ferrous sulfate (equivalent to 10 mg/kg of elemental iron) was coadministered with magnesium hydroxide (1 mg for every 5 mg of elemental iron ingested) in a group of healthy, fasting male subjects. In contrast, absorption of iron from ferrous sulfate and ferrous fumarate tablets was reduced by 37% and 31%, respectively, following administration of an antacid containing magnesium carbonate, magnesium hydroxide, and aluminum hydroxide in a study of healthy, iron-replete volunteers. Similarly, in a study of nine patients, coadministration of 5 mg of ferrous sulfate with a 35 gram dose of magnesium trisilicate was found to reduce iron absorption by an average of more than 70%. The interaction reportedly does not occur in the presence of ascorbic acid, which may competitively bind with iron and prevent the interference with iron absorption.

MANAGEMENT: To minimize the potential for interaction, it may be appropriate to administer oral iron preparations at least two hours apart from antacids or other agents with acid-neutralizing effects.

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