Drug Interactions between calcium / ferrous fumarate / vitamin d and fludrocortisone

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.

MONITOR: Use of systemic corticosteroids may reduce the effects of vitamin D and its analogs, though the exact mechanism is likely multifaceted. In general, corticosteroid use leads to increased excretion of calcium, whereas vitamin D promotes calcium absorption and is often administered with calcium to increase the absorption. Another potential mechanism involved is that long-term steroid use can contribute to weight gain and vitamin D is a fat-soluble vitamin; therefore, the bioavailability of vitamin D may be reduced in overweight and/or obese patients. Additionally, some studies have suggested that corticosteroid use increases the breakdown of 25-hydroxyvitamin D (25(OH)D), the active metabolite of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). However, several studies examining this theory found no significant differences when the levels of 25(OH)D in patients treated with corticosteroids were compared to the levels measured either pretreatment or in control groups. The results may be demonstrating a lack of effect on 25(OH)D or could be related to limitations in the studies themselves. Regardless of the exact mechanism, the 2001-2006 National Health and Nutrition Examination Survey from the United States reported that 25(OH)D deficiency (levels less than 25 nmol/L or 10 ng/mL) was more than twice as common among children and adults who reported oral steroid use (11%) than in nonusers (5%).

MANAGEMENT: Increased monitoring of calcium and vitamin D levels may be advisable in patients on systemic corticosteroids. Depending on the patient's levels, increased vitamin D supplementation may be required during coadministration. The severity of this interaction is likely impacted by the dosage and/or duration of the systemic corticosteroid. Consultation with relevant local and/or national guidelines may be helpful when deciding on vitamin D dosing as well as goal vitamin D levels.

Antacids and agents with acid-neutralizing effects may impair the oral absorption of dexamethasone, prednisolone, prednisone, and other orally administered corticosteroids, although data from published studies are somewhat conflicting. The mechanism of interaction and clinical significance are unknown. No particular intervention is necessary during concomitant therapy with these agents, but clinicians should be aware of the potential for interaction.