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

MONITOR: Coadministration of thiazide diuretics with high dosages of calcium and/or vitamin D has been associated with reports of hypercalcemia in some patients. Thiazide diuretics inhibit the renal excretion of calcium and may also enhance responsiveness of bone and renal tubule to parathyroid hormone, thus concurrent use of large amounts of calcium or vitamin D can lead to excessively high plasma levels of calcium. Patients who are particularly susceptible include those with hyperparathyroidism, those being treated for osteoporosis, and those receiving high dosages of vitamin D for hypoparathyroidism. Metabolic alkalosis and the milk-alkali syndrome have been reported during prolonged therapy with thiazide diuretics and calcium.

MANAGEMENT: Patients receiving thiazide diuretic therapy should be cautioned against self-treatment with calcium and vitamin D supplements without first talking to their healthcare provider. Serum calcium should be monitored if thiazide diuretics are coadministered with high dosages of calcium and/or vitamin D. Patients should be advised to seek medical attention if they experience signs and symptoms of hypercalcemia such as dizziness, weakness, lethargy, headache, myalgia, anorexia, nausea, vomiting, and seizures.

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: Coadministration of thiazide diuretics with high dosages of calcium and/or vitamin D has been associated with reports of hypercalcemia in some patients. Thiazide diuretics inhibit the renal excretion of calcium and may also enhance responsiveness of bone and renal tubule to parathyroid hormone, thus concurrent use of large amounts of calcium or vitamin D can lead to excessively high plasma levels of calcium. Patients who are particularly susceptible include those with hyperparathyroidism, those being treated for osteoporosis, and those receiving high dosages of vitamin D for hypoparathyroidism. Metabolic alkalosis and the milk-alkali syndrome have been reported during prolonged therapy with thiazide diuretics and calcium.

MANAGEMENT: Patients receiving thiazide diuretic therapy should be cautioned against self-treatment with calcium and vitamin D supplements without first talking to their healthcare provider. Serum calcium should be monitored if thiazide diuretics are coadministered with high dosages of calcium and/or vitamin D. Patients should be advised to seek medical attention if they experience signs and symptoms of hypercalcemia such as dizziness, weakness, lethargy, headache, myalgia, anorexia, nausea, vomiting, and seizures.