Absorption of levothyroxine when coadministered with various calcium formulations

Abstract

Background: Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption.

Materials and methods: The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs.

Results: Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone.

Conclusions: Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations.

FIG. 1.

Mean serum concentrations of thyroxine (T4) over a 6-hour period after administration of levothyroxine with and without calcium formulations in eight subjects. Standard error bars are omitted for clarity. Standard errors were 0.37–0.49 μg/dL at baseline, 0.43–1.13 μg/dL at 60 minutes, and 0.50–0.76 μg/dL at 240 minutes; the standard errors overlapped at all time points for all tests.

FIG. 2.

Area (above baseline) under the serum T4 concentration curve in eight normal subjects receiving levothyroxine alone or simultaneously with study medications. Closed circles show values for individual subjects, whereas open circles indicate the mean value for each test; bars indicate standard error of the mean.