Ferrous sulfate does not reduce serum levels of famotidine or cimetidine after concurrent ingestion.
A series of randomized crossover studies were performed to determine whether there was a reduction in serum levels of cimetidine and famotidine when coingested with ferrous sulfate (300 mg). Coingestion of a ferrous sulfate tablet with cimetidine (300 mg) was associated with little reduction in serum cimetidine area under the curve (AUC) (mean versus mean, 20.8 versus 23.4 mumol.hr/L; mean percentage difference, -11%; 95% confidence interval [CI] of percentage difference, -26% to 4.2%) or peak concentration (Cmax) (mean versus mean, 5.1 versus 6.1 mumol/L; mean percentage difference, -16%; CI of percentage difference, -36% to 4%). Similarly, ferrous sulfate solution coingested with cimetidine caused little change in cimetidine AUC (mean versus mean, 19.9 versus 23.0 mumol.hr/L; mean percentage difference, -13%; CI of percentage difference, -34% to 7%) or Cmax (mean versus mean, 5.0 versus 5.0 mumol/L; mean percentage difference, 1%; CI of percentage difference, -18% to 20%). Concurrent ingestion of famotidine (40 mg) with a ferrous sulfate tablet did not result in significant reductions in serum famotidine AUC (mean versus mean, 1.78 versus 1.99 mumol.hr/L; mean percentage difference, -10%; CI of percentage difference, -34% to 13%) or Cmax (mean versus mean, 0.31 versus 0.32 mumol/L; mean percentage difference, -3%; CI of percentage difference, -27% to 22%). The formation of famotidine:iron(III) complexes was shown in methanol but was not observed in an aqueous buffer at pH 6.5. Ranitidine did not bind iron in an aqueous buffer and only weakly bound iron in methanol. Coingestion of ferrous sulfate with either cimetidine or famotidine does not cause a clinically relevant reduction in serum histamine H2-receptor blocker levels and, on the basis of in vitro binding experiments, iron is unlikely to interact with ranitidine.
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