Drug Interactions between ferric carboxymaltose and moexipril

MONITOR: Limited data suggest that ACE inhibitors may increase the risk and/or severity of systemic adverse effects associated with parenteral administration of iron. The exact mechanism of interaction is unclear. Certain systemic reactions stemming from intravenous iron therapy are thought to be mediated by inflammatory substances such as bradykinin in response to iron-catalyzed generation of toxic free radicals. Since ACE inhibitors decrease the breakdown of kinins, it is conceivable that they may potentiate these reactions. In one report, the authors described three patients treated with enalapril who developed systemic reactions to intravenous ferrigluconate (sodium ferric gluconate). The first patient was a 55-year-old man with iron deficiency anemia 20 years after a partial gastrectomy. He received ferrigluconate 125 mg daily for 3 days without incident. However, a day after enalapril was added to his medication regimen, the patient experienced diffuse erythema, nausea, vomiting, abdominal cramps, and hypotension following infusion of only a few drops of ferrigluconate solution. The patient recovered after treatment with 200 mg of hydrocortisone hemisuccinate. Subsequently, he was able to tolerate a 10-day course of ferrigluconate in the absence of enalapril, and later resumed enalapril therapy uneventfully. The other two patients were women, 37 and 48 years old, who were treated with enalapril for 6 and 12 months, respectively. Both had similar reactions to their first ferrigluconate infusion as reported in the previous case. They received no further treatment with ferrigluconate and were able to continue taking enalapril alone. The authors noted that during the same period at that clinic, 15 patients who were not on ACE inhibitors received intravenous iron therapy without notable problems. In contrast, a single-dose study conducted in over 2500 chronic hemodialysis patients comparing the safety of sodium ferric gluconate complex (SFGC) to placebo and historical iron dextran controls found no significant difference in the rates of adverse events among subjects who received concomitant ACE inhibitor therapy (n=707) and those who didn't. Results from a follow-up study to evaluate the long-term safety of SFGC over nine months also found no effect of ACE inhibitor use on frequency or severity of adverse reactions following repeated SFGC infusion.

MANAGEMENT: No specific intervention is necessary to avert a potential interaction. However, patients should be closely monitored during and after parenteral iron treatment.