Patients with renal anemia should allow at least a 1 hour interval between taking oral iron and molidustat to improve efficacy of the latter, investigators reported in the European Journal of Clinical Pharmacology.

“The decreased exposure of molidustat in the presence of oral iron supplementation may result from reduced absorption owing to chelation,” Silvia Lentini, a clinical pharmacist at Bayer AG in Wuppertal, Germany, and colleagues explained.

Dr Lentini’s team assessed the drug-drug interaction of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) under investigation for renal anemia, with oral iron (II sulphate or glycine sulphate) and calcium supplements. In 3 crossover studies, 42 healthy men received molidustat alone, under fasting conditions or with food, or combined with iron or calcium given immediately before or between 4 hours before and 1 hour after molidustat intake.

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Depending on whether men fasted or ate, concomitant iron intake reduced molidustat’s area under the curve (AUC) and maximum concentration (Cmax) by 50% to 75% and 46% to 84%, respectively, compared with molidustat monotherapy. Concomitant iron also reduced endogenous erythropoietin (EPO) AUC and Cmax by 31% to 44% and 36% to 48%, respectively. Iron’s interference declined as more time elapsed from molidustat ingestion. Taking iron 4 hours before molidustat, for instance, was associated with much smaller reductions in molidustat AUC and Cmax of 9% and 10%, respectively. Endogenous erythropoietin also was less affected as more time elapsed between iron and molidustat intake.

Concomitant calcium proved less troublesome. In a study, it reduced molidustat AUC and Cmax by 15% and 47%, respectively, without influencing erythropoietin response.

All treatments were well tolerated with relatively mild symptoms reported, including syncope, diarrhea, headache, and skin blemishes.

Dr Lentini and her collaborators suggested separating administration of the 2 drugs by at least 1 hour. The investigators do not anticipate that intravenous iron will affect molidustat exposure.

Disclosure: This clinical trial was supported by Bayer AG, the developers of molidustat. Please see the original reference for a full list of authors’ disclosures.

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Lentini S, Kaiser A, Kapsa S, Matsuno K, van der Mey D. Effects of oral iron and calcium supplement on the pharmacokinetics and pharmacodynamics of molidustat: an oral HIF–PH inhibitor for the treatment of renal anaemia [published online January 10, 2020]. Eur J Clin Pharmacol. doi: 10.1007/s00228-019-02813-y