Hypomagnesemia Associated with Omeprazole Use in Patients Treated with Platinum Derivatives: An Exploratory Randomized Placebo-Controlled Clinical Trial.

Background: Hypomagnesemia, characterized by decreased levels of magnesium in the blood, is common among patients with cancer and may be related to the administration of proton pump inhibitors (PPIs) and/or platinum derivatives. Objective: To evaluate the safety and potential impact on serum magnesium levels of concomitant use of the PPI omeprazole in patients receiving a platinum derivative. Methods: This prospective, randomized, double-blind, single-dose, placebo-controlled study involved fixed doses of PPI administered on an outpatient basis. It spanned 4 cycles of platinum-based combination chemotherapy (21 days per cycle), and entailed a screening period (14 days before chemotherapy), 2 PPI treatment periods (total of 60 days), and a follow-up period (1 cycle). Patients recruited between May 2019 and March 2020 at 3 hospitals in Brazil were randomly assigned to receive placebo or PPI in a 1:1 ratio. Data analysis employed a linear mixed-effects model and Kaplan-Meier analysis. Results: A total of 164 patients were included in the study, 83 in the placebo group and 81 in the PPI group. Blood magnesium levels showed a modest decrease over time (by approximately 20%) across all patients. A correlation was observed between treatment duration and decrease in serum magnesium in the total sample (β = -0.035, 95% confidence interval [CI] -0.048 to -0.0021; Conclusion: These exploratory findings suggest that the concomitant use of omeprazole with platinum derivatives may be associated with a slightly faster rate of serum magnesium depletion than occurs with chemotherapy alone, but without clinical relevance or occurrence of frank hypomagnesemia. Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2.