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; p < 0.001). Compared with the placebo group, the PPI group showed a slightly greater decline (β = -0.121, 95% CI -0.231 to -0.011; p = 0.031). Additionally, no differences were noted between groups regarding the occurrence of neuropathy (p = 0.77), anorexia (p = 0.77), diarrhea (p = 0.34), or constipation (p = 0.39). Omeprazole use was associated with a lower incidence of nausea and vomiting (p = 0.005).

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.