Omeprazole Interactions

Long-term omeprazole use (typically >1 year) is associated with hypomagnesemia, likely via impaired active intestinal magnesium transport through TRPM6/TRPM7 channels. The FDA issued a formal Drug Safety Communication in 2011 warning of serious adverse events including arrhythmia, tetany, and seizures.

St. John's wort potently induces CYP3A4 and CYP2C19, the enzymes responsible for omeprazole metabolism. Co-administration significantly lowers omeprazole plasma concentrations, reducing its acid-suppressing efficacy and potentially compromising treatment of GERD, ulcers, or H. pylori eradication.

Omeprazole impairs absorption of calcium carbonate (the most common supplemental form) because dissolution and ionization require an acidic gastric environment. Long-term PPI use is associated with increased risk of hip, wrist, and spine fractures, prompting an FDA labeling change in 2010-2011.

Omeprazole suppresses gastric acid, which is required to cleave vitamin B12 from dietary proteins before it can bind intrinsic factor and be absorbed in the ileum. Long-term use (typically >2 years) is associated with measurably lower serum B12 levels and increased risk of clinical deficiency.

Omeprazole reduces absorption of nonheme (plant and supplemental) iron by raising gastric pH, which prevents the reduction of ferric (Fe3+) to absorbable ferrous (Fe2+) iron. Recent research also shows PPIs upregulate hepcidin and downregulate duodenal ferroportin, directly blocking iron export from enterocytes.