Omeprazole Interactions

Long-term omeprazole use (typically more than a year, occasionally sooner) can lower body magnesium, likely by impairing active intestinal magnesium transport through the TRPM6/TRPM7 channels. The FDA issued a formal Drug Safety Communication in 2011 warning that prescription proton pump inhibitors can cause hypomagnesemia, with serious cases involving abnormal heart rhythm, muscle spasm (tetany), and seizures.

St. John's wort induces the liver enzymes CYP3A4 and CYP2C19 that break down omeprazole. Taking the two together speeds up omeprazole clearance, lowers its blood levels, and can weaken its acid-suppressing effect — potentially undermining treatment of GERD, ulcers, or H. pylori eradication.

Omeprazole strongly suppresses stomach acid, and calcium carbonate (the most common supplemental form) needs that acid to dissolve and be absorbed efficiently, especially on an empty stomach. Calcium citrate absorbs well regardless of stomach acid. Long-term proton pump inhibitor use is also associated with a modestly increased risk of hip, wrist, and spine fractures, which prompted an FDA labeling change.

Omeprazole suppresses gastric acid, which is needed to release vitamin B12 from dietary proteins before it can bind intrinsic factor and be absorbed. With long-term use this can lower serum B12 and, over time, contribute to deficiency. Supplemental (crystalline) B12 is not affected because it does not depend on stomach acid.

Omeprazole reduces absorption of nonheme (plant and supplemental) iron by raising stomach pH, which hinders the conversion of ferric (Fe3+) iron to the absorbable ferrous (Fe2+) form. Population data link long-term proton pump inhibitor (PPI) use with a higher risk of iron deficiency. A second, hormonal mechanism involving hepcidin and ferroportin has been proposed but rests on laboratory and animal work, not human outcomes.