From the Guidelines
Long-term use of proton pump inhibitors (PPIs) can cause isolated hypomagnesemia in some patients, with a 71% higher risk reported in a meta-analysis of 16 observational studies 1. This side effect typically occurs after at least three months of continuous PPI therapy, though it's more commonly reported after a year or more of use. PPIs such as omeprazole, esomeprazole, pantoprazole, lansoprazole, and rabeprazole have all been associated with this condition. The mechanism involves decreased intestinal magnesium absorption, as PPIs inhibit active magnesium transport in the intestine by affecting TRPM6 and TRPM7 channels. Some key points to consider include:
- Patients may experience symptoms including muscle cramps, tremors, seizures, arrhythmias, and tetany when magnesium levels fall significantly.
- Those at highest risk include elderly patients, those on diuretics, and individuals with other conditions affecting electrolyte balance.
- Regular monitoring of magnesium levels is recommended for patients on long-term PPI therapy, particularly those with risk factors.
- If hypomagnesemia develops, options include magnesium supplementation, reducing the PPI dose, switching to an H2 receptor antagonist, or discontinuing the PPI if clinically appropriate, as suggested by recent clinical practice updates 1. It is essential to weigh the benefits and risks of PPI use and to regularly review the ongoing indications for use, as recommended by expert reviews 1.
From the FDA Drug Label
Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Low magnesium levels in your body. This problem can be serious Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment.
Long-term PPI use can cause hypomagnesemia, which is a condition of isolated low magnesium levels in the blood. This condition can be serious and may occur after at least three months of PPI treatment, usually after a year of therapy.
- Symptoms of low magnesium levels may include:
From the Research
Long-term PPI Use and Isolated Hypomagnesemia
- Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of hypomagnesemia, as reported in several studies 4, 5, 6, 7.
- A case report published in 2014 described a 73-year-old woman who developed hypomagnesemia while taking lansoprazole, which resolved after stopping the PPI 4.
- A quasi-experimental study conducted in 2022-2023 found that patients taking omeprazole for 12 months had significantly lower levels of magnesium compared to those taking sucralfate and famotidine 5.
- A population-based cohort study published in 2015 found that PPI use was associated with a lower serum magnesium level and an increased risk of hypomagnesemia, particularly with prolonged use and concomitant loop diuretic use 6.
- An analysis of FDA data from 1997 to 2012 found that 1.0% of PPI users reported hypomagnesemia, with pantoprazole having the highest rate and esomeprazole having the lowest rate 7.
- A review article published in 2019 noted that long-term PPI use may be responsible for an increased risk of magnesium deficiency, among other adverse effects 8.
Key Findings
- PPI use is associated with an increased risk of hypomagnesemia, particularly with prolonged use and concomitant loop diuretic use 6.
- Different PPIs have varying rates of hypomagnesemia, with pantoprazole having the highest rate and esomeprazole having the lowest rate 7.
- Hypomagnesemia is often associated with other electrolyte imbalances, such as hypocalcemia and hypokalemia 7.
- Long-term PPI use may be responsible for an increased risk of magnesium deficiency, among other adverse effects 8.