Does pantoprazole (Proton Pump Inhibitor) cause hypomagnesemia (low magnesium levels)?

From the Guidelines

Pantoprazole can cause hypomagnesemia, particularly with long-term use, as evidenced by the potential adverse associations reported in the literature 1. The association between proton pump inhibitors (PPIs), including pantoprazole, and hypomagnesemia has been noted in various studies, although the evidence is not entirely consistent due to limitations such as study heterogeneity and variable definitions of hypomagnesemia 1. Key points to consider include:

• The mechanism by which pantoprazole might interfere with magnesium absorption in the intestines, potentially leading to hypomagnesemia.
• The increased risk with longer durations of treatment and potential interactions with other medications that can lower magnesium levels.
• Symptoms of hypomagnesemia, such as fatigue, muscle cramps, tremors, seizures, and cardiac arrhythmias, which should prompt monitoring of magnesium levels in patients on long-term pantoprazole therapy. Given the potential for hypomagnesemia, monitoring of magnesium levels is recommended for patients on long-term pantoprazole therapy, especially if they develop unexplained symptoms 1. Considerations for management include:
• Magnesium supplementation if hypomagnesemia occurs.
• Discontinuation of pantoprazole in severe cases.
• Alternative acid-reducing medications like H2 blockers for patients who experience PPI-induced hypomagnesemia. It's also worth noting that while the American Gastroenterological Association does not currently recommend routine screening for nutrient deficiencies in individuals taking PPIs, FDA drug labels include precautionary notices regarding risks for hypomagnesemia, among other nutritional deficiencies 1.

From the FDA Drug Label

Low magnesium levels in your body can happen in people who have taken pantoprazole sodium delayed-release tablets for at least 3 months. Tell your doctor if you have symptoms of low magnesium levels, including seizures, dizziness, irregular heartbeat, jitteriness, muscle aches or weakness, and spasms of hands, feet or voice. Hypomagnesemia Advise patients to report any clinical symptoms that may be associated with hypomagnesemia to their healthcare provider, if they have been receiving pantoprazole sodium for at least 3 months [see WARNINGS AND PRECAUTIONS (5. 7)].

Yes, pantoprazole (Proton Pump Inhibitor) can cause hypomagnesemia (low magnesium levels), especially if taken for at least 3 months. Patients should be advised to report any clinical symptoms associated with hypomagnesemia to their healthcare provider 2 2 2.

From the Research

Association between Pantoprazole and Hypomagnesemia

• Pantoprazole, a proton pump inhibitor (PPI), has been associated with hypomagnesemia (low magnesium levels) in several studies 3, 4, 5, 6.
• A case report published in 2024 described a patient on long-term pantoprazole who presented with generalized tonic-clonic seizures and had severe hypomagnesemia, hypocalcemia, hypokalemia, and secondary hyperparathyroidism 3.
• Another study published in 2010 reported 10 cases of severe hypomagnesemia associated with long-term PPI therapy, including pantoprazole, and found that stopping PPI therapy led to prompt resolution of the hypomagnesemia 4.
• A 2020 case report described two patients who developed severe hypomagnesemia and hypocalcemia while taking pantoprazole, and found that discontinuation of the medication led to resolution of the electrolyte abnormalities 5.
• An analysis of FDA data published in 2013 found that pantoprazole had the highest rate of hypomagnesemia among all PPIs, with a significant association between hypomagnesemia and both hypocalcemia and hypokalemia 6.

Risk Factors for Pantoprazole-Associated Hypomagnesemia

• Long-term use of pantoprazole is a significant risk factor for developing hypomagnesemia 3, 4, 5.
• Age is also a risk factor, with elderly subjects (age >65 years) being at increased risk of PPI-associated hypomagnesemia 6.
• Male subjects are at higher risk of developing hypomagnesemia than female subjects 6.
• Hypocalcemia and hypokalemia commonly coexist with PPI-associated hypomagnesemia 6.

Short-Term Use of Pantoprazole and Hypomagnesemia

• A 2018 study found that short-term high-dose pantoprazole treatment did not significantly affect serum and urinary magnesium levels in patients 7.
• However, the study suggested that age and other contributing factors may have more impact on PPI-induced hypomagnesemia, and that patients aged over 60 years might be handled carefully under proton pump inhibitors treatment 7.