Can esomeprazole cause leg pain? Exploring Potential Links and Mechanisms

October 11, 2025 •

3 min read

While not a common side effect, prolonged use of esomeprazole can lead to deficiencies that manifest as leg pain. This article explores the specific ways this medication may affect musculoskeletal health, leading to discomfort in the legs, and what steps you can take.

Quick Summary

Esomeprazole, a proton pump inhibitor (PPI), can cause leg pain indirectly through complications like low magnesium (hypomagnesemia) and vitamin B12 deficiency, particularly with long-term use. Other less common causes include peripheral edema and kidney issues.

Key Points

Leg pain is a possible, though uncommon, side effect: While not directly caused by the medication in most cases, esomeprazole use, especially long-term, can lead to conditions that cause leg pain.
Hypomagnesemia is a key cause: Prolonged use of esomeprazole can cause low magnesium levels, which can lead to muscle cramps, spasms, and weakness in the legs.
Vitamin B12 deficiency is another factor: Long-term use can interfere with Vitamin B12 absorption, potentially causing nerve pain, tingling, and numbness in the legs.
Musculoskeletal issues can contribute: The medication has been associated with general muscle and joint pain, as well as an increased risk of bone fractures with long-term use.
Fluid retention can cause discomfort: Some individuals may experience peripheral edema (swelling of the legs and feet) as an infrequent side effect, which can feel like pain.
Always consult a healthcare provider: If you experience persistent leg pain while on esomeprazole, speak with your doctor to determine the underlying cause and appropriate treatment.

Understanding Esomeprazole and Its Role

Esomeprazole, commonly known by the brand name Nexium, is a proton pump inhibitor (PPI) used to reduce stomach acid production. It is prescribed for conditions like gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome. PPIs work by blocking the enzyme in the stomach wall that produces acid. While generally safe for short-term use, the potential for side effects, including leg pain, increases with prolonged therapy.

Potential Causes of Esomeprazole-Related Leg Pain

When patients experience leg pain while on esomeprazole, it is often not a direct effect of the medication but a consequence of long-term use. Several mechanisms are at play, primarily related to the medication's impact on nutrient absorption.

Hypomagnesemia (Low Magnesium Levels)

Long-term use of PPIs, typically for more than one year, can lead to decreased magnesium absorption in the gut, resulting in hypomagnesemia. Magnesium is vital for proper nerve and muscle function. A deficiency can cause a range of symptoms, including:

Muscle cramps in the hands, feet, and legs
Muscle weakness and fatigue
Muscle spasms and tremors

In severe cases, hypomagnesemia can also lead to more serious issues like irregular heartbeats and seizures. For individuals on long-term esomeprazole therapy, healthcare providers may monitor magnesium levels, especially if symptoms arise.

Vitamin B12 Deficiency

Another potential long-term effect of esomeprazole is a reduction in vitamin B12 absorption. Stomach acid is needed to release vitamin B12 from food so it can be absorbed. By reducing stomach acid, PPIs can impede this process. A prolonged vitamin B12 deficiency can lead to neurological issues, including:

Tingling or numbness in the hands and feet
Generalized muscle weakness
Nerve pain, which can be felt in the legs

Musculoskeletal Issues

Esomeprazole has been linked to various musculoskeletal side effects, though they are less common. These can include joint pain (arthralgia), muscle pain (myalgia), and generalized muscle weakness. Some studies have also indicated that prolonged, high-dose PPI therapy can increase the risk of osteoporosis-related bone fractures, particularly in the hip, wrist, or spine. Changes in bone metabolism could potentially contribute to overall lower body discomfort.

Fluid Retention (Peripheral Edema)

Infrequently, some individuals may experience fluid retention, or peripheral edema, as a side effect of esomeprazole. This can cause swelling in the legs, ankles, and feet, which may result in a feeling of heaviness or discomfort that some interpret as pain.

Kidney Problems

Though less frequent, long-term use of esomeprazole has been associated with kidney problems. Kidney injury can lead to swelling in the legs and feet, a symptom that could be confused with pain or soreness.

Comparison of Esomeprazole-Related Leg Pain Causes


Cause	Symptom Characteristics	Associated Factors	Treatment/Action
Hypomagnesemia	Muscle cramps, spasms, weakness, pain in legs.	Long-term use (>1 year), high doses, use with diuretics/digoxin.	Magnesium supplementation, potentially stopping PPI.
Vitamin B12 Deficiency	Numbness, tingling, nerve pain, general leg weakness.	Long-term use (>3 years).	B12 supplementation (oral or injections).
Musculoskeletal Effects	Joint and/or muscle pain, increased fracture risk.	Prolonged use.	Pain management, dose review by doctor.
Peripheral Edema	Swelling in ankles, feet, or legs.	Infrequent side effect.	Diuretic therapy, review of medication dose.
Kidney Problems	Swelling of legs/feet, changes in urination.	Long-term use.	Medical evaluation and kidney function monitoring.

When to Contact Your Doctor

It is important to differentiate between minor aches and more serious medication-related issues. You should contact your healthcare provider if you experience any of the following while taking esomeprazole:

Persistent or worsening muscle cramps or spasms
Unusual numbness or tingling in your hands or feet
Significant muscle weakness or unusual fatigue
Swelling in your legs, ankles, or feet
Signs of a more serious allergic reaction, such as a rash or swelling
Concerns about long-term use and potential mineral or vitamin deficiencies

Conclusion

While esomeprazole is a safe and effective treatment for many gastrointestinal conditions, it is crucial to be aware of its potential long-term side effects, including those that can lead to leg pain. The link between esomeprazole and leg pain is most commonly due to mineral deficiencies, specifically hypomagnesemia, and vitamin B12 deficiency resulting from reduced absorption over an extended period. Infrequently, other issues like fluid retention and kidney problems may contribute to symptoms. If you are experiencing persistent leg pain while on esomeprazole, it is essential to consult your healthcare provider for an accurate diagnosis and appropriate management plan. Adjusting dosage, supplementing nutrients, or switching medication may be necessary to resolve the issue.

For more detailed drug safety information, you can consult reliable sources like the FDA: FDA Drug Safety Communication.

Frequently Asked Questions

Esomeprazole can cause low magnesium levels by reducing the absorption of this mineral in the intestines, particularly with long-term use. This can lead to symptoms like muscle cramps and spasms in the legs.

While leg pain itself may not be severe, it can be a sign of underlying issues like hypomagnesemia or vitamin B12 deficiency. Severe deficiencies can lead to serious complications such as heart rhythm problems or neurological damage, so it is important to consult a doctor.

If leg pain is confirmed to be a result of esomeprazole, your doctor might recommend switching to a different medication. However, other PPIs can have similar effects on mineral and vitamin absorption, so an alternative class of medication or a different approach may be necessary.

If leg pain is caused by hypomagnesemia due to esomeprazole, magnesium levels often return to normal within days of stopping the medication. However, other causes or the severity of the deficiency may impact the timeline for improvement.

Prolonged and high-dose use of esomeprazole has been linked to an increased risk of bone fractures, especially in the hip, wrist, or spine. This is more concerning for older adults, and maintaining adequate calcium and vitamin D intake is recommended.

Yes, for leg cramps caused by low magnesium, magnesium supplementation is often required. In some cases, magnesium supplements alone are not enough, and the PPI may need to be discontinued.

The risk of leg pain from deficiencies like hypomagnesemia or vitamin B12 is very low with short-term use, such as the 14-day over-the-counter course. These issues are primarily linked to prolonged therapy.