What are the side effects of vonoprazan?

October 8, 2025 •

4 min read

An integrated safety analysis of vonoprazan clinical trials in adults with gastroesophageal reflux disease (GERD) found it was well-tolerated and had a safety profile similar to proton pump inhibitors (PPIs). However, like all medications, it can cause various side effects, which range from common and mild gastrointestinal issues to rarer, more serious complications. Knowing what are the side effects of vonoprazan is important for anyone considering or currently taking this medication.

Quick Summary

This article outlines the side effects of vonoprazan, detailing common gastrointestinal complaints, infections, and rarer, more severe reactions. It also compares vonoprazan's safety profile with traditional PPIs and discusses the importance of monitoring for potential long-term risks like bone fractures, vitamin deficiencies, and hypergastrinemia.

Key Points

Common Side Effects: Mild gastrointestinal issues like diarrhea, nausea, abdominal pain, and bloating are frequently reported with vonoprazan use.
Potential for Serious Reactions: Though rare, vonoprazan can cause severe skin reactions (SJS/TEN), acute tubulointerstitial nephritis (kidney inflammation), and C. difficile-associated diarrhea.
Increased Risk with Long-Term Use: Prolonged therapy may increase the risk of bone fractures, fundic gland polyps, and deficiencies in magnesium and vitamin B12.
Hypergastrinemia Concern: Vonoprazan can raise serum gastrin levels more than PPIs, with long-term implications like mucosal hyperplasia requiring further study and monitoring.
Comparable Safety Profile to PPIs: Short-term studies show that vonoprazan's safety profile is comparable to proton pump inhibitors, with similar rates of most treatment-emergent adverse events.
Immediate Medical Attention: Seek immediate help for severe allergic reactions (swelling, breathing problems), signs of kidney issues, or severe, persistent diarrhea.

Understanding the Most Common Side Effects

Clinical trials have identified several frequently reported side effects associated with vonoprazan (brand name Voquezna), particularly those affecting the gastrointestinal system. These effects are often mild and may subside as the body adjusts to the medication. Common side effects reported by patients include:

Diarrhea
Nausea
Abdominal pain
Bloating
Gastritis (stomach lining inflammation)
Indigestion or upset stomach
Constipation
Altered sense of taste (dysgeusia)
Headache
Dizziness
Upper respiratory tract infections, like the common cold
Urinary tract infections (UTIs)

In most cases, these common adverse effects are manageable. For example, staying hydrated with electrolyte-containing fluids can help mitigate diarrhea, while avoiding certain foods may alleviate abdominal discomfort.

Serious Side Effects and Associated Risks

While less common, some serious side effects have been reported with vonoprazan and other acid-suppressing medications. It is important to be aware of these potential risks and contact a healthcare provider immediately if any of the following symptoms occur.

Acute Tubulointerstitial Nephritis (TIN)

This is a sudden inflammation of the kidneys that has been reported in people taking vonoprazan. Signs of kidney problems include:

A decrease or significant change in the amount of urine passed
Blood in the urine
Significant weight gain
Fever, rash, nausea, or vomiting

Severe Cutaneous Adverse Reactions (SCARs)

Rare but life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), can occur. Symptoms include:

Painful skin rash that may blister, peel, or bleed
Sores in the mouth, throat, nose, or eyes
Fever, body aches, and chills
Swollen lymph nodes

Clostridioides difficile (C. diff)-Associated Diarrhea (CDAD)

Treatment with acid-suppressing drugs may increase the risk of developing this severe form of diarrhea, especially in hospitalized patients. Symptoms include watery, severe, or bloody stools, stomach pain or cramps, and fever.

Bone Fractures

Observational studies have suggested a link between long-term, high-dose use of certain acid-reducing medications and an increased risk of osteoporosis-related bone fractures of the hip, wrist, or spine. To minimize risk, vonoprazan should be used for the shortest duration necessary.

Vitamin and Mineral Deficiencies

Vitamin B12 Deficiency: Long-term acid suppression can impair the body's ability to absorb vitamin B12. This can lead to symptoms like shortness of breath, fatigue, tingling or numbness in the limbs, and mood changes.
Low Magnesium (Hypomagnesemia): Low magnesium levels can occur with prolonged use and may lead to other electrolyte problems. Symptoms can include muscle cramps, seizures, and an irregular heartbeat.

Fundic Gland Polyps

Long-term use, especially beyond one year, is associated with a risk of fundic gland polyps, which are small growths in the stomach lining. These are typically asymptomatic and benign.

Hypergastrinemia

Vonoprazan can cause serum gastrin levels to increase more significantly than PPIs. While the long-term effects are not fully understood, some studies suggest a potential link between hypergastrinemia and gastric mucosal hyperplasia or malignancies. Regular gastroscopic examinations may be recommended for long-term users.

Comparing Vonoprazan and Proton Pump Inhibitors (PPIs): Side Effect Profile

Although vonoprazan and PPIs both suppress stomach acid, their mechanisms differ, which can influence their side effect profiles. Vonoprazan works by reversibly binding to the potassium site of the proton pump, while PPIs bind irreversibly.


Feature	Vonoprazan	Proton Pump Inhibitors (PPIs)	Comment
Mechanism of Action	Reversible, competitive inhibition of the gastric proton pump.	Irreversible inhibition of the gastric proton pump.	Vonoprazan's reversible action leads to faster onset and more sustained acid suppression.
Common Side Effects	Diarrhea, abdominal pain, bloating, nausea, gastritis, headache, and infection.	Similar common GI side effects, with some differences in prevalence.	Rates are generally comparable, but specific frequencies can vary.
Long-Term Risks	Bone fractures, Vitamin B12 deficiency, hypomagnesemia, fundic gland polyps.	Similar long-term risks, including bone fractures, Vitamin B12 deficiency, and hypomagnesemia.	The risk profile is generally similar for long-term adverse events, though specifics can differ.
Hypergastrinemia	Shown to increase serum gastrin levels more significantly than PPIs.	Increases serum gastrin levels, but typically less pronouncedly than vonoprazan.	Potential long-term implications of higher gastrin levels are under investigation.
Kidney Inflammation	Reports of acute tubulointerstitial nephritis.	Also associated with acute tubulointerstitial nephritis.	A potential risk for both drug classes, requiring evaluation if symptoms arise.

Conclusion

Vonoprazan offers a promising alternative to traditional PPIs for managing acid-related disorders like GERD and H. pylori infection, with a generally favorable short-term safety profile. While most patients experience mild and manageable side effects, it is crucial to be aware of the potential for more serious adverse reactions, especially with long-term use. These include kidney inflammation, severe skin reactions, C. difficile-associated diarrhea, and issues related to nutrient deficiencies and hypergastrinemia. Patients should always use the medication for the shortest duration appropriate for their condition and discuss all health history and concerns with their healthcare provider to weigh the benefits against potential risks. Prompt medical attention is necessary if any serious symptoms arise.

For more detailed information, consult the prescribing information for vonoprazan.

Frequently Asked Questions

Overall, the short-term safety profile of vonoprazan is comparable to that of traditional proton pump inhibitors (PPIs). Both share similar common gastrointestinal side effects. However, some long-term risks, like elevated gastrin levels, may differ between the two drug types.

Yes, vonoprazan can cause low magnesium levels (hypomagnesemia) in the body, which has been reported post-marketing. This risk increases with prolonged use, and regular monitoring may be necessary for patients on long-term therapy.

Vonoprazan can be prescribed for long-term use under medical supervision. However, prolonged use is associated with potential risks such as vitamin B12 deficiency, hypomagnesemia, bone fractures, and fundic gland polyps. A healthcare provider will weigh the benefits and risks of long-term therapy for each patient.

Published observational studies suggest that acid-suppressing drugs, including vonoprazan, may increase the risk of Clostridioides difficile-associated diarrhea (CDAD). Patients experiencing severe, watery diarrhea should contact their doctor.

Studies have suggested that PPI therapy and possibly vonoprazan, particularly with high-dose and long-term use (a year or more), may be associated with an increased risk of hip, wrist, or spine fractures. The shortest effective treatment duration is recommended.

If you experience any serious side effects, such as a severe skin rash with blistering, difficulty breathing, or symptoms of kidney problems or low magnesium, you should contact your doctor or seek emergency medical help immediately.

Hypergastrinemia is an elevation of serum gastrin levels. Vonoprazan is known to increase these levels more significantly than PPIs. While the long-term clinical implications are not fully known, it has been linked to gastric mucosal changes and requires monitoring in some patients.