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Protonix side effects and how to avoid them

Protonix side effects may include headache, diarrhea, and malabsorption of certain nutrients. Learn how to avoid these and other risks while taking PPIs like Protonix.

Common Protonix side effects | Headache | Diarrhea | Serious side effects | Infections | Malabsorption | Kidney problems | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Protonix (pantoprazole sodium) is a powerful stomach acid reducer, most renowned for its treatment benefits in gastroesophageal reflux disease (GERD), also known as acid reflux. The severity of GERD cases can range from simple heartburn to erosive esophagitis (an ulcerated and inflamed esophagus). Treatment with Protonix is also indicated for hypersecretory conditions of the stomach (excessive acid secretion such as in Zollinger-Ellison Syndrome), H. pylori bacterial infections of the stomach, and upper gastrointestinal bleeding. 

The drug falls within the proton pump inhibitor (PPI) class of medications, whose other brand names in this drug class include Nexium (esomeprazole), Prilosec (omeprazole), and Prevacid (lansoprazole). Like these other PPIs, Protonix has great utility for the treatment of stomach conditions, but enthusiasm for its use must be tempered by the knowledge of its potential side effects.

RELATED: What is Protonix?

Common side effects of Protonix

The following are the most commonly reported Protonix side effects:

  • Nausea or vomiting
  • Diarrhea or constipation
  • Stomach pain
  • Flatulence (excess gas)
  • Headache or dizziness
  • Arthralgias (joint pains)
  • Elevated AST or ALT liver enzymes
  • Fever, upper respiratory infection, or rash in pediatric patients
  • Thrombophlebitis (vein inflammation) with intravenous use
  • Vitamin B12 deficiency with long-term use
  • Stomach polyps with long-term use


Headache is one of the most commonly experienced adverse effects of Protonix. One study found 14% of subjects taking pantoprazole had headaches. A persistent, severe, or worsening headache warrants medical attention.


Another of the more common adverse reactions, diarrhea can be experienced by 4% to 9% of individuals during Protonix therapy. Compared with two other PPIs, lansoprazole and omeprazole, in one study, pantoprazole did not have a higher incidence of diarrhea. When diarrhea becomes severe and watery or accompanied by fever or abdominal pain, a healthcare provider should be consulted. These symptoms could be caused by clostridium difficile (c. diff) infection, a bacterial infection that usually follows an antibiotic course that wipes out the good bacteria in the intestinal tract.

Serious side effects of Protonix

Protonix is also associated with some more severe adverse reactions, such as:

  • C. diff-associated diarrhea
  • Allergic reactions or anaphylaxis
  • Severe skin rash or blistering (Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme)
  • Kidney function impairment or tubulointerstitial nephritis (inflammation within the kidney)
  • Liver function impairment
  • Pancreatitis (pancreas inflammation)
  • Rhabdomyolysis (muscle damage and breakdown)
  • Bone fractures
  • Systemic lupus erythematosus
  • Low sodium levels
  • Low magnesium levels with prolonged use
  • Abnormal blood cell counts


Certain infections seem to occur more often during PPI therapy. A heightened incidence of C. diff infection and other intestinal infections, such as salmonella, has been noted with PPI use. An increased risk of pneumonia has also been suggested but not proven.

Malabsorption of nutrients

Reducing the amount of acid in the stomach can affect nutrient absorption in the intestinal tract and may explain why certain nutrient levels can be low during therapy with Protonix or other PPIs. Hypomagnesemia (low magnesium levels) occurs more frequently in those taking PPIs. Low magnesium levels can cause weakness, tremors, and adverse effects on the heart. 

Vitamin B12-deficiency is more common during PPI treatment as well. A deficiency in vitamin B12 can lead to symptoms such as weakness, tiredness, and altered sensation and memory.

Calcium absorption is another concern for those taking PPIs like Protonix since calcium levels are one contributor to bone health. The Food and Drug Administration (FDA) has placed a warning on Protonix and other PPIs about a possible elevated risk of osteoporosis-related fracture, related to thinning of the bones. Consuming more dairy products and eating more acidic meals to augment calcium absorption can both help to maintain adequate calcium levels, as can supplemental calcium citrate if advised by a healthcare professional. 

Kidney problems

Clinical trials have shown PPI use to be associated with a higher risk of chronic kidney disease. The association may simply be coincidental, as a direct causal link has not been proven. In addition, an acute kidney disease termed tubulointerstitial nephritis can occur in rare instances with Protonix and other PPI use. These risks, compared with the medication’s benefits, are best discussed with the treating medical provider.

How long do Protonix side effects last?

Many adverse effects from Protonix, such as headache or mild diarrhea, can be expected to resolve shortly after stopping the medication. Others, like hypomagnesemia or c. diff infection, may require active treatment.

Protonix contraindications and warnings

Abuse and dependence

Protonix is not habit-forming. However, stopping Protonix abruptly after prolonged use may cause a rebound effect on gastric acid production and resultant GERD or heartburn symptoms. Discussing how best to stop Protonix with a healthcare professional is advisable, since they may recommend a gradual taper off the drug.


The typical maximum oral dose of Protonix is 40 mg twice daily, but high doses are used occasionally. An overdose of Protonix warrants emergency medical attention and a call to the Poison Help line at 1-800-222-1222.


Pre-existing low magnesium levels are reason for caution before initiating Protonix therapy. Age is another important consideration, as approval extends down only to age 5, and data from clinical studies in children younger than 5 years is limited. 

Caution is advised before use during pregnancy due to potential risks and limited data. Similarly, given the paucity of clinical trials during lactation, it’s believed that a limited amount of drug is excreted into breast milk but it’s not known whether Protonix affects milk production. Careful discussion of potential risks and benefits is necessary before using Protonix while breastfeeding.

Protonix interactions

The list of potential drug interactions with Protonix is lengthy. Most of the interactions involve a change in the effectiveness of the other medication.

  • Protonix should not be used with the antiviral medications nelfinavir and rilpivirine and avoidance in the setting of other antivirals, like atazanavir, may be advisable as well. The antiviral activity of the drugs could be negatively affected.
  • The antifungal ketoconazole may also need to be avoided due to altered absorption and effectiveness. 
  • Warfarin, digoxin, and methotrexate are some of the common medications with serious potential adverse reactions whose effects need to be closely monitored when taken concurrently with Protonix.

How to avoid Protonix side effects

  1. Take Protonix delayed-release tablet or packet of granules on an empty stomach at least 30 minutes before the morning meal to maximize effectiveness.
  2. Review your list of over-the-counter (OTC) and prescription drugs with the healthcare provider and inspect for interactions prior to starting Protonix and at every appointment.
  3. While Protonix may need to be used indefinitely, unnecessary long-term use of this drug is not uncommon, and the adverse effects of the drug become more of a concern over time. Consequently, it is worthwhile to discuss the intended duration of Protonix at each appointment. The discussion can also involve less potent alternatives like OTC antacids and Pepcid.
  4. Monitoring magnesium and vitamin B12 levels may be recommended during long-term Protonix use.