Proton Pump Inhibitor Allergy

Allergic reactions to proton pump inhibitors (PPIs) are not common, but it's possible that you could have an allergy to one or more PPI. Reported reactions have included urticaria, asthma, and, rarely, anaphylaxis.

These medications are commonly used for the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer disease, as well as in conjunction with antibiotics for the treatment of certain stomach infections. They are generally very safe, with few side effects.

PPIs include:

  • Prilosec (omeprazole)
  • Nexium (esomeprazole)
  • Protonix (pantoprazole)
  • Aciphex (rabeprazole)
  • Prevacid (lansoprazole)

Omeprazole, lansoprazole, and esomeprazole are available over-the-counter (OTC), without a prescription, and pantoprazole and rabeprazole are available only by prescription.

Woman looking at medication
BSIP / UIG / Universal Images Group / Getty Images


It is often difficult to identify a PPI as the cause of an allergic reaction since other potentially allergy-inducing medications, including non-steroidal anti-inflammatories (NSAIDs) and antibiotics such as penicillins, are often given in conjunction with PPIs. There is no FDA-approved blood or skin test to help rule in or out a diagnosis of PPI allergy.

A few small studies have been performed on people who have experienced allergic reactions as a result of taking PPIs.

Experimental skin testing, including both prick and intradermal methods, has been performed using PPIs A small study included nine participants who had a definite history of immediate reactions due to PPIs. The experimental skin tests appeared to be helpful in identifying the cause of their allergic reactions, especially when the PPI was the cause. Oral challenges using the culprit PPI resulted in symptoms of an allergic reaction when the skin test was positive, and there was over a 90% correlation between the skin test and the oral challenge.

Cross-Reactivity Between Proton Pump Inhibitors

PPIs work by blocking acid pumps in the stomach, which decreases acid production. Because they are effective in treating a variety of gastrointestinal conditions, your healthcare provider might consider prescribing a different PPI for you than the one that caused your allergic reaction.

The five different PPIs don’t share the same chemical structure, which suggests that if a person were allergic to one PPI, one or more of the other PPIs might be tolerated.

Studies performed on the cross-reactivity of proton pump inhibitors have found that:

  • People allergic to omeprazole may be allergic to pantoprazole
  • People allergic to lansoprazole may be allergic to rabeprazole.
  • People allergic to omeprazole or pantoprazole are often able to take lansoprazole or rabeprazole
  • People allergic to lansoprazole or rabeprazole are often able to take omeprazole or pantoprazole.

However, if you've had an allergic reaction, your healthcare provider might confirm that you aren't allergic to a different PPI before prescribing another one for you—especially if you had a severe reaction.

After you've had an allergic reaction as a result of taking a particular PPI, your allergist might perform a skin test using the PPI(s) in question. If skin testing for the culprit PPI is positive, then skin testing to a non-cross-reacting PPI may be performed in an attempt to find a PPI that you can tolerate. Depending on your previous allergic reaction, a medically supervised oral challenge may be done to determine which PPIs(s), if any, you could safely tolerate in the future.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. González P, Soriano V, López P, Niveiro E. Anaphylaxis to proton pump inhibitors. Allergol Immunopathol (Madr). 2002;30(6):342-3. doi: 10.1016/s0301-0546(02)79150-7

  2. Bonadonna P, Lombardo C, Bortolami O, et al. Hypersensitivity to proton pump inhibitors: diagnostic accuracy of skin tests compared to oral provocation test. J Allergy Clin Immunol. 2012;130(2):547-9. doi: 10.1016/j.jaci.2012.04.048

  3. Lobera T, Navarro B, Del pozo MD, et al. Nine cases of omeprazole allergy: cross-reactivity between proton pump inhibitors. J Investig Allergol Clin Immunol. 2009;19(1):57-60.

  4. Pérez pimiento AJ, Prieto lastra L, Rodríguez cabreros MI, González sánchez LA, Mosquera MR, Cubero AG. Hypersensitivity to lansoprazole and rabeprazole with tolerance to other proton pump inhibitors. J Allergy Clin Immunol. 2006;117(3):707-8. doi:10.1016/j.jaci.2005.11.001

Additional Reading
  • Chang YS. Hypersensitivity Reactions to Proton Pump Inhibitors. Curr Opin Allergy Clin Immunol. 2012;12:348-53.

By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.