Nexium side effects and how to avoid them

Common Nexium side effects include nausea and diarrhea. Learn how to avoid these and other side effects.

By Chad Shaffer, MD | Sep. 15, 2021

Marketed as “The Purple Pill” for decades, Nexium (esomeprazole magnesium) has been a popular treatment for acid reflux or gastroesophageal reflux disease (GERD). Nexium is a potent reducer of stomach acid and is also approved by the FDA to treat stomach ulcers and helicobacter pylori (H. pylori) stomach infections. It can also reduce the risk of gastric ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs). Nexium is a proton pump inhibitor (PPI), which includes alternatives like Prilosec (omeprazole), Prevacid (lansoprazole), and Protonix (pantoprazole). Being aware of Nexium side effects and drug interactions can be particularly helpful, as they may be avoidable.

Common side effects of Nexium

Nausea
Diarrhea
Constipation
Abdominal pain
Flatulence (excess gas)
Headache
Dizziness
Dry mouth
Vitamin B12 deficiency with long-term use
Stomach polyps with long-term use

Nausea and diarrhea

Gastrointestinal side effects may occur when taking Nexium. Nausea occurs in about 2% of people taking Nexium, and diarrhea is experienced by about 3%. If nausea is persistent or progresses to vomiting, then the attention of a healthcare professional is warranted. Also requiring medical attention, unrelenting diarrhea could be an indicator of a serious adverse effect called colitis. Two varieties of this disease of the large intestine occur at increased rates in those treated with PPIs. Microscopic colitis is related to inflammation of the bowel and clostridium difficile colitis (C.Diff) is caused by the proliferation of the bacterium clostridium difficile, usually due to the lack of good intestinal bacteria following antibiotic use. Both types of colitis manifest as severe, watery diarrhea.

Serious side effects of Nexium

C.Diff-associated diarrhea
Microscopic colitis
Hives, allergic reactions, or anaphylaxis
Severe skin rashes or blistering (Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme)
Kidney problems such as kidney function impairment or acute interstitial nephritis (inflammation within the kidney)
Liver function impairment
Pancreas inflammation
Bone fractures
Systemic lupus erythematosus
Barrett’s esophagus or esophageal ulcers, swollen veins, or tightening
Stomach ulcers
Low magnesium levels (hypomagnesemia) with prolonged use
Hernia
Abnormal blood cell counts

Side effects from long-term use of Nexium

Certain side effects of Nexium become a concern with prolonged use. For example, low levels of magnesium and vitamin B12 can be an issue after months to years of treatment. Long-term and even lifelong treatment with PPIs is not uncommon. At times, this may be related to an ongoing risk of stomach ulcers or GERD symptoms, and in other instances, the option for stoppage has simply never been revisited after an initial indication.

Consulting with a healthcare professional about whether or not to stop PPIs like Nexium has become more pertinent in recent years, largely due to questions being raised about other possible long-term PPI side effects. One such concern involves reduced bone density (osteoporosis), which may explain the finding of increased fracture risk after years of PPI use, although further study is still needed.

Cancer

Another worrisome question is related to a potential link between Nexium’s drug category and cancer. Stomach cancer risk has been elevated in clinical studies of long-term PPI use, but researchers are unsure whether this was coincidental or was caused by PPI use. Conversely, PPIs are recommended in the setting of Barrett’s esophagus to reduce the risk of esophageal cancer. The issue of cancer risk is one that calls for a discussion between the patient and their healthcare provider.

Dementia

Providers are also frequently asked about dementia risk with Nexium or other PPIs. Alarm was generated when a study found a heightened dementia risk among older users of PPIs. Other studies and reviews have not found the risk to be elevated. For the time being, PPI-related dementia risk has not been proven.

Kidney damage

Clinical trials have demonstrated a higher risk of chronic kidney disease among PPI users. However, it is uncertain if this has been merely coincidental. Coupled with the knowledge that Nexium and its fellow PPIs are linked to the acute kidney disease interstitial nephritis, the concern relating to chronic kidney disease may generate fear both in the short and long term. These risks, along with the medication’s benefits, are best discussed with a healthcare professional.

Hair loss

Another fear among some long-term Nexium users is hair loss. The concern is based on study data showing PPI use associated with an increased risk of alopecia areata, a condition marked by patchy hair loss. The jury is still out on whether PPIs can actually cause the condition.

How long do Nexium side effects last?

The duration of an adverse effect from Nexium can be quite variable. Short-term side effects like mild diarrhea, nausea, or headache will likely resolve with cessation of the medication. Long-term side effects, like low magnesium or vitamin B12 levels, may require treatment in order to resolve.

Nexium contraindications and warnings

Abuse and dependence

Nexium is not habit-forming. Nonetheless, it can be difficult to stop taking it. The reason is that GERD symptoms like heartburn and indigestion can strongly recur upon discontinuing Nexium. This experience is related to a surge in stomach acid production when a PPI is stopped. Consequently, slowly tapering off Nexium may be best.

Overdose

The maximum dose of Nexium is 40 mg twice daily, used for conditions like Zollinger-Ellison in which the amount of acid production is extremely high. High doses of Nexium can produce uncomfortable and sometimes dangerous effects, so emergency medical attention and a call to the Poison Control center at 1-800-222-1222 are necessary.

Restrictions

Age is typically not a restriction that applies often with Nexium use since dosing guidelines exist for 1-month-olds all the way up to seniors. Advanced liver disease and pre-existing low magnesium levels are two reasons for caution when considering the use of Nexium. Likewise, caution is advisable prior to use during pregnancy, as other types of acid reducers may have more safety data. Data on the safety of Nexium use while breastfeeding is also inadequate.

Nexium interactions

The list of potential drug interactions for Nexium is a long one. This relates to its metabolism through the liver’s p450 enzymes. Genetic differences can cause some individuals to have more severe interactions than others. A healthcare professional must review the medication list at the start and during the course of Nexium therapy. Certain examples are worth mentioning here.

Rilpivirine should not be used with Nexium. Other antivirals like saquinavir, nelfinavir, and atazanavir may need to be avoided or monitored.
Methotrexate, digoxin, tacrolimus, and warfarin are all medications with dangerous side effect potentials which may require extra monitoring if used concurrently with Nexium.
Concurrent Nexium may need to be avoided with the antifungals ketoconazole and voriconazole and the antibiotic rifampin.
Concerns exist about the blood thinner clopidogrel’s effectiveness being reduced when used alongside Nexium.
The antidepressant St. John’s Wort may diminish Nexium’s effectiveness.

How to avoid Nexium side effects

Taking Nexium on an empty stomach at least 30 minutes before the morning meal helps to generate maximum effectiveness.
Review the list of medications for interactions at every appointment with the healthcare provider. Interactions may occur between Nexium and prescription drugs, over-the-counter (OTC) medicine, and even natural products.
Discuss the intended duration of Nexium or potential discontinuation at each appointment.
Ask about monitoring magnesium and vitamin B12 levels during long-term Nexium use.