Omeprazole Is Not Working For Acid Reflux: 9 Causes & Solutions.


What you need to know (Quick insights):


Too many factors contribute to the efficacy of Omeprazole for acid reflux (GERD). We can summarize the reasons why Omeprazole is not working in 3 broad categories: drug factors, patient factors, and disease factors.

The most common reasons why omeprazole is not working for acid reflux are not taking the right dose, not taking omeprazole at the right time, resistance to omeprazole. Also, some patient and disease factors may contribute to the resistance of omeprazole. For example, non-compliance to food and lifestyle modifications or the presence of GERD-like conditions.

A summary of the causes of resistance to Omeprazole:

  • Your body is breaking down Omeprazole too fast. 
  • You are not taking the right dose of Omeprazole.
  • You are not taking Omeprazole at the right time.
  • You are not sticking to the standard food and lifestyle advice for GERD.
  • Non-acid or Weak acid reflux.
  • Hiatus hernia causing severe acid reflux symptoms.
  • Other rare GERD-like Conditions such as residual acid reflux, esophageal hypersensitivity, and others.

Defining the cause of Omeprazole resistance is important, read the causes carefully. Also, it is vital to discuss the issue with your doctor. Your doctor will help you to safely and effectively choose the best solution.

1- You are not taking the right Proton Pump Inhibitor (PPI).

The Problem

One of the most common Problems we (doctors) encounter is the variable response to Proton Pump Inhibitors (PPIs). PPIs are the most effective acid reflux treatments.

Several medications present in this category such as:

  • Omeprazole (Prilosec ®).
  • Esomeprazole (Nexium ®).
  • Pantoprazole (Protonix ®).
  • Rabeprazole (Aciphex ®).
  • Dexlansoprazole (Kapidex ®, Dexilant ®).

What a PPI basically does is inhibiting the production of stomach acid. This will prevent the damaging effects of acid reflux in your esophagus (ref).

But what researchers found is that people respond differently to PPIs. Two people with the same GERD symptom severity taking the same dose of omeprazole can respond differently (ref).

This is different people handle omeprazole differently. Some will “deactivate” omeprazole more rapidly than others. 

After you take omeprazole, your body starts to break it down to eliminate it inside your liver. Your body uses specific types of liver enzymes called “Cytochromes” to deactivate medications such as omeprazole.

Different people have different amounts and levels of activities of cytochromes.

The difference between people is genetic in nature. Meaning that people are born with a natural ability to metabolize and deactivate omeprazole (they are called rapid metabolizers). While other people have a lower ability to metabolize omeprazole.

And as a result, omeprazole will not work effectively for acid reflux in people who are “rapid metabolizers”. While “slow metabolizer’ can benefit from omeprazole.

The solution:

Fortunately, PPIs are not deactivated by the same cytochrome enzyme inside your liver. And as a result, you have different responses to different groups of PPIs (ref).

If omeprazole is not working for you, switching to another PPI might be effective. For example, you can switch to:

  • Esomeprazole (Nexium ®).
  • Pantoprazole (Protonix ®).
  • Rabeprazole (Aciphex ®).
  • Dexlansoprazole (Kapidex ®, Dexilant ®).

But when to switch from omeprazole to another PPI?

Acid reflux is a complex medical condition. Don’t switch or change your medication without a discussion with your doctor.

Before you switch from omeprazole you should ensure that:

  • You are taking the right doses of omeprazole at the right time.
  • You’re following the standard diet and lifestyle advice.
  • You spend at least 8 weeks on the optimized omeprazole dose without response.
  • And switch only with permission from your doctor.

In people who are genetically resistant to omeprazole, switching to another PPI can dramatically improve the acid reflux symptom.

2- You are not taking the right dose of Omeprazole, at the right time.


Am I taking the right dose of omeprazole?

This is the first and most important question to ask when omeprazole is not working for your acid reflux.

Before deciding that omeprazole is not for you, you should first ensure that you’re:

  • Taking the right dose
  • At the right time
  • With the proper splitting of the doses
  • For a sufficient amount of time.

The right dose of omeprazole for acid reflux:

If you are not taking a suitable dose of omeprazole, it will not work for you. The usual dose of omeprazole is 20 to 40 mg once daily (ref). 

Omeprazole is considered not effective when taken in the maximum dose twice per day (40mg before breakfast and 40 mg before dinner).

  • If you are on omeprazole 20mg once daily, your doctor shall double the dose (40mg once or better,20mg twice)
  • If you are taking 40mg once daily, your doctor shall split the dose (20mg twice) as it is more effective than 40mg once).
  • If you are taking 20 mg of omeprazole twice, your doctor may consider maximizing the dose to 40 mg twice daily.

We consider omeprazole ineffective when there no response after 4-8 weeks of omeprazole 40 mg twice daily. After that, your doctor usually will decide to shift to another medication or request further investigations.

The right time to take omeprazole for acid reflux.

Any faulty use of omeprazole can lead to limiting its effects on acid reflux. 

Common examples of wrong use of omeprazole:

  • Taking omeprazole after meals.
  • Taking omeprazole directly before meals.
  • Taking omeprazole once daily AT NIGHT.
  • Not splitting the dose twice daily after a poor response from the once-daily regimen.

The general rules for taking omeprazole:

  • Must be on daily basis (taking sporadic doses will not allow your esophagus to heal from the damage caused by acid reflux).
  • Must be taken 30 to 60 minutes before food to work properly.
  • If you are planning to take it once daily, the dose should be before breakfast. It is evidenced that the morning dose is better than taking omeprazole before dinner.
  • Splitting into two doses is evidenced to be more effective than the once-daily dose ( 20 mg twice is better than 40 mg omeprazole once).
  • 40 mg twice daily is the maximum dose your doctor can prescribe. If no response after 4-8 weeks, you should shift to another medication.

5- Eating the wrong food.

Medications are only a part of the formula of acid reflux relief. Many foods can worsen your GERD symptoms. This counteracts the positive effects of omeprazole on acid reflux.


Foods to avoid with GERD:

  • Foods that are high in fat such as junk food.
  • Caffeine, Chocolates.
  • Carbonated beverages.
  • Spicy food.
  • Peppermint.
  • Too muchoalcohol.


Also, some dietary habits may contribute to the worsening of your acid reflux symptoms. Such as:

  • Eating large meals: eating one or two big meals leads to fullness of your stomach. A full stomach will increase the chance of reflux into your esophagus (even if you are on omeprazole).
  • Eating before you sleep: gravity affects the food inside your stomach. While you lie down or sleep directly after eating, this will increase the risk of acid reflux.

For omeprazole to work properly for acid reflux, you have to:

  • Avoid the offending foods that are mentioned above.
  • Eat smaller, more frequent meals.
  • Avoid eating before your bedtime (for at least 2-3 hours).
  • Avoid lying down flat for at least one hour after meals.


6- Having a “Non-acid reflux” or “weak acid reflux”.


Omeprazole works by inhibiting acid secretion inside your stomach. This will prevent the refluxed stomach contents from damaging your esophageal tissues.

Omeprazole doesn’t decrease the volume of the refluxate or prevent the abnormal motility of the esophageal sphincter.

Unfortunately, acid is not the only factor that causes injury to the esophagus. Many factors contribute to the disease such as (ref):

  • The amount of the refluxate: in some cases, the refluxate is large in amount. Also, the refluxate may be slightly acidic “weakly acidic”, or not acidic at all “Non-acid reflux”. The large volume of the refluxate (without being acidic) can cause harm and symptoms. Thus, omeprazole will not work in such cases.
  • The time it stays inside your esophagus: The longer the refluxate stays inside your esophagus, the more damage and more symptoms will occur.
  • Esophageal injury from non-acid refluxate contents: such as stomach enzymes (Pepsin and trypsin), Bile acids, and the food itself can cause damage to the esophageal wall.

In the above 3 scenarios, omeprazole will not help with GERD. Discuss the issue with your doctor. 


The solution:

Measuring the acidity of the refluxate is done via special devices. And according to the results, your doctor will discuss the best options for the treatment.

MORE: Is Omeprazole an Antacid? Differences Explained.

7- GERD-like Conditions.

Acid reflux is the cause of heartburn in the majority of cases. However, other causes can cause heartburn and other GERD-like symptoms:


A- Reflux hypersensitivity.

The esophageal wall tolerates small amounts of physiological (normal) reflux. This physiological reflux occurs in the majority of people without symptoms. And it usually causes no harm to your esophageal lining.

However, some people are more sensitive to pain than others. The condition is called “esophageal hypersensitivity”. In such a case, People perceive non-painful esophageal stimuli as being painful (ref). 

In such a case, omeprazole and other PPIs may not work for your symptoms. And your doctor may prescribe a Pain-modulating medication. Discuss the issue with your doctor.

There is limited data on research about how common is reflux hypersensitivity.


B- Residual acid reflux.

Normally, after the reflux episode, your esophagus will start to clear the refluxed contents into the stomach again. Failure or delay to remove the refluxate from the esophagus will result in worsening of symptoms. Omeprazole may become ineffective for your symptoms in this case (ref).


C- Other conditions that mimic GERD symptoms:

Not having acid reflux at all is undoubtedly one of the causes omeprazole is not working. Many rare conditions can cause persistent symptoms mimicking acid reflux:

  • Biliary reflux.
  • Eosinophilic esophagitis.
  • Achalasia.
  • Esophageal cancer.
  • Rumination syndrome.


8- Not elevating your head while you’re sleeping.

One of the most effective modifications is to elevate your head during sleep. Lying flat will cause more reflux episodes (especially at night). And this can happen despite the optimum dose of omeprazole for acid reflux.

Using a wedge pillow can dramatically improve your GERD symptoms (ref).

wedge pillow for gerd

9- Functional dyspepsia and Functional Heartburn.

Functional dyspepsia is a very common condition. It affects 10-20% of people (ref). Commonly, people with functional dyspepsia are misdiagnosed as acid reflux. Consequently, acid reflux medications (as omeprazole) will not work.

Learn more about functional dyspepsia.

Functional heartburn is another functional gut disorder. People with functional heartburn complain of typical GERD symptoms without any evidence of the presence of acid reflux.

The diagnosis of such conditions can be challenging, even to experienced gastroenterologists. Discussing the issue with your doctor will determine the best option for you.

Defining the cause of omeprazole non-response is important to determine the best alternative.