H2 Blockers vs PPI: Which Is Best for Acid Reflux?

A pharmacists explains the difference

Medically reviewed by Femi Aremu, PharmD

Acid reflux (gastroesophageal reflux) occurs when stomach contents enter your esophagus.

Up to one in five adults in the U.S. experience symptoms of acid reflux at least once a week. These symptoms can include the following:

• Heartburn, a burning sensation in the middle of the chest

• Sour taste in the mouth

• Regurgitation, stomach contents coming into the mouth or throat

• Chest pain

• Full feeling

Medications are often necessary to manage discomfort and prevent complications of acid reflux, such as:

• Gastroesophageal reflux disease (GERD)

• Gastrointestinal (GI) bleeding

• Ulcers

• Difficulty swallowing (dysphagia)

• Barrett's esophagus

H2 blockers and PPIs are the two main classes of medications used for acid reflux relief. These medicines can be prescribed by your healthcare provider or purchased over the counter (OTC). Read on for more details.

H2 Blockers vs PPI: How They Work

Both histamine-2 receptor antagonists (H2 blockers) and proton pump inhibitors (PPIs) decrease stomach acid but work differently.

H2 blockers reduce the production of stomach acid through a histamine receptor blockade.

Medications in this class include the following:

• Tagamet HB (cimetidine)

• Pepcid AC (famotidine)

• Axid AR (nizatidine)

In contrast to H2 blockers, PPIs directly block the proton pump responsible for producing stomach acid. For best results, take PPIs 30 to 60 minutes before your meal.

Medications in this class include the following:

• Prilosec (omeprazole)

• Nexium (esomeprazole)

• Prevacid (lansoprazole)

• Dexilant (dexlansoprazole)

• Protonix (pantoprazole)

• Aciphex (rabeprazole)

H2 Blockers vs. PPI Effectiveness

PPIs are the most effective medicines for acid reflux across the board. They relieve heartburn in up to 77% of people with esophagitis (inflammation of the esophagus) and 60% without esophagitis. They are even more effective in healing the esophagus and work in about 80% of esophagitis cases.

H2 blockers are less effective at treating reflux symptoms than PPIs. H2 blockers relieve heartburn in about 50% of people who take them for up to 12 weeks. They heal esophagitis in about 40% of people who take them.

How Long Do H2 Blockers vs. PPI Take to Work?

H2 blockers start working faster than PPIs, typically within one to three hours. In contrast, it may take up to four days to see the effects of PPIs.

The effects of PPIs last longer than those of H2 blockers. PPIs block stomach acid 15 to 21 hours a day versus about eight hours for H2 blockers.

Indications and Usage

PPIs are recommended for most cases of acid reflux. They are broadly used for conditions like the following:

• Severe cases of GERD

• Esophagitis

• Peptic ulcers

• Helicobacter pylori infections, in combination with antibiotics

However, there are some situations in which H2 blockers are typically recommended instead. Some of these include the following:

• "On demand" for occasional heartburn symptoms

• Maintenance, after successful treatment with PPIs has been stopped

• Breakthrough symptoms at night in people already taking PPIs

• Pregnancy

Side Effects and Safety

Taking prescription or over-the-counter (OTC) H2 blockers or PPIs may cause side effects and drug interactions. Some precautions for certain groups are also important to note.

Side Effects

The side effects of these two drug classes are similar, primarily affecting the gastrointestinal tract.

Common side effects of H2 blockers include the following:

• Diarrhea

• Constipation

• Drowsiness

• Headache

• Muscle pain

More serious side effects of these medicines include the following:

• Male breast enlargement

• Infections like pneumonia and gastrointestinal infections

Tolerance (tachyphylaxis) to H2 blockers can develop within as little as three days. This means the medicine doesn't work as well after the body gets used to it, and higher doses may be necessary to get the same results.

PPIs can cause the following side effects:

• Headache

• Nausea

• Diarrhea

• Stomach pain

Long-term use of PPIs is associated with some significant risks, which include the following:

• Bone fractures. Hip, wrist, or spine fractures are more likely when high doses of PPIs are taken for a year or more.

• Infections like pneumonia and gastrointestinal infections.

• Kidney disease.

• Vitamin B12 deficiency. This is more likely a concern if PPIs are taken over two years.

• Dementia. More robust research is necessary, but some data shows that taking PPIs for over four years increases the risk of dementia.

Deciding how long to use PPIs can be a tricky situation. Drug manufacturers recommend taking PPIs for less than eight weeks to reduce the risk of side effects. However, many people who use PPIs for GERD will stay on them indefinitely (lifelong) because stopping treatment often causes reflux symptoms to return.

Be sure to discuss the risks and benefits of prolonged PPI therapy with your healthcare provider for optimal safety.

Precautions

Keep in mind these precautions for the following groups:

• Pregnancy: H2 blockers plus antacids are recommended over PPIs. The long-term use of PPIs is not recommended during pregnancy due to a possible risk of congenital disabilities. Prilosec, for instance, has caused toxicity to fetuses in animal studies.

• Older adults: PPIs are typically not recommended for prolonged use in this population due to the risk of side effects.

• Children: Though H2 blockers and PPIs are generally safe in children, PPIs are preferred because they are more effective.

Interactions

H2 blockers and PPIs can cause some significant drug interactions. Here are a few important ones to keep in mind:

• H2 blocker Tagamet HB (cimetidine) interacts with medications broken down by liver enzymes. Tagamet HB can increase the effects of some seizure medicines, heart medicines, and antidepressants.

• PPIs can decrease magnesium levels in the body, particularly if taken for over one year. Your healthcare provider may monitor your magnesium levels, particularly if you take other medicines that can lower them, like digoxin or diuretics (water pills).

• PPIs Prilosec (omeprazole) and Nexium (esomeprazole) can decrease levels of the blood thinner Plavix (clopidogrel).

• Prilosec can increase the levels of methotrexate (a medicine taken for rheumatoid arthritis) and cause toxicity if they're taken together.

Recall Information

In 2020, the H2 blocker Zantac (ranitidine) was pulled from the market due to the presence of N‐nitrosodimethylamine (NDMA). NDMA is thought to be a carcinogen (cancer-causing agent).

The U.S. Food and Drug Administration (FDA) determined that levels of NDMA found in ranitidine could increase if stored at high temperatures.

Keep in mind that the product Zantac 360 that's currently available contains famotidine, not ranitidine.

How to Choose

The choice of which medicine to take for acid reflux may come down to factors such as the following:

• Symptom severity. If you're diagnosed with GERD or have complications of acid reflux, like ulcers or esophagitis, a PPI will work best.

• Frequency of symptoms. If symptoms of acid reflux happen rarely or are only associated with specific foods or drinks, taking H2 blockers only when you need them may be your best bet. On the other hand, if you're having reflux symptoms consistently (more than twice a week), taking a PPI daily will be more effective.

• Other health concerns or medications you take. H2 blockers, not PPIs, are typically recommended during pregnancy if lifestyle modifications and antacids aren't working. Do keep in mind your medication list when choosing a treatment for acid reflux. H2 blockers can interact with some antidepressants, seizure medicines, and heart medicines. PPIs can interact with methotrexate and Plavix, among others.

Consult your healthcare professional or pharmacist for personalized evaluation and treatment recommendations.

Lifestyle Modifications and Alternative Treatments

Lifestyle modifications, alone or in conjunction with medications, can help control symptoms of acid reflux.

Some recommended strategies include the following:

• Achieving a healthy weight

• Raising the head of the bed at night

• Limiting triggers such as spicy foods, caffeine, chocolate, and alcohol

• Chewing gum to increase saliva

• Smoking cessation

• Wearing loose clothes around the waist

Additionally, supplements that may help with acid reflux symptoms include the following:

• Apple cider vinegar

• Ginger

• Licorice

• Fenugreek

• Aloe vera

More research is necessary before these can be routinely recommended.

Remember that the FDA doesn't approve supplements before products are marketed like they do for prescription medications. This means they don't have to be proven safe or effective. Check out tips for choosing a supplement.

Summary

PPIs and H2 blockers are the most commonly taken medications to treat acid reflux and its complications, including GERD and esophagitis.

In many cases, PPIs are recommended first because they are more effective than H2 blockers at reducing stomach acid and symptoms like heartburn. Though the side effects of these two classes are similar, the prolonged use of PPIs is associated with severe adverse effects like fractures, infections, and even dementia.

If you are experiencing acid reflux, discuss treatment options with your healthcare provider to help you achieve your health goals.

Read the original article on Verywell Health.