Taking A PPI With An H2 Blocker And Other Related Questions

In our latest question and answer, the pharmacist discusses several points regarding PPI therapy, including whether or not you can take one with an H2 Blocker.


My GI doctor wants me to take 2 different PPIs...one in the morning and one in the evening plus ranitidine. Is there any benefit to this? Will my insurance pay for 2 different ones taken on the same day? And can I take a PPI without eating first? Thank you!

Asked by Flhusker On Jan 23, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jan 23, 2019

Since there are many parts to your question, I will break them up and answer each separately.

Can You Take A PPI Without Eating First?

PPIs (proton pump inhibitors) are ideally taken on an empty stomach, about 60 minutes before meals. This is necessary for optimal effectiveness.

PPIs work to decrease gastric acid secretion by binding to and inhibiting the 'H+/K+ ATPase pump' on parietal cells in the stomach.

However, 'H+/K+ ATPase pumps' need to be active in order for PPI drugs to bind to and inhibit them.

These 'H+/K+ ATPase pumps' become active in response to stimuli, like food. Taking a PPI about an hour before food allows time for the drug to be absorbed, concentrate in the area of action, and begin working when you start eating.

Taking a PPI without food will result in significantly decreased effects since the 'H+/K+ ATPase pumps' will never be activated. Taking a PPI at the same time as food will result in a delayed response. So, ideally, take your PPI about 60 minutes before you plan on eating.

It is important to note that not all proton pumps are active after a single serving of food. In fact, it appears that only 60-70% are, leaving a large percentage of pumps uninhibited after one dose. This is why it can sometimes take a few days of continuous dosing for a PPI to reach maximum effectiveness.

Additionally, administration timing with regard to food can affect some PPI drugs more than others. Ones that have a longer half-life (i.e. are eliminated more slowly) may be less affected if you have food more than 60 minutes after dosing.

Can you take a PPI with an H2 blocker?

Yes, you can take a PPI with an H2 blocker. H2 blocker drugs include:

  • Zantac (ranitidine)
  • Pepcid (famotidine)
  • Tagamet (cimetidine)

Although more studies are needed to determine just how efficacious it is to add an H2 blocker to a PPI, several have shown benefit, especially at nighttime.

In fact, one study reports that 70% of individuals taking a PPI two times a day have episodes of 'breakthrough acid' at nighttime, which can cause discomfort. Adding a nightly dose of an H2 blocker can be beneficial in this regard.

The addition of an H2 blocker can be effective as they work differently from PPI drugs. PPIs bind to the 'H+/K+ ATPase pumps' while H2 blockers inhibit the binding of histamine to receptors on parietal cells, which reduces gastric acid secretion. Therefore PPIs and H2 blockers can have synergistic effects.

Again, there haven't been many studies on this subject, but if you are still having symptoms, even after taking a PPI two times daily, adding on an H2 blocker is generally safe and worth trying.

Can You Take A PPI Twice A Day?

Studies are conflicting on how much more effective twice daily dosing is of a PPI when compared to once daily dosing.

Some suggest there is no significant benefit to dosing twice a day while others do show positive effects.

Overall, there does appear to be some additional benefit with twice daily dosing in those with treatment resistance acid reflux (i.e. not responding well to conventional therapy) and in those with pathological conditions, such as Zollinger–Ellison syndrome.

Dosing in these individuals is generally on a case by case basis. Below is from the prescribing information for Prilosec, a commonly used PPI drug:

The dosage of PRILOSEC in patients with pathological hypersecretory conditions varies with the individual patient. The recommended adult oral starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 120 mg three times daily have been administered. Daily dosages of greater than 80 mg should be administered in divided doses
Prilosec Package Insert

Can You Take Two Different PPIs?

There are no medical guidelines that recommend taking two different PPI drugs. Most studies suggest that the comparative efficacy among the entire class is fairly similar.

Nevertheless, it most likely wouldn't hurt to try taking two different ones (one in the AM and one in the PM) if you are not getting the effects you are looking for with a single drug.

Although all PPI drugs work the same, they do have different pharmacokinetic profiles, which could lead to small variations in efficacy among individuals. Some work faster than others, some last longer than others and some are metabolized differently. Your doctor may be experimenting to find the best combination for your particular situation.

Will Insurance Cover Two PPIs?

This completely depends on your individual insurance plan. However, for most, the answer is likely to be 'no', at least not without what is known as a 'prior authorization' from your insurance company.

Without any additional information, your insurance company will see two PPI drugs as a 'therapeutic duplication', and will probably not cover a second drug initially. Sometimes, a prior authorization will allow for the second PPI to be paid for, but your doctor will have to provide sufficient evidence that this represents the best and next progression in therapy for you. Your pharmacist can give you more information on the prior authorization process if the situation arises.

If your insurance does not cover two PPI drugs, a few are available over the counter and you may be able to get one via prescription, and one over the counter. Be sure to ask your doctor if this is an option for you. Over the counter (i.e. available without a prescription) PPI drugs include:

  • Prilosec (omeprazole)
  • Nexium (esomeprazole)
  • Prevacid (lansoprazole)
  • Elsevier ClinicalKey: Prilosec Monograph (Accessed 1/23/19)
  • Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough: a Cochrane systematic review. PubMed (Accessed 1/23/19)
  • Nocturnal acid breakthrough: clinical significance and correlation with esophageal acid exposure. PubMed (Accessed 1/23/19)
  • 25 Years of Proton Pump Inhibitors: A Comprehensive Review. PubMed (Accessed 1/23/19)
  • Choosing One PPI Treatment Over Another. American Family Physician. PubMed (Accessed 1/23/19)
  • Issues Related to BID Dosing of PPIs. PubMed (Accessed 1/23/19)
  • Twice-daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance-pH testing. PubMed (Accessed 1/23/19)
  • Efficacy of twice-daily rabeprazole for reflux esophagitis patients refractory to standard once-daily administration of PPI: the Japan-based TWICE study. PubMed (Accessed 1/23/19)

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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