Do Pepcid AC Or Zantac Interact With Methotrexate?

In our latest question and answer, the pharmacist discusses whether or not there is a drug interaction between Pepcid or Zantac and methotrexate.

Do Pepcid AC Or Zantac Interact With Methotrexate?
Nov 18, 2019

maya asked

What is the difference between Zantac and Pepcid AC and do they interact with methotrexate?

At a glance

  • There is no known drug interaction between Zantac (ranitidine) or Pepcid (famotidine) and methotrexate.
  • Zantac and Pepcid are both classified as H2-blockers and are generally thought to be equally effective in most cases.

Answer

Wooden Spoon With Multiple Pills And Capsules On It

Hello and thank you for submitting your question to us!

There is no known interaction between methotrexate and either Zantac (ranitidine) or Pepcid (famotidine).

In fact, the use of Zantac or Pepcid, which are classified as 'H2 blockers', are generally preferred over the use of another class of acid-reducing drugs, proton pump inhibitors, or PPIs.

Numerous drug interaction studies have shown that PPI drugs can decrease how quickly our bodies eliminate methotrexate, which may increase the risk of toxicity and subsequent side effects. PPI drugs include:

One such study stated the following:

"There is evidence to suggest that concomitant use of methotrexate (primarily at high doses) with PPIs such as omeprazole, esomeprazole, and pantoprazole may decrease methotrexate clearance, leading to elevated serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities."

This study specifically noted that when patients were switched from a PPI to an H2 blocker, like ranitidine, no interaction was seen.

Based on current evidence, you can feel safe taking either Pepcid or Zantac with methotrexate.

Pepcid Vs. Zantac

Getting on to the other part of your question, regarding the difference between Pepcid and Zantac, they are very similar.

As stated, they are both in the same class of drugs known as H2-blockers.

They work by inhibiting (or 'blocking') the binding of histamine to their receptors (H2 receptors) on 'parietal cells' in the stomach. This has the effect of reducing gastric acid secretion.

Most clinical trials show that H2 blockers are relatively equivalent in terms of their effectiveness at reducing stomach acid secretion and for the treatment of stomach ulcers. Generally speaking, they are considered interchangeable, with no specific one being more effective than another.

There are some other considerations though aside from effectiveness, such as cost and potential for drug interactions.

One H2 blocker, in particular, Tagamet (cimetidine), is known to have far more drug interactions and often isn't recommend as a first choice in the class, but Pepcid and Zantac are quite similar and you could safely try either.

Some studies show that famotidine may have a slightly longer duration of action than ranitidine, but this doesn't appear to be overly clinically significant.

Clinical Pharmacology, one of the most utilized and trustworthy drug information resources, states the following on the matter:

"Evidence demonstrates that the efficacy of H2-blockers at approved doses is broadly equivalent both for inhibition of acid secretion and for treatment of acid-related disorders. As such, H2-blockers are generally considered to be interchangeable with one another."

Some individuals may see more benefit with one or the other, but it would be near impossible to predict which drug would be more effective for you. You can try either and stick with the one you feel works better.

References
  1. Methotrexate Prescribing Information. FDA
  2. H2 Drug Class Overview. Clinical Key (Subscription Required)
  3. Comparison of 40 mg famotidine nightly and 150 mg ranitidine b.d.: ulcer healing and symptom relief in benign gastric ulcer. PubMed
  4. Accumulating Evidence for a Drug–Drug Interaction Between Methotrexate and Proton Pump Inhibitors. PubMed

Ready for a more personal experience with your meds?