H2RAs

These work to block the H2 receptors that receive histamine signals that tell the stomach to produce acid.

These work proactively to reduce the amount of acid by preventing histamine signals reaching the parietal cells telling them to make acid. They are not an instant antacid and are often prescribed to be taken in the evening to reduce nighttime acid.

(Other H2 blockers: Lafutidine, Loxtidine, Niperotidine, Roxatidine.)

* Please note doses shown are not guaranteed to be equivalent. Do not assume because a dose is shown it is the safe dose. It may vary according to age and body build. 

Unlike PPIs, a paper in 2014 found H2 blockers could induce tachyphylaxis. That is when patients gain a tolerance to the drug and may require larger doses to achieve the same result.

In 2019, some batches of Zantac were found to have a higher level of NDMA than they should. Although there is no evidence to prove it, NDMA (N-nitroso dimethylamine) is thought to be carcinogenic. Ranitidine was removed from the shelves. The levels of NDMA found, however, were no higher than found on grilled meat. Further investigaton showed the samples were tainted by incorrect storage.

This paper from February 2023 ruled out any cancer  risk. Study rules out link between use of ranitidine & cancer risk.
"The recent study provided no evidence of the association of NDMA impurities in ranitidine products with cancer risk, which further substantiates the US district court findings in which the Florida court dismissed almost 2,500 lawsuits alleging links between heartburn medication Zantac (Ranitidine) and cancer. The judge had said that almost 2,500 lawsuits filed in federal court by plaintiffs were based on flawed science and that the only reliable testing of the blockbuster drug undertaken showed an ‘unprovable risk of cancer’."

Research using a new H2 blocker, lafutidine, looked at its use for Nocturnal Acid Breakthrough (NAB) for those taking PPIs. 

The paper published in Nature in June 2025, "Addition of bedtime lafutidine inhibits nocturnal acid-breakthrough and improves sleep quality" concluded, "The addition of bedtime lafutidine to esomeprazole significantly increased nocturnal intragastric pH > 4 holding time ratios and decrease the occurrence of NAB. GERD patients with the addition of lafutidine experienced a more pronounced improvement in sleep quality correlated with NAB reduction."

"Although 29.2% of patients ... still suffered NAB, none occurred in the early morning." Results were self reported from patient follow-up questionnaires.

Although the article heavily promotes the new drug and the trial was with twice daily dosing of PPIs, it is probable similar results may be found with other H2 blockers and once a day dosing.

Page updated 3 July 2025