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Famotidine vs Ranitidine: Differences and Similarities

In this article, we will take a close look at Famotidine and Ranitidine, two H2-histamine receptor antagonists used to treat conditions that cause excess stomach acid. We will review their mechanisms of action, uses, and potential side effects, as well as compare their potency and duration of action.

Jakub Hantabal

Author - Jakub Hantabal

Postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist.

Jakub used MediSearch to find sources for this blog.
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What is Ranitidine?

Ranitidine is a H2-histamine receptor agonist, meaning that it blocks histamine binding to the H-2 receptor in the parietal cells, which are cells lining the stomach. These cells produce the hydrochloric acid that is in the stomach to help digest food.

Ranitidine was first marketed in 1981 and has been widely used in the treatment of conditions related to gastric acid hypersecretion, including:

  • peptic ulcer disease,
  • Zollinger-Ellison syndrome (which is a condition characterised by numerous tumours in the upper gastrointestinal tract which induces acid hypersecretion),
  • acute duodenal ulcer disease,
  • ystemic mastocytosis with gastric hypersecretion,
  • and gastroesophageal reflux disease (GERD) [1, 2, 3, 4].

Additionally, ranitidine can be used as one of the drugs given in general anesthesia as a prophylactic treatment to reduce the risk of aspiration (an occurence where the patient regurgitates and the stomach contents are subsequently inhaled and disrupt the lungs).

By blocking the H-2 receptor, ranitidine regulates the production of the acid. It is important to note that ranitidine does not completely stop the acid secretion, but rather regulates it, thus maintaining a balance that is disrupted in the above conditions [3, 4].

In terms of adverse effects, ranitidine is generally well-tolerated, with side effects occurring in less than 2% of patients. The most common side effects include include:

  • headaches,
  • tiredness,
  • dizziness,
  • mild gastrointestinal disturbances such as diarrhea, constipation, and nausea.

These side effects are generally not serious, and do not result in stopping treatment [1].

In rare cases, ranitidine can cause cardiovascular side effects, particularly after rapid intravenous administration. However, these effects are extremely rare, occurring in at most 1 in 1 million patients, and usually recede after treatment is stopped [1]. Neuropsychiatric complications, such as confusion, disorientation, hallucinations, and delirium, have also been reported, especially in critically ill patients or those with chronic renal or hepatic failure [1].

What is Famotidine?

Famotidine is a H-2 receptor antagonist. This means that, similarly to ranitidine, it blocks the H-2 receptor, and also regulates gastric acid secretion [5].

Similarly to ranitidine, famotidine is used to treat conditions associated with increased acid secretion in the stomach, namely:

  • GERD,
  • duodenal and gastric ulcers,
  • Zollinger-Ellison syndrome [6].

In addition, possible benefits in treatment of COVID-19 have been described for famotidine, due to its potential immunomodulatory roles [5].

The mechanism of action of famotidine is a little more complex than that of ranitidine. Besides direct action on the H-2 receptor, the molecule has been shown to interact with other enzymes, including the viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Furthermore, famotidine has also been shown to interact with neutrophils and eosinophils, which are cells of the immune system, and modulate their cytokine secretion [5]. Cytokines are chemical messenger molecules that cells of the immune system use to initiate or dampen inflammation. Additionally, famotidine's anti-inflammatory effects are also attributed to its activation of the inflammatory reflex, a brain-integrated vagus nerve mechanism that inhibits inflammation via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction [7].

In terms of adverse effects, famotidine is well-tolerated, with the overall incidence of side effects between 1-2% [8]. Common side effects include:

  • dizziness,
  • constipation,
  • diarrhea,
  • and headache [9].

Mild side effects may also include muscle or joint pain, decreased libido, insomnia, nausea, and dry mouth [9]. Serious side effects are not common, however can include mood problems such as depression or anxiety, seizures, liver damage, low platelet count, heart palpitations, and severe allergic reactions [9].

What are the differences between famotidine and ranitidine?

Ranitidine and famotidine are both H2-receptor antagonists, a class of drugs used to reduce the production of stomach acid. They are commonly used to treat conditions like gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome. Despite their similarities, there are some differences between the two drugs in their potency, duration of action, and pharmacokinetics.

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Potency

Famotidine is considered more potent than ranitidine. Studies have shown that famotidine is approximately 7.5 to 9 times more potent than ranitidine (and even more potent than other H-2 antagonists) [10, 11, 12]. This increased potency may offer clinical advantages, such as lower dose needed and less frequent dosing to achieve the same acid-lowering effect [13].

Duration of effect

The effect of famotidine lasts for longer than ranitidine. Famotidine was observed to last 30% longer than ranitidine [14, 11]. This may be advantageous in a more sustained relief from symptoms.

Furthermore, famotidine has a longer plasma half-life than ranitidine. In a study on healthy volunteers, the plasma half-life of famotidine was found to be 4.42 hours, significantly longer than ranitidine's 3.14 hours [15].

Use cases and indications

Both famotidine and ranitidine have been shown to be effective in treating conditions involving hypersecretion of acid. Multiple studies concluded that the drugs can be used interchangeably [16, 17]. However, due to its greater potency and longer duration of action, famotidine may be the preferred choice in treating more complex conditions like Zollinger-Ellison syndrome [12].

Summary

In summary, while both ranitidine and famotidine are effective H2-receptor antagonists, they differ in their potency and duration effect, with famotidine displaying longer effect and increased potency over ranitidine. However, both are very effective drugs, and the choice between the two will ultimately depend on the specific needs and circumstances of the patient.

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