Which H2 (histamine 2) receptor blocker is most effective?

From the Guidelines

Famotidine is the most effective H2 receptor blocker, with a modest protective effect in patients taking aspirin, as evidenced by a randomized trial showing fewer gastroduodenal ulcers developed over 12 weeks among patients assigned to famotidine (3.8%) than to placebo (23.5%; P0.0002) 1. The use of H2RAs, such as famotidine, can suppress gastric acid production by 37% to 68% over 24 hours, providing a beneficial effect in patients with peptic ulcers or esophagitis who are taking aspirin 1. Some key points to consider when using famotidine include:

• Typical dosage: 20 mg twice daily or 40 mg once daily for active ulcers, and 20 mg once daily for maintenance therapy
• Fewer drug interactions compared to cimetidine, which can interfere with the metabolism of many medications through the cytochrome P450 system
• Lower incidence of side effects such as gynecomastia, impotence, and confusion that can occur with other H2 blockers, particularly cimetidine
• Mechanism of action: selectively blocking histamine H2 receptors on the parietal cells in the stomach, reducing gastric acid production While proton pump inhibitors (PPIs) provide stronger acid suppression, famotidine remains valuable for mild to moderate acid-related conditions and has a better safety profile for long-term use compared to other H2 blockers 1.

From the FDA Drug Label

Famotidine is a competitive inhibitor of histamine-2 (H2) receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Single evening oral doses of 20 mg and 40 mg inhibited basal and nocturnal acid secretion in all subjects; mean nocturnal gastric acid secretion was inhibited by 86% and 94%, respectively, for a period of at least 10 hours Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells.

The FDA drug label does not answer the question.

From the Research

H2 Receptor Blockers

• The most commonly used H2 receptor antagonists are cimetidine, ranitidine, famotidine, and nizatidine 2.
• All four H2 receptor antagonists are equally effective when used at the usual recommended dose, and are generally very safe 2.

Famotidine

• Famotidine is a highly selective histamine H2-receptor antagonist, approximately 20 to 50 times more potent than cimetidine and 8 times more potent than ranitidine on a weight basis 3.
• Famotidine is effective in healing both duodenal and gastric ulcers, with healing rates and symptom relief similar or superior to those achieved by cimetidine and ranitidine 3, 4.
• Famotidine has a longer duration of action than either ranitidine or cimetidine, and does not interact with cytochrome P-450 of the hepatic enzyme system 5.
• Famotidine is well tolerated, with a low incidence of side effects, and is free of the antiandrogenic effects infrequently reported with cimetidine 3, 4, 5.

Comparison of H2 Receptor Blockers

• Famotidine is the most potent, selective H2-receptor antagonist yet available for ulcer therapy, approximately 8 times more potent than ranitidine and 40 times more potent than cimetidine on a weight basis 5.
• The overall number of side-effects of the H2-receptor antagonists is in the range of 2-3%, with no irreversible adverse effects known 5.
• Famotidine has been found to be generally well tolerated, with a low incidence of side effects, making it a safe and potent H2-receptor blocker of acid secretion 3, 4, 5.