Gastroesophageal Reflux Disease Medication

Updated: Nov 27, 2023
  • Author: Marco G Patti, MD; Chief Editor: BS Anand, MD  more...
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Medication Summary

The goals of pharmacotherapy are to prevent complications and to reduce morbidity in patients with gastroesophageal reflux disease (GERD). The agents used include antacids, proton pump inhibitors, H2-receptor antagonists, potassium-competitive acid blockers, and prokinetic agents. 


Proton Pump Inhibitors

Class Summary

Proton pump inhibitors (PPIs) inhibit gastric acid secretion by inhibition of the H+/K+ ATPase enzyme system in the gastric parietal cells. These agents are used in cases of severe esophagitis and in patients whose conditions do not respond to H2 receptor antagonist therapy. Options include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), and esomeprazole (Nexium).

PPIs are the most powerful medications available for treating GERD. These agents should be used only when this condition has been objectively documented. They have few adverse effects. However, data have shown that PPIs can interfere with calcium homeostasis and aggravate cardiac conduction defects. Long-term use of these agents has also been associated with bone fractures in postmenopausal women, chronic renal disease, acute renal disease, community-acquired pneumonia, and Clostridium difficile intestinal infection. [31, 32]

Omeprazole (Prilosec)

Omeprazole is used for up to 4 weeks to treat and relieve the symptoms of active duodenal ulcers. It may be used for up to 8 weeks to treat all grades of erosive esophagitis.

Lansoprazole (Prevacid)

Lansoprazole inhibits gastric acid secretion. It is used for up to 8 weeks to treat all grades of erosive esophagitis.

Rabeprazole (Aciphex)

Rabeprazole is for short-term (4- to 8-wk) treatment and relief of symptomatic erosive or ulcerative GERD. In patients who are not healed after 8 weeks, consider an additional 8-wk course.

Esomeprazole (Nexium)

Esomeprazole is an S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

Pantoprazole (Protonix)

Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the intravenous preparation has only been studied for short-term use (ie, 7-10 d).


Potassium-Competitive Acid Blockers

Class Summary

Potassium-competitive acid blockers (PCABs) suppress basal and stimulated gastric acid secretion at the secretory surfaces of gastric parietal cells through inhibition of the H+, K+-ATPase enzyme system in a potassium-competitive manner. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, vonoprazan has been characterized as a type of gastric proton-pump inhibitor, as it blocks the final step of acid production. It does not require activation by acid and may selectively concentrate in parietal cells in both resting and stimulated states. 

Vonoprazan (Voquezna)

Vonoprazan is indicated for treatment and maintenance of healing of all grades of erosive esophagitis.


H2-Receptor Antagonists

Class Summary

Histamine-2 receptor antagonists (H2RAs) are the first-line agents for patients with mild to moderate symptoms and grades I-II esophagitis. Options include cimetidine (Tagamet), famotidine (Pepcid), and nizatidine (Axid).

The H2RAs are reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. They are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. Although IV administration of H2 blockers may be used to treat acute complications (eg, gastrointestinal bleeding), the benefits are not yet proven.

These agents are effective for healing only mild esophagitis in 70%-80% of patients with GERD and for providing maintenance therapy to prevent relapse. Tachyphylaxis has been observed, suggesting that pharmacologic tolerance can reduce the long-term efficacy of these drugs.

Additional H2 blocker therapy has been reported to be useful in patients with severe disease (particularly those with Barrett esophagus) who have nocturnal acid breakthrough.

Ranitidine (Zantac)

Ranitidine inhibits histamine stimulation of the H2 receptor in the gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen concentrations. As of April 1, 2020, ranitidine was withdrawn from the market due to an increasing number of products containing the contaminant known as N-nitrosodimethylamine (NDMA), a possible carcinogen.

Cimetidine (Tagamet)

Cimetidine inhibits histamine at H2 receptors of the gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Famotidine (Pepcid)

Famotidine competitively inhibits histamine at H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Nizatidine (Axid)

Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.



Class Summary

Antacids were the standard treatment in the 1970s and are still effective in controlling mild symptoms of GERD. Antacids should be taken after each meal and at bedtime. These agents are used as diagnostic tools to provide symptomatic relief in infants. Associated benefits include symptomatic alleviation of constipation (aluminum antacids, such as ALternaGEL and Amphojel) or loose stools (magnesium antacids, such as Phillips Milk of Magnesia).

Aluminum hydroxide (ALternaGEL, Amphojel)

Aluminum hydroxide increases gastric pH to greater than 4 and inhibits the proteolytic activity of pepsin, reducing acid indigestion. Antacids can initially be used in mild cases. They have no effect on the frequency of reflux, but they decrease its acidity.

Magnesium hydroxide (DiGel, Gas X)

Magnesium hydroxide is used as an antacid to relieve indigestion. It also causes osmotic retention of fluid, which distends the colon and increases peristaltic activity that provides a laxative effect. In vivo, it forms magnesium chloride after reacting with stomach hydrochloric acid.



Class Summary

Prokinetic agents, such as metoclopramide (Reglan), improve the motility of the esophagus and stomach and increase the lower esophageal sphincter (LES) pressure to help reduce reflux of gastric contents. They also accelerate gastric emptying.

Prokinetic agents are somewhat effective but only in patients with mild symptoms; most patients usually require acid-suppressing medications, such as PPIs. Long-term use of prokinetic agents may have serious, even potentially fatal, complications and should be discouraged.

Metoclopramide (Reglan)

Metoclopramide is a GI prokinetic agent that increases GI motility, increases resting esophageal sphincter tone, and relaxes the pyloric sphincter.