What Is the Pharmacotherapy of GERD?

Gastroesophageal reflux disease (GERD) is a common gastrointestinal (GI) disorder characterized by the regurgitation of stomach contents into the esophagus causing troublesome symptoms and/or damage to the esophageal mucosa.

GERD affects approximately 20% of the US population, and it is one of the most common GI disorders seen by health care practitioners in the outpatient setting.^1,2

The clinical manifestations of GERD are variable. Classic symptoms include heartburn and regurgitation or the flow of gastric contents into the upper esophagus and pharynx. Other clinical manifestations of GERD include belching, dysphagia, epigastric pain, nausea, and odynophagia. Extraesophageal symptoms can occur in an atypical GERD presentation, and they include asthma, chest pain, cough, dysphonia, hoarseness, and laryngitis.³

GERD Treatment
Treatment of GERD requires a combination of lifestyle modifications and pharmacologic therapy. Lifestyle modifications for GERD include avoiding alcohol, avoiding foods that worsen symptoms, avoiding meals 2 to 3 hours before bedtime, elevating the head of one’s bed by 6 inches, and smoking cessation. Weight loss in patients who are obese or overweight also improves GERD.⁴

The frequency and severity of GERD symptoms, and/or the presence of Barrett’s esophagus or erosive esophagitis guide pharmacologic therapy. Patients with mild symptoms that occur infrequently, such as less than twice per week, can use low-dose H2 receptor antagonists (H2RAs): cimetidine 200 mg twice daily; famotidine 10 mg twice daily; or nizatidine 75 mg twice daily. H2 antagonists can be used as needed, and they begin working within 60 to 90 minutes and last several hours.⁵ H2 antagonists are generally well-tolerated, though cimetidine can cause gynecomastia and impotence with long-term use. Cimetidine is a potent inhibitor of the P450 system and can cause drug interactions. Antacids can be used as needed for symptoms which occur less than once a week. Antacids containing aluminum hydroxide, calcium carbonate, or magnesium trisilicate combinations work within 5 to 10 minutes and last for up to an hour. Aluminum containing antacids may cause aluminum retention in patients with significant renal impairment.

Patients who have 2 or more episodes per week of GERD or with severe GERD symptoms who fail to improve with H2RAs and/or patients with erosive esophagitis require proton pump inhibitors (PPIs) therapy. Proton pump inhibitors, such as dexlansoprazole, esomeprazole lansoprazole, omeprazole, pantoprazole, and rabeprazole, taken once daily at standard dosages are recommended for 8 weeks.⁶

PPIs dosages for GERD are as follows:

• Dexlansoprazole: 30 mg once daily
• Esomeprazole: 20 mg once daily
• Lansoprazole: 15 mg once daily
• Esomeprazole: 20 mg once daily
• Lansoprazole: 15 mg once daily
• Omeprazole: 20 mg once daily
• Pantoprazole: 20 mg once daily
• Rabeprazole: 20 mg once daily

PPIs are most effective when taken 30 to 60 minutes prior to meals, usually before breakfast. Patients who develop recurrent GERD symptoms after an 8-week PPI course can be retreated with repeated 8-week courses and may require long-term maintenance therapy. Patients with early (<3 months of discontinuing acid suppression) and/or refractory recurrent symptoms may require referral for an upper endoscopy.7 PPIs are associated with adverse effects, particularly with long-term therapy. GI effects include increased risk for enteric infections, including C. difficile and multi-drug resistant Enterobacterales colonization. Long-term PPIs can cause malabsorption of minerals and vitamins, specifically hypomagnesemia, and vitamin B12 and PPIs may affect oral iron absorption. Long-term PPI therapy may slightly increase the risk for fractures of the hip, spine, and wrist. Patients with risk factors for osteoporosis who require PPIs should take calcium citrate and vitamin D supplements.⁸ PPIs can cause acute interstitial nephritis, and they may increase the risk for the development or progression of chronic kidney disease.⁹ PPIs may increase the risk for pneumonia, particularly in patients who are hospitalized.¹⁰

Lifestyle modifications are recommended for all patients with GERD. Patients with infrequent, intermittent, or mild symptoms can use low-dose histamine 2 receptor antagonists, such as antacids or famotidine, as needed. Patients with erosive esophagitis, failure to respond to H2As, or frequent or severe symptoms require once-daily standard dose PPIs for 8 weeks.

References

1. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871-880. doi:10.1136/gutjnl-2012-304269

2. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143:1179-1187.e3. doi:10.1053/j.gastro.2012.08.002

3. Hom C, Vaezi MF. Extraesophageal manifestations of gastroesophageal reflux disease. Gastroenterol Clin North Am. 2013;42(1):71-91. doi:10.1016/j.gtc.2012.11.004

4. Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022;117(1):27-56. doi:10.14309/ajg.0000000000001538

5. Richter JE, Vaezi MF. Gastroesophageal reflux disease. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed. Elsevier. 2021;46.

6. Kahrilas PJ, Howden CW, Hughes N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol. 2011;106(8):1419-1425;quiz 1426. doi:10.1038/ajg.2011.146