Drugs In Practice Drugs for GERD and Peptic Ulcer Disease

Table 2 – Some oral drugs for GERD and PUD

ODTs = orally disintegrating tablets; OTC = over the counter; soln = solution; susp = suspension

1 The lower end of the range is generally used for initial treatment of GERD. Higher or more frequent doses may be needed for patients with erosive esophagitis, peptic ulcer disease, hypersecretory conditions such as Zollinger-Ellison syndrome, or for treatment of H. pylori infection. Dosage adjustments may be needed for renal or hepatic impairment.

2. In April 2020, the FDA requested that all OTC and prescription ranitidine products be removed from the market because they may contain the carcinogen N-nitrosodimethylamine (NDMA).

3. Taking the total daily dose in the evening may also be effective.

4. Also available in combination with ibuprofen.

5. PPIs are generally taken 30-60 minutes before the first meal of the day. Taking one dose before the evening meal or taking the drug twice daily may be more effective for nocturnal acid control. PPIs should generally be swallowed whole and should not be crushed or chewed. Dexlansoprazole can be taken with or without food. Omeprazole/sodium bicarbonate should be taken on an empty stomach at least 1 hour before a meal.

6. Capsules can be opened and their contents sprinkled on soft food such as applesauce and consumed immediately.

7. Also available in combination with naproxen.

8. Also available in combination with amoxicillin/clarithromycin.

9. Immediate-release formulation of omeprazole. Should be used with caution in patients on a low-sodium diet.

10. Since each capsule contains 1.1 g of sodium bicarbonate, two 20-mg capsules are not equivalent to one 40-mg capsule.

11. FDA-approved only for prevention of NSAID-induced gastric ulcers.

12. Also available in combination with diclofenac (Arthrotec, and generics).

13. FDA-approved only for short-term treatment and maintenance therapy of duodenal ulcers.

14. Should be taken on an empty stomach.

Drug Interactions

H2RAs can decrease serum concentrations of drugs that require gastric acidity for absorption, such as itraconazole and the antiretroviral drugs rilpivirine and atazanavir. Cimetidine is a moderate inhibitor of CYP1A2, 2C19, and 2D6; it can increase serum concentrations of drugs that are metabolized by these enzymes, such warfarin and fluoxetine.7 Famotidine and nizatidine are less likely to affect the hepatic metabolism of other drugs.

Pregnancy

H2RAs are generally considered safe for use during pregnancy, but adequate studies are lacking.

Proton Pump Inhibitors

PPIs bind to the activated proton pump on the apical membrane of parietal cells, resulting in variably potent inhibition of acid secretion into the gastric lumen (see Table 1). They are more effective than H2RAs in relieving chronic heartburn and regurgitation and in healing erosive esophagitis. Treatment with a PPI for 8 weeks is recommended for healing of erosive esophagitis.2 Almost all patients with erosive esophagitis will have a relapse of symptoms within 6 months of stopping the PPI and most will require long-term maintenance therapy.

PPIs have short serum half-lives, but their duration of action is longer than that of H2RAs, allowing for oncedaily dosing in most patients with GERD. For patients who continue to have symptoms, switching to twice-daily dosing is more effective than increasing the dose.8 Addition of an H2RA as needed may be helpful for patients who still have symptoms despite twice-daily PPI treatment.

PPIs generally are most effective when taken on an empty stomach, 30-60 minutes before a meal. Dexlansoprazole can be taken without regard to meals. Other antisecretory drugs such as H2RAs should not be taken at the same time as a PPI. Unlike H2RAs, tolerance to PPIs does not develop with continuous use.

Adverse Effects

Short-term use of PPIs is generally well tolerated. Headache, nausea, abdominal pain, constipation, flatulence, and diarrhea can occur. Gynecomastia, hepatic failure, subacute myopathy, arthralgia, severe rash, lupus erythematosus, and acute interstitial nephritis have been reported.

In observational studies, long-term PPI use has been associated with a number of safety concerns, including dementia, vitamin B12 deficiency, chronic kidney disease, and increased all-cause mortality.9,10 Most of these concerns are not supported by a causal mechanism or consistent data. The FDA has issued safety warnings about an association between long-term PPI use and hypomagnesemia, increased fracture risk, and Clostridioides difficile infection. In a population-based cohort study in new users of PPIs and H2RAs, use of PPIs was associated with a 45% greater risk of gastric cancer, but the absolute risk was low.11 The benefits of PPI treatment generally outweigh the risks in patients with a clear indication for long-term treatment.12

Drug Interactions

PPIs may decrease serum concentrations of drugs that require gastric acidity for absorption, such as itraconazole and the antiretroviral drugs rilpivirine and atazanavir.

Most PPIs are metabolized primarily by CYP2C19. Patients who are CYP2C19 ultra-rapid metabolizers may have a decreased response to PPI treatment, and poor metabolizers (many Asian patients) may have higher PPI serum concentrations.13 Lansoprazole and dexlansoprazole are metabolized primarily by CYP3A4. Omeprazole and esomeprazole are moderate inhibitors of CYP2C19 and could increase serum concentrations of drugs metabolized by this pathway, such as warfarin and phenytoin.7,14

The antiplatelet drug clopidogrel is converted to its active form by CYP2C19; inhibition of CYP2C19 may interfere