If you suffer from gastroesophageal reflux disease (GERD), characterized by the frequent backflow of stomach acid into the esophagus, causing heartburn and other symptoms, you know that managing this chronic condition requires a comprehensive, multi-pronged approach. In some cases, lifestyle changes such as weight loss and avoidance of certain foods may suffice. But bothersome symptoms often return despite these changes, and in that case, a number of effective medications are fortunately available.

However, if conventional treatments are not sufficiently effective — especially if reflux symptoms are severe or frequent, or if years of accumulated reflux have damaged the esophagus — a new class of drugs known as potassium-competitive acid blockers (P-CABs) offers a "useful alternative," says Dr. Lawrence Friedman, chief of medicine at Newton-Wellesley Hospital and professor at Harvard Medical School.

How are P-CAB drugs used? The only P-CAB drug currently available in the United States is vonoprazan (Voquezna), approved and available by prescription only for the following conditions in adults:

* Erosive esophagitis, which damages the lining of the esophagus due to chronic acid reflux.

* Heartburn associated with non-erosive GERD, where symptoms such as heartburn and reflux occur without visible damage to the esophagus.

* Refractory (treatment-resistant) peptic ulcer disease.

* Infections with H. pylori, a bacterium that infects the stomach lining and is a common cause of ulcers. In cases of H. pylori infection, vonoprazan is taken alongside antibiotics.

Dr. Friedman adds that other P-CAB drugs may become available soon, including tegoprazan, keverprazan, and fexuprazan, which are currently available in some Asian countries.

Conventional GERD treatments

Clinical trials suggest that P-CAB drugs may benefit those who have not responded well to conventional reflux treatment. Below is a brief overview of the most commonly used medications in managing this disease, to understand where P-CABs fit in the treatment framework.

* Acid buffers, such as Tums and Rolaids, help neutralize stomach acid temporarily. They are inexpensive, available over the counter, and an excellent option for occasional heartburn. However, they do not reduce the amount of acid the body produces, making them less effective for frequent or severe reflux.

* H2 blockers, such as famotidine (Pepcid) and cimetidine (Tagamet), work by blocking signals that stimulate the stomach to produce acid. They are available in both over-the-counter and prescription doses, are more effective than acid buffers for moderate symptoms, and can be taken before meals to prevent heartburn. However, the body may develop tolerance to them over time.

* Proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) and esomeprazole (Nexium), are the most prescribed for reflux patients. They reduce stomach acid by inhibiting proteins in the stomach lining responsible for pumping hydrogen ions into it to raise acid levels. They are often the first choice for those with frequent symptoms. However, PPIs do not work immediately and may take several days to reach peak effectiveness. Dr. Friedman explains that they also require stomach acid for activation, necessitating taking them 30 to 60 minutes before meals, which can be burdensome and often leads to patient non-compliance. Moreover, PPIs may cause stomach upset and diarrhea. Dr. Friedman warns that long-term use may increase the risk of bone fractures, kidney disease, and nutritional deficiencies; therefore, they should be taken at the lowest effective dose for short periods. He adds, "You can stop them and return to them, or switch between them and other drugs."

What makes P-CAB drugs different?

P-CAB drugs work similarly to PPIs in inhibiting the acid-producing pumps in the stomach, but they do so by a slightly different mechanism: Instead of needing activation by stomach acid first, P-CABs block a key molecule (potassium) that the pump requires to function. This means they can be taken with or without food. P-CABs also work more quickly than PPIs in suppressing stomach acid, reaching peak effectiveness within the first day of use. And because their effect is long-lasting, they provide more consistent and stable control of acid levels throughout the night and day. Dr. Friedman notes that the side effects of P-CABs appear similar to those of PPIs. He explains that because these new drugs have not yet established long-term safety records like the more established ones, some doctors "may take a wait-and-see approach before prescribing them." He adds that one of the biggest barriers to P-CAB use currently is their cost, as insurance does not always cover newer drugs. He concludes, "But if all other factors are equal, they would be a good option for many people."

* Harvard Health Letter - Tribune Media Services