PPIs
Ariel Clark, PharmD
Coinciding with their OTC status in 2003, the popularity of PPIs has steadily risen, which has only given patients with heartburn, GERD, and related conditions more access to them. But as use of these medications has increased, there’s a growing need to evaluate their place in practice, especially given the growing body of evidence that links long-term PPI use to a series of adverse events.
In their April 2022 clinical practice update, the American Gastroenterology Association (AGA) compiled a list of “Best Practice Advice” (BPA) statements to help providers assess if the risk outweighs the benefits for this class of medications. The AGA update is intended to serve as a guide for physicians and pharmacists to use as they discuss optimizing PPIs for their patients.
Potential adverse events
Randomized controlled trials of PPIs highlighted the expected and even unexpected adverse effects that pharmacists know to share with their patients. However, after-market research and patient experiences has opened a different lens to what long-term use of these medications may look like.
An ever-growing body of evidence links long-term PPI use to little-known and potentially dangerous adverse events. The AGA BPA statements note that these can include an increased risk of developing Clostridium difficile, kidney infections, and dementia as well as an increased risk of fractures. As with many other drugs, balancing these associated risks with the potential benefits is a challenge for clinicians: they must ensure patients who need PPIs still have access to them but should reduce use in patients whose risk for adverse effects outweighs the benefits.
When to consider deprescribing
The AGA BPA statements agree that any patient with an active prescription for a PPI should have both an indication and a regular review to ensure that there is still a need for the medication. When there is no clear indication or if the needs of the patient change, the drug should be discontinued. Patients with a clear indication who are prescribed twice-daily dosing should be considered for step-down therapy to once-daily dosing as opposed to full discontinuation.
Current evidence does not support twice-daily dosing of PPIs except, as the AGA notes, in very rare cases of Zollinger-Ellison syndrome and to prevent rebleeding of ulcerations in the GI tract. A study cited in the AGA update noted that in cases of step-down therapy trials, “80% successfully stepped down to standard doses of PPI without significant recurrence of symptoms.”
When not to consider deprescribing
There is no doubt among experts that there are significant clinical benefits to PPIs. These can be particularly evident in patients with complicated GERD or a history of erosive esophagitis. In patients with these conditions, the AGA BPA statements state that deprescribing should not be considered. Long-term complications of these conditions can include ulceration or peptic stricture, which outweigh the risks of PPI use. Likewise, patients with Barrett’s esophagus and eosinophilic esophagitis should not be considered for deprescribing due to the long-term effects of these conditions, which can include esophageal adenocarcinoma. The BPA statements note that PPIs provide protective benefits for patients with these conditions.
It is important to remember, and reiterate to patients, that both step-down therapy and discontinuation of PPIs can cause rebound symptoms as parietal cells overproduce acid. In communicating this news with patients, health care providers should share the temporary nature of these symptoms and that they can be managed using H2 receptor agonists (e.g., famotidine) or antacids. In cases where patients find rebound symptoms unmanageable, dose tapering may be considered, though clinical trials have failed to show any difference in hypersecretion symptoms to date.
As pharmacists begin to consider whether or not deprescribing PPIs is the right choice for their patients, AGA authors urge them to review the BPA statements as they make the recommendations for their patients and to focus on whether or not a clinical indication exists in each individual patient’s case. ■