PPI safety and side-effects

John Horn PharmD: Proton pump inhibitors are really very safe drugs. One of the reasons for that is that most of the drug is found in the canalicular space of the parietal cell, so there's not much drug elsewhere in the body.

Having said that, there are, of course, side effects that are seen with the PPIs. They generally fall into two areas. One is headaches, and the other is diarrhea and lower GI symptoms. I don't think anybody knows why these drugs cause headaches. Headaches are very common phenomena; in fact, they are the most common side effect with placebo. Long-term therapy with these drugs - and we're talking now about ten or twelve years of therapy and experience - has proven to be remarkably safe. There was a concern initially that there might be an increased risk of tumors, as was seen in rats that were given omeprazole early on. That's simply not been shown to occur in humans.

One of the concerns that has been around for some years about the use of proton pump inhibitors is that, because they're so good at suppressing acid secretion, might that have some long-term negative effect?

One of the things that occurs with long-term acid suppression is an increase in gastrin secretion, which can lead to an increased number of parietal cells. Now as long as you're taking your proton pump inhibitor, that's not a problem, because you just block those cells. But it has been noted that when proton pump inhibitors are suddenly discontinued in patients, some people will have a rebound increase secretion of acid for a few days or a week, while they readjust the number of parietal cells and the secretion of those cells. Usually that doesn't cause any great problems for anybody.

The other area that has been of some concern-again, mostly theoretical - is that by increasing the pH in the stomach, you might interfere with the absorption of some nutrients; most notably, vitamin B12 and iron. That's also not proven to be much of a problem, and I suspect the reason is that there are periods of time - notably, through the evening and night-time hours - that the pH in the stomach actually does get pretty close to where it would be without the proton pump inhibitor, so that nutrient absorption does still continue to occur. Even if you reduce the absorption of iron or B12, you don't completely block it. So for most patients, this is not going to produce any anemias.