PPI-Related Hypomagnesemia: Putting it in Perspective

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PPI-Related Hypomagnesemia: Putting it in Perspective

A. , MD

Authors and Disclosures

Posted: 03/07/2011

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Hello. I'm Dr. , Professor of Medicine and Chief of

Gastroenterology at Eastern Virginia Medical School in Norfolk,

Virginia. Today is March 2nd and the US Food and Drug Administration

(FDA) has put out an advisory warning that patients on proton pump

inhibitors (PPIs) may be at risk for hypomagnesemia. Now before you jump

to call all your patients on proton pump inhibitors and tell them to

have their magnesium levels checked, let me give you some perspective on

these data and some guidance as to how I am handling this in my practice.

Let's start with the background. This alert was based on a number of

reports over the course of the last several years, during which patients

have presented with relatively profound hypomagnesemia, prompting

hospitalization. Patients can present with profound muscle weakness,

twitching, and cardiac dysrhythmias that may prompt the diagnosis of

hypomagnesemia. In patients who were hospitalized, about 25% did not

respond even to magnesium repletion until the proton pump inhibitor was

stopped, and then they reabsorbed normally and their magnesium levels

normalized. On occasion, these patients were rechallenged and the same

event occurred.

Why does this occur with proton pump inhibitors? Magnesium, first of

all, is basically passively transported and absorbed in the small bowel.

This is where the bulk of magnesium transport occurs. To a smaller

degree, active transport mechanisms in the small bowel are now

recognized, including transient receptor potential melastatin 6 (TRPM6)

and TRPM7. These have been described as active transport pathways for

magnesium. We don't know what degree of magnesium is transported this

way, but we do know that patients who have a homozygous mutation of

these pathways actually [have] significant hypomagnesemia. This accounts

for at least some of the patients who have normal calcium absorption.

How this interacts with proton pump inhibitors is unknown. We don't know

if PPIs affect active or passive transport of magnesium, or whether in

patients prone to have some TRPM deficiency, PPI use may trigger

hypomagnesemia. The FDA alert put us on notice that this can potentially

occur, albeit rarely. In the absence of mechanistic studies, we don't

really know why hypomagnesemia would occur with PPI use.

The FDA's advice is if you consider starting a patient on a proton pump

inhibitor, before doing so, the patient's magnesium level should be

checked (especially if long-term use of PPIs is anticipated).

Before we jump to that, and I'll leave the FDA's advice to your own

judgment, the way I look at this is that in patients who have other

reasonable reasons to have hypomagnesemia (eg, malabsorption syndromes

in the small bowel, renal losses, or if they're on some medication such

as a diuretic that may predispose them to have an ongoing magnesium

loss), there may be reason to check magnesium level when you're having a

follow-up [appointment] with these patients. I'm not sure that I'm ready

to start checking magnesium levels in every patient going on a proton

pump inhibitor, even in that population, but it's probably not unreasonable.

Magnesium level deficiency or hypomagnesemia may present with some

unusual circumstances, such as profound cardiac dysrhythmias or

seizures. Sometimes simple things like muscle twitching can be a protean

manifestation. Again, magnesium deficiency is something to consider in

patients on proton pump inhibitors who present with unusual symptoms and

who may have some magnesium loss risk.

Putting this in perspective, I would at least have this in the back of

your mind when considering the population of patients on PPIs. It's

extremely rare, as are many other side effects such as interstitial

nephritis that we see with proton pump inhibitors. The mechanism of

hypomagnesemia is not well understood. Every time we prescribe a PPI we

should certainly consider: Does this patient really need this

medication? If they do, appropriate use of a proton pump inhibitor

certainly should not be preempted by concern for hypomagnesemia. I'll

leave this to your best clinical judgment. I look forward to seeing you

again soon. Thanks.

References

1. US Food and Drug Administration. Proton pump inhibitor drugs

(PPIs): Drug Safety Communication -- low magnesium levels can be

associated with long-term use. Available at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedical\

Products/ucm245275.htm

Accessed March 4, 2011.

http://www.medscape.com/viewarticle/738442?src=mp & spon=20