Proton Pump Inhibitors and Severe Hypomagnesaemia

Tim Cundy; Jonathan Mackay


Curr Opin Gastroenterol. 2011;27(2):180-185. 

In This Article

Prevalence of Proton Pump Inhibitor-induced Hypomagnesaemia

The prevalence is unknown, but given the extent of PPI use, the severe syndrome of hypomagnesaemia, hypocalcaemia and hypokalaemia is probably not very common. A single suspected UK Adverse Drug Reaction report through the yellow card scheme was made to the UK Medicines and Healthcare products Regulatory Agency (MHRA) in 1996, but since the 2006 report of Epstein et al.,[7] adverse events notifications and published case reports have increased substantially (Commission on Human Medicines/Medicines and Healthcare products Regulatory Agency, personal communication) (Fig. 3).

Figure 3.

Number of patients with proton pump inhibitor-associated hypomagnesaemia reported either in peer-reviewed journals or to the UK Medical and Healthcare products Regulatory Agency according to calendar year
MHRA, UK Medical and Healthcare products Regulatory Agency. *First 7 months only.

We have identified 28 cases described in 11 peer-reviewed publications since 2006[7–16,17•] (Table 1), and several other cases have been published in abstract form[13,17•] or communicated to us personally. It is evident from these reports that physicians had failed to recognize the association. Many of these patients were hypomagnesaemic for years and had multiple hospital admissions before the significance of their PPI therapy was recognized.[10,15,17•] The prevalence of asymptomatic, milder degrees of hypomagnesaemia is unknown.

Hypomagnesaemia has been described with all the PPIs that are substituted pyridylmethylsulphonyl benzimidazadole derivatives (in order of potency: rabeprazole, esomeprazole, omeprazole, lansoprazole and pantoprazole). Several studies have documented recurrence when one PPI is substituted for another, so it is a true class effect.[7,12,15,16] It has not yet been described with PPIs that are derivatives of imidazopyridine (such as tenatoprazole), but these have been in use for only a short time.