Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients

Recart, Delfina; Ferraris, Augusto; Petriglieri, Carla Ines; Serena, Marina Alonso; Bonella, María Belén; Posadas‐Martinez, María Lourdes

doi:10.1007/s11739-020-02501-1

Cited by 11 publications

(19 citation statements)

References 26 publications

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“…There are two main pathways responsible for absorption: paracellular absorption regulated by tight junction-associated claudin proteins and transcellular absorption facilitated by transient receptor potential melastatin 6 and 7 channels (TRPM6 and TRPM7), and basocellular cyclin M4 (CNNM4) Mg2+ channels [1,3] . PPIs are a mainstay treatment for gastric acid-related diseases and are extensively used worldwide [2,4] . Several concerns about the long-term use of PPIs have been emerging, with hypomagnesaemia being reported in the later years.…”

Section: Discussionmentioning

confidence: 99%

“…Several concerns about the long-term use of PPIs have been emerging, with hypomagnesaemia being reported in the later years. Some studies have been showing controversial results [2,4,5] . A medium prevalence of hypomagnesaemia of 19-27% has been reported among PPI users [2,4] , as well as an increased odd risk of hypomagnesaemia among PPI users (pooled odds ratio of 1.5 [95% confidence interval, 1.1-2.0]) after adjustment for possible confounders such as the use of diuretics, particularly in chronic use cases [5] .…”

Section: Discussionmentioning

confidence: 99%

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Hypomagnesaemia – One Cause To Remember!

Viegas

Lopes

Almeida

et al. 2022

European Journal of Case Reports in Internal Medicine

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A 71-year-old female presented with 5 days of diarrhoea and asthenia. Past medical history of rheumatoid arthritis, arterial hypertension, hypertrophic cardiomyopathy and chronic gastritis was treated with leflunomide, deflazacort, esomeprazole, carvedilol and spironolactone. At admission, the patient’s physical examination showed signs of dehydration. Lab results revealed leucocytosis, increased C-reactive protein, hypomagnesaemia, hypocalcaemia and hypokalaemia. A presumption of acute infectious diarrhoea causing hypomagnesaemia with hypocalcaemia and hypokalaemia was made. She was started on ciprofloxacin, IV hydration and electrolyte supplementation with an adequate response. However, magnesium levels fell repeatedly. After excluding other causes for hypomagnesaemia, chronic use of proton pump inhibitors (PPIs) was considered a plausible cause therefore PPI was discontinued, with normalisation of magnesium levels. Hypomagnesaemia is a common disturbance, mainly caused by diarrhoea, gastrointestinal malabsorption, medications, alcoholism and volume expansion. Clinical manifestations include neuromuscular symptoms, cardiovascular manifestations, hypokalaemia and changes in calcium metabolism. PPI-related hypomagnesaemia has been described in later years particularly in chronic use cases, with a medium prevalence of 27%, but further studies remain necessary to clarify its pathophysiologic mechanism. Since PPIs are widely used, it is essential to be aware of hypomagnesaemia as a possible side effect, particularly in refractory cases and after excluding other common causes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypomagnesaemia – One Cause To Remember!

Viegas

Lopes

Almeida

et al. 2022

European Journal of Case Reports in Internal Medicine

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“…It has been observed that PPI use may favor hypomagnesemia with the onset of muscle cramps, paraesthesia, and eventually the potentially serious cardiac arrhythmias. This association was firstly reported in two patients in 2006 [101], followed by the publication of other case reports and case series [102][103][104][105][106], and a recent cross-sectional study [107]. However, available data are conflicting with other authors not confirming this association.…”

Section: Magnesium Deficiency and Anti-secretory Drugsmentioning

confidence: 98%

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Carabotti¹,

Annibale²,

Lahner³

2021

Nutrients

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Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.

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“…In 2011, the US FDA released a warning about low serum magnesium levels associated with long-term PPI use. A cross-sectional study in hospitalised patients in Buenos Aires demonstrated that 36% of patients with chronic PPI use had hypomagnesaemia on admission [ 28 ]. Association with other drugs used in oncology, and sometimes themselves, the cause of severe hypomagnesaemia, such as cisplatin and EGF receptor antagonists (monoclonal antibodies and tyrosine kinase inhibitors), requires regular follow-up of magnesaemia.…”

Section: Systemic Toxicity Linked To Long-term Ppi Use With a Possibl...mentioning

confidence: 99%

Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper

Raoul

Edeline

Simmet

et al. 2022

Cancers

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Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician.

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Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients

Cited by 11 publications

References 26 publications

Hypomagnesaemia – One Cause To Remember!

Hypomagnesaemia – One Cause To Remember!

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper

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