Preventing recurrent hypomagnesaemia: oral magnesium glycerophosphate

Condition

Hypomagnesaemia is the presence of abnormally low levels of serum magnesium. It is relatively common, being estimated to affect 2.5% to 15% of the general population and up to 65% of patients in intensive care settings. However, most patients with hypomagnesaemia are asymptomatic; symptoms are not usually seen until serum magnesium concentration falls below 0.5 mmol/litre^[7].

Causes of hypomagnesaemia include inadequate dietary intake, reduced intestinal absorption and increased renal excretion^[7],[8]. Magnesium salts are not well absorbed from the gastrointestinal tract, with most being absorbed in the small intestine^[7],[9]. Excessive losses in diarrhoea, stomata or fistulae are reportedly the most common causes of hypomagnesaemia^[9]. Small bowel bypass surgery and diseases that cause malabsorption can also lead to hypomagnesaemia^[7].

Magnesium is primarily excreted by the kidneys^[9]. Inherited renal tubular reabsorption defects that result in increased excretion of magnesium, such as Gitelman's syndrome, are associated with hypomagnesaemia^[7]. Other conditions associated with hypomagnesaemia include malnutrition, anorexia nervosa, chronic alcoholism, total parenteral nutrition, acute pancreatitis, diabetic ketoacidosis, hypersecretion of aldosterone and lactation^[7],[8].

Certain drug treatments including diuretics, antibiotics (such as amphotericin B and aminoglycosides), immunosuppressants and chemotherapy drugs (particularly cisplatin) have been associated with hypomagnesaemia^[7],[8]. The number of cases of hypomagnesaemia associated with proton pump inhibitors reported in the literature is increasing^[7].

The signs and symptoms of hypomagnesaemia include neuromuscular, cardiovascular and metabolic features. Neuromuscular effects include muscle weakness, ataxia, tremor and spasms of the feet and hands. Severe hypomagnesaemia can cause seizures (especially in children) and coma. Cardiovascular effects include arrhythmias and electrocardiogram (ECG) abnormalities^[7],[8].

Hypomagnesaemia is often associated with other biochemical and electrolyte abnormalities, such as hypocalcaemia, hypokalaemia, hyponatraemia and metabolic acidosis^[7],[9]. Some of the symptoms seen in hypomagnesaemia may relate to these associated abnormalities^[7],[8].

There are no national UK guidelines for treating and preventing hypomagnesaemia. The BNF suggests that, for symptomatic hypomagnesaemia, intravenous infusion of magnesium sulfate is initially used and oral magnesium supplements can be given subsequently to prevent recurrence. Intramuscular injection of magnesium sulfate is another option for initial treatment but is painful.

Other sources advise that oral magnesium may be used as first-line treatment, the selection of route of administration being influenced by severity and oral tolerability^[8],[10]. Practice varies between hospital trusts^[11].

The BNF states that magnesium glycerophosphate tablets or liquid are suitable (unlicensed) preparations for preventing recurrent hypomagnesaemia.

Alternative treatment options

There are no licensed oral medicines for treating and preventing hypomagnesaemia in the UK. Many unlicensed oral magnesium salts are available in the UK, such as magnesium aspartate, magnesium carbonate, magnesium citrate, magnesium lactate, magnesium orotate, magnesium oxide and magnesium pidolate. Magnesium hydroxide is licensed for use as an antacid, so its use for hypomagnesaemia is off-label. A Medicines Q&A written by UK Medicines Information in 2010 provides a table of examples of oral magnesium preparations available at that time in the UK^[12].

Several small studies in healthy volunteers have compared the bioavailability of magnesium preparations. The results are inconclusive but suggest that bioavailability may differ between magnesium salts^{[13],[14],[15],[16]}.

The BNF for children lists magnesium-L-aspartate as an option alongside magnesium glycerophosphate for preventing recurrent hypomagnesaemia in children.