Long-term PPI use associated with hypomagnesaemia and fractures

An increased risk of fracture and cases of severe hypomagnesaemia have been reported in patients receiving long-term treatment with proton pump inhibitors (PPIs).

Long-term treatment with PPIs for conditions such as gastric ulcers (shown here) can cause hypomagnesaemia or fractures | SCIENCE PHOTO LIBRARY
Long-term treatment with PPIs for conditions such as gastric ulcers (shown here) can cause hypomagnesaemia or fractures | SCIENCE PHOTO LIBRARY

Increased risk of fractures

Observational studies have suggested that there may be a modest increase in the risk of hip, wrist or spine fracture with PPIs, especially if high doses are used for a year or longer.

Reports of hypomagnesaemia

In addition, severe hypomagnesaemia has been reported infrequently in patients taking PPIs. The majority of cases occurred after 1 year of treatment and improved after magnesium replacement and discontinuation of the PPI. Severe manifestations of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia; however, these can begin insidiously and may be overlooked.

MHRA recommendations

Healthcare professionals should treat patients at risk of osteoporosis according to current clinical guidelines and ensure adequate intake of vitamin D and calcium.

If prolonged PPI treatment is expected, the MHRA advises prescribers to consider measuring magnesium levels before and during use, particularly if there is concomitant use of digoxin or other drugs that may cause hypomagnesaemia (eg, diuretics).

Consideration should also be given to the use of PPIs obtained over-the-counter (OTC).

Advice for patients

  • OTC PPIs should not be taken for longer than four weeks without medical advice
  • A doctor should be consulted if symptoms of hypomagnesaemia (eg, muscle twitches, tremors, vomiting, fatigue and anorexia) occur.

Further information

Proton pump inhibitors in long-term use: increased risk of fracture

Proton pump inhibitors in long-term use: reports of hypomagnesaemia

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