Proton Pump Inhibitor Labeling Change

    On March 2nd, 2011 the Food and Drug Administration (FDA) released a drug safety communication to healthcare professionals and the public regarding proton pump inhibitors (PPI) and their potential to cause low levels of magnesium magnesemia). The FDA reviewed 38 cases in the Adverse Event Reporting System (AERS) and 23 cases reported in medical literature regarding hypomagnesemia in patients on PPI therapy. The FDA review suggests there is a link between low levels of magnesium and prolonged PPI use, but there is insufficient data at this time to quantify an incidence rate.

     

    Hypomagnesemia can lead to serious adverse events, such as muscle spasms (tetany), irregular heartbeat (arrhythmias), and seizures. Low serum levels of magnesium have been reported in patients taking PPIs for 3 months but it is more commonly associated with prolonged use (greater than 1 year). In almost one-quarter of the cases reviewed, the discontinuation of PPI therapy was necessary in addition to magnesium supplementation to resolve symptoms and hypomagnesemia. The mechanism for magnesium loss is unknown, but the FDA believes it may be related to changes in intestinal absorption of magnesium.

     

    In 2009, nearly 21 million patients received prescription PPIs and continued therapy for an average of 6 months, putting several patients at risk of hypomagnesemia. Information regarding the potential for low magnesium levels associated with prolonged use of PPI therapy will be added to the WARNINGS/PRECAUTIONS section in package inserts for all of the prescription PPIs. The FDA believes there is little risk of hypomagnesemia with over-the-counter (OTC) PPIs if used according to package labeling (14 days of therapy); therefore, the DRUG FACT boxes will remain unchanged for the time being.

     

    The following is a list of recommendations from the FDA for both the patient and healthcare professional:

     

    Recommendations for the patient:

  • Seek immediate care if you experience abnormal heart rate, racing heartbeat, palpitations, muscle spasm, tremor, or convulsions while taking a PPI. In children, abnormal heart rates may be associated with fatigue, upset stomach, or dizziness/lightheadedness.
  • Tell your healthcare professional if you have ever been told you have low magnesium levels in your blood.
  • Tell your healthcare professional if you are taking drugs, such as digoxin or diuretics, which may cause or contribute to low magnesium levels.
  • Do not stop taking your prescription PPI without discussing it with your healthcare professional.
  • Follow the directions on the package labeling carefully if you are taking or are going to begin taking an over-the-counter PPI.
  • Inform your healthcare professional if you have been taking an over-the-counter PPI for a long period of time.
  • Discuss any questions/concerns you may have about your PPI with your healthcare professional.
  • Report any adverse events to the FDA MedWatch program.

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    Recommendations for the healthcare professional:

  • Consider obtaining magnesium levels prior to initiating PPI therapy in a patient and check levels periodically in patients expected to be on therapy for a prolonged period of time or who are also taking digoxin or diuretics.
  • Educate patients on the signs/symptoms of low magnesium levels.
  • Advise patients to seek immediate care from a healthcare professional if they experience any of the symptoms associated with low magnesium levels.
  • Consider PPIs as a possible cause of hypomagnesemia, and know that patients who develop symptoms may require magnesium supplementation, as well as discontinuation of PPI therapy.
  • Be aware that consumers may be taking over-the-counter PPIs for an extended period of time and communicate the risk of prolonged PPI use.
  • Report any adverse events to the FDA MedWatch program.