After receiving a report of cardiac arrest in a patient who was taking long-term esomeprazole therapy, CredibleMeds® analyzed the available cardiac safety data for each of the six proton pump inhibitors (PPIs) marketed in the US for the treatment of gastro-esophageal reflux disease (GERD). All six PPIs have uniform product labeling that includes a warning of rare but serious episodes of hypomagnesemia (low serum magnesium) associated with prolonged therapy (>3-12 months) (See FDA warning March 2011). These warning are supported by numerous case reports in the medical literature and hundreds of reports submitted to the FDA’s Adverse Event Reporting System (AERS).
Because the prolonged use of a PPI can cause hypomagnesemia and hypokalemia, conditions that prolong cardiac repolarization and facilitate torsades de pointes (TdP) cardiac arrhythmia, it is biologically plausible that chronic PPI therapy can result in TdP. After review of the available evidence, CredibleMeds® has concluded that, at this time, pantoprazole (Protonix® brand in the US)* should be added to the list of drugs with “Conditional Risk of TdP.” For the other PPIs (omeprazole, esomeprazole, lansoprazole, dexlansoprazole and rabeprazole), there are case reports in the literature and numerous reports of QT prolongation, TdP and cardiac death in AERS but the evidence has not yet met the CredibleMeds® threshold for causality.
In summary, CredibleMeds® has added pantoprazole to the “Conditional TdP Risk” list because of substantial and convincing evidence that, when taken for extended periods of time, this drug can cause hypomagnesemia and/or hypokalemia and indirectly result in TdP. Pantoprazole has also been added to the list of “Drugs to Avoid in Patients with congenital Long QT. Prolonged use (>14 days) of any PPI should be discouraged in this special population because of their inherent high risk of TdP.
*Other international brand names are Pantazone, Pantop-D, Pantasan, Pantrol, Prazolin, Pantochem, Pansev, Pantec, Somac, API, Tecta, Protium, Pantodac, Perizole, Pansped, Percazole, Astropan, Fenix, Pantecta, Pantoloc, Controloc, Somac, Tecta, Protium, Inipomp, Eupantol, Pantozol, Pantodac, Perizole, Pansped, Zurcazol, Pantup,Pantomed, TopZole, Nolpaza, Controloc, UXL-D, Pantid, Pantogen, Pantpas and Prazolin.