Drug Profile

Mesoridazine is the active breakdown product of the antipsychotic drug thioridazine (MELLARIL), which we have also listed as a Do Not Use drug. Mesoridazine, like thioridazine, required extensive new safety warnings, including a boxed warning, in its professional product labeling or package insert in September 2000 because of life-threatening heart rhythm disturbances and death associated with the use of the drug. The only FDA-approved use for mesoridazine is now “the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs.”[1]

We have listed mesoridazine as a Do Not Use drug because there are a number of safer antipsychotic drugs available on the market. There is simply no longer any reason to expose patients to the risks of mesoridazine.

Mesoridazine causes an adverse effect known as QTc interval prolongation. The QTc interval is the length of time it takes the large chambers of the heart (ventricles) to electrically discharge and recharge. A prolongation of the QTc interval can lead to a type of heart rhythm disturbance, or cardiac arrhythmia, known as Torsades de pointes, and sudden death. The QTc interval is measured by an electrocardiogram (EKG or ECG) in milliseconds. The lowercase “c” indicates that the QT interval has been corrected for the patient’s heart rate. The QTc prolongation seen with mesoridazine increases with increasing doses of the drug. The new labeling also warns that mesoridazine should not be started if the QTc is greater than 450 milliseconds. In patients already taking the drug, if the QTc is found to be over 500 milliseconds the drug should be stopped. Torsades de pointes is a French phrase that means “twisted point,” which describes the appearance of this rhythm disturbance on the EKG tracing.

Mesoridazine is now contraindicated in combination with other drugs that can prolong the QTc interval, and in patients who naturally have a long QT interval. The only extensive list of drugs that prolong QT intervals is maintained by the University of Arizona Health Sciences Center: http://www.torsades.org. A naturally long QT interval called “congenital long QT syndrome” and can be detected only by an EKG. Furthermore, mesoridazine is contraindicated in patients with a history of heart rhythm disturbances.

The new warnings in mesoridazine’s labeling are based primarily on the FDA’s review of a published study involving nine schizophrenic patients who had normal EKG tracings at baseline and no significant heart, kidney, or liver disease.[2] EKG tracings were obtained at baseline, during weeks two, three and four, and two weeks after the drug’s discontinuation. At the lowest dose of mesoridazine, four of nine patients displayed mild to moderate prolongation of the QT interval. At the highest dose, all nine patients had moderate prolongation of the QT interval. Two weeks after discontinuation, EKGs for eight of the nine patients had normalized.

This drug is no longer marketed in the U.S., either because it was withdrawn for safety reasons or because its manufacturer discontinued its production.[3]