• CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid)
One of the ongoing safety reviews concerns two drugs used to prevent organ rejection, CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid). CellCept is approved to prevent heart, liver and kidney transplant rejection. Myfortic is approved to prevent kidney transplant rejection.
This safety review focuses on a potential association between these drugs and a rare, life-threatening CNS disorder called or progressive multifocal leukoencephalopathy (PML). PML occurs when a latent polyoma virus called the JC virus is activated and attacks the myelin sheath surrounding nerve cells. Most adults carry the virus, which becomes activated mainly in immuno-compromised patients. Symptoms of PML include vision changes, apathy, memory loss or confusion, ataxia and muscular weakness.
FDA is reviewing data on the possible association between CellCept and PML. Roche, the manufacturer of CellCept, and Novartis, the manufacturer of Myfortic, have proposed changes in the labeling of these drugs to include information on PML.
Until FDA has more information, healthcare professionals should be alert to the localized neurologic signs and symptoms that could signal PML in patients taking CellCept and Myfortic. They should also consider reducing the amount of immuno-suppression if a patient develops PML.
• Singulair (montelukast)
In another communication, FDA is informing healthcare professionals about a possible association between the use of Singulair and behavior and mood changes, suicidality and suicide. Singulair (montelukast) is used to treat asthma and allergic rhinitis, and to prevent exercise-induced asthma.
Singulair's manufacturer, Merck & Co., has updated the adverse events information in the drug's labeling several times over the past year. Those adverse events include tremor, depression, suicidality and anxiety. Merck plans to highlight these changes to prescribers, and to provide patient information leaflets on the drug.
FDA is reviewing reports of behavior and mood changes, suicidality and suicide in patients on Singulair, and has asked Merck to review its own clinical trial data for more information about suicide and suicidality. FDA will let clinicians and patients know about the results of these evaluations as soon as they're complete. In the meantime, patients on Singulair should be monitored for suicidality and changes in mood or behavior, and they should be instructed not to discontinue the drug without medical advice.
FDA is also reviewing reports of mood and behavioral changes in other asthma drugs, including Accolate (zafirlukast) and Zyflo (zileuton), and will decide whether further investigation is needed.
FDA's Ongoing Drug Safety Issues On CellCept, Singulair, And Spiriva Handihaler.
• Spiriva Handihaler (tiotropium)
In another communication, FDA informed health professionals of a possible increase in the risk of stroke among patients using the Spiriva Handihaler. This product, which contains tiotropium bromide, is used to treat bronchospasm associated with chronic obstructive pulmonary disease.
The manufacturer, Boehringer Ingelheim, conducted a pooled analysis of 29 studies of two tiotropium products, including the Spiriva Handihaler. In this analysis, patients using Spiriva experienced a stroke risk of 8/1000 per year compared with 6/1000 per year for those using a placebo. Pooled analyses like this one have inherent limitations, and so these results must be confirmed by further investigation using other data sources.
FDA has asked for more information from Boehringer Ingelheim, and is also reviewing adverse event reports for this product. The company has conducted a large, four-year study of the Spiriva Handihaler which should provide more information on the potential risks of this product. Results are expected soon. At that point, FDA will analyze all of the data and report its results to health professionals and the public. In the meantime, patients should not stop using the Spiriva Handihaler without talking to their doctors.
Again, these communications are preliminary information, and they're in keeping with FDA's commitment to inform the public about its ongoing drug safety reviews. FDA urges healthcare professionals and patients to report adverse reactions from any of the products discussed here through FDA's Medwatch program at 1-800-FDA-1088 or at the link below.
FDA MedWatch Page. Voluntary Reporting by Health Professionals.