FDA is aware of reports of infants born with serious congenital anomalies, including microtia and cleft lip and palate, following exposure to mycophenolate mofetil (MMF) during pregnancy. MMF, the active drug substance in CellCept, is an ester of the active metabolite mycophenolic acid (MPA), the active drug substance in Myfortic. In most cases, the mothers were taking MMF following an organ transplant to prevent organ rejection. However, some mothers taking MMF were being treated for immune-mediated conditions such as systemic lupus erythematosus (SLE) and erythema multiforme. Treatment began before their pregnancies and continued into the first trimester or until the pregnancy was detected. MMF is approved in the U.S. for use in the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants and MPA is approved in the U.S. for use in the prophylaxis of organ rejection in patients receiving allogeneic renal transplants. In patients who are transplant recipients, these drugs are almost always used in combination with other immunosuppressant drugs.
MMF and MPA increase the risk of spontaneous abortion in the first trimester and can cause congenital malformations in the offspring of women who are treated during pregnancy. The labeling for both MMF and MPA was revised in November 2007 to change the Pregnancy Category to "D" (positive evidence of human fetal risk, but potential benefits may warrant use of the drug in pregnant women despite the potential risk) and to add these findings about the risk of early pregnancy loss and congenital malformations to the boxed warning.
FDA is continuing to work with the manufacturers of these drug products to develop and implement means to mitigate the risks of fetal exposure.
This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.
FDA is investigating a potential association between the use of CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid), medicines used to prevent organ rejection, and the development of progressive multifocal leukoencephalopathy (PML), a life-threatening disease.
PML is a rare disorder that affects the central nervous system. When it occurs, it is usually in patients with immune systems suppressed by disease or medicines. It happens when the polyomavirus, also known as the JC virus, is activated. The JC virus is found in most adults but does not usually cause symptoms. Scientists do not know exactly how the JC virus is activated. Once activated, the JC virus attacks the cells that make myelin, the protective coating around nerve cells. Signs and symptoms of PML can include localized neurologic signs and symptoms including vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and weakness in the legs. Many patients who develop PML die. Patients who survive may have permanent disability due to irreversible nerve damage. More information on PML can be found at the National Institutes of Health website.
CellCept is approved to prevent heart, liver, and kidney transplant rejection and Myfortic is approved to prevent kidney transplant rejection. Mycophenolate mofetil, the drug ingredient in CellCept, is metabolized by the body to mycophenolic acid, the drug ingredient in Myfortic. Both CellCept and Myfortic are used with other drugs to suppress the immune system.
On November 8, 2007, Roche, the maker of CellCept, submitted an evaluation of its PML cases in patients who have received CellCept in addition to other immunosuppressive medicines. Roche also submitted recommendations to the FDA for including information about PML in the CellCept prescribing information. On March 14, 2008, Roche informed the FDA of the Dear Health Care Professional letter 
Roche is aware of cases of PML in transplant recipients and patients with systemic lupus erythematosus (SLE), an autoimmune disorder that is sometimes treated with CellCept; however, CellCept and Myfortic are not approved for treating SLE or similar autoimmune disorders.
Roche is aware of cases of PML in transplant recipients and patients with systemic lupus erythematosus (SLE), an autoimmune disorder that is sometimes treated with CellCept; however, CellCept and Myfortic are not approved for treating SLE or similar autoimmune disorders.
FDA is reviewing data, including postmarketing reports it has received of PML in patients who took CellCept, and the proposed revisions to the CellCept prescribing information. FDA has asked Novartis, the maker of Myfortic to revise the Myfortic prescribing information to include the same information about PML included in the CellCept prescribing information.
FDA anticipates it may take about 2 months to complete its review of the postmarketing reports and the proposed revised prescribing information for CellCept and Myfortic about PML. As soon as FDA completes the review, FDA will communicate the conclusions and recommendations to the public. Until further information is available, patients and healthcare professionals should be aware of the possibility of PML, such as localized neurologic signs and symptoms in the setting of a suppressed immune system, including during therapy with CellCept and Myfortic. Decreasing total immunosuppression may improve the outcome of patients who develop PML.
This communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.
FDA urges both healthcare professionals and patients to report side effects from the use of CellCept and Myfortic to the FDA's MedWatch Adverse Event Reporting program
- online at [www.fda.gov/medwatch/report.htm];
- by returning the postage-paid FDA form 3500 [available in PDF format at [www.fda.gov/medwatch/getforms.htm] to 5600 Fishers Lane, Rockville, MD 20852-9787;
- faxing the form to 1-800-FDA-0178; or
- by phone at 1-800-332-1088
No comments:
Post a Comment