CellCept—generically known as mycophenolate mofetil—is part of a class of drugs called immunosuppressants and was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart, and liver. When CellCept is used with cyclosporine and corticosteroids, it greatly reduces the patient’s immune system from attacking the transplanted organ. As with all immunosuppressants, CellCept carries certain risks, including development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.
According to a "Dear Healthcare Provider" letter issued by Roche AG, cases of PRCA have been reported in patients treated with CellCept in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of CellCept therapy. In transplant patients, however, reduced immunosuppression may place the transplanted organ at risk, the letter said.
PRCA is a type of anemia that can cause fatigue, lethargy or abnormal paleness of the skin. Approximately 5% of all cases of PRCA are drug induced. According to a Reuters report, 41 PRCA cases were reported to Roche from 1995 through February 2008.
According to the FDA, The WARNINGS and ADVERSE REACTIONS sections of the CellCept Prescribing Information have been revised to reflect this new safety information.
Earlier this summer, we also reported that several patients taking CellCept developed progressive multifocal leukoencephalopathy (PML), a severe and often deadly brain infection sometimes seen in people taking immunosuppression drugs. In June, the "Warnings” and “Adverse Reactions” sections of the CellCept prescribing information was update to include information on its association with several cases of PML.
According to a statement on the Food & Drug Administration's (FDA) website, the decision to update the labeling for CellCept, Rapamune and the other drugs followed an analyses of its Adverse Event Reporting System (AERS) to characterize the association between BK virus-associated nephropathy and the use of these immunosuppressant drugs. The occurrence of BK virus-associated nephropathy is primarily observed in kidney transplant patients, the FDA said. The virus can be serious enough to cause rejection of the kidney.
The FDA advised health care professionals that monitoring for this serious risk and early intervention by the health care provider is critical. Adjustments in immunosuppression therapy should be considered for patients who develop BK virus-associated nephropathy.
According to the FDA statement, the association of BK virus-associated nephropathy has previously been reported for another immunosuppressant drug, tacrolimus (marketed as Prograf). Information about the increased risk for opportunistic infections, including activation of latent viral infections, is included in the prescribing information for Prograf. Currently the prescribing information for the other immunosuppressant drugs does not adequately warn about this possible serious adverse event.
Based on this new safety information, FDA is requiring, under the authorities granted under the Food and Drug Administration Amendments Act (FDAAA) of 2007, that manufacturers of these immunosuppressants update their prescribing information to include stronger warnings about the risk of BK virus-associated nephropathy.
This is not the first time some of these drugs have been associated with a risk of opportunistic infections. Last year, the labeling for CellCept and Myfortic were updated to Progressive Multifocal Leukoencephalopathy (PML). PML is caused by a polyomavirus, called the JC virus. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply.
The maker of CellCept, Swiss Drug Maker Roche, has informed healthcare providers that it has modified the "Warnings" and "Adverse Reactions" sections of the CellCept prescribing information to include information on its association with several cases of Progressive Multifocal Leukoencephalopathy (PML).
CellCept—generically known as mycophenolate mofetil—is part of a class of drugs called immunosuppressants and was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart, and liver. When CellCept is used with cyclosporine and corticosteroids, it greatly reduces the patient’s immune system from attacking the transplanted organ. As with all immunosuppressants, CellCept carries certain risks, including development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.
PML attacks the brain and central nervous system and is usually fatal. Symptoms include vision problems, loss of coordination, and memory loss. According to the FDA, patients who survive the disease are often permanently disabled. In April, the Food & Drug Administration (FDA) announced that it was reviewing the safety of CellCept due to a possible association with PML. At the time, Roche said that it had confirmed 10 cases of PML in CellCept users.
PML is associated with at least one other drug, Tysabri, which is used to treat multiple sclerosis. Tysabri was actually removed from the market for a short time in 2005 because several patients taking it had died of the disorder. In 2005, the law firm of Parker Waichman Alonso LLP filed suit against Elan Inc. and Biogen Idec, the makers of Tysabri, on behalf of a woman who died from progressive multi-focal leukoencephalopathy while taking that drug. When contacted, Jerry Parker, the managing partner of Parker Waichman said that Tysabri case had been resolved, but that the resolution remained confidential.
Last October, CellCept was linked to miscarriage and birth defects, prompting the FDA to add a new boxed warning to its label last November. That labeling remains under FDA review. The potential for side effects was considered so great that the FDA advised women of childbearing age to use two methods of birth control before, during, and after CellCept treatment. The FDA reposted that warning in May.
Last October, the FDA issued its first warning. At the time, agency spokesperson Christopher Kelly said it was concerned that some physicians might not have seen the initial warning. Kelly also said that most of the reported problems affected those women who took CellCept before they realized that they were pregnant. Also, some of the women took the drug for off-label uses—for conditions the drug was not approved to treat—such as rheumatoid arthritis and lupus.
Last November, Roche alerted the FDA about reports of a neurological disease—progressive multi-focal leukoencephalopathy—that is often fatal and was showing up in patients taking CellCept. Now, regulators are trying to determine whether organ transplant drugs made by Roche and Novartis increase the risk of the often-fatal disease. The FDA also said is currently reviewing such risks in Novartis’ Myfortic, used in the prevention of kidney transplant rejection.
The FDA’s initial warning cited National Transplantation Pregnancy Registry data that was published in December 2006 and looked at 24 women exposed to CellCept with a total of 33 pregnancies; 15 resulted in a miscarriage, 18 in live births. Of the 18 live births, four infants had birth defects. According to post-marketing data derived from he Daily Women’s Health Policy Report 10/31/07, which were collected by Roche and involved reviewed 77 women on CellCept, 25 suffered miscarriages and 14 birth defects among fetuses and infants were realized.
CellCept—generically known as mycophenolate mofetil—is part of a class of drugs called immunosuppressants and was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart, and liver. When CellCept is used in collaboration with cyclosporine and corticosteroids, it greatly reduces the patient's immune system from attacking the transplanted organ. As with all immunosuppressants, CellCept carries certain risks, including development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.
The FDA announced the process to review the reports and consider revised labeling for the medications, which takes approximately two months. Until then, regulators advise doctors and patients to watch for neurological symptoms. Progressive multi-focal leukoencephalopathy attacks the brain and central nervous system and is usually fatal. Symptoms include vision problems, loss of coordination, and memory loss. According to the FDA, patients with the disease are often permanently disabled.
Christopher Vancheri, a Roche company spokesman, confirmed 10 cases of progressive multi-focal leukoencephalopathy in CellCept patients, adding that over 500,000 patients have used CellCept since 1995, when it was approved in the US.
Last October, Roche’s CellCept and Myforic by Novartis labeling were updated to include a boxed warning over the potential for miscarriages and birth defects. The new CellCept labeling classified the risk as Category D (Positive Evidence of Fetal Risk). The concern about side effects was so great that the FDA warned women of childbearing age to use two methods of birth control before, during, and after CellCept treatment.
FDA spokesman Christopher Kelly said it has not received new reports of pregnancy-related problems; however, the FDA reissued the warning over concerns some doctors may not have seen the initial warning. Roche previously reported 25 miscarriages among 77 women exposed to the drug between 1995 and 2007. In a notice posted online Friday, the FDA said that before prescribing the drugs doctors should confirm their transplant patients are not pregnant and are using effective contraception.
Meanwhile, the potential for side effects was considered so great that, in October, the FDA advised women of childbearing age to use two methods of birth control before, during, and after CellCept treatment. This February, Roche confirmed problems were reported in kidney, heart, and lung transplant patients and the neurological disorder was seen in patients taking the drug for a form of lupus, a CellCept use not approved by regulators. The FDA said most of the problems came from mothers taking CellCept before their pregnancies were detected; some were taking the drug for off-label uses such as rheumatoid arthritis in addition to lupus.
Last month, the FDA said it was investigating 16 patients who developed a rare neurological disease—progressive multifocal leukoencephalopathy—while on CellCept. The disease attacks the brain and central nervous system and is generally fatal with symptoms that include vision problems, loss of coordination, and memory loss. Those who survive are often left permanently disabled.
CellCept is generically known as mycophenolate mofetil and is part of drug class called immunosuppressants. CellCept carries other risks, including the development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.
Progressive multi-focal leukoencephalopathy is associated with at least one other drug, Tysabri, which is used to treat multiple sclerosis. Tysabri was removed from the market in 2005 after several patients taking it had died of the disorder. In 2005, the law firm of Parker Waichman Alonso filed suit against Elan Inc. and Biogen Idec—makers of Tysabri—on behalf of a woman who died from the disease while taking that drug. When contacted, Jerry Parker, the managing partner of Parker Waichman said that Tysabri case had been resolved, but that the resolution remained confidential.
CellCept—generically known as mycophenolate mofetil—is part of a class of drugs called immunosuppressants and was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart, and liver. When CellCept is used in with cyclosporine and corticosteroids, it greatly reduces the patient's immune system from attacking the transplanted organ. As with all immunosuppressants, CellCept carries certain risks, including development of lymphoma and other malignancies and is also linked to an increased risk of developing opportunistic infections and sepsis.
The FDA announced the process to review the reports and consider revised labeling for the medications takes approximately two months. Until then, regulators advise doctors and patients to watch for neurological symptoms. Progressive multi-focal leukoencephalopathy attacks the brain and central nervous system and is usually fatal. Symptoms include vision problems, loss of coordination, and memory loss. According to the FDA, patients who the disease are often permanently disabled.
Christopher Vancheri, a Roche company spokesman, confirmed 10 cases of progressive multi-focal leukoencephalopathy in CellCept patients, adding that over 500,000 patients have used CellCept since 1995, when it was approved in the US.
Last October, CellCept was linked to miscarriage and birth defects, prompting the FDA to add a new boxed warning to its label last November. That labeling remains under FDA review. The potential for side effects was considered so great that the FDA advised women of childbearing age to use two methods of birth control before, during, and after CellCept treatment. Meanwhile, European regulators added language about the neurological disease to CellCept packaging and, this February, Roche sent a letter to European doctors, highlighting the labeling changes. The letter stated problems were reported in kidney, heart, and lung transplant patients and the neurological disorder was seen in patients taking the drug for a form of lupus, a CellCept use not approved by regulators.
Roche said it is difficult to sort out the role of its drug in the reports since many patients had other diseases and were taking other drugs. According to the Roche letter—which the FDA posted to its Website today, determining the role of the drug in the reports poses some challenges because many patients taking the drug were suffering with other illnesses and also on other drugs, "However, the contributory role of CellCept cannot be excluded."
A spokeswoman for Novartis said the company is not aware of any instances of the neurological disease in patients taking its drug and plans to cooperate with any labeling changes recommended by regulators.
Progressive multi-focal leukoencephalopathy is associated with at least one other drug, Tysabri, which is used to treat multiple sclerosis. Tysabri was actually removed from the market in 2005 because several patients taking it had died of the disorder. In 2005, the law firm of Parker Waichman Alonso filed suit against Elan Inc. and Biogen Idec, the makers of Tysabri, on behalf of a woman who died from progressive multi-focal leukoencephalopathy while taking that drug. When contacted, Jerry Parker, the managing partner of Parker Waichman said that Tysabri case had been resolved, but that the resolution remained confidential.
CellCept, also known by its generic name mycophenolate mofetil, is part of a class of drugs called immunosuppressants. It was approved in 1995 to prevent rejection of solid organ transplants, including kidney, heart and liver. When used in combination with cyclosporine and corticosteroids, CellCept can greatly reduce the chance that a patient's immune system will attack a transplanted organ. However, like all immunosuppressant drugs, CellCept does carry certain risks, including the development of lymphoma and other malignancies. Like other drugs in its class, CellCept is also linked to an increased risk of developing opportunistic infections and sepsis.
A recent analysis of data regarding CellCept from the National Transplantation Pregnancy Registry has led the FDA to conclude that pregnant women taking CellCept have a significantly higher risk of miscarriage during the first trimester, and that their babies are more likely to develop birth defects, including external ear and facial abnormalities such as cleft palate and lip, and problems with the distal limbs, esophagus and kidney. While it was known previously that CellCept could cause problems during pregnancy, the FDA had classified the risk as Category C (Risk of Fetal Harm Cannot be Ruled Out). These side effects are now classified as Category D (Positive Evidence of Fetal Risk).
The FDA is now warning that doctors should tell female patients of childbearing age about CellCept miscarriage and birth defect risks. Women of childbearing age who receive CellCept must be counseled on contraceptive use, and they should be made aware that the drug can interfere with the effectiveness of oral contraceptives.
The FDA is also now requiring women of childbearing age to undergo pregnancy testing within one week of beginning CellCept therapy. A female patient prescribed CellCept should begin using contraceptives four weeks prior of starting the drug, and for six weeks after stopping. The FDA is also advising that female patients of child bearing age use two methods of birth control while taking CellCept. Finally, the FDA is advising that a woman planning a pregnancy should not be prescribed CellCept unless no other immunosuppressant drugs have been successful in avoiding organ rejection.
Finally, to further monitor fetal outcomes of pregnant women exposed to CellCept, a National Transplantation Pregnancy Registry has been established. The FDA is encouraging doctors to register their female CellCept patients by calling 1-877-955-6877.