Safety Update for Transplant Drugs Mycophenolate (CELLCEPT) and Mycophenolic Acid (MYFORTIC)

The Food and Drug Adminis­tration (FDA) has informed health care professionals that it will investigate a potential link between immunosuppressants mycophenolate (CELLCEPT) and mycophenolic acid (MYFORTIC) and a sometimes fatal condition.

The condition, progressive multi­focal leukoencephalopathy (PML), has been reported in patients taking these drugs. Patients taking myco­phenolate and mycophenolic acid are at an increased risk for opportunistic infections, including activation of the virus that causes PML. When the virus is activated, it attacks the protective coating around nerve cells.

The most frequent characteristics of PML are weakness on one side of the body, lack of feeling or emo­tion, confusion, thinking difficulties and inability to coordinate muscle movement.

During its investigation, the FDA will try to determine how often this condition occurs, after what duration of using the drugs and whether the simultaneous use of other drugs can contribute to the problem.

Mycophenolate is approved by the FDA to prevent organ rejection in kidney, heart and liver transplant recipients. Mycophenolic acid, a closely related product, is approved only for use in kidney transplant patients. Both drugs are immunosup­pressants, meaning they suppress the immune system.

In 2008, there were more than 1 million prescriptions dispensed for mycophenolate in pharmacies, making CELLCEPT one of the top 200 most prescribed drugs that year — more than would be expected for a drug used to prevent transplant rejection.

While both of these products are important for transplant recipients, they also are being prescribed, for ex­ample, for the kidney complications associated with the disease lupus, a use that is not approved by the FDA.

Although there is nothing illegal about prescribing a medication off-label, the safety and effectiveness of drugs prescribed for off-label uses have not been reviewed or approved by the FDA.

Both mycophenolate and myco­phenolic acid are required to display black box warnings at the beginning of their professional product labels (package inserts), informing patients of increased risks of developing infections, a type of cancer known as lymphoma, possible loss of pregnan­cy and risk of birth defects.

Women of childbearing age should have a negative pregnancy test within one week before starting these drugs. Two different types of effective birth control should be used at the same time for four weeks before start­ing and during treatment and for six weeks after stopping the drugs, unless sexual intercourse is avoided completely. Both mycophenolate and mycophenolic acid decrease the blood levels of the hormones in birth control pills, and the birth control pills may not work as well while taking myco­phenolate or mycophenolic acid.

The black box warning for myco­phenolate appears above. The lan­guage appearing in the mycophenolic acid black box warning is the same.

Other potentially serious adverse effects associated with the use of these drugs are discussed below. While the risks associated with the use of these drugs may be acceptable for transplant recipients, they may not be when they are prescribed for untested, unapproved off-label uses.

Decrease in red blood cells

In late 2009, health care provid­ers were notified that cases of pure red cell aplasia (PRCA) had been reported with these drugs. PRCA is a type of anemia in which there is a selective reduction of red blood cells that carry oxygen to the body. Patients with PRCA may experience fatigue, lethargy and/or abnormal paleness of the skin.

In some cases, PRCA was found to be reversible with dose reduction or cessation of treatment with these drugs.

Decrease in white blood cells

A severe decrease in a type of white blood cell known as neutrophils can develop in patients using these drugs.

White cells are important in fighting infections, and patients taking these drugs should have their white blood cell counts monitored.

Patients taking these drugs should report immediately any evidence of infection.

Decrease in platelets

Platelets are another type of blood cell. They are crucial in allowing blood to clot normally and, because these drugs can also decrease the platelet count, patients should also report immediately to their doctors any unexpected bruising or bleeding.

What You Can Do

You should not stop or change the dosage of mycophenolate or myco­phenolic acid without consulting the health care provider who prescribed the drug.

Read the FDA-approved Medica­tion Guide for these drugs before you start your treatment. Also, re-read the Medication Guide when you have your prescription refilled as the information may have been updated. The Medication Guides for mycophenolate and mycophenolic acid can be obtained from the FDA’s website at http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm or by asking a pharmacist.

Consumers may report serious adverse events or product quality problems with the use of vitamins to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

Online: https://www.accessdata.fda.gov/scripts/medwatch/med­watch-online.htm
Regular Mail: Use postage-paid FDA form 3500 and mail to Med­Watch, 5600 Fishers Lane, Rock­ville, MD 20852-9787
Fax: (800) 332-0178
Phone: (800) 332-1088