FDA: impurity found in Cubicin (daptomycin for injection)
 

Audience: Infectious disease healthcare professionals, hospital risk managers, and nursing service managers
[Posted 04/09/2008] Cubist Pharmaceuticals, Inc. informed healthcare professionals that a potentially significant impurity, 2-mercaptobenzothiazole (MBT), has been isolated from reconstituted Cubicin stored in with ReadyMED elastomeric infusion pumps manufactured by Cardinal Health, Inc. MBT is used in the manufacture of rubber and has been reported to leach from rubber stoppers and syringe components into medicinal products in the past. Cutaneous exposure to MBT has been associated with dermal sensitization, and chronic administration of MBT to laboratory rodents has been associated with an increased risk of certain tumors. No MBT has been identified in reconstituted Cubicin in other standard types of infusion systems that have been tested. Healthcare professionals are advised to discontinue using ReadyMED elastomeric infusion pumps with Cubicin until the issue has been addressed.

[April, 2008 - Letter - Cubist Pharmaceuticals, Inc.]

FDA: Recall of Neupro (rotigotine transdermal system)
 

Audience: Neurologists, other healthcare professionals, patients
[Posted 04/09/2008] Schwarz Pharma informed healthcare professionals and patients of the recall of Neupro, a transdermal delivery system worn on the skin and used to treat early stage Parkinson’s disease, at the end of April 2008, because of the formation of rotigotine crystals in the patches. When the drug crystallizes, less drug is available to be absorbed through the skin and the efficacy of the product may vary. Healthcare professionals should not initiate any new patients on Neupro and should begin to down-titrate all patients currently using the product per the guidelines in the product labeling. Patients should NOT abruptly discontinue therapy. Abrupt withdrawal of dopamine agonists has been associated with a syndrome resembling neuroleptic malignant syndrome or akinetic crises.

[April 8, 2008 - Drug Shortage Information - FDA.]

FDA: Pfizer updates warning about Exubera (insulin human rDNA origin) Inhalation Powder
 

Audience: Endocrinologists, pulmonologists, pharmacists, patients
[Posted 04/09/2008] Pfizer informed healthcare professionals and patients of updated safety information in the WARNINGS section of prescribing information for Exubera, a short-acting insulin you breathe in through your mouth using the Exubera inhaler that helps to control high blood sugar in adults with diabetes. There have been 6 newly diagnosed cases of primary lung malignancies in clinical trials among Exubera-treated patients, and 1 newly diagnosed case among comparator treated patients. There has also been 1 post-marketing report of a primary lung malignancy in an Exubera-treated patient. There were too few cases to determine whether the emergence of these events is related to Exubera. All patients who were diagnosed with lung cancer had a prior history of cigarette smoking. Because of limited availability of Exubera, healthcare professionals should seek alternative treatment options to maintain patients' glycemic control.

[April 9, 2008 - Dear Healthcare Professional Letter - Pfizer, Inc.]
[April 9, 2008 - Dear Patient Letter - Pfizer, Inc.]

 

Communication About an Ongoing Safety Review of
CellCept (mycophenolate mofetil) and Myfortic (mycophenolate acid)

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  it issued in Europe on February 18, 2008. 

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 submitted by Roche, including post marketing reports it has received of PML in patients who took CellCept or Myfortic, and the proposed revisions to the CellCept prescribing information.  FDA has asked Novartis, the maker of Myfortic, for data on PML cases and 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 post marketing 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