Mycophenolate Mofetil

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 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. FDA is continuing to work with the manufacturers of these drug products to develop and implement means to mitigate the risks of fetal exposure. See the FDA Healthcare Professional Information Sheet containing considerations and recommendations for clinicians prior to prescribing MMF or MPA to women of childbearing potential.
Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/mycophelolateHCP.htm

Etanercept

Amgen and Wyeth Pharmaceuticals informed healthcare professionals of revisions to prescribing information for Enbrel (Etanercept). The revisions include a BOXED WARNING about infections, including serious infections leading to hospitalization or death that have been observed in patients treated with Enbrel. Infections have included bacterial sepsis and tuberculosis. The ADVERSE REACTIONS section of the label was updated to include information regarding global clinical studies and the rate of occurrence of tuberculosis in patients treated with Enbrel. Healthcare professionals should screen patients for latent tuberculosis infection before beginning Enbrel. Patients should be educated about the symptoms of infection and closely monitored for signs and symptoms of infection during and after treatment with the drug. Patients who develop an infection should be evaluated for appropriate antimicrobial treatment and, in patients who develop a serious infection, Enbrel should be discontinued.

Source: http://www.fda.gov/medwatch/safety/2008/AmgenDearHCPLetter.pdf

Zanamivir

GlaxoSmithKline informed healthcare professionals of changes to the WARNINGS AND PRECAUTIONS sections of prescribing information for Relenza regarding information from postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury in patients with influenza who are receiving neuraminidase inhibitors, including Relenza. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of Relenza to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms which can include seizures, hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient.

Source: http://www.fda.gov/medwatch/safety/2008/relenza_DHCP.pdf

Exubera (insulin human rDNA origin) Inhalation Powder

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.

Source: http://www.fda.gov/medwatch/safety/2008/Exubera_DHCP.pdf

Mycophenolate mofetil, Mycophenolate acid

FDA informed healthcare professionals that the Agency is investigating a potential association between the use of CellCept and Myfortic, 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 usually occurring in patients with immune systems suppressed by disease or medicines. FDA is reviewing data submitted by Roche, including postmarketing 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 postmarketing reports and the proposed revisions to the prescribing information. As soon as the review is completed, 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.

Source: http://www.fda.gov/cder/drug/early_comm/mycophenolate.htm

Bortezomib

The European Medicines Agency (EMEA) has recommended that Velcade (bortezomib) should not be used in patients with certain severe pulmonary or heart problems (acute diffuse infiltrative pulmonary and pericardial disease). Velcade is used to treat progressive multiple myeloma in patients who have failed to respond to at least one other treatment and who have already undergone or are unsuitable for bone marrow transplantation.

Source: http://www.emea.europa.eu/humandocs/PDFs/EPAR/velcade/Q&A_Velcade_13838708en.pdf

Montelukast

FDA informed healthcare professionals and patients of the Agency's investigation of the possible association between the use of Montelukast and behavior/mood changes, suicidality (suicidal thinking and behavior) and suicide. Montelukast is a leukotriene receptor antagonist used to treat asthma and the symptoms of allergic rhinitis, and to prevent exercise-induced asthma. Patients should not stop taking Montelukast before talking to their doctor if they have questions about the new information. Healthcare professionals and caregivers should monitor patients taking Montelukast for suicidality (suicidal thinking and behavior) and changes in behavior and mood.
This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. Due to the complexity of the analyses, FDA anticipates that it may take up to 9 months to complete the ongoing evaluations. As soon as this review is complete, FDA will communicate the conclusions and recommendations to the public.

Source: http://www.fda.gov/cder/drug/early_comm/montelukast.htm

Becaplermin Gel

The FDA is conducting a safety review based on study data suggesting there may be an increased risk of death from cancer in diabetic patients using Regranex (becaplermin) Gel, a skin product used to heal leg and foot ulcers. While the review is ongoing, the FDA recommends health care professionals discuss the potential risks and benefits of using Regranex with their patients.This communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. As soon as this review is complete, FDA will communicate the conclusions and recommendations to the public.

Source: http://www.fda.gov/cder/drug/early_comm/becaplermin.htm

Abacavir and Didanosine

The FDA issued an Early Communication about recent findings of The Data Collection on Adverse Events of Anti-HIV Drugs Study. Data analyses from this study indicate a higher risk of heart attack in patients infected with HIV-1 who were taking Ziagen (abacavir) or Videx (didanosine) as part of their drug therapy. The study is a large observational study of 33,347 HIV-1 infected patients living in North America, Europe and Australia. Patients in this study are being followed to evaluate the short and long term adverse effects of treatment with anti-HIV drugs. FDA continues to evaluate the overall risks and benefits of abacavir and didanosine. This evaluation may result in the need to revise labeling for the products. Until the FDA’s review is complete, health care professionals should evaluate the potential risks and benefits of each HIV-1 antiretroviral drug their patients are taking.
This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. As soon as this review is complete, FDA will communicate the conclusions and recommendations to the public.

Source: http://www.fda.gov/cder/drug/early_comm/abacavir.htm

Erythropoiesis Stimulating Agents: Aranesp (darbepoetin alfa), Epogen (epoetin alfa), and Procrit (epoetin alfa)

Amgen and FDA notified healthcare professionals of changes to the Boxed Warnings/WARNINGS: Increased Mortality and/or Tumor Progression section of the Aranesp and EPOGEN/PROCRIT labeling to update information describing the results of two additional studies showing increased mortality and more rapid tumor progression in patients with cancer receiving ESAs. Based on the results of these studies, the prescribing information has been revised as follows: ESAs shortened overall survival and/or time to tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of ≥ 12 g/dL.
Source: http://www.fda.gov/medwatch/safety/2008/epo_DHCP_03102008.pdf

Darunavir

FDA and Tibotec Therapeutics notified healthcare professionals of changes to the WARNINGS section of the prescribing information for Prezista (darunavir) tablets regarding the risk of hepatotoxicity. In clinical trials and postmarketing experience, drug induced hepatitis has been reported in patients receiving combination therapy with Prezista/ritonavir. Appropriate laboratory testing should be conducted prior to initiating therapy with Prezista/ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of Prezista/ritonavir treatment.
Source: http://www.fda.gov/medwatch/safety/2008/prezista_DHCP.pdf

Denture Cleanser Allergic Reactions and Misuse

FDA notified dental healthcare professionals and patients of the risk of serious allergic reactions in users of denture cleansers. These adverse events, including abdominal pain, vomiting, seizures, hypotension and difficulty breathing, have occurred both when the product has been used properly as well as from improper use. These events can occur soon after first use or after years of use. FDA believes that the ingredient responsible for these reactions is persulfate, a known allergen. Persulfates are used in most denture cleansers to help clean and bleach the dentures. FDA is recommending that all manufacturers of denture cleansers modify their labeling to include warning information that the product contains persulfates and recommends improving the directions for use on their labeling in order to reduce misuse.
Source: http://www.fda.gov/cdrh/safety/022508-denturecleansers.html

Natalizumab

Biogen Idec, Elan and FDA notified healthcare professionals of reports of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose of Tysabri. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Physicians should inform patients that Tysabri may cause liver injury.
Source: http://www.fda.gov/medwatch/safety/2008/Tysabri_PI.pdf

Tamiflu (oseltamivir phosphate)

Roche and FDA informed healthcare professionals of neuropsychiatric events associated with the use of Tamiflu, in patients with influenza.The label has been revised as follows: Influenza can be associated with a variety of neurologic and behavioral symptoms which can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. There have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving Tamiflu. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on Tamiflu usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of Tamiflu to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient.
Source: http://www.fda.gov/medwatch/safety/2008/Tamiflu_PI.pdf