Olanzapine induced Tardive Dystonia

A case of a 32 years old male suffering from Olanzapine induced tardive dystonia has been reported in Indian Journal of Pharmacology.
Reference: Indian J Pharmacol 2008;40:237-8
Source: http://www.ijp-online.com/text.asp?2008/40/5/237/44158

Quetiapine induced myoclonus

Cases of 2 young females who developed myoclonic jerks while on quetiapine have been reported in Indian Journal of Medical Sciences.
Reference: Indian J Med Sci 2008;62:422-3
Source: http://www.indianjmedsci.org/text.asp?2008/62/10/422/44024

Paracetamol induced angioedema

A case of a 4-year-old boy with a presumed viral infection who developed allergic rash and angioedema probably related to paracetamol exposure.
Causality analysis (Naranjo's algorithm) gave a score of 6 (probable reaction).
Reference: Indian J Med Sci 2008;62:420-2
Source: http://www.indianjmedsci.org/article.asp?issn=0019-5359;year=2008;volume=62;issue=10;spage=420;epage=422;aulast=Panchabhai

Multifocal bullous fixed drug eruption due to fluconazole

A case of a 35-year-old female patient who presented with multifocal bullous FDE due to fluconazole has bee reported in the Indian Journal of Dermatology.

Reference- Indian J Dermatol 2008;53(3):156-157
Source: http://www.e-ijd.org/article.asp?issn=0019-5154;year=2008;volume=53;issue=3;spage=156;epage=157;aulast=Nath

Phenytoin and Fosphenytoin Sodium

FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) from phenytoin therapy in Asian patients positive for human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais. Until the FDA evaluation is completed, healthcare providers who are considering the use of phenytoin or fosphenytoin should be aware of the risks and benefits described in the current prescribing information for this drug. Healthcare providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/phenytoin_fosphenytoinHCP.htm

Bisphosphonates and Atrial Fibrilation

FDA issued an update to the Agency's review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication.

Source: http://www.fda.gov/cder/drug/early_comm/bisphosphonates_update_200811.htm

Efalizumab (Raptiva)

FDA notified healthcare professionals of extensive labeling changes, including a Boxed Warning, to highlight the risks of life-threatening infections, including bacterial sepsis, viral meningitis, invasive fungal disease, progressive multifocal leukoencephalopathy and other opportunistic infections with the use of Raptiva. In addition, the prescribing information will be updated to describe a potential risk for the permanent suppression of the immune system with repeat administration of Raptiva in children. Raptiva is not approved for children under 18 years of age. Doctors and other prescribers should carefully evaluate and weigh the risk/benefit profile of Raptiva for patients who would be more susceptible to these risks. Health care professionals should monitor patients treated with Raptiva for the signs and symptoms of these adverse events and also instruct patients to report any such signs and symptoms to them without delay. Patients identified to begin therapy with Raptiva should have received all their age-appropriate vaccinations before starting the drug.Patients with pre-existing infections or who have a compromised immune system should notify their health care professional before beginning treatment with Raptiva.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01905.html

Over The Counter Cough and Cold Medications

FDA notified healthcare professionals and consumers that the Consumer Healthcare Products Association (CHPA) is voluntarily modifying the product labels for consumers of over the counter (OTC) cough and cold medicines to state "do not use" in children under 4 years of age. FDA supports CHPA members to help prevent and reduce misuse and to better inform consumers about the safe and effective use of these products for children. FDA continues to assess the safety and efficacy of these products and to revise its OTC list of approved ingredients and amounts for these medicines. Parents and care givers should adhere to the dosage instructions and warnings on the label that accompanies OTC cough and cold medications before giving the product to children, and should consult their healthcare professionals if they have any questions or concerns.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01899.html

Statin drugs and amyotrophic lateral sclerosis (ALS)

An FDA analysis provides new evidence that the use of statins does not increase incidence of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease often referred to as "Lou Gehrig's Disease." The FDA analysis, undertaken after the agency received a higher than expected number of reports of ALS in patients on statins, is based on data from 41 long-term controlled clinical trials. The results showed no increased incidence of the disease in patients treated with a statin compared with placebo.The FDA is anticipating the completion of a case-control or epidemiological study of ALS and statin use. Results from this study should be available within 6-9 months. FDA is also examining the feasibility of conducting additional epidemiologic studies to examine the incidence and clinical course of ALS in patients taking statins. Based on currently available information, health care professionals should not change their prescribing practices for statins and patients should not change their use of statins.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01892.html

Epoetin alfa

FDA has been made aware of preliminary safety findings from a clinical trial conducted in Germany investigating the use of epoetin alfa to treat acute ischemic stroke. The clinical trial utilized doses of epoetin alfa that were considerably higher than the doses recommended for the treatment of anemia as described in the FDA-approved labeling for the product. Over a period of ninety days after the start of the trial, there were more deaths in the group of patients who received epoetin alfa compared to patients who received the placebo (16% versus 9%). Roughly half of all deaths in both groups occurred within the first seven days after starting the drug, with death from intracranial hemorrhage (bleeding within the brain) occurring among approximately 4% of patients who received epoetin alfa compared to 1% of patients in the placebo group. FDA anticipates the receipt of additional data within the next several weeks. As soon as the review of these data is complete, FDA will communicate our conclusions and recommendations to the public. The finding of increased mortality in patients receiving epoetin alfa in the German trial suggests the need to closely monitor patients enrolled in other ongoing trials for adverse outcomes and to evaluate whether the potential benefits for enrolled patients outweigh the risks in these trials.
Source: http://www.fda.gov/cder/drug/early_comm/epoetin_alfa.htm

Erlotinib

OSI and Genentech notified healthcare professionals that cases of hepatic failure and hepatorenal syndrome, including fatalities, have been reported during use of Tarceva (Erlotinib), particularly in patients with baseline hepatic impairment. Patients with hepatic impairment receiving Tarceva should be closely monitored during therapy and the product should be used with extra caution in patients with total bilirubin >3x ULN. Dosing should be interrupted or discontinued if changes in liver function are severe, such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside the normal range. New information from a pharmacokinetic study in patients with moderate hepatic impairment associated with significant liver tumor burden has been provided in the revised prescribing information, and other recommendations are included in the WARNINGS and DOSAGE AND ADMINISTRATION sections.

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

Rituximab

Genentech informed healthcare professionals of revisions to prescribing information for Rituxan regarding a case of progressive multifocal leukoencephalopathy (PML) leading to death in a patient with rheumatoid arthritis who received Rituxan in a long-term safety extension clinical study. The patient developed a JC virus infection with resultant PML and death 18 months after taking the last dose of Rituxan. Healthcare professionals treating patients with Rituxan should consider PML in any patient presenting with new onset neurologic manifestations. Additionally, consultation with a neurologist, brain MRI and lumbar puncture should be considered as clinically indicated.

Source: http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf

Tumor necrosis factor-alpha blockers (TNF blockers), Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab)

FDA notified healthcare professionals that pulmonary and disseminated histoplasmosis, coccidioidomycosis, blastomycosis and other opportunistic infections are not consistently recognized in patients taking tumor necrosis factor-α blockers (TNF blockers). This has resulted in delays in appropriate treatment, sometimes resulting in death. For patients taking TNF blockers who present with signs and symptoms of possible systemic fungal infection, such as fever, malaise, weight loss, sweats, cough, dypsnea, and/or pulmonary infiltrates, or other serious systemic illness with or without concomitant shock, healthcare professionals should ascertain if patients live in or have traveled to areas of endemic mycoses. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/TNF_blockersHCP.htm

Natalizumab

FDA informed healthcare professionals of two new cases of progressive multifocal leukoencephalopathy (PML) in European patients receiving natalizumab monotherapy for multiple sclerosis for more than one year. PML, which is usually fatal, is a known risk of natalizumab treatment, but previous cases in patients with multiple sclerosis were seen in combination with other immunomodulatory therapies. Approximately 39,000 patients have received treatment with natalizumab worldwide, with approximately 12,000 patients receiving treatment for a least one year. No new cases have been seen in the US, where about 7,500 patients have received the drug for greater than one year and approximately 3,300 patients have received the drug for at least one and one-half years. In the U.S., natalizumab is available only to patients with relapsing multiple sclerosis or Crohn's disease who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under this program, every natalizumab-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections. While the two patients who developed PML were on monotherapy, the FDA still believes that natalizumab monotherapy may confer a lower risk of PML than when natalizumab is used together with other immunomodulatory medications. Prescribing information for natalizumab will be revised to include information informing prescribers and patients that cases of PML have occurred in patients taking natalizumab as monotherapy. Healthcare professionals should continue to monitor patients for sign and symptoms of PML. Additionally, natalizumab should not be infused if PML is suspected.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/natalizumab2008HCP.htm

Ezetimibe/Simvastatin (marketed as Vytorin)

FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.
FDA anticipates receiving a final SEAS study report in about 3 months and the Agency's review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency.

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

Naltrexone

FDA informed healthcare professionals of the risk of adverse injection site reactions in patients receiving naltrexone. Naltrexone is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment. Naltrexone is administered as an intramuscular gluteal injection and should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Physicians should instruct patients to monitor the injection site and contact them if they develop pain, swelling, tenderness, induration, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians should promptly refer patients with worsening injection site reactions to a surgeon.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/naltrexoneHCP.htm

Simvastatin Used With Amiodarone

FDA notified healthcare professionals of the risk of muscle injury, rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. Although a revision of the simvastatin labeling in 2002 described an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses greater than 20 mg daily, FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin. Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/simvastatin_amiodaroneHCP.htm

Erythropoiesis Stimulating Agents (ESAs)

FDA informed healthcare professionals of modifications to certain sections of the Boxed Warnings, Indications and Usage, and Dosage and Administration sections of prescribing information for Erythropoiesis Stimulating Agents (ESAs). The changes clarify the FDA-approved conditions for use of ESAs in patients with cancer and revise directions for dosing to state the hemoglobin level at which treatment with an ESA should be initiated. Additional revisions to prescribing information that ESAs are not intended for use in patients receiving myelosuppressive therapy when the expected outcome is cure and when to initiate and discontinue ESA dosing will be forthcoming. FDA continues to encourage healthcare professionals to discuss with their patients before starting or continuing therapy with ESAs, the benefits of treatment with ESAs and the potential and demonstrated risks of ESAs for thrombovascular events, shortened time to tumor progression or recurrence, and shortened survival time.

Source: http://www.fda.gov/cder/drug/infopage/RHE/default.htm

Abacavir

FDA informed healthcare professionals that serious and sometimes fatal hypersensitivity reactions (HSR) caused by abacavir therapy are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*5701. FDA reviewed data from two studies that support a recommendation for pre-therapy screening for the presence of the HLA-B*5701 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*5701 are available and all patients should be screened for the HLA-B*5701 allele before starting or restarting treatment with abacavir or abacavir-containing medications. Development of clinically suspected abacavir HSR requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*5701.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm

Mitoxantrone Hydrochloride

FDA reminded health care professionals who treat patients with mitoxantrone about recommendations that left ventricular ejection fraction (LVEF) be evaluated before initiating treatment and prior to administering each dose of mitoxantrone. FDA offered additional recommendations for cardiac monitoring to detect late-occurring cardiac toxicity, and provided information for patients with multiple sclerosis who receive the drug.
These recommendations were established in 2005 in response to post-marketing reports and case reports in the medical literature that described decreases in LVEF or frank congestive heart failure in patients with MS who had received cumulative doses of mitoxantrone that were lower than 100 mg/m2. Since that time, FDA has received information from a post-marketing safety study that demonstrated there is poor adherence to these recommendations in clinical practice. FDA is working with the manufacturers to educate healthcare providers to adhere to cardiac monitoring recommendations for patients with MS.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/mitroxantroneHCP.htm

Antipsychotics, Conventional and Atypical

FDA notified healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. In April 2005, FDA notified healthcare professionals that patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Since issuing that notification, FDA has reviewed additional information that indicates the risk is also associated with conventional antipsychotics. Antipsychotics are not indicated for the treatment of dementia-related psychosis. The prescribing information for all antipsychotic drugs will now include the same information about this risk in a BOXED WARNING and the WARNINGS section.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/antipsychotics_conventional.htm

Tumor Necrosis Factor (TNF) Blockers

FDA issued an Early Communication About an Ongoing Safety Review to inform healthcare professionals that the Agency is investigating a possible association between the use of Tumor Necrosis Factor (TNF) blockers and the development of lymphoma and other cancers in children and young adults. FDA is investigating approximately 30 reports of cancer in children and young adults. These reports were submitted to FDA's Adverse Event Reporting System over a ten-year interval, beginning in 1998 through April 29, 2008. These reports describe cancer occurring in children and young adults who began taking TNF blockers (along with other immuno-suppressive medicines such as methotrexate, azathioprine or 6-mercaptopurine), when they were ages 18 or less, to treat juvenile idiopathic arthritis, Crohn's disease or other diseases. Approximately half of the cancers were lymphomas, including both Hodgkin's and non-Hodgkin's lymphoma. Long-term studies are necessary to provide definitive answers about whether TNF blockers increase the occurrence of cancers in children because cancers may take a long time to develop and may not be detected in short-term studies. Until the evaluation is completed, healthcare providers, parents, and caregivers should be aware of the possible risk of lymphoma and other cancers in children and young adults when deciding how to best treat these patients.

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

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

Gardasil

The European Medicines Agency (EMEA) has received reports of deaths in women who had
previously received Gardasil, including two reports concerning the sudden and unexpected deaths of two young women in the European Union (EU). Gardasil is a vaccine approved in the EU for the prevention of cervical cancer and other diseases caused by human papillomavirus (HPV) types 6, 11, 16 and 18. It is estimated that about 1.5 million patients have been vaccinated with this HPV vaccine in Europe.
The two European cases were reported as part of the continuous monitoring of the safety of medicines. One of the cases occurred in Austria and the other in Germany. In both cases, the cause of death could not be identified. No causal relationship has been established between the deaths of the young women and the administration of Gardasil.
On the basis of the currently available evidence, the EMEA’s Committee for Medicinal Products for Human Use (CHMP) is of the opinion that the benefits of Gardasil continue to outweigh its risks and that no changes to its product information are necessary.
The EMEA will continue to closely monitor the safety of Gardasil and take appropriate actions should new information emerge that has an impact on the benefit-risk profile of Gardasil.

Source: http://www.emea.europa.eu/humandocs/PDFs/EPAR/gardasil/Gardasil_press_release.pdf

EMEA recommends new warnings and contraindications for rosiglitazone

The European Medicines Agency (EMEA) has recommended updating the product information for rosiglitazone-containing antidiabetic medicines. Rosiglitazone is available in the European Union as Avandia (rosiglitazone maleate), Avandamet (rosiglitazone maleate/metformin) and Avaglim (rosiglitazone maleate/glimepiride).
During its January 2008 meeting, the Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a scientific opinion recommending the inclusion of a new warning stating that the use of rosiglitazone in patients with ischemic heart disease and/or peripheral arterial disease is not recommended.
The CHMP also adopted an opinion recommending the addition of a new contraindication stating that rosiglitazone must not be used in patients with an acute coronary syndrome, such as angina or some types of myocardial infarction, because the medicine has not been studied in controlled trials in this specific patient group.

Source: http://www.emea.europa.eu/pdfs/human/press/pr/4223208en.pdf

Botox, Botox Cosmetic (Botulinum toxin Type A), Myobloc (Botulinum toxin Type B)

FDA issued an early communication about an ongoing safety review regarding Botox and Botox Cosmetic. FDA has received reports of systemic adverse reactions including respiratory compromise and death following the use of botulinum toxins types A and B for both FDA-approved and unapproved uses. The reactions reported are suggestive of botulism, which occurs when botulinum toxin spreads in the body beyond the site where it was injected. The most serious cases had outcomes that included hospitalization and death, and occurred mostly in children treated for cerebral palsy-associated limb spasticity. Use of botulinum toxins for treatment of limb spasticity (severe arm and leg muscle spasms) in children or adults is not an approved use in the U.S.

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

Injectable Colchicine (including drugs containing colchicine)

FDA announced its intention to take enforcement action against companies marketing unapproved, injectable colchicine, a drug used to treat gout. Colchicine is a highly toxic drug that can easily be administered in excessive doses, especially when given intravenously. There is a narrow margin between an effective dose of the drug and a toxic dose that can result in serious health risks, including death. The FDA is aware of 50 reports of adverse events associated with the use of intravenous colchicine, including 23 deaths. Potentially fatal effects include low blood cell counts, cardiac events, and organ failure. This action does not affect colchicine products that are dispensed in tablet form.

Individuals and companies must stop making these products within 30 days and stop shipping the product within 180 days or face regulatory action. After these dates, all injectable colchicine drug products must have FDA approval to be manufactured or shipped interstate.

Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01791.html

Enalaprilat Induced Acute Parotitis

A case of Enalaprilat induced acute parotitis has been published in the latest issue of the Journal of Association of Physicians of India.
A female patient developed acute bilateral parotitis within minutes of i.v. enalaprilat injection and recovered within 24 hours of stopping the drug and with symptomatic treatment.
This adverse reaction was tested on Naranjo’s algorithm and a score of 8 was obtained which puts this reaction as probable in the algorithm.

Reference: J Assoc Physc India 2008;56:128-129.

Source: http://www.japi.org/february2008/CR-128.htm

Antiepileptic Drugs

FDA informed healthcare professionals that the Agency has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. In the FDA's analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. The relative risk for suicidality was higher in patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

Healthcare professionals should closely monitor all patients currently taking or starting any antiepileptic drug for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

The drugs included in the analyses include (some of these drugs are also available in generic form):
Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

Although the 11 drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all antiepileptic drugs and anticipates that the class labeling changes will be applied broadly.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm

Varenicline

FDA informed healthcare professionals and consumers of important revisions to the WARNINGS and PRECAUTIONS sections of the prescribing information for Chantix regarding serious neuropsychiatric symptoms experienced in patients taking Chantix. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. While some patients may have experienced these types of symptoms and events as a result of nicotine withdrawal, some patients taking Chantix who experienced serious neuropsychiatric symptoms and events had not yet discontinued smoking. In most cases, neuropsychiatric symptoms developed during Chantix treatment, but in others, symptoms developed following withdrawal of Chantix therapy.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/vareniclineHCP.htm

Public Health Advisory

Ezetimibe/Simvastatin

FDA provided healthcare professionals with an early communication about an ongoing data review for Ezetimibe/Simvastatin (marketed as Vytorin), Ezetimibe (marketed as Zetia), and Simvastatin (marketed as Zocor).

This early communication is in keeping with FDA’s commitment to inform the public about ongoing postmarketing drug issues.Merck/Schering Plough Pharmaceuticals reported preliminary results from the Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) trial. This trial was designed to evaluate the amount of atherosclerotic plaque in blood vessels located in the neck based on images obtained through ultrasound in patients treated with Vytorin (ezetimibe plus simvastatin) or simvastatin alone. Merck/Schering Plough stated that there was no significant difference between Vytorin and simvastatin in the amount of atherosclerotic plaque in the inner walls of the carotid (neck) arteries despite greater lowering of LDL-cholesterol (bad cholesterol) with Vytorin compared to simvastatin. Once Merck/Schering Plough completes the analysis of the unblinded data from ENHANCE, it will submit a final study report to FDA. Once FDA receives the final study report, FDA estimates it will take approximately 6 months to fully evaluate the data. After reviewing the data from the ENHANCE study, and considering all other available information about the link between LDL lowering and reduction of cardiovascular events, FDA will determine whether any further regulatory action is warranted with regard to Zetia and Vytorin and also whether any changes to FDA’s current approach to drugs that lower LDL cholesterol are warranted.

Patients should talk to their doctors if they have any questions about the information from the ENHANCE trial.

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

Leukine (sargramostim)

Bayer and FDA informed healthcare professionals of the market withdrawal of the current liquid formulation of Leukine, a growth factor that helps fight infection and disease in appropriate patients by enhancing immune cell function. The product was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change in the formulation of liquid Leukine to include edetate disodium (EDTA). The upward trend in adverse reaction reporting rates has not been observed with the use of lyophilized Leukine. Healthcare professionals should immediately stop using liquid Leukine and return unused vials to the manufacturer.

Source: http://www.fda.gov/medwatch/safety/2008/Leukine_DHCP_01-23-2008.pdf

Heparin Sodium Injection 1000 units/mL recalled due to multiple adverse reactions

Baxter Healthcare and FDA notified healthcare professionals of a voluntary recall of certain lots of Heparin as a precaution due to an increase in reports of adverse patient reactions associated with these lots. Baxter is in the process of an in-depth investigation to determine the root cause of the reported reactions.

Reported adverse events include abdominal pain, decreased blood pressure, burning sensation, chest pain, diarrhea, dizziness, drug ineffectiveness, dyspepsia, dyspnea, erythema, flushing, headache, hyperhidrosis, hypoesthesia, hypotension, increased lacrimation, loss of consciousness, malaise, nausea, pallor, palpitations, paresthesia, pharyngeal edema, restlessness, vomiting/retching, stomach discomfort, tachycardia, thirst, trismus, and unresponsiveness to stimuli. There have been no reports involving fatality.

Source: http://www.fda.gov/medwatch/safety/2008/Heparin_recall_01-17-2008.pdf

Ortho Evra Contraceptive Transdermal Patch

FDA modified the prescribing information for the Ortho Evra Contraceptive Transdermal (Skin) Patch to include the results of a new epidemiology study that found that users of the birth control patch were at higher risk of developing serious blood clots, also known as venous thromboembolism (VTE), than women using birth control pills. VTE can lead to pulmonary embolism. The label changes are based on a study conducted by the Boston Collaborative Drug Surveillance Program on behalf of Johnson and Johnson. The patch was studied in women aged 15-44. These findings support an earlier study that also said women in this group were at higher risk for VTE.
FDA believes that Ortho Evra is a safe and effective method of contraception when used according to the labeling, which recommends that women with concerns or risk factors for serious blood clots talk with their health care provider about using Ortho Evra versus other contraceptive options.

Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01781.html

Cough and Cold Medications in Children Less Than Two Years of Age

FDA informed consumers and healthcare professionals that the Agency has completed its review of information regarding the safety of over-the-counter (OTC) cough and cold medicines in children under 2 years of age and recommends that these drugs not be used to treat children in this age group because serious and potentially life-threatening side effects can occur. FDA's recommendation is based on both the review of the information the Agency received about serious side effects in children in the referenced age group and the discussion and recommendations made at the October 18 -19, 2007, public advisory committee meeting at which this issue was discussed. FDA has not completed its review of information about the safety of OTC cough and cold medicines in children 2 through 11 years of age.

Source: http://www.fda.gov/cder/drug/advisory/cough_cold_2008.htm

Edetate Disodium (marketed as Endrate and generic products)

FDA notified healthcare professionals and patients about important safety information concerning Edetate Disodium. There have been cases where children and adults have died when they were mistakenly given Edetate Disodium instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or when Edetate Disodium was used for "chelation therapies" and other uses that are not approved by the FDA.

Edetate Disodium was approved as an emergency treatment for certain patients with hypercalcemia (very high levels of calcium in the blood) or certain patients with heart rhythm problems as a result of very high amounts of digitalis in the blood. Edetate Calcium Disodium was approved to reduce dangerously high blood lead levels (severe lead poisoning).

The two drugs have very similar names and are commonly referred to only as EDTA. As a result, the two products are easily mistaken for each other when prescribing, dispensing, and administering them. Edetate Disodium and Edetate Calcium Disodium works by binding with heavy metals or minerals in the body allowing them to be passed out of the body through the urine. Read the FDA Public Health Advisory for recommended and important safety considerations for healthcare professionals until the FDA's ongoing evaluation of the risks and benefits of Edetate Disodium is complete.

Source: http://www.fda.gov/cder/drug/advisory/edetate_disodium.htm

Musculoskeletal Pain Associated with Bisphosphonate use

FDA informed healthcare professionals and patients of the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates.

Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics. The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonates. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.

Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug.

Source: http://www.fda.gov/cder/drug/infopage/bisphosphonates/default.htm

Methotrexate-Induced Papular Eruption Following Treatment of Psoriasis

A case of a 52-year-old woman presenting with an extensive flare of psoriasis associated with joint pain, especially in her knees and elbows on being treated with intramuscular injections of methotrexate 20 mg/wk has been published in the latest issue of The Annals of Pharmacotherapy.

According to the Naranjo probability scale, the papular eruption was probably caused by methotrexate. The drug was discontinued and papular lesions gradually disappeared.

Source: Annals of Pharmacotherapy 2007;42(1):138-141.

http://www.theannals.com/cgi/content/abstract/42/1/138

Simultaneous Erythema Nodosum and Erythema Multiforme After Local Lidocaine Injection

A case of a 33-year-old female experiencing coexisting erythema nodosum and erythema multiforme after lidocaine spray whichwas used for upper gastrointestinal endoscopy has been published in the latest issue of The Annals of Pharmacotherapy.

The reaction was exacerbated after localized injection of 2% lidocaine for a skin biopsy. An objective causality assessment revealed that an adverse drug reaction was highly probable.

Source: Annals of Pharmacotherapy 2007;42(1):127-130.

http://www.theannals.com/cgi/content/abstract/42/1/127

Clozapine-induced double incontinence

A case of clozapine-induced double incontinence in a 23 years old male diagnosed with schizophrenia and started on clozapine 25 mg/day has been reported in the latest isuue of Indian Journal of Medical Sciences.

On the Naranjo probability scale, the adverse drug reaction probability score for this patient to develop clozapine-induced double incontinence was nine, suggesting a definitive adverse reaction due to clozapine.

Source: Indian J Med Sci 2007;61:665-6

http://www.indianjmedsci.org/article.asp?issn=0019-5359;year=2007;volume=61;issue=12;spage=665;epage=666;aulast=Mendhekar