Antiepileptic drug may cause cleft lip or palate, manufacturer warns
FDA cautions against ingestion of high-strength hydrogen peroxide
Azathioprine tablets possibly switched with methotrexate, recall initiated
Aptivus/ritonavir combo may carry risk of intracranial hemorrhage
Triaminic Vapor Patch unsafe for small children, Novartis initiates recall
Major congenital malformations found with maternal ACE inhibitor use in first trimester
Three long-acting beta agonists now carry strong warning of bronchospasm
Risk of renal failure associated with oral sodium phosphate bowel cleansing
Fatal breathing problems may occur with promethazine in patients younger than 2 years
Consumers alerted to check Diastat AcuDial syringes for cracks
Risk of bronchospasm warnings added to labeling of 2 long-acting beta agonists
Microbial contamination spurs nationwide recall of Hanford Pharmaceuticals’ Cefazolin for Injection
FDA warns of renal and cardiovascular toxicity connected to aprotinin use
Bristol-Myers Squibb updates safety information for Hydrea and Droxia
Warning added to labeling for atopic dermatitis meds, cancer risk cited
GlaxoSmithKline warns of macular edema danger with rosiglitazone
One lot of hydralazine hydrochloride injection may contain particulates, vials recalled
Bismacine/chromacine, used to treat Lyme disease, may be dangerous
Triptans taken with certain antidepressants may cause serotonin syndrome, FDA warns
Products promoted for sexual enhancement may be dangerous, FDA warns
New safety information to be added to product labeling for Ketek
Possible link between nephrogenic fibrosis and gadolinium-containing contrast agents used in MRA
Incorrect labeling prompts IVAX to recall Genapap and Genebs nationwide
FDA approves inhalation aerosol for 4- to 11-year-olds with asthma
Steroid products sold as dietary supplements illegal and unsafe, FDA warns
Methemoglobinemia may be associated with benzocaine topical anesthetics
Intravenous administration of nimodipine carries fatal danger, warning stresses
Novartis adds safety data to Clozaril prescription information
Warnings added to WinRho SDF labeling, Baxter Healthcare announces
August 10, 2006
ST. LOUIS (MD Consult) - Less than 2 weeks after recalling a single lot of its Ultravist (iopromide) Injection x-ray contrast agent, Berlex, Inc, announced on July 31, 2006, the recall of all lots worldwide. The recall, limited to the 370-mgI/mL concentration, is made on the basis of the potential that "particulate material in conjunction with crystallization may be present in the product," according to the company. This recall does not include other concentrations of Ultravist (ie, 150 mgI/mL, 240 mgI/mL, or 300 mgI/mL).
As reported by MD Consult on July 24, 2006, the previous recall of a single lot (No. 41500A; expiration, 1/2007) was triggered by an investigation of 2 customer reports of vials that showed crystallization. Patients receiving the recalled material are potentially at risk for thrombosis of the blood vessels and injury to the heart, kidney, and brain, Berlex said. It has notified the FDA of the recall and is investigating the situation. The company reminded users, including hospitals, imaging centers, and other health care facilities, that they should visually inspect all parenteral drug products for particulate matter and discoloration before administration and should not use them if particulates are observed or marked discoloration has occurred. This is standard practice and is included on the Ultravist package insert.
Ultravist Injection 370 mgI/mL should not be used for patient care and should be immediately quarantined for return. Berlex will credit accounts for all returned product relevant to the recall. For more information about the return process, call 1-800-950-5479, menu option 1.
The FDA requests that any adverse reactions or quality problems experienced with the use of this product be reported to FDA's MedWatch Adverse Event Reporting program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
Ultravist is a nonionic, iodinated, low-osmolar radiologic contrast agent for intravascular administration. All nonionic, iodinated contrast media currently available inhibit blood coagulation in vitro less than ionic contrast media. Therefore, meticulous intravascular administration technique is necessary to minimize thromboembolic events. As with all iodinated contrast agents, serious or fatal reactions have been associated with their use. Ultravist injection is not indicated for intrathecal use.
For more information about Berlex, a US affiliate of German pharmaceutical company Schering AG, Germany, visit berlex.com or call 1-866-237-5395.
August 9, 2006
ST. LOUIS (MD Consult) - After discussions with Health Canada, GlaxoSmithKline Inc informed patients on August 8, 2006, of new safety information concerning the antiepileptic agent Lamictal (lamotrigine) tablets. New data from a pregnancy registry suggest an association between taking Lamictal in the first trimester of pregnancy and increased risk of cleft lip, cleft palate, or both in babies.
Such oral clefts are a failure of the normal closure of the mouth structures as the unborn baby develops, resulting in a gap in the upper lip and/or the roof of the mouth (ie, soft or hard palate). Oral clefts are among the most common of the major birth defects occurring in the general population, with background rates from 0.5 to 2.16 per 1,000 births. A genetic aspect is involved, in that an unborn baby with an affected parent or sibling is at increased risk. According to the literature, several antiepileptic drugs have been shown to be associated with oral cleft, and other factors are also suspected, including maternal smoking, heavy alcohol intake, infections, folic acid deficiency, and vitamin A intoxication.
Regarding Lamictal, the ongoing North American Antiepileptic Drug Pregnancy Registry detected an elevated rate of isolated, nonsyndromic cleft palate deformity occurring in infants exposed to lamotrigine monotherapy during the first trimester of pregnancy, compared with the reference population used in this registry. Data from additional pregnancy registries are required to get a more complete picture of the risk.
As is currently stated in the product information, patients should notify their physicians if they become pregnant or intend to become pregnant during therapy with Lamictal. Although pregnant women and their unborn children may face significant health risks from uncontrolled epilepsy, Lamictal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Patients should not start or stop these medications without consulting their doctors. Sudden discontinuation of antiepileptic therapy may lead to breakthrough seizures, with serious consequences for both the mother and the fetus, so this should be avoided.
GlaxoSmithKline has sent a letter to health care professionals informing them of this new safety information. This information is available at gsk.ca.
GlaxoSmithKline requests that any cases of cleft lip, cleft palate, or other serious or unexpected adverse reactions in patients receiving Lamictal be reported to the company (1-800-387-7374) or to Health Canada by phone (1-866-234-2345), e-mail (cadrmp@hc-sc.gc.ca), or Internet (fda.gov/medwatch/report.htm).
August 9, 2006
ST. LOUIS (MD Consult) - On August 3, 2006, the US Food and Drug Administration (FDA) and Luitpold Pharmaceuticals, Inc, notified health care professionals of a voluntary recall of 1 lot of the antihypertensive agent hydralazine hydrochloride injection (20 mg/mL, 1-mL single-dose vials). Recall of this product, which is distributed by American Regent, Inc, was initiated because some vials may contain particulates.
The recalled lot, number 5561 NO, carries an expiration date of December 2006 and is packaged with a NOVAPLUS label. The FDA announced that further use or distribution of this lot of product should cease.
Pharmacists are instructed to isolate their inventory of the above lot number and return the product to American Regent, Inc. The distributor requests that customers who may have purchased product from this lot number after October 21, 2005, be notified of this recall. Product should be returned directly to the American Regent facility in Shirley, NY. The recipient company will be responsible for all shipping costs incurred by pharmacists or their customers.
For more information, contact American Regent, Inc, at americanregent.com or 1-800-645-1706.
July 28, 2006
ST. LOUIS (MD Consult) - On July 27, 2006, the US Food and Drug Administration (FDA) warned consumers not to purchase nor to use high-strength hydrogen peroxide products, including a product marketed as "35 Percent Food Grade Hydrogen Peroxide," for medicinal purposes because they can cause serious harm or death when ingested. The FDA recommends that consumers who are currently using high-strength hydrogen peroxide stop immediately and consult a health care provider.
The agency is working to stop companies that sell high-strength hydrogen peroxide from making illegal medical claims about their products. These claims are illegal because these products do not have FDA approval and are therefore being sold illegally for medical indications without any proven clinical value. The products can instead cause significant harm.
High-strength hydrogen peroxide has never been approved by the FDA to be taken internally, and the agency considers hydrogen peroxide at 35% strength dangerous, even if handled according to the manufacturer's directions. This high-strength hydrogen peroxide—more than 10 times stronger than the solution used in over-the-counter drugs to disinfect minor cuts—is highly corrosive. Ingesting hydrogen peroxide can cause gastrointestinal irritation or ulceration. Intravenous administration of hydrogen peroxide can cause inflammation of the blood vessel at the injection site, gas embolisms, and potentially life-threatening allergic reactions.
As part of its efforts to stop manufacturers from making false claims about their products, the FDA issued warning letters to 2 firms illegally selling "35 percent hydrogen peroxide" products on Web sites for the treatment of acquired immunodeficiency syndrome, cancers, emphysema, and other serious and life-threatening diseases. These warning letters are available accessdata.fda.gov/scripts/wlcfm/recentfiles.cfm.
In an April 1989 press release, the FDA warned consumers about the illegal promotion of industrial-strength hydrogen peroxide to treat AIDS and cancer, after the occurrence of at least 1 related death in Texas and several injuries requiring hospitalization.
July 24, 2006
ST. LOUIS (MD Consult) - On July 21, 2006, the US Food and Drug Administration (FDA) warned consumers and health care providers not to use a product called bismacine, also known as chromacine. The FDA is investigating 1 report of a death and several reports of injury related to the administration of bismacine.
Bismacine is an injectable product that has been used to treat Lyme disease. However, the FDA stresses that the compound has not received approval for anything, including Lyme disease. This product is not a pharmaceutical and is mixed individually by druggists. It is prescribed or administered by doctors of "alternative health" or by persons claiming to be medical doctors. Bismacine contains high amounts of bismuth, a heavy metal that is used in some medications taken by mouth to treat Helicobacter pylori infection, but that is not approved in any form for use by injection.
On April 20, 2006, 1 person died as a result of treatment with bismacine, and on March 29, 2005, another person was hospitalized after receiving a bismacine treatment. Other persons who have used or who have been administered this product have also experienced serious adverse events. Possible effects of bismuth poisoning include cardiovascular collapse and kidney failure.
The FDA is advising consumers and health care providers not to use bismacine. Persons who believe they have experienced adverse events from receiving bismacine may wish to seek medical attention.
The agency requests that any adverse reactions experienced with the use of this product be reported to the FDA's MedWatch adverse event reporting program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, Rockville, MD 20852-9787).
July 24, 2006
ST. LOUIS (MD Consult) - On July 21, 2006, Berlex, Inc, and the US Food and Drug Administration (FDA) announced a voluntary nationwide recall of a single lot (No. 41500A; expiration, 1/2007) of Ultravist (iopromide) Injection 370 mgI/mL, 125 mL, an intravenous x-ray contrast agent. The presence of particulate matter in conjunction with crystallization within the agent prompted the recall; the potential for serious safety problems exists if this contaminated Ultravist Injection is administered to patients. These problems may include thrombosis of blood vessels, thromboembolism, and injury or infarction of end organs such as the heart, kidney, and brain.
Berlex, Inc, is recalling this lot after an investigation of 2 customer complaints of vials that exhibited crystallization. The company immediately placed remaining inventory of Ultravist 370 mgI/125 mL, lot number 41500A, on hold to prevent further distribution. The investigation is ongoing regarding this matter to determine whether any other lots of this product might be affected.
As is standard practice and per the Ultravist package insert, all parenteral drug products should be inspected visually for particulate matter and discoloration before administration and should not be used if particulates are observed or marked discoloration has occurred.
Hospitals, imaging centers, and other health care facilities should not use any of the affected lot number of Ultravist Injection 370 mgI/mL, 125 mL, for patient care and should immediately quarantine any product for return. Berlex will credit accounts for all returned products from lot number 41500A, including shipping costs. Persons with questions should contact the company at 1-866-BERLEX-5.
The FDA requests that any adverse reactions or quality problems experienced with the use of this product be reported to FDA's MedWatch Adverse Event Reporting program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
July 20, 2006
ST. LOUIS (MD Consult) - On July 19, 2006, the US Food and Drug Administration (FDA) issued a public health advisory announcing new safety information about taking 5-hydroxytryptamine receptor agonists (ie, triptans), commonly used to treat migraine headaches, together with certain types of antidepressant medicines. The antidepressant medicines of concern are selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), both of which are used to treat depression and other mood disorders. Names of the triptans, SSRIs, and SNRIs are listed at fda.gov/cder/drug/advisory/SSRI_SS200607.htm#drugs.
The life-threatening condition serotonin syndrome may occur when triptans are used together with a SSRI or a SNRI. Serotonin syndrome occurs as a result of systemic circulation of excess serotonin. Symptoms of this syndrome include restlessness, hallucinations, loss of coordination, tachycardia, rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting, and diarrhea. Serotonin syndrome may be more likely to occur when a patient is starting or increasing the dose of a triptan, SSRI, or SNRI.
The FDA determined that serotonin syndrome occurs with combined use of triptans and a SSRI or SNRI after reviewing reports describing serotonin syndrome in persons taking these medications together. Each of these types of medicine increases serotonin levels on its own, as well.
Patients who are taking a triptan along with an SSRI or SNRI should talk to their doctors before stopping their medications. Patients should know which medicines they take and should keep their health care providers informed as to what these medicines are.
Physicians prescribing triptans, SSRIs, or SNRIs should take the following actions:
The FDA has requested that all manufacturers of triptans, SSRIs, and SNRIs update their prescribing information to warn of the possibility of serotonin syndrome when triptans and SSRIs or SNRIs are taken together.
July 17, 2006
ST. LOUIS (MD Consult) - On July 12, 2006, the US Food and Drug Administration (FDA) warned consumers not to purchase or consume Zimaxx, Libidus, Neophase, Nasutra, Vigor-25, Actra-Rx, or 4EVERON. These products are sold on Web sites as "dietary supplements" for treating erectile dysfunction (ED) and enhancing sexual performance, but they are in fact illegal drugs that contain potentially harmful undeclared ingredients. These products have not been approved by the FDA, and there is no guarantee of their safety and effectiveness, nor of the purity of their ingredients.
The FDA advises consumers who have used any of these products to discontinue use and to consult a health care provider. The agency encourages anyone experiencing ED to seek guidance from a health care provider before purchasing a product to treat this medical condition.
Chemical analysis by the FDA revealed that Zimaxx contains sildenafil, which is the active pharmaceutical ingredient in Viagra, a prescription drug approved in the United States to treat ED. The other products contain chemical ingredients that are analogs of either sildenafil or vardenafil, the active ingredient in Levitra, which is another FDA-approved treatment of ED. There is no mention of any of these ingredients in any of the illegal products’ labeling.
These products pose a threat to consumers because the undeclared ingredients may interact with nitrates found in some prescription drugs (eg, nitroglycerin) and may lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates. Erectile dysfunction is a common problem in men with these conditions, and these patients may seek products like the ones noted above because these products claim that they are "all natural" or that they do not contain the active ingredients used in FDA-approved ED drugs. In addition, because the manufacturing source of the active ingredients in these "dietary supplements" is unknown, there is no assurance that the ingredients are safe, effective, or pure.
FDA warning letters to the firms marketing these products state that the products are illegal drugs based on claims made for the products or their ingredients. The letters also state that the products’ labeling is false and misleading because it fails to disclose the presence of the chemical ingredients or the potential adverse effects associated with the products’ consumption. The FDA instructed agency staff to stop the importation of Libidus, and the agency recently stopped a shipment of 4EVERON from entering the United States. Depending on responses to these actions, the FDA may take additional enforcement steps.
July 17, 2006
ST. LOUIS (MD Consult) - Roxane Laboratories, Inc, announced on July 13, 2006, that it is conducting a nationwide voluntary recall of a single manufacturing lot of azathioprine tablets, USP 50 mg. Azathioprine is used to help prevent rejection in patients receiving kidney transplant and can also be used to manage severe rheumatoid arthritis.
It was discovered that a single bottle of azathioprine tablets from lot 558470A (NDC 00054-4084-25; expiration date, March 2009) contained methotrexate tablets USP 2.5 mg. Although representatives at Roxane Laboratories believe this issue may be limited to that single bottle, which was not dispensed to a patient, the decision was made to recall manufacturing lot 558470A to preclude any possibility of another such bottle being dispensed or used. To date, no injuries have been reported in relation to this issue.
If methotrexate 2.5-mg tablets are taken in place of azathioprine 50-mg tablets in accordance with dosing instructions that may be prescribed for azathioprine, serious toxic effects may occur. Effects may include mouth ulcers, reduced blood counts, vomiting, diarrhea, decreased resistance to infection, or liver, kidney, or lung injury. There have also been reports of death when high doses of methotrexate are taken, such as might result from a substitution of methotrexate 2.5-mg tablets for azathioprine 50-mg tablets.
Information has been sent to pharmacists alerting them of the details pertaining to this recall. As described in these recall communications, pharmacists who may have dispensed azathioprine tablets to patients from the lot in question are instructed to contact those patients to ensure they did not inadvertently receive methotrexate tablets.
Patients taking azathioprine tablets should be instructed as follows:
Pharmacists and wholesalers who have any bottles of azathioprine from manufacturing lot 558470A have been instructed to discontinue distribution and use of this lot immediately and contact Capital Returns at 1-800-950-5479 (menu option 1) with any questions regarding the recall returns. Requests for additional information should be referred to Roxane Laboratories Technical Product Information at 1-800-962-8364.
July 7, 2006
ST. LOUIS (MD Consult) - On June 30, 2006, Boehringer Ingelheim and the US Food and Drug Administration (FDA) informed health care professionals of important new safety information for Aptivus (tipranavir) capsules, coadministered with ritonavir (500 mg/200 mg). An addition has been made to the drug’s black box warning regarding reports of both fatal and nonfatal intracranial hemorrhage (ICH).
Over the course of clinical trials with Aptivus capsules in anti–human immunodeficiency virus (HIV) combination treatment, Boehringer Ingelheim has received 14 reports of ICH events, including 8 fatalities, in 13 of 6,840 persons infected with HIV-1. There have been no spontaneous reports of ICH on marketed Aptivus so far, nor have any of these events been observed in the pediatric or treatment-naïve clinical trials of Aptivus.
Many of the patients experiencing ICH in the Aptivus clinical development program had other medical conditions (eg, central nervous system lesions, head trauma, recent neurosurgery, coagulopathy, hypertension or alcohol abuse) or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.
No pattern of abnormal coagulation parameters were observed in patients receiving Aptivus in general, nor preceding the development of ICH. Routine measurement of coagulation parameters is not currently indicated in the management of patients taking Aptivus.
An increased risk of ICH was previously observed in patients with advanced HIV-1 disease/acquired immunodeficiency syndrome (AIDS). The rate of ICH events in Aptivus clinical trials corresponds to a rate of 0.2/100 patient exposure years (PEY). A literature review of ICH in persons infected with HIV found that the rate observed in patients with AIDS who are not receiving combination antiretroviral therapy is in the same range (0.2/100 PEY) as reported in Aptivus clinical trials.
Boehringer Ingelheim has informed regulatory authorities and is in the process of notifying investigators and health care professionals about the occurrence of ICH in clinical trials. The company is also updating the Warnings and Precautions section of the Aptivus product labeling and patient package insert. Further investigations are ongoing to assess the role of Aptivus in ICH.
In vitro experiments have revealed that tipranavir inhibits human platelet aggregation. Therefore, Aptivus/ritonavir should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other medical conditions or who are receiving medications known to increase the risk of bleeding such as antiplatelet agents or anticoagulants. However, patients taking Aptivus/ritonavir should not discontinue or modify their treatment with these or any other medications without first speaking with their doctor to evaluate the appropriate course of therapy for their individual needs.
The positive benefit-risk profile of Aptivus/ritonavir remains unchanged, the drugmaker notes. At the approved dose (Aptivus 500 mg/ritonavir 200 mg twice daily), this combination has demonstrated significant benefit for the patient population for which it is indicated—adult patients infected with HIV-1 with evidence of viral replication, who are highly treatment experienced or have HIV-1 strains resistant to multiple protease inhibitors (PIs).
Aptivus is a non-peptidic PI that works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. On the basis of available clinical and in vitro data, the drug is active against most strains of HIV-1 that are resistant to commercially available PIs. The safety and efficacy of Aptivus in pediatric patients has not yet been established. Currently, phase 2 and 3 studies in pediatric and other populations are fully enrolled and ongoing.
In studies to date, Aptivus has been well tolerated by most patients and has a safety profile similar to other PIs. The most commonly reported side effects of at least moderate intensity in patients enrolled in the Randomised Evaluation of Strategic Intervention in Multi-drug Resistant Patients with Tipranavir (RESIST) studies taking Aptivus are gastrointestinal, including diarrhoea, nausea, vomiting, and abdominal pain. Fever, fatigue, headache, bronchitis, depression, and rash also occurred.
Aptivus boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C coinfection because these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzyme and lipid levels. Most laboratory abnormalities were asymptomatic, and most patients were successfully treated without discontinuation.
Aptivus does not cure HIV infection/AIDS, nor does it prevent the transmission of HIV to others. Patients taking this medication may continue to develop opportunistic infections and other complications associated with HIV disease.
Aptivus received marketing authorization from the FDA and was launched in the United States in June 2005. Full revised prescribing information is available on the FDA Web site. For more information, visit aptivus.com.
June 30, 2006
ST. LOUIS (MD Consult) - On June 29, 2006, the US Food and Drug Administration (FDA) completed a safety assessment of Ketek (telithromycin) and notified health care professionals and patients of rare but potentially serious health risks associated with the drug. Ketek is indicated for the treatment of acute exacerbation of chronic bronchitis, acute bacterial sinusitis, and community-acquired pneumonia of mild to moderate severity, including pneumonia caused by resistant Streptococcus infections.
The drug has been associated with rare cases of serious liver injury and liver failure with 4 reported deaths and 1 liver transplantation after the administration of the medication. The FDA has determined that additional warnings are required, and the drug’s manufacturer, Sanofi Aventis, is revising the product labeling to address this safety concern. The revised prescribing information contains a bolded warning and additional information relating to the nature and characterization of hepatic events, as well as revised recommendations for the use of Ketek in patients with myasthenia gravis.
Although it is difficult to determine the exact frequency of Ketek-associated adverse events on the basis of the FDA’s mandatory and voluntary reporting systems, the agency has concluded that the drug’s benefit to patients for the approved indications outweighs its risk, including the rare risk of liver failure, and supports its continued availability.
Patients taking Ketek and their doctors are advised to be alert for signs and symptoms of liver problems, said Dr Steven Galson, director for the FDA’s Center for Drug Evaluation and Research. He continued, "Patients experiencing such signs or symptoms should discontinue Ketek and seek medical evaluation, which may include tests for liver function." Signs and symptoms of liver failure include fatigue, malaise, loss of appetite, nausea, jaundice, and dark-colored urine.
The warning results from the FDA’s vigilant monitoring of all drugs after their introduction to the market. When the agency approved the drug in 2004 on the basis of data in the marketing application, the risk of liver injury with Ketek was similar to that of other marketed antibiotics. A safety evaluation conducted 1 year after approval was consistent with this. However, as the product entered into wider use, the FDA’s adverse-event monitoring system received some reports of serious liver problems in patients taking Ketek, including some cases of acute liver failure leading to death or requiring liver transplantation.
Following receipt of these reports, the FDA conducted a rigorous and thorough assessment of existing data and continued to engage in US and ex-US monitoring of additional postmarket events. This work involved efforts by experts in the agency’s Office of Surveillance and Epidemiology and the Office of New Drugs as well as by recognized external liver disease experts. The FDA tracked reports of adverse events associated with Ketek via MedWatch and also had the benefit of 3 case reports described in the March 21, 2006, issue of Annals of Internal Medicine.
The FDA will continue to evaluate Ketek-associated safety issues and take further actions if warranted. It is important to note that negative effects on liver function are a known and potential complication with some antibiotics, including Ketek, and as drug usage becomes more widespread, it is expected that rare adverse events may be detected or reported in greater numbers.
For additional information regarding the update to Ketek prescribing information in the United States, visit ketek.com.
June 20, 2006
ST. LOUIS (MD Consult) - On June 19, 2006, the US Food and Drug Administration (FDA) warned consumers not to use the Triaminic Vapor Patch marketed by Novartis Consumer Health because of reports of serious adverse events associated with accidental ingestion by children. Novartis Consumer Health also announced that it is conducting a nationwide voluntary recall of all Triaminic Vapor Patch products.
The FDA is advising consumers who have used the product and have concerns or questions to contact their physician or health care practitioner. In addition, the company is advising consumers to either discard or return the product to their point of purchase for a refund.
Sold over the counter at pharmacies and retail outlets nationwide, Triaminic Vapor Patch contains camphor, eucalyptus oil, and menthol. The reported adverse effects from swallowing or chewing on products containing camphor or eucalyptus oils vary from minor symptoms, such as a burning sensation in the mouth, headache, nausea, and vomiting, to more severe and life-threatening reactions, such as seizures.
Triaminic Vapor Patch is labeled as a cough suppressant for children aged 2 years and older. The directions on the label indicate the patch is to be applied to the throat or chest to allow the vapors to reach the nose and mouth. Multiple patches can be applied at one time. Once applied, the patch would be within close reach for a child to remove and place the product into his or her mouth. The Vapor Patch is a topical cough product applied externally and is not for oral consumption.
The FDA requests that any adverse reactions experienced with the use of this product be reported to the FDA’s MedWatch reporting program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
For more information, contact Novartis Consumer and Professional Affairs Call Center at 1-800-452-0051 or visit triaminic.com.
June 12, 2006
ST. LOUIS (MD Consult) - On June 8, 2006, the US Food and Drug Administration (FDA) announced it is evaluating important safety information about gadolinium-containing contrast agents and a disease known as nephrogenic systemic fibrosis or nephrogenic fibrosing dermopathy (NSF/NFD) that occurs in patients with kidney failure. New reports have identified a possible link between NSF/NFD and exposure to gadolinium-containing contrast agents used at high doses for magnetic resonance angiography (MRA).
The FDA has learned of 25 cases of NSF/NFD in patients with kidney failure who received Omniscan, a gadolinium-containing contrast agent, and took the MRA test. Among these cases, reported by the Danish Medicines Agency on May 29, 2006, 20 cases occurred in Denmark and 5 cases occurred in Austria. The patients developed NSF/NFD within 3 months (range, 2 weeks to 3 months) after receiving the gadolinium-containing contrast agent.
NSF/NFD appears to occur in patients with kidney failure along with acidosis, which is common in patients with kidney failure. Patients with NSF/NFD have tight and rigid skin, making it difficult to bend joints. NSF/NFD may also result in fibrosis of body organs, resulting in the inability of body organs to work properly, and this can lead to death. Diagnosis of NSF/NFD is done by looking at a sample of skin under a microscope.
Scientists first identified NSF/NFD in 1997 and the cause of NSF/NFD is unknown. Worldwide, approximately 200 reports of NSF/NFD exist.
The FDA is actively investigating whether exposure to a gadolinium-contrast agent for MRA is associated with the development of NSF/NFD. While the FDA conducts its investigation, the following recommendations are being provided to health care providers and patients:
Five gadolinium-containing contrast agents are FDA-approved for use during magnetic resonance imaging (MRI). The trade names of the US-approved gadolinium-containing contrast agents are Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance. None of these drugs are FDA approved for MRA. The dose of gadolinium-containing contrast agent given to patients undergoing MRA is often up to 3 times higher than the approved dose for MRI.
The FDA has not yet determined whether exposure by patients with kidney failure to gadolinium-containing contrast agents during MRA causes NSF/NFD. The FDA is gathering additional information about NSF/NFD and investigating whether other patients who received gadolinium-containing contrast agents developed NSF/NFD.
The FDA urges health care providers and patients to report adverse event information to the FDA via the MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
For more details on this topic, including an information sheet for health care professionals and the regulatory history of US-approved gadolinium-containing contrast agents, visit fda.gov/CDER/drug/infopage/gcca/default.htm.
June 8, 2006
ST. LOUIS (MD Consult) - On June 8, 2006, The New England Journal of Medicine reported that infants whose mothers had taken an angiotensin-converting enzyme (ACE) inhibitor medication during the first trimester of pregnancy had an increased risk of major congenital malformations compared with infants who had not undergone first-trimester exposure to ACE inhibitors. The number of cases of birth defects is small and the findings of this study have not yet been repeated.
According to the approved labels, ACE inhibitor drugs are labeled as pregnancy category C for the first trimester of pregnancy, though they are labeled pregnancy category D during the second and third trimesters, and the existing prescribing information recommends discontinuing ACE inhibitor therapy as soon as possible if a patient becomes pregnant.
Because of the preliminary nature of the newly published data, the US Food and Drug Administration (FDA) does not plan to change the pregnancy categories at this time, but health care professionals should take these findings into consideration with other information about a patient’s medical situation during early pregnancy. The FDA recommends the following:
ACE inhibitor drugs are used to treat hypertension by slowing the body’s production of a hormone that constricts blood vessels. The labels for all drugs of this type begin with a boxed warning that the drugs may harm unborn babies in the second and third trimester of pregnancy. ACE inhibitors include benazepril (Lotensin), captopril (Capoten), enalapril/enalaprilat (Vasotec oral and injectable), fosinopril (Monopril), lisinopril (Zestril and Prinivil), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik).
For more information about the pregnancy categories and also about the risk of leaving diseases untreated in pregnant women, see "Pregnancy and the Drug Dilemma," available at fda.gov/fdac/features/2001/301_preg.html.
May 19, 2006
ST. LOUIS (MD Consult) - Spectrum Laboratory Products, Inc, announced on May 11, 2006, that it is initiating a voluntary nationwide recall of the active pharmaceutical ingredient (API) tacrolimus after learning some lots are less than potent. Tacrolimus is an immunosuppressive drug used to prevent rejection of transplanted solid organs such as the heart or kidney. Blood levels of tacrolimus in some patients were significantly lower than would be expected based solely on the lower assay results.
The use of subpotent tacrolimus in compounded drugs for transplant recipients may lead to subtherapeutic tacrolimus blood levels and an unacceptably increased risk of solid organ transplant rejection. At least 1 injury has been reported. The US Food and Drug Administration (FDA) has been informed of this action.
Tacrolimus is identified as Catalog Number T3192. Recalled lots include TA1210, UD1060, UF0298, UL0964, and VB0031.
Spectrum tacrolimus API has been used by pharmacies for compounding purposes. Patients receiving tacrolimus for solid organ transplant should not stop taking their medication, but rather should check with their physician or pharmacist. This recall does not apply to tacrolimus marketed in finished dosage form as Prograf (Astellas Pharma, US) nor to Prograf oral capsules that have been used for compounding.
Tacrolimus API was distributed to pharmacies, 1 university (1 bottle), and 1 pharmacy distributor (2 bottles) for use in compounding. Pharmacies that have used the Spectrum tacrolimus API that is being recalled should stop using it and should contact Spectrum to make arrangements to return it. Spectrum is notifying its distributors and customers by telephone and recall letter.
Pharmacies are urged to examine their supplies for any of the recalled tacrolimus API and immediately discontinue its use. Users are requested to notify the FDA of any complaints or problems associated with these products. Any adverse reactions should be reported to the FDA’s MedWatch Program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
May 17, 2006
ST. LOUIS (MD Consult) - As reported by MD Consult on November 21, 2005, the US Food and Drug Administration (FDA) alerted health care professionals and patients in November 2005 that several long-acting bronchodilator medicines have been associated with possible increased risk of bronchospasm in some people, and requested that manufacturers update warnings in their existing product labeling.
On May 15, 2006, the FDA updated a public health advisory to announce that the manufacturers of these drugs have acted in accordance with this request. GlaxoSmithKline has revised new safety labeling and medication guides for patients for Serevent Diskus (salmeterol xinafoate) and Advair Diskus (fluticasone propionate; salmeterol xinafoate), and Schering-Plough Corporation has updated the safety information for Foradil Aerolizer (formoterol fumarate inhalation powder).
The new information is being added to alert health care professionals and patients that these medicines may increase the chance of severe asthma episodes and death when those episodes occur.
The drugs’ new labels, medication guides for patients, and information sheets for health care professionals are available on the fda.gov/CDER/drug/infopage/LABA/default.htm.
May 12, 2006
ST. LOUIS (MD Consult) - On May 12, 2006, GlaxoSmithKline and the US Food and Drug Administration (FDA) notified health care professionals of changes to the Warnings and Information for Patients sections of the prescribing information for Paxil (paroxetine hydrochloride) and Paxil CR (paroxetine hydrochloride). These labeling changes relate to a higher frequency of suicidal behavior in adult patients, particularly those who are younger adults.
GlaxoSmithKline recently conducted a meta-analysis of suicidal behavior and ideation in placebo-controlled clinical trials of paroxetine in adult patients with psychiatric disorders including major depressive disorder (MDD), other depression, and non-depression disorders. Results of this analysis showed a higher frequency of suicidal behavior in young adults treated with paroxetine compared with placebo.
Furthermore, in the analysis of adults (all ages) with MDD, the frequency of suicidal behavior was higher in patients treated with paroxetine compared with placebo. This difference was statistically significant; however, as the absolute number and incidence of events are small, these data should be interpreted with caution. All of the reported events of suicidal behavior in the adult patients with MDD were nonfatal suicide attempts, and the majority of these attempts (8 of 11) were in younger adults, 18 to 30 years old. These MDD data suggest that the higher frequency observed in the younger adult population across psychiatric disorders may extend beyond the age of 24 years.
The possible increase in risk of suicidal behavior in the MDD studies was observed despite substantial evidence for efficacy in the paroxetine-treated patients (compared with placebo) as determined by standardized disease-specific instruments (eg, Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale for depression). Most patients had an identified social stressor at the time of the event.
It is important that all patients, especially young adults and those whose conditions are improving, receive careful monitoring during the course of their paroxetine therapy regardless of the condition being treated.
Paxil is indicated for the treatment of MDD, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder in adults. Paxil CR is indicated for the treatment of MDD, panic disorder, social anxiety disorder, and premenstrual dysphoric disorder in adults.
Full prescribing information for Paxil and Paxil CR, including the new text highlighted in Clinical Worsening and Suicide Risk subsection of the Warnings section and the Information for Patients subsection of the Precautions section, are available at fda.gov/medwatch/safety/2006/safety06.htm#paxil.
GlaxoSmithKline requests that any adverse events associated with Paxil or Paxil CR be reported to the company at 1-888-825-5249 or to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
May 8, 2006
ST. LOUIS (MD Consult) - On May 5, 2005, the US Food and Drug Administration (FDA) notified health care professionals and consumers of reports of acute phosphate nephropathy, a rare but serious adverse event associated with the use of oral sodium phosphates (OSP) for bowel cleansing. Documented cases of acute phosphate nephropathy include 21 patients who used an OSP solution (such as Fleet Phospho-soda or Fleet Accu-Prep) and 1 patient who used OSP tablets (Visicol).
Persons at increased risk of acute phosphate nephropathy include those of advanced age, those with kidney disease or decreased intravascular volume, and those using medicines that affect renal perfusion or function (eg, diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).
Acute phosphate nephropathy presents as acute renal failure with minimal proteinuria and a bland urine sediment in patients recently exposed to OSP. Renal biopsy reveals acute or chronic renal tubular injury (depending on time to diagnosis), calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histologic injury. These pathologic findings are consistent with nephrocalcinosis.
Health care professionals should consider the following when choosing a bowel cleanser for their patients:
The FDA requests that all adverse events associated with use of OSP be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
Additional information, including labeling for Phospho-soda and Accu-Prep, a patient information sheet, and data on the regulatory history of Visicol, are available at fda.gov/cder/drug/infopage/osp_solution/default.htm.
May 3, 2006
ST. LOUIS (MD Consult) - Incorrect labeling prompts IVAX to recall Genapap and Genebs nationwide May 3, 2006
ST. LOUIS (MD Consult) - IVAX Pharmaceuticals, Inc, a distributor of Goldline-labeled product, is initiating a recall of Goldline brand Extra Strength Genapap (acetaminophen) 500-mg Caplets and Tablets and Extra Strength Genebs (acetaminophen) 500-mg Caplets and Tablets, the company announced on May 2, 2006. The product lots identified on the US Food and Drug Administration (FDA) Web site (fda.gov/oc/po/firmrecalls/ivax05_06.html) are being recalled as a result of a labeling error. (The tablets/caplets themselves meet product specification.) Specifically, the product label should indicate that usage should not exceed 8 tablets or caplets in a 24-hour period. The erroneous label indicates not to exceed 12 tablets or caplets in a 24-hour period.
In the event the maximum dosage of 8 tablets or caplets in a 24-hour period is exceeded, there may be an increased risk of acetaminophen toxicity to the liver, which may cause adverse health effects. There have been no reports of serious illness or injury relating to this labeling matter.
Consumers who purchased Extra Strength Genapap 500-mg Caplets and Tablets or Extra Strength Genebs 500-mg Caplets or Tablets with the identified lot numbers should cease usage and return the product to the location of purchase.
IVAX Pharmaceuticals is instructing wholesalers and retailers to cease distribution and to examine inventories immediately. The manufacturer requests that all indicated lots be returned to the IVAX Distribution Center at the following address:
IVAX Distribution CenterThese products are sold over the counter and have been distributed nationwide and in Puerto Rico. IVAX Pharmaceuticals is voluntarily recalling the specified lots. In addition, IVAX is notifying direct account customers/distributors and direct ship customers who have purchased these products and lots via first class mail recall notification. All affected inventory is currently on hold. The FDA has been notified of this action.
Consumers can direct questions to IVAX at 1-866-262-1243.
The FDA requests that any adverse reactions experienced with the use of these products be reported to the agency’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet, or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
April 26, 2006
ST. LOUIS (MD Consult) - On April 25, 2006, the US Food and Drug Administration (FDA) notified health care professionals and patients that medications containing the antihistamine promethazine hydrochloride should not be used for children younger than 2 years because of the potential for fatal respiratory depression. This includes promethazine hydrochloride in any form: syrups, suppositories, tablets, or injectables. Serious adverse events, including 7 deaths and 22 cases of respiratory depression, have been reported with use of promethazine hydrochloride in children younger than 2 years.
The labeling on all products, brand name and generic, has been changed to reflect these strengthened warnings. Wyeth, a company that markets tablets and suppositories under the brand name Phenergan, has notified health care professionals of the changed label. The FDA is issuing this safety alert to make sure that health care professionals, other caregivers, and patients realize that the warnings apply to promethazine hydrochloride syrups as well.
Other potential risks and adverse effects associated with the use of promethazine include severe drowsiness and reduced mental alertness, increased risk of seizures, bone marrow problems and blood cell production, neuroleptic malignant syndrome, changes in blood pressure, skin reactions, and blood cell changes. Increased excitability or abnormal movements may occur after 1 dose of promethazine. If these events do occur, alternate pharmacologic treatment should be prescribed.
Promethazine hydrochloride is indicated for allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, transfusion reaction, adjunct anaphylaxis, motion sickness, adjunct pain, sedation, dermographism, urticaria, nausea, vomiting, and allergic reactions.
The FDA requests that any unexpected adverse or serious events associated with the use of this drug be reported to the FDA’s MedWatch program. Reports can be made by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
Prescribing information for Phenergan is available at fda.gov/cder/foi/label/2004/07935s030lbl.pdf.
April 10, 2006
ST. LOUIS (MD Consult) - On April 7, 2006, (OSI)Eyetech/Pfizer and the US Food and Drug Administration (FDA) notified health care professionals of important changes in the approved product labeling for Macugen (pegaptanib sodium injection). Rare reports of anaphylaxis/anaphylactoid reactions, including angioedema after the administration of Macugen along with various medications administered as part of the injection preparation, were described. A direct relationship to pegaptanib or any of the various medications administered as part of the injection preparation procedure or other factors has not been established in these cases.
Macugen is indicated for the treatment of neovascular (ie, wet) age-related macular degeneration and is administered once every 6 weeks by intravitreous injection. Health care professionals should evaluate the patient’s medical history for hypersensitivity reactions to Macugen before using this product.
The revisions to the Contraindications section of the Macugen labeling are as follows:
| Contraindications Macugen is contraindicated in patients with known hypersensitivity to pegaptanib sodium or any other excipient in this product. |
The new information in the Precautions section reads as follows:
| Precautions General Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, have been reported in the post-marketing experience following the Macugen intravitreal administration procedure (see Adverse Events and Dosage and Administration). |
The Adverse Events section of the labeling has been revised to include the following text:
| Adverse Events Post-Marketing Experience: Anaphylaxis/anaphylactoid reactions, including angioedema, have been identified during postapproval use of Macugen. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure (see Precautions and Dosage and Administration). |
Finally, the changes to the Dosage and Administration section read as follows:
| Dosage and Administration The patient’s medical history for hypersensitivity reactions should be evaluated prior to performing the intravitreal procedure (see Precautions and Adverse Events). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection. |
(OSI)Eyetech and Pfizer encourage health care professionals to report any serious adverse events associated with the use of Macugen to Pfizer at 1-800-438-1985. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
To view the complete drug label for Macugen, visit fda.gov/medwatch/safety/2006/Macugen_PI_mar0g.pdf.
March 31, 2006
ST. LOUIS (MD Consult) - According to a US Food and Drug Administration (FDA) public health advisory dated March 30, 2006, cracks in the applicator tips for Diastat AcuDial (diazepam rectal gel) Delivery Systems have occurred. Patients with epilepsy and their family members or caregivers should look carefully at their Diastat AcuDial prefilled syringes immediately, as explained below. The cap must not be removed when looking for applicator cracks, and the directions on how to look for cracks must be followed carefully. These cracks can result in leakage of the drug product when it is given, preventing full dosing and potentially resulting in a suboptimal therapeutic response.
If the product leaks when being given, or if the patient continues to have seizures, emergency medical help should be sought immediately.
Patients or their caregivers should check syringes every month, without removing the cap, to check whether the applicator tip is cracked. For directions on how to look for cracks on the applicator tip, visit diastat.com/HTML-INF/pdf/Diastat_AcuDial_Caregiver_Letter.pdf. Alternatively, assistance is available from Valeant Pharmaceuticals at 1-877-361-2719.
Cracked syringes should be returned to the pharmacy and exchanged for new ones. Even if no cracks are seen, the syringes should be reinspected frequently (every month) because cracks may appear over time.
The cracks have been reported in both the 10- and 20-mg syringes (but not the 2.5-mg syringes). Diastat AcuDial Delivery Systems are prefilled syringes containing diazepam. They are designed to deliver the drug rectally in patients with acute repetitive seizures. This condition, if inadequately treated, can progress to status epilepticus, a life-threatening condition in which seizures are continuous. The drug is typically administered by family members or caregivers at home.
There have been over 100 reports of cracked applicator tips in this product, which is manufactured by Valeant Pharmaceuticals of Costa Mesa, Calif. The frequency of cracks has varied, but as many as 6% of syringes in some lots have shown cracking. When present, the cracks are easily seen. The manufacturer has sent letters to pharmacists directing them to inspect the product before dispensing and inform patients about the need to inspect the syringes. The manufacturer has also sent letters to physicians who treat patients with epilepsy.
Representatives from Valeant have stated that they have identified the source of the manufacturing problem, but they will not have new product on the market until June or July 2006. Until then, the current product will continue to be sold because there are no other available treatments for this condition that can be administered at home.
Diastat is indicated for rectal administration in the management of selected refractory patients with epilepsy on stable regimens of antiepileptic drugs, who require intermittent use of diazepam to control bouts of increased seizure activity. For more information on Diastat, including full drug labeling and a patient information sheet, visit fda.gov/CDER/drug/infopage/diazepam_RG/default.htm.
March 20, 2006
ST. LOUIS (MD Consult) - On March 17, 2006, the US Food and Drug Administration (FDA) announced that it has been informed of 2 additional deaths occurring after medical abortion with Mifeprex (mifepristone). The agency received verbal notification of the deaths in the United States from the manufacturer, Danco Laboratories.
At this time, the FDA is investigating all circumstances associated with these cases and is not able to confirm the causes of death. However, the agency cautions that all providers of medical abortion and their patients must be aware of the specific circumstances and directions for use of this drug and all risks including sepsis when considering treatment. In particular, physicians and their patients should fully discuss early potential signs and symptoms that may warrant immediate medical evaluation.
The approved Mifeprex regimen for a medical abortion through 49 days’ pregnancy is as follows:
The safety and effectiveness of other Mifeprex dosing regimens, including use of oral misoprostol tablets intravaginally, has not been established by the FDA.
These recommendations are consistent with warnings in the Mifeprex prescribing information and information in the patient medication guide. The FDA also emphasizes that health care professionals and patients should be aware of the following:
As previously stated in the FDA’s July 19, 2005, Public Health Advisory, updated on November 4, 2005, the agency is aware of 4 previous confirmed deaths from sepsis in the United States, occurring between September 2003 and June 2005, in women after medical abortion with mifepristone and misoprostol. All 4 cases of fatal infection tested positive for C sordellii. All 4 cases involved the off-label dosing regimen consisting of 200 mg of oral Mifeprex followed by 800 mcg of intravaginally placed misoprostol. In addition, the FDA tested drug from manufacturing lots of mifepristone and misoprostol and found no contamination with C sordellii. The FDA does not claim to know whether these new deaths were caused by sepsis or, if they were, if they were caused by infection with C sordellii.
More information pertaining to Mifeprex, including links to full prescribing information and information sheet for patients and health care professionals, can be found at fda.gov/cder/drug/infopage/mifepristone/default.htm.
March 16, 2006
ST. LOUIS (MD Consult) - On March 15, 2006, the US Food and Drug Administration (FDA) announced that Ligand Pharmaceuticals has made changes to the Warnings and Adverse Reactions sections of the prescribing information for Ontak (denileukin diftitox), indicated for the treatment of persistent or recurrent cutaneous T-cell lymphoma. According to a Ligand Pharmaceuticals letter dated March 3, 2006, the changes to the product labeling for Ontak were made to alert health care professionals to new postmarketing adverse events.
The following new information has been added to the Warnings section of the drug labeling:
| Visual Loss: Loss of visual acuity usually with loss of color vision with or without retinal pigment mottling has been reported following administration of Ontak. Recovery was reported in some of the affected patients; however, most patients reported persistent visual impairment. |
The following statements have been added to the Adverse Reactions section:
| Postmarketing: The following adverse reactions have been identified during post-approval use of Ontak. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Special Senses: See Warnings: Visual Loss. |
Ligand Pharmaceuticals has requested that any adverse events related to Ontak be reported to Ligand Professional Services at 1-800-964-5836. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
Full prescribing information for Ontak, including boxed warning, is available fda.gov/medwatch/safety/2006/ONTAK_PI_3-1-06.pdf.
March 10, 2006
ST. LOUIS (MD Consult) - On March 9, 2006, the US Food and Drug Administration (FDA) warned several manufacturers and distributors of unapproved drugs containing steroids that continued distribution and sale of these products without FDA approval could result in regulatory action including seizure and injunction. The FDA is concerned that the use of these products, which are marketed as dietary supplements and promoted for building muscle and increasing strength, may cause serious long-term adverse health consequences in consumers.
These products claim to be anabolic, and problems associated with anabolic steroids include liver toxicity, testicular atrophy and male infertility, masculinization of women, breast enlargement in males, short stature in children, adverse effects on blood lipid levels, and a potential to increase the risk of heart attack and stroke.
The agency urges consumers who have any of the products listed below to stop taking them and return them to their place of purchase. The FDA issued warning letters for the following so-called dietary supplement products:
In a related action, in March 2004 the FDA sent warning letters to 23 manufacturers and distributors of products containing androstenedione. These letters are available at fda.gov/bbs/topics/news/2004/hhs_031104.html.
March 13, 2006
ST. LOUIS (MD Consult) - As reported by MD Consult on November 21, 2005, the US Food and Drug Administration (FDA) alerted health care professionals and patients in November 2005 that several long-acting bronchodilator medicines have been associated with possible increased risk of bronchospasm in some people, and requested that manufacturers update warnings in their existing product labeling.
In accordance with this request, GlaxoSmithKline revised new safety labeling and medication guides for patients for Serevent Diskus (salmeterol xinafoate) and Advair Diskus (fluticasone propionate; salmeterol xinafoate), and on March 2, 2006, the FDA approved the materials for both products.
The new information is being added to alert health care professionals and patients that these medicines may increase the chance of severe asthma episodes and death when those episodes occur.
The drugs’ new labels, medication guides for patients, and information sheets for health care professionals are available at fda.gov/CDER/drug/infopage/LABA/default.htm.
March 6, 2006
ST. LOUIS (MD Consult) - In a letter dated March 1, 2006, Swiss biopharmaceutical company Actelion notified health care professionals of changes to the prescribing information for Tracleer (bosentan) based on cases of hepatotoxity that were reported to Actelion and thus to the US Food and Drug Administration (FDA).
In one case, a female patient treated for pulmonary arterial hypertension since childhood with multiple comorbidities who was taking multiple drug therapies was administered Tracleer for 21 months at the recommended dosage. After her first year of treatment, the results of her liver function tests (LFTs) (ie, aminotransferases, alkaline phosphatase, and total bilirubin) remained near her baseline values, but about 1 year after starting treatment with Tracleer her alanine aminotransferase (ALT) level gradually rose from baseline to 2 to 4 times baseline, although it stayed within normal limits. After another 9 months of treatment, marked elevations in aminotransferase and bilirubin levels were noted, and treatment with Tracleer was stopped. After the discontinuation of Tracleer, the patient’s aspartate aminotransferase and ALT levels remained elevated, and bilirubin continued to rise. In this period, she was hospitalized for an intravenous catheter line infection. The patient developed liver failure and biopsy-confirmed cirrhosis. A contribution of Tracleer to the development of liver failure could not be ruled out. Eventually, her liver failure abated and her LFTs recovered; this was about 7 months after discontinuation of Tracleer.
Patients prescribed Tracleer receive the drug through the Tracleer Access Program (TAP). The most important feature of TAP is that each patient is called by the distributor each month to remind him or her of the need for monthly LFT and, if a female patient is of childbearing potential, to have a pregnancy test done, before the monthly refill shipment of Tracleer. In cases where the patients says that he or she has not had an LFT/pregnancy test in the preceding month, or when the patient does not remember whether he or she had such a test, the Tracleer distributor calls the prescribing physician to inform him or her of the patient’s response.
Actelion stresses that the reported case of liver failure underscores the need to continue monthly monitoring for the duration of Tracleer treatment. It also emphasizes the need to adhere to the recommended dosage adjustment and monitoring guidelines described in the product labeling.
Full prescribing information for Tracleer is available at fda.gov/medwatch/safety/2006/TracleerPI_012006.pdf.
Actelion strongly encourages health care professionals to report any serious adverse events that occur in association with the use of Tracleer to the company by calling 1-888-835-5445. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
March 6, 2006
ST. LOUIS (MD Consult) - On February 24, 2006, Hanford Pharmaceuticals Inc of Syracuse, NY, announced that it is voluntarily recalling 4 lots (379,975 vials) of Cefazolin for Injection, USP (1 g/10 mL vials), an antibiotic used in hospitals. Certain lots of the active ingredient used to manufacture the product have been shown to contain microbial contamination (Bacillus pumilus, Staphylococcus hominis, Propionibacterium acnes, or Micrococcus luteus) that may pose a serious or life-threatening risk for some patients. Cefazolin for Injection, USP, is used to treat skin and skin structure, respiratory, and other infections.
The affected lot numbers, which should be promptly returned to the manufacturer, are as follows:
The firm is notifying its customers and users of the recall by letter and asking that they stop distribution, recall from their accounts, and request the return of the recalled lots. Hospitals, clinics, and users should stop using the affected lots immediately. The letter states that the product was distributed by Sandoz, Inc, of Broomfield, Colo, and Watson Pharmaceuticals, Inc, of Corona, Calif.
Patients who think they may have experienced an adverse reaction to recalled product should seek medical assistance. Patients or users can contact Hanford at 1-315-476-7418. To date, the firm has not received any confirmed reports of adverse events or complaints related to the recalled lots.
Adverse reactions or problems experienced with the use of this product should also be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
February 20, 2006
ST. LOUIS (MD Consult) - On February 16, 2006, Bristol-Myers Squibb notified the US Food and Drug Administration and health care professionals about proposed revisions to the prescribing information for Tequin (gatifloxacin). Tequin is indicated for the treatment of various infections caused by susceptible strains of designated microorganisms.
The new package insert includes a contraindication in patients with diabetes because of serious reports of hypoglycemia and hyperglycemia. Additionally, the Warnings and Precautions sections have been updated to identify other risk factors for dysglycemia (including older age, renal insufficiency, and concomitant glucose-altering medication use) while taking Tequin, and to include a recommendation for close medical monitoring.
Details of the proposed changes are highlighted in the "Dear Healthcare Provider" letter issued February 2006 by Bristol-Myers Squibb. Specific wording of these additions and revisions to the labeling is pending FDA review and approval.
When prescribing or dispensing Tequin, Bristol-Myers Squibb encourages health care professionals to discuss with patients who may be at risk for hypoglycemia and/or hyperglycemia how they can detect changes in their blood glucose levels, and measures they should take if such changes occur.
Bristol-Myers Squibb requests that any serious adverse events suspected to be associated with the use of Hydrea or Droxia be reported to the company at 1-800-321-1335. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
February 14, 2006
ST. LOUIS (MD Consult) - On February 13, 2006, the US Food and Drug Administration (FDA) delivered a letter to Cytosol Laboratories, Inc, of Braintree, Mass, to request a recall of all brands and sizes of Balanced Salt Solution (BSS) that the firm manufactures. BSS is a drug used by health professionals to irrigate a patient’s eyes, ears, nose, or throat during a variety of surgical procedures including cataract surgery.
The FDA requested the recall because product lots were found to have elevated levels of endotoxin. Endotoxins, also known as pyrogens, are substances found in certain bacteria that cause a wide variety of serious reactions such as fever, shock, and changes in blood pressure and in other circulatory functions. The FDA has received reports of a serious and potentially irreversible eye injury called toxic anterior segment syndrome, which occurs when a contaminant such as endotoxin enters the anterior segment of the eye during surgery and causes an inflammatory reaction. The agency has also received complaints relating to injuries in more than 300 patients who were given BSS manufactured by Cytosol Laboratories, Inc.
The FDA requests that the company take immediate action to retrieve all inventories of the product, including any existing stock at physician offices and hospitals. An FDA-requested recall is initiated to protect the public health when a product that has been distributed represents a risk of illness or injury and the firm has not initiated a recall of the product. The governmental agency is instructing hospitals, physicians, and consumers to immediately stop using any of these products, quarantine any remaining product, and, if no return instructions from Cytosol are received, destroy the product.
An estimated 1 million units of BSS products were distributed between December 2003 and December 2005. The BSS products subject to the recall order were manufactured by Cytosol Laboratories, Inc, for distribution under the following 3 labels:
Questions should be directed to the FDA at 1-888-463-6332. Any adverse reactions or problems experienced in association with the use of this product should also be reported to the FDA MedWatch Program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
February 14, 2006
ST. LOUIS (MD Consult) - On February 10, 2006, the US Food and Drug Administration (FDA) issued a public health advisory regarding benzocaine sprays marketed under different names, including Hurricaine, Topex, and Cetacaine. This advisory applies only to benzocaine sprays used in the mouth and throat, not to other benzocaine products or to benzocaine sprays applied to exterior skin.
Benzocaine sprays are used in medical practice for locally anesthetizing mucous membranes of the mouth and throat for minor surgical procedures or when a tube must be inserted into the stomach or airways. Their use is known to be occasionally associated with methemoglobinemia. However, cases of methemoglobinemia have also resulted from medication errors caused by incorrect use of benzocaine sprays (eg, longer duration or more frequent sprays than recommended). On February 8, 2006, the Veterans Health Administration (VA) announced its decision to stop using benzocaine sprays for these purposes. The FDA is aware of the reported adverse events and is reviewing all available safety data, but at this time is not planning action to remove the drugs from the market. Up until now, the FDA has concluded that the number of reported adverse events with these sprays has been low and, when properly used, these products can help make important procedures less uncomfortable for patients.
With its new public health advisory, the FDA is again highlighting safety information previously addressed by the agency and will make further announcements or take action as warranted by the ongoing review. At present, the FDA suggests considering the following points about the use of benzocaine sprays in procedures requiring that a tube be inserted in the larynx or pharynx or in minor surgical procedures performed in these locations.
Methemoglobinemia is a condition in which too much of the hemoglobin in red blood cells becomes unable to bind and carry oxygen. Although treatment is available, until the condition is reversed oxygen is not effectively delivered throughout the patient’s body. Patients with methemoglobinemia can experience effects ranging from headache to cyanosis that can be life-threatening in the most severe cases. Patients with underlying breathing problems, such as asthma or emphysema, patients with heart disease, and those who smoke may be more susceptible to the problems from methemoglobinemia and may experience adverse effects from this condition at lower levels of methemoglobin than healthy persons. Similarly, some patients may lack or have reduced level of enzymes that help reverse the methemoglobinemia, and they are also more susceptible to risks associated with benzocaine sprays.
The VA health system has announced its decision to remove benzocaine sprays from their practice because they believe other topical anesthetics are less likely to cause methemoglobinemia and because the procedures themselves might cause similar signs, suggesting that methemoglobinemia may occur but go unrecognized in some cases. The FDA has received adverse event reports involving benzocaine sprays together with symptoms that probably indicated methemoglobinemia. However, the agency notes that these cases were received over a period of many years, and this is an uncommon adverse event. The FDA will continue to review all available safety information for these affected products.
February 9, 2006
ST. LOUIS (MD Consult) - On February 8, 2006, the US Food and Drug Administration (FDA) issued a public health advisory and other advisory information to notify both health care professionals and consumers of recently published studies of serious renal and cardiovascular toxicity occurring after the administration of Trasylol (aprotinin injection) to patients undergoing coronary artery bypass grafting surgery (CABG). The New England Journal of Medicine published an article in its January 26, 2006, issue by Mangano et al reporting an association of Trasylol with serious renal toxicity and ischemic events (ie, myocardial infarction and stroke) in patients undergoing CABG. In addition, an article by Karkouti et al published in the January 20, 2006, online edition of Transfusion suggests an association between aprotinin administration and renal toxicity among patients undergoing cardiac surgery with cardiopulmonary bypass. The FDA is evaluating these studies, along with other studies in the literature and reports submitted to the FDA through the MedWatch program, to determine whether labeling changes or other actions are warranted.
The FDA evaluation is ongoing; in the meantime, the agency has provided the following recommendations to health care providers and patients:
The study reported in The New England Journal of Medicine was an observational study of patients undergoing CABG who received either Trasylol, 1 of 2 other drugs intended to decrease perioperative bleeding (ie, aminocaproic acid or tranexamic acid), or no specific drug treatment.
A limitation of the study was that patients were not assigned at random to receive the treatments, but rather had their treatment chosen by their physician as part of their standard medical care. Consequently, patients receiving Trasylol may have been at higher risk to begin with for these serious adverse events compared with patients receiving no treatment or treatment with another drug intended to decrease bleeding. This possibility prevents a direct assessment of whether Trasylol altered the risk for serious adverse events. The study investigators used statistical procedures (multivariable logistic regression and propensity-score adjustment) to try to adjust for known differences between the treatment groups. Using these procedures, the researchers concluded that Trasylol was associated with more adverse outcomes. Other findings in the study suggested that patients receiving higher dosages of Trasylol were at greater risk than those receiving lower dosages.
The study reported in Transfusion was also an observational study that used statistical methodology to compare outcomes from patients undergoing CABG. The patients in this study received, at physician direction, either Trasylol or another drug intended to decrease the risk for perioperative bleeding. The findings of this study suggested that Trasylol administration increased the risk for renal dysfunction. This study has some of the same limitations as the article published in The New England Journal of Medicine.
In premarketing clinical studies conducted among approximately 3,000 patients undergoing CABG, the risks and benefits of Trasylol were determined in clinical studies that randomly assigned patients to receive either a placebo or Trasylol. In these studies, the risks for serious renal toxicity and cardiovascular events were determined to be similar between patients receiving Trasylol and those receiving placebo. However, in one study assessing coronary graft patency, Trasylol administration was associated with an increased risk of graft closure.
The FDA plans to work with the authors of the publications and the manufacturer of Trasylol to carefully evaluate the risks and benefits associated with use of Trasylol in CABG. The agency anticipates the public presentation of the recently reported information and other data at an advisory committee in the near future. The FDA has stated it will notify health care providers and patients in a timely fashion as new information becomes available.
The FDA urges health care providers and patients to report adverse event information to the agency via the MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
For more information on Trasylol, including full prescribing information and a patient information sheet, visit fda.gov/cder/drug/infopage/aprotinin/default.htm.
February 1, 2006
ST. LOUIS (MD Consult) - On January 30, 2006, the US Food and Drug Administration (FDA) announced it has requested that Bayer add a boxed warning to the labeling for its drug Nimotop (nimodipine) to warn about medication administration errors with nimodipine.
Nimodipine is a calcium-channel blocker that lowers blood pressure. It is approved for oral administration to improve neurologic outcome after subarachnoid hemorrhage. When the drug is administered intravenously or parenterally instead of orally, the effect can be much stronger, leading to cardiovascular collapse and possibly to death. Nimodipine must not be administered intravenously or by any parenteral route.
The FDA has received reports of medication administration errors in which nimodipine was given intravenously or parenterally, rather than orally. In addition to a fatal case reported in 2005, there has been a history of these errors. Two cases were reported in 1995. Another case, which resulted in death, was reported in 1996. Additional nonfatal cases were reported in 1999 and in 2002 (2 cases).
After the 1996 case, the manufacturer, Bayer, included a bolded statement in the labeling, warning against incorrect administration. Because cases are still occurring, the FDA has asked Bayer to add a boxed warning to the nimodipine labeling to describe the life-threatening risk of parenteral administration. Additionally, the FDA has requested that Bayer develop an oral solution of nimodipine for use in patients who cannot swallow a capsule.
The FDA recommends that health care providers who prescribe, dispense, or administer nimodipine take the following steps:
The revised labeling for Nimotop is available at fda.gov/cder/foi/label/2006/018869s014lbl.pdf.
January 26, 2006
ST. LOUIS (MD Consult) - Bristol-Myers Squibb notified health care professionals on January 26, 2006, about revisions to the Warnings and Adverse Reactions sections of the prescribing information of two of its products: Hydrea (hydroxyurea capsules) and Droxia (hydroxyurea capsules). Hydrea is an antineoplastic agent, and its indications include melanoma and resistant chronic myelocytic leukemia. Droxia is indicated to reduce the frequency of sickle cell crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia.
The new package insert text describes cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, in patients with myeloproliferative disorders during therapy with hydroxyurea. These dangers have been most often reported in patients who have a history of or are currently receiving interferon therapy. The Precautions and Dosing and Administration sections have been revised to provide updated information on the safe handling of these products.
Details of the proposed changes are highlighted in the "Dear Healthcare Provider" letters issued January 2006 by Bristol-Myers Squibb. Specific wording of these additions and revisions to the labeling is pending FDA review and approval.
Significant tumor response to Hydrea has been demonstrated in melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary. Hydroxyurea used concomitantly with irradiation therapy is intended for use in the local control of primary squamous cell carcinomas of the head and neck, excluding the lip.
Droxia is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months).
Bristol-Myers Squibb requests that any serious adverse events suspected to be associated with the use of Hydrea or Droxia be reported to the company at 1-800-321-1335. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
January 23, 2006
ST. LOUIS (MD Consult) - On January 20, 2006, Annals of Internal Medicine published an article reporting 3 patients who experienced serious liver toxicity after administration of Ketek (telithromycin). These cases have also been reported to the US Food and Drug Administration’s (FDA’s) MedWatch program. Telithromycin is marketed and used extensively in many other countries, including countries in Europe and Japan.
Although it is difficult to determine the actual frequency of adverse events from voluntary reporting systems such as the MedWatch program, the FDA is continuing to evaluate the issue of liver problems in association with use of telithromycin to determine whether labeling changes or other actions are warranted. As a part of this, the FDA is continuing to work to understand better the frequency of liver-related adverse events reported for approved antibiotics, including telithromycin.
Although the FDA is continuing its investigation of this issue, the agency provided the following recommendations to health care providers and patients:
The case review in the January 20, 2006, online publication by Annals of Internal Medicine reports 3 serious adverse events occurring after administration of telithromycin. All 3 patients developed jaundice and abnormal liver function. One patient recovered, 1 required a transplant, and 1 died. When the livers of the latter 2 patients were examined in the laboratory, they showed massive tissue death. These 2 patients had reported some alcohol use. All 3 patients had previously been healthy and were not taking other prescription drugs. The FDA is also aware that these patients were all treated by physicians in the same geographic area. The significance of this observation is not clear at the present time.
In premarketing clinical studies, including a large safety trial and data from other countries, the occurrence of liver problems was infrequent and usually reversible. On the basis of the premarketing clinical data, it appeared that the risk of liver injury with telithromycin was similar to that of other marketed antibiotics. Nonetheless, the product label advises doctors about the potential for liver-related adverse events associated with the use of telithromycin.
Telithromycin is an antibiotic of the ketolide class. It was the first antibiotic of this class to be approved by the FDA in April 2004 for the treatment of respiratory infections in adults caused by several types of susceptible microorganisms including Streptococcus pneumoniae and Haemophilus influenzae.
The FDA has created a Questions and Answers page (available at fda.gov/cder/drug/infopage/telithromycin/qa.htm) that summarizes the latest information on telithromycin.
January 20, 2006
ST. LOUIS (MD Consult) - On January 19, 2006, the US Food and Drug Administration (FDA) announced the approval of updated labeling for 2 topical eczema treatments: Elidel Cream (pimecrolimus) and Protopic Ointment (tacrolimus). The labeling will now include a boxed warning about a possible risk of cancer, and a patient medication guide will be distributed to help ensure that patients using these prescription medicines are aware of this concern. The new labeling also clarifies that these drugs are recommended for use as second-line treatments. Use of these drugs in children younger than 2 years is not recommended.
Eczema (ie, atopic dermatitis) is one of the most common skin disorders seen in infants and children, affecting 10% to 15% of the childhood population. Although the cause of atopic dermatitis is not known, it is thought that there may be an allergic or immune-mediated component. Affected persons have chronic itching and dry skin, which results in redness and damage to the skin due to rubbing and scratching. Both products are applied to the skin to help control eczema. It is not known exactly how the products work, but they have various effects on the body’s immune system.
On February 15, 2005, FDA’s Pediatric Advisory Committee recommended that the labeling should be updated with a boxed warning and a medication guide about the possible cancer risk for these drugs. The FDA issued a public health advisory in March 2005 advising physicians about the possible cancer risk. At the same time, the agency indicated it would ask the sponsors to update the labeling to address this possible risk. Although a causal link has not been established, rare reports of cancer (eg, skin cancer and lymphoma) have been reported in patients who had been receiving these products.
The boxed warning informs health care professionals that the long-term safety of these drugs has not been established. Although studies are being conducted by the manufacturers of both drugs to try to answer questions about cancer risk, it could be many years before the research is concluded. In the meantime, there is a benefit associated with these drugs when used appropriately. For instance, they may be effective when other prescription topical medications do not work or are not advisable for a patient. The drugs are intended to be used for short periods, but if a patient requires a longer period of treatment, the treatment can be repeated after a period during which treatment is suspended. Patients are advised to call their doctors if symptoms worsen, if they develop an infection, or if symptoms do not improve within the 6 weeks of treatment.
The medication guide will provide consumer-friendly information to patients about how to use the drugs safely. Pharmacists are required to provide the guide to patients when dispensing the drug. Patients are advised to read the material in its entirety and talk to their health care providers if they have further questions.
Materials for health care professionals and patients, as well as a history of actions taken by the FDA with regard to Elidel and Protopic, are available on the FDA Web site at fda.gov/cder/drug/infopage/elidel/default.htm and fda.gov/cder/drug/infopage/protopic/default.htm, respectively.
January 18, 2006
ST. LOUIS (MD Consult) - On January 13, 2006, the US Food and Drug Administration (FDA) warned consumers not to use 2 unapproved drug products that are being marketed as dietary supplements for weight loss. Emagrece Sim Dietary Supplement, also known as the "Brazilian Diet Pill" and "Herbathin Dietary Supplement," may contain several active ingredients found in prescription drugs that could lead to serious adverse effects or injury.
Both products are made in Brazil by Fitoterapicos (also spelled Fytoterapicos) and Phytotherm Sim. The FDA has increased its efforts to prevent the importation of these products by issuing an alert to its field personnel. Import alerts are used to advise FDA field personnel about certain imported products that should not enter the United States.
Consumers are advised not to use the Emagrece Sim and Herbathin products and to return them to the suppliers. There may be other manufacturers or suppliers of imported Emagrece Sim and Herbathin, and consumers should exercise caution in using any of these imported products.
"There are dangers to consumers who purchase diet pills that contain drugs of unknown origin and quality," said Dr Steven Galson, Director of the FDA’s Center for Drug Evaluation and Research. "These products are not approved by [the] FDA and if people experience side effects, it is difficult to trace problems and for physicians to treat them."
Emagrece Sim and Herbathin are labeled as "dietary supplements," but they contain prescription drugs including several controlled substances that, if not used properly as prescribed by a physician, can be harmful. They contain chlordiazepoxide hydrochloride (the active ingredient in Librium) and fluoxetine hydrochloride (the active ingredient in Prozac). Chlordiazepoxide hydrochloride is used to relieve anxiety and to control the symptoms of alcohol withdrawal. It may be habit forming, can cause drowsiness and dizziness, and can impair a person’s ability to drive. Fluoxetine hydrochloride is an antidepressant medication used to treat obsessive-compulsive disorder, panic disorder, and bulimia. It has been linked to several serious drug interactions and certain serious adverse events, including suicidal thinking and behaviors in pediatric patients, anxiety and insomnia, and abnormal bleeding. These drugs should only be taken by patients who are under the supervision of a health care provider.
Emagrece Sim and Herbathin were also found to contain fenproporex, a stimulant that is not approved for marketing in the United States. Fenproporex is converted in the body to amphetamine and as a result has been noted to show up in urinalysis as a test result positive for amphetamines.
Emagrece Sim and Herbathin are sold in packages containing 1 bottle of Formula 1 capsules and 1 bottle of Formula 2 capsules. Both products are available in 5 levels, and the product labels instruct consumers to begin with level 1 and continue to the higher levels until they lose the desired amount of weight. Emagrece Sim also has a "Weight Stabilizer" package containing Formula 1 and Formula 2 capsules, to be used after the desired weight loss has been achieved.
The products are offered for sale on the Internet. They are also imported and distributed by Emagrece Sim Laboratories, Inc, Miami, Fla, and Herbathin, Inc (dba EMIEX Corp), Miami, Fla. The FDA is aware of commercial imports of these products and persons importing them for personal use.
The FDA urges consumers, health care providers, and caregivers to cease using and dispose of these products and report any adverse events related to these products to MedWatch, the FDA’s voluntary reporting program, by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, Food and Drug Administration, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
January 18, 2006
ST. LOUIS (MD Consult) - On January 11, 2006, the US Food and Drug Administration (FDA) alerted health care professionals and consumers that filling their prescriptions abroad may have adverse health consequences because of confusion with drug brand names that could inadvertently lead consumers to take the wrong medication. An FDA investigation has found that many foreign medications, although marketed under the same or similar-sounding brand names as those in the United States, contain different active ingredients than in the United States. Taking a different active ingredient may not help, and may even harm, the user.
"Consumers who fill US prescriptions abroad, either when traveling or when shopping at foreign Internet pharmacies, need to be aware of this potential health hazard," said Dr Murray Lumpkin, Deputy Commissioner for International and Special Programs. "The name of a drug bought from another country may be identical or similar to the name on the US prescription, but the active ingredient in the medicine may be different and not provide the right treatment."
The FDA’s investigation illustrates this health risk inherent in filling US prescriptions abroad and highlights the lack of standardization of drug trade names internationally. For example, in the United States, "Flomax" is a brand name for tamsulosin, a treatment for an enlarged prostate, whereas in Italy, the active ingredient in the product called "Flomax" is morniflumate, an anti-inflammatory drug. In the United States, "Norpramin" is the brand name for an antidepression drug containing desipramine, but in Spain, the same brand name is used for a drug that contains omeprazole, a treatment for stomach ulcers. Although some of the identical brand names have different active ingredients appropriate for the same health condition, even these products should not be substituted without the guidance of a health care professional because of the potential for different doses, adverse effects, allergies, and interactions with other drugs.
The FDA also has found 105 US brand names that have foreign counterparts that look or sound so similar that consumers who fill such prescriptions abroad may receive a drug with the wrong active ingredient. For example, in the United Kingdom, "Amyben," a brand name for a drug product containing amiodarone, used to treat abnormal heart rhythms, could be mistaken for "Ambien," a US brand name for a sleep aid. Using Amyben instead of Ambien could have a serious adverse outcome.
The FDA’s Public Health Advisory on the topic (fda.gov/oc/opacom/reports/confusingnames.html) contains more information, including list of US and foreign brand names that are identical or similar and their respective active ingredients.
January 17, 2006
ST. LOUIS (MD Consult) - On January 13, 2006, Novartis and the US Food and Drug Administration (FDA) notified health care professionals of revisions to the Boxed Warning, Warnings, Contraindications, Precautions (Information for Patients and Pharmacokinetic-Related Interactions subsections), and Adverse Reactions (Postmarketing Clinical Experience subsection) sections of the prescribing information for Clozaril (clozapine) tablets. Recommendations from the FDA’s Psychopharmacological Drugs Advisory Committee regarding the white blood cell (WBC) monitoring schedule, required for all clozapine users, has resulted in modification in the monitoring schedule. Additional labeling changes address safety issues related to dementia-related psychosis, paralytic ileus, hypercholesterolemia, and pharmacokinetic interaction with citalopram.
Clozaril is indicated for the management of severely schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia.
The major changes regarding the frequency and parameters of the monitoring schedule include the following:
Modifications to the frequency of monitoring after interruptions in therapy were also made; see the revised prescribing information for details.
Patients receiving Clozaril who are being monitored on the previous schedule of weekly for the first 6 months are to continue this monitoring schedule and report ANCs from this point forward. If WBC ≥ 3,500/mm3 and ANC ≥ 2,000/mm3, patients may transition to monitoring every 2 weeks for the next 6 months.
Patients who are currently being monitored on the previous schedule of every other week are to continue this monitoring schedule for a total of 6 months and should report ANCs from this point forward. If WBC ≥ 3,500/mm3 and ANC ≥ 2,000/mm3, patients may transition to monthly monitoring.
Health care providers are to submit all WBC and ANC values after the discontinuation of Clozaril therapy to the Clozaril National Registry for all non-rechallengeable patients (WBC < 2,000/mm3 and/or ANC < 1,000/mm3), until WBC ≥ 3,500 mm3 and ANC ≥ 2,000/mm3.
Dementia-related Psychosis
Recently, the FDA reviewed data related to the use of atypical antipsychotics for the treatment of behavioral symptoms in elderly patients with dementia. They have concluded that the labeling for all atypical antipsychotics should be updated to include information about an increased risk of mortality in elderly patients with dementia-related psychosis. This labeling change is based on a meta-analysis of 17 placebo-controlled trials of 4 atypical antipsychotic drugs (aripiprazole, olanzapine, risperidone, or quetiapine). Because the increase in mortality was consistent across all 3 relevant chemical classes, the FDA concluded that the effect is likely related to the common pharmacologic effects of all atypical antipsychotics, including those that were not included in the meta-analysis (eg, Clozaril). The Boxed Warning section of the Clozaril prescribing information was revised to reflect this warning. Clozaril is not approved for use in dementia-related psychosis.
Paralytic Ileus
Paralytic ileus has been a listed adverse event associated with Clozaril use as reflected in both the Precaution and Adverse Reactions sections of the prescribing information. However, based on a review and evaluation of the global postmarketing safety and clinical trial databases for Clozaril, Novartis has concluded that paralytic ileus should be listed as a contraindication. The Contraindications section of the prescribing information was revised accordingly.
Metabolic Disorders
On the basis of data from the global postmarketing safety database, the Adverse Reactions (Postmarketing Clinical Experience) section of the prescribing information was revised to reflect reports of hypercholesterolemia and/or hypertriglyceridemia associated with Clozaril treatment.
Citalopram
After a review of the data from the medical literature as well as data from the Novartis global postmarketing safety database, the FDA and Novartis have determined that the concomitant use of Clozaril and citalopram results in clinically significant elevations of Clozaril blood concentrations. Consequently, the Precautions (Pharmacokinetic-related Interactions) section of the prescribing information was revised to include a warning about citalopram.
Additional Information
All patients being treated with Clozaril and their caregivers should be fully informed of all these revisions to the prescribing information. More information is available at clozaril.com/index.jsp.
Novaris requests that health care professionals report all serious adverse events suspected to be associated with the use of Clozaril to the company (by phone at 888-NOW-NOVARTIS, or by Internet at novartis.com/contact/en/index.shtml). Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
January 6, 2006
ST. LOUIS (MD Consult) - On January 5, 2006, the US Food and Drug Administration (FDA) and GlaxoSmithKline notified health care professionals about postmarketing reports of new-onset and worsening diabetic macular edema for patients receiving rosiglitazone. In the majority of these cases, the patients also reported concurrent peripheral edema. In some cases, the macular edema resolved or improved after discontinuation of therapy, and in 1 case macular edema resolved after dose reduction.
GlaxoSmithKline products containing this medication include Avandia (rosiglitazone maleate) and Avandamet (rosiglitazone maleate/metformin hydrocholoride), both indicated for the treatment of type 2 diabetes mellitus. This new safety information will be added to product information for prescribers and patient information materials for both Avandia and Avandamet.
Macular edema typically occurs in association with diabetic retinopathy, although it is more likely to occur as retinopathy progresses. Risk factors for macular edema include duration of diabetes, presence of retinopathy, hypertension, and poor glycemic control. Symptoms suggestive of macular edema include blurred or distorted vision, decreased color sensitivity, and decreased dark adaptation.
For more details on Avandia, visit www.avandia.com. Product and safety information on Avandamet is available at avandia.com/about_avandamet/avandamet.html.
January 6, 2006
ST. LOUIS (MD Consult) - On January 5, 2006, Cangene, Baxter Healthcare, and the US Food and Drug Administration notified health care professionals of revisions to the Warnings, Precautions, and Adverse Reactions sections of the prescribing information for WinRho SDF (Rho[D] immune globulin intravenous [human]) to address the following 2 important safety concerns:
Cangene and Baxter Healthcare request that health care professionals report any serious adverse events associated with the use of WinRho SDF to Baxter at 1-800-423-2090. Alternatively, this information can be reported to the FDA’s MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), Internet (fda.gov/medwatch/report.htm), or mail (MedWatch Office, 5600 Fishers Lane, HFD-410, Rockville, MD 20852-9787).
Patient information regarding WinRho SDF is available at fda.gov/medwatch/safety/2006/WinRho_Patient_Leaflet_Final_11-30-2005.pdf. The revised drug labeling for the product can be accessed at fda.gov/medwatch/safety/2006/WinRho_PI_%2005-DEC-2005.pdf.
January 3, 2006
ST. LOUIS (MD Consult) - On December 29, 2005, the US Food and Drug Administration (FDA) notified health care professionals and patients that it has issued warning letters to 9 companies marketing bogus anti-influenza products with claims that their products could be effective against preventing the avian flu or other forms of influenza. The FDA is not aware of any scientific evidence that demonstrates the safety or effectiveness of these products for treating or preventing avian flu, and the agency is concerned that the use of these products could harm consumers or interfere with conventional treatments.
"The use of unproven flu cures and treatments increases the risk of catching and spreading the flu rather than lessening it because people assume they are protected and safe and they aren’t," said Andrew von Eschenbach, MD, Acting FDA Commissioner. "I consider it a public health hazard when people are lured into using bogus treatments based on deceptive or fraudulent medical claims."
The warning letters were issued to the 9 firms on December 13, 2005. Eight of the products purported to be dietary supplements. Examples of the unproven claims cited in the warning letters include: "prevents avian flu," "a natural virus shield," "kills the virus," and "treats the avian flu." These alternative therapies are promoted as "natural" or "safer" treatments that can be used in place of an approved treatment or preventive medical product.
In the warning letters, the FDA advises the firms that it considers their products to be drugs because they claim to treat or prevent disease. The warning letters further state that the FDA considers these products to be "new drugs" that require FDA approval before marketing. In addition, the letters note that the claims regarding avian flu are false and misleading because there is no scientific basis for concluding that the products are effective to treat or prevent avian flu. The companies were given 15 days to respond to the FDA.
Links to the individual warning letters are available at fda.gov/bbs/topics/NEWS/2005/NEW01274.html.
Consumers who believe they have seen a fraudulent product can report it to the FDA online at fda.gov/oc/buyonline/buyonlineform.htm.
For information on helping to prevent flu, visit cdc.gov/flu/protect/preventing.htm.
News Updates are brought to you by
An Imprint of .
To order a Mosby's Drug Consult product or to check on your order, please call Elsevier Science Customer Service Department at 800-545-2522 or Order Online