Recalls and Alerts Pfizer Terminates Manufacturing of Inhaled Insulin (Exubera) Pfizer Inc announced that it is no longer making inhaled insulin (Exubera). The decision is not based on any safety concerns but is due to economic feasibility resulting from too few patients taking the inhaled insulin. Pfizer will work with physicians to transition patients from inhaled insulin to other treatment options over the next several months. Exubera was approved by the US Food and Drug Administration in January 2006 as the first inhaled insulin. For additional information: http://www.exubera.com PDE5 Inhibitors and Hearing Loss The prescribing information for phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil [Viagra, Revatio], tadalafil [Cialis], vardenafil [Levitra]) has been changed to include information regarding sudden decreases in hearing or loss of hearing. PDE5 inhibitors are indicated for the treatment of erectile dysfunction, and sildenafil (Revatio) is specifically indicated for the treatment of pulmonary arterial hypertension. In some individuals, tinnitus and dizziness accompanied the hearing impairment. Medical follow-up on these reports was often limited, causing difficulty in determining if the hearing loss was related to the use of one of the drugs, an underlying medical condition, other risk factors for hearing loss, a combination of these factors, or other unknown variables. More information is available at FDA MedWatch. Exenatide (Byetta) and Acute Pancreatitis The prescribing information for exenatide (Byetta) has been updated to include reports of acute pancreatitis. Thirty incidences of acute pancreatitis have been reported in patients taking exenatide, a drug used to treat adults with type 2 diabetes mellitus. An association between exenatide and acute pancreatitis is suspected in some of these cases. Health care professionals should be alert to the signs and symptoms of acute pancreatitis. Symptoms include persistent severe abdominal pain that may radiate to the back and may be accompanied by nausea and vomiting. Elevated serum amylase and/or lipase levels are characteristic laboratory values associated with acute pancreatitis. Patients taking exenatide who experience these adverse effects should seek prompt medical care. If pancreatitis is suspected, exenatide should be discontinued. If pancreatitis is confirmed, exenatide should not be restarted unless another etiology is identified. More information is available at FDA MedWatch. Medtronic Sprint Fidelis Defibrillation Leads—Marketing and Sales Suspended Medtronic has voluntarily suspended distribution of its Sprint Fidelis defibrillation leads because fractures have been detected. Sprint Fidelis leads will no longer be sold or manufactured, and any remaining product should be pulled from inventory and returned to the company. When a defibrillator lead is slightly more prone to fracture, most leads will function well. However, infrequently, a lead may actually break, or "fracture"; the lead may send false signals that cause inappropriate or undelivered defibrillator shocks. About 268,000 leads have been implanted worldwide, and fractures have occurred in less than 1%. Patients who are implanted with this lead should contact their physicians for further information. More information is available at FDA MedWatch. FulLife Natural Options Products Seized by US Marshals US Marshals seized approximately $71,000 worth of dietary supplements from FulLife Natural Options, Inc (Boca Raton, FL). Charantea Ampalaya capsules and Charantea Ampalaya Tea are dietary supplements confiscated because of claims made by the manufacturer that they treat serious illnesses (eg, diabetes mellitus, anemia, hypertension). According to US Food and Drug Administration (FDA) standards, these products are considered unapproved new drugs because they make claims related to the prevention or treatment of diseases in the products’ labeling. Before a new drug product may be legally marketed, it must be shown to be safe and effective and must be approved by the FDA. This action protects consumers who may rely on unapproved products and unsubstantiated claims associated with these products when making important decisions about their health. Following an investigation of the firm's marketing practices, the FDA told FulLife that the claims related to prevention or treatment of diseases made these products subject to regulation as drugs. Despite the FDA's warnings, the firm failed to bring its marketing into compliance with the law. During subsequent inspections, the FDA inspectors found that the offending claims were still being made. More information is available at FDA MedWatch. Two Microbubble Contrast Agents for Echocardiography Now Include Boxed Warnings The US Food and Drug Administration (FDA) has requested that boxed warnings be added to the labeling of 2 contrast agents used in echocardiography. The contrast agents affected by this request are perflutren liquid microspheres (Definity; Bristol-Myers Squibb) and perflutren protein-type A microspheres for injection (Optison; General Electric). The warning following reports of 11 deaths and 199 serious cardiopulmonary reactions associated with the use of the aforementioned microbubble contrast agents during or within 30 minutes following echocardiography. Ten of the deaths and 190 of the serious reactions were related to the use of Definity. The Optison product has not been on the market since 2005 because of a manufacturing problem but is expected to be reintroduced in the near future. The use of Definity has not been established with exercise or pharmacological stress testing. Also, use is contraindicated in patients at risk for cardiopulmonary reactions, particularly patients with cardiac shunts; patients who are clinically unstable or who have had recent worsening of congestive heart failure; and patients with symptomatic arrhythmias or those who are at high risk for arrhythmias due to QT prolongation, respiratory failure, severe emphysema, pulmonary emboli, or other conditions that compromise pulmonary arterial vasculature. More information is available at FDA MedWatch. Full Immunization Emphasized With Cochlear Implants The US Food and Drug Administration (FDA) has received 2 reports of cochlear implants associated with death secondary to an increased risk of bacterial meningitis caused by Streptococcus pneumoniae. Children with cochlear implants with a positioner component are at a greater risk (see previous eMedicine Alerts from February 6, 2006 and August 1, 2003). The cochlear implant devices are used in patients who are profoundly deaf or have severe hard of hearing. The 2 deaths from meningitis were reported within the past year in children implanted with the cochlear implant with the positioner component. These children were not fully immunized according to the Centers for Disease Control and Prevention (CDC) recommended vaccination schedule (see the 2nd link provided below). These children, aged 9 and 11 years, had completed only part of the recommended pneumococcal vaccinations for their age group. At least one of the children had meningitis caused by a serotype of S pneumoniae that may have been prevented by proper vaccinations. Recipients of cochlear implants must be fully immunized according to the CDC vaccination recommendations. Because children with cochlear implants are at increased risk for pneumococcal meningitis, the CDC recommends that they receive pneumococcal vaccination under the same schedules that apply to other individuals at high risk for invasive pneumococcal disease. More information is available at FDA MedWatch. For additional information: http://www.cdc.gov/vaccines/vpd-vac/mening/cochlear/dis-cochlear-hcp.htm FDA Evaluates Risk of Atrial Fibrillation With Bisphosphonates The US Food and Drug Administration (FDA) published an early communication that discusses the relationship of atrial fibrillation (AF) with the use of bisphosphonates. This communication is in response to recently published articles in the May 3, 2007, New England Journal of Medicine. In one of the studies, the use of intravenous zoledronic acid resulted in decreased vertebral and hip fractures compared with the placebo group. The unexpected adverse effect of serious AF was also observed and occurred more frequently in the zoledronic acid group compared with placebo (50 vs 20 patients, p<0.001). However, among the 50 patients taking zoledronic acid who experienced AF, the arrhythmia occurred more than 30 days after the zoledronic acid infusion (N Engl J Med. 2007;356[18]:1809-1822). See the second link provided below for abstract. In the same issue of the New England Journal of Medicine, a letter to the editor described AF events in a separate study of another bisphosphonate, alendronate. This study showed 47 serious AF events (1.5%) among patients who received alendronate compared with 31 events (1%) among those receiving placebo during an average of 4 years (N Engl J Med. 2007;356[18]:1895-96). See the third link provided below for abstract. Upon initial review, it is unclear how these data on serious atrial fibrillation should be interpreted. The FDA does not believe that health care providers or patients should change either their prescribing practices or their use of bisphosphonates at this time. Because of these data, the FDA is further examining the possibility of an increased risk of AF with the use of bisphosphonates. The FDA is continuing to monitor spontaneous postmarketing reports of AF in patients taking bisphosphonates and is seeking additional data to allow for an in-depth evaluation of the entire class of bisphosphonates. Bisphosphonates are a class of drugs used to increase bone mass and to reduce the risk for fracture in patients with osteoporosis. Bisphosphonates are also used to slow bone turnover in patients with Paget disease of the bone and to treat bone metastases and lower elevated blood calcium levles in patients with cancer. The 7 FDA-approved bisphosphonates are alendronate (Fosamax, Fosamax Plus D), etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel, Actonel with calcium), tiludronate (Skelid), and zoledronic acid (Reclast, Zometa). More information is available at FDA MedWatch. For additional information: http://content.nejm.org/cgi/content/abstract/356/18/1809   http://content.nejm.org/cgi/content/extract/356/18/1895 Class I Recall Issued for Exacta-Mix 2400 Operating Software Version 1.07 Pharmacy Compounding System A class I recall has been issued for Exacta-Mix 2400 Operating Software Version 1.07 Pharmacy Compound System (Model No. 8300-0073, Baxa Corporation). The recall affects 32 devices that were distributed to 14 customers in the United States and to 1 customer outside of the United States from June 4, 2007 through June 25, 2007. The device is a compounding system used in pharmacies to add and mix various ingredients into one intravenous (IV) solution. The recall was issued because a software failure allowed up to 50 mL extra volume of an ingredient to be added to the IV solution that can be life-threatening, particularly in newborns. Immediately stop using the admixing system and contact the manufacturer for a replacement. A class I recall is issued when a drug or device has a reasonable probability of causing serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. Axcil and Desirin Dietary Supplements Recalled A nationwide recall has been issued for Axcil and Desirin, both of which are marketed as dietary supplements and are promoted for erectile dysfunction. The products contain undeclared ingredients that are potentially harmful to consumers. The US Food and Drug Administration (FDA) laboratory analysis of Axcil and Desirin found that lot number 02B07 contained 3 mg/g of sildenafil. The products also contained sulfosildenafil and sulfohomosildenafil, which are analogs of sildenafil. Sildenafil is an FDA-approved product (marketed as Viagra) and is indicated for erectile dysfunction. Sildenafil and sildenafil analogs may interact with nitrates found in some prescription drugs (eg, nitroglycerin) and may cause profound hypotension. Consumers with diabetes, hypertension, hypercholesterolemia, or cardiovascular diseases are often prescribed nitrates. Sexual dysfunction is a common problem with these conditions, and consumers may seek these types of products to enhance sexual performance. Consumers who have these products should immediately stop using them and consult with their health care professional if they experience any problems that may be due to these products. Cryptosporidium Infection Linked to Baby’s Bliss Gripe Water A recall has been issued for the apple flavor of Baby’s Bliss Gripe Water (distributed by MOM Enterprises, Inc.). The product affected by the recall is coded with 26952V and an expiration date of October 2008 (10/08). The recall was initiated because laboratory findings confirmed the presence of Cryptosporidium in the product during an investigation into an illness in a 6-week old infant who consumed the product. Baby’s Bliss Gripe Water is an herbal supplement promoted to ease gas and stomach discomfort often associated with colic, hiccups, and teething in infants and children. Cryptosporidium is a parasite that can cause intestinal infections. Infected infants, children, pregnant women, and those with weakened immune systems are particularly susceptible to severe dehydration that results from diarrhea caused by Cryptosporidium infection. Other symptoms include dehydration, weight loss, stomach cramps or pain, fever, nausea, and vomiting. Onset of symptoms is typically 2-10 days after infection with the parasite and lasts about 1-2 weeks. For more information, see the eMedicine topic Cryptosporidiosis. Children who have recently consumed the apple flavor of Baby's Bliss Gripe Water and have these symptoms need immediate medical attention. Consumers should stop using this product and immediately discard or return bottles of the product. More information is available at FDA MedWatch. Class I Recall Issued for MRL/Welch Allyn AED 20 Automatic External Defibrillators The United States Food and Drug Administration (FDA) has issued a class I recall for MRL/Welch Allyn AED 20 Automatic External Defibrillators. The recall affects the devices manufactured between October 2003 and January 2005 and includes serial numbers 205787 through 207509. Emergency or medical personnel use the devices to treat adult and pediatric patients in cardiopulmonary arrest. The recalled devices may display a "Defib Comm" error message during use that results in a terminal failure of the device to analyze the patient's ECG and deliver the appropriate therapy. The FDA advises to stop using the recalled AEDs immediately and contact the manufacturer for a replacement. A class I recall is issued when a drug or device has a reasonable probability of causing serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. Intravenous Haloperidol May Cause Life-Threatening Arrhythmias The United States Food and Drug Administration (FDA) has announced that the prescribing information for haloperidol (Haldol, generic versions) has been revised to include a new cardiovascular subsection in the Warnings section. Life-threatening arrhythmias (eg, sudden death, QT prolongation, torsades de pointes) have been reported in patients treated with haloperidol, especially when haloperidol is administered intravenously (IV) or at doses higher than recommended. Injectable haloperidol is only FDA-approved for intramuscular injection, although considerable evidence exists that intravenous administration is a fairly common off-label clinical practice. A minimum of 28 cases of QT prolongation and torsades de pointes have been reported following intravenous administration, and some have resulted in death. More information is available at FDA MedWatch. Normal Saline Flush Syringes Recalled Because of Particles in Solution A recall has been issued for Normal Saline Flush Syringes (by B. Braun Medical Inc) with lot numbers ending in "SFR". The recall was prompted because of increased customer complaints of particulate matter in the saline. The introduction of particular matter into the bloodstream may result in phlebitis, damage to vital organs, or both. Pulmonary embolism or silicone embolism syndrome, which could cause severe injury, death, or both, are rare possibilities. To date, B. Braun Medical Inc has received no reports of any patient injury associated with this issue. The recalled normal saline syringes are described as follows: Product code 513584 and lot number SFR 3 mL (in 12-mL syringes) Approximately 33,000 units distributed between June 11 and July 18, 2007 Product code 513587 and lot number SFR 10 mL (in 12-mL syringes) Approximately 1.2 million units distributed between June 11 and July 18, 2007 Customers and patients who possess the recalled syringes should discontinue use immediately. More information is available at FDA MedWatch. Fentanyl Buccal Tablets Require Proper Patient Selection and Precise Dosage Cephalon issued two "Dear Health Care Professional" letters to inform prescribers and other health care providers of important safety information regarding fentanyl buccal tablets (Fentora). Fentanyl buccal tablets are indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Serious adverse events, including deaths, have occurred in patients treated with Fentora. These deaths occurred as a result of improper patient selection (eg, use in patients not tolerant to opioid therapy), improper dosing, and/or improper product substitution. Appropriate patient selection and proper dosing and administration of Fentora are essential to reduce the risk of respiratory depression. Key safety information for Fentora is as follows: Do NOT use in patients not tolerant to opioid therapy. Use only for labeled indications. Do not prescribe for patients with acute pain, postoperative pain, headache, migraine, or sports injuries. Do not substitute; Fentora is not a generic version of Actiq or other fentanyl-containing products. Follow dosing instructions carefully. For unrelieved breakthrough pain (BTP), patients should NOT take more than 2 Fentora tablets per BTP episode. Patients must wait at least 4 hours before treating another BTP episode with Fentora. More information is available at FDA MedWatch. Ceftriaxone and Calcium Warning Roche has contacted health care professionals to clarify the potential risk associated with concomitant use of intravenously (IV) administered ceftriaxone (Rocephin) with calcium or calcium-containing IV solutions or products. Ceftriaxone and calcium-containing solutions (including continuous IV infusions of calcium, such as parenteral nutrition) should not be mixed or coadministered to any patient irrespective of age, even via different IV infusion lines at different sites. Also, do not administer ceftriaxone within 48 hours of IV calcium-containing solutions. Fatalities caused by calcium-ceftriaxone precipitants in the lung and kidney have been reported (see eMedicine Recalls and Alerts July 5, 2007). Interaction data is unavailable regarding ceftriaxone and oral calcium-containing products or intramuscular ceftriaxone and calcium-containing products (IV or oral). More information is available at FDA MedWatch. Blood Glucose Meters—Screen Malfunction When Dropped Abbott notified users of blood glucose meters (Precision Xtra, Optium, ReliOn Ultima, Rite Aid, Kroger, manufactured after January 31, 2007) to check the meter’s screen if dropped onto a hard surface. When dropped, part of the display can be jarred or disconnected, resulting in the inability to read the lot number or date information. Dropping the meter can also cause the screen to appear blank, and blood glucose test results can not be seen. This may cause a significant risk for hypoglycemia or hyperglycemia. Patients should stop using the meter immediately if unable to read the screen. The meters come with a wallet that provides additional protection for the meter. If dropped, immediately perform a meter display check. Instructions on how to do this are detailed in the meter’s Users Guide. If no problems are encountered during the automatic display check, the meter is ready for use. More information is available at FDA MedWatch. Nelfinavir (Viracept) Impurity Prompts New Guidelines for Children and Pregnant Women Pfizer has alerted health care professionals about the possible presence of a process-related impurity in nelfinavir (Viracept). The impurity is ethyl methanesulfonate (EMS), a potential human carcinogen. Guidance regarding nelfinavir’s use in pregnant women and pediatric patients was also provided. Data from animal studies indicate EMS is teratogenic, mutagenic, and carcinogenic; however, no data from humans exist. The US Food and Drug Administration (FDA) has asked Pfizer to implement new specifications to limit the presence of EMS in nelfinavir. The FDA and Pfizer agree that pediatric patients who are stable on nelfinavir-containing regimens, should continue to receive nelfinavir because the benefit-to-risk ratio remains favorable. Pediatric patients who need to begin human immunodeficiency virus (HIV)-treatment should not start regimens that contain nelfinavir until further notice. Also, pregnant women who need to begin antiretroviral therapy should not be offered regimens that contain nelfinavir until further notice. As a precautionary measure, pregnant women currently receiving nelfinavir should be switched to an alternative antiretroviral therapy while Pfizer and the FDA work to implement the long-term EMS specification for nelfinavir. For pregnant women with no alternative treatment options, the FDA and Pfizer agree that the riskto--benefit ratio remains favorable for the continued use of nelfinavir. Other patients should continue to receive nelfinavir because available information shows the benefits of HIV-1 antiretroviral treatment outweigh the risk of stopping HIV treatment. More information is available at FDA MedWatch.   Zencore Dietary Supplement Recalled – Contains Undeclared Drug Ingredients The US Food and Drug Administration (FDA) has issued a nationwide recall for the dietary supplement, Zencore Tabs. Upon analysis by the FDA laboratory, Zencore Tabs were found to contain aminotadalafil, an analog of tadalafil (Cialis) and sildenafil (Viagra), and sulfosildenafil and sulfohomosildenafil, also analogs of sildenafil. Tadalafil and sildenafil are active ingredients of drugs that are FDA-approved for erectile dysfunction. All of these undeclared ingredients may interact with nitrates (eg, nitroglycerin) and cause dangerous hypotension. Consumers should immediately stop using Zencore and consult their health care provider if problems occur. More information is available at FDA MedWatch. Metabolism Apple Cider Vinegar Dietary Supplement Recalled Metabolism Apple Cider Vinegar brand dietary supplement capsules have been recalled because one lot contained the undeclared drug sibutramine (Meridia), a US Food and Drug Administration (FDA)-approved appetite suppressant for weight loss. The affected lot number is 3001006, expiration October 2009 (UPC Code: 9248300102). Metabolism Apple Cider Vinegar is not an approved drug. The use of sibutramine may cause hypertension and tachycardia, thereby posing significant risk for patients with coronary artery disease, congestive heart failure, arrhythmias, or stroke. Consumers should return any unused product to the manufacturer. More information is available at FDA MedWatch. Codeine Rapid Metabolizer Use Cautioned When Breastfeeding The US Food and Drug Administration (FDA) has issued a Public Health Advisory warning about very rare but serious adverse effects (eg, excessive sleeping, breathing difficulties, limpness) in nursing infants whose mothers are taking rapidly metabolize codeine. Codeine may be prescribed for analgesia or as an antitussive agent. Following ingestion, codeine is metabolized to morphine. Numerous variables affect codeine metabolism, including genetic make-up. Some individuals have a variation in a liver enzyme (ie, CYP2D6) and may rapidly and completely metabolize codeine to morphine. If breastfeeding mothers rapidly metabolize codeine, the morphine levels in the breast milk may be increased. These higher levels of morphine may lead to life-threatening or fatal adverse effects in nursing infants. Physicians should choose the lowest effective dose for the shortest period of time when prescribing codeine-containing drugs to breastfeeding mothers and should closely monitor the infant. In most cases, the rate at which the mother metabolizes codeine is unknown. A test can determine the patient’s CYP2D6 genotype; however, this test is not routinely used in clinical practice but is available through a number of different laboratories. The test results reveal whether a person converts codeine to morphine at a faster rate than average, resulting in higher morphine levels in the blood. If these morphine levels are too high, patients have an increased risk of adverse events. More information is available at FDA MedWatch. Specific Genes Affect Warfarin Dosage Requirements The prescribing information for warfarin (Coumadin) has been updated with information that explains how genetic makeup may influence drug response. Specifically, individuals with variations in 2 genes may need lower warfarin doses than individuals without these genetic variations. The 2 genes are called CYP2C9 and VKORC1. The CYP2C9 gene is involved in warfarin metabolism, and the VKORC1 gene helps to regulate the ability of warfarin to prevent blood from clotting. Patients carrying at least one copy of the CYP2C9*2 allele or CYP2C9*3 allele required a mean daily warfarin dose that was 17% and 37% less than patients who carry the CYP2C9*1 allele, respectively. Vitamin K epoxide reductase (VKOR) is a multiprotein enzyme complex and, when inhibited by warfarin, reduces the regeneration of vitamin K. Single nucleotide polymorphisms in the VKORC1 gene (particularly the 1639G>A allele) are associated with lower warfarin dose requirements. Warfarin is used for a broad range of indications that require anticoagulation. Warfarin dosage and administration is highly individualized. Measurements of prothrombin time (PT) and international normalized ratios (INRs) are required to precisely adjust the dose on a regular basis. In addition to current standards of practice regarding warfarin dosage and monitoring, the new information regarding the impact of genetic information on the initial dose and the response to warfarin will further assist clinicians. More information is available at FDA MedWatch. Cardiovascular Risk Warning Added to Entire Thiazolidinedione Drug Class The United States Food and Drug Administration (FDA) has determined that the prescribing information for the entire antidiabetic drug class of thiazolidinediones (ie, rosiglitazone, pioglitazone) should contain a boxed warning that describes heart failure risks. This decision follows an extensive review of postmarketing adverse event reports. The strengthened warning advises health care professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain; shortness of breath; and edema after starting drug therapy. Discontinuation or dose reduction should be considered if the aforementioned symptoms occur. Additionally, initiating thiazolidinediones are contraindicated in patients with New York Heart Association (NYHA) Class III or IV heart failure. The proprietary names of drugs whose prescribing information will contain a black boxed warning include the following: Avandia (rosiglitazone) Actos (pioglitazone) Avandaryl (rosiglitazone and glimepiride) Avandamet (rosiglitazone and metformin) Duetact (pioglitazone and glimepiride) More information is available at FDA MedWatch. Accidental Overdose of Kaletra Causes Infant Death Abbott Laboratories has sent a global communication to health care providers to alert them regarding an accidental overdose involving lopinavir/ritonavir oral solution (Kaletra), which resulted in the death of an infant. The accidental overdose occurred in a 44-day-old infant, born at 30 weeks gestation with human immunodeficiency virus (HIV) infection. The infant was administered 6.5 mL (about 10 times the calculated dose) and died 9 days later of cardiogenic shock. Accurate dose calculation of the medication order, dispensing information, and dosing instructions are essential to minimize the risk of errors. Lopinavir/ritonavir oral solution is highly concentrated and contains 80 mg of lopinavir and 20 mg of ritonavir per mL. The prescribing information contains precise dosage guidelines for children. Dosage for children whose weight is less than 15 kg is 12 mg/kg orally twice daily (dose calculation is based on lopinavir component). Current prescribing information can be viewed in the second link provided below. More information is available at FDA MedWatch. For additional information: http://www.fda.gov/medwatch/safety/2007/Mar_PI/Kaletra_PI_200703.pdf Red Yeast Rice Dietary Supplements Found to Contain Lovastatin The US Food and Drug Administration (FDA) has warned consumers not to buy or consume 3 red yeast rice products sold on Web sites and promoted as dietary supplements used to lower cholesterol. FDA testing revealed that the products contained the prescription drug lovastatin (the active ingredient in Mevacor), which is approved for marketing in the United States and other countries to treat high cholesterol. The suspect products include the following: Red Yeast Rice (Sold by Swanson Healthcare Products, Inc; manufactured by Nature’s Value Inc) Policosonal Complex (Sold by Swanson Healthcare Products, Inc; manufactured by Kabco Inc) Cholestrix (Sold by Sunburst Biorganics) Lovastatin is known to cause rhabdomyolysis, a myopathy that may lead to renal failure. The risk of developing rhabdomyolysis increases when high doses are administered or when lovastatin is concurrently administered with some food (eg, large quantities of grapefruit juice) or drugs, such as nefazodone, other cholesterol agents (eg, gemfibrozil, niacin), certain antibiotics (eg, erythromycin, clarithromycin), antifungal agents (eg, itraconazole, ketoconazole), cyclosporine, or drugs used to treat human immunodeficiency virus HIV infection (eg, amprenavir, atazanavir, ritonavir). Consumers should consult their health care provider regarding the use of dietary supplements. More information is available at FDA MedWatch. Baxter Expands Class I Recall for Volumetric Infusion Pumps Baxter Healthcare and the US Food and Drug Administration (FDA) have expanded the previous class I recall (see eMedicine Recalls and Alerts 7/20/07) for Colleague and Flo-Gard volumetric infusion pumps to include an additional 986 Colleague infusion pumps. Models of the infusion pumps affected by the recall include the following: Colleague Mono (Product code 2M8151 and 2M8153) Colleague CX (Product code 2M8161 and 2M8163) Flo-Gard 6201 (Product code 2M8063) Flo-Gard 6301 (Product code 2M8064) The products were recalled because Baxter identified falsified data sheets for repair, inspection, and testing (including electrical safety data). As a result, pumps sent to be serviced, repaired, or corrected were possibly returned without receiving service. More information is available at FDA MedWatch. Moricizine (Ethmozine) Discontinued From Market Shire Pharmaceuticals has announced that they will discontinue moricizine (Ethmozine) because of diminished market demand. Supplies of moricizine will diminish over the next several months, and no generic version is available. Physicians should contact patients currently taking moricizine to evaluate alternative forms of antiarrhythmic therapy. Moricizine is indicated for the treatment of documented ventricular arrhythmias (eg, sustained ventricular tachycardia) that in the judgment of the physician are life-threatening. Caution is advised when moricizine is tapered at the same time that another antiarrhythmic drug is initiated because of possible additive pharmacologic effects. Please refer to important safety information in the prescribing information. During the tapering process, patients are at high risk for life-threatening arrhythmias. Because of this high risk, a cardiologist should initiate moricizine tapering and withdrawal with close patient monitoring in place. More information is available at FDA MedWatch. Restricted Use of Tegaserod (Zelnorm) Permitted The US Food and Drug Administration (FDA) is permitting restricted use of tegaserod (Zelnorm) under a treatment investigational new drug (IND) protocol. The treatment IND allows tegaserod administration in women younger than 55 years who have irritable bowel syndrome (IBS) with constipation or chronic idiopathic constipation (CIC). Its use is further restricted to those in critical need who have no known or preexisting heart disease. Information regarding the treatment IND is available from Novartis Pharmaceuticals Corp at (888) 669-6682. Earlier this year, tegaserod marketing was suspended because of safety analysis findings that revealed an increased risk of heart attack, stroke, and unstable angina in patients treated with tegaserod compared with patients treated with placebo (see eMedicine Recalls and Alerts from March 30, 2007). More information is available at FDA MedWatch. Class I Recall Issued for Baxter Upgraded Colleague Triple Channel Volumetric Infusion Pumps A class I recall has been issued for Baxter Upgraded Colleague Triple Channel Volumetric Infusion Pumps. The model numbers affected by the recall include 2M8153, 2M8163, and 2M9163. The infusion pumps are used to deliver controlled amounts of injectable medications or other fluids by intravenous (IV), intra-arterial (IA), epidural, or other direct routes into the bloodstream. The recall is due to a software problem that causes the newly upgraded pumps to display an error code (16:310:867:0002) and to stop the infusion. The software malfunction has occurred when programmed with all 3 channels simultaneously infusing fluids. Reports of serious injuries associated with this issue due to the pump stopping the infusion and interrupting therapy have been described. All affected triple channel pumps need to be immediately removed from service. Baxter Medical Delivery Services may be contacted at 1 (800) 843-7867. A class I recall is issued when a drug or device has a reasonable probability of causing serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. Class I Recall of Ascencia Contour Blood Glucose Monitoring System A class I recall has been issued for Bayer Ascensia Contour Blood Glucose Monitoring System, Product 7152A. This system is used by patients with diabetes for outpatient measurement of blood glucose and as an aid to monitor blood glucose control. The recall was initiated because the meters reported the wrong measurement units for Canadian users. Instead of mmol/L, which is the appropriate measurement for Canadian users, the meters were reporting mg/dL. This error may cause misinterpretation of the blood glucose results displayed, particularly an overestimation of blood glucose levels. As a result, hypoglycemia may occur if doses of antidiabetic agents are increased based on misinterpreted results. Patients with questions should call Bayer Healthcare at 1 (574) 256-3441. More information is available at FDA MedWatch. Ceftriaxone and Calcium Incompatibility Causes Neonatal Deaths The prescribing information for ceftriaxone (Rocephin, Roche Laboratories Inc) has been updated to include new information that describes the risk associated with concomitant use of calcium or calcium-containing solutions. Fatalities caused by calcium-ceftriaxone precipitants in the lung and kidney have been reported in both full-term and premature neonates. The drug must not be mixed with simultaneously administered with calcium-containing solutions or products, even via separate infusion lines. Ceftriaxone and calcium-containing solutions or medications were administered via different routes and at different times in some fatal cases. Additionally, calcium-containing solutions or products must not be administered within 48 hours of ceftriaxone administration. The new information has been added to several sections of the prescribing information, including contraindications, warnings, dosage and administration, directions for use, and compatibility and stability. More information is available at FDA MedWatch. Ertapenem (Invanz) Recalled A recall has been issued for ertapenem injection (Invanz, Merck & Co). The affected lots include 0803930, 0803940, and 0803950. All lots have an expiration date of October 2008. The recall was prompted by 2 reports of broken glass pieces in the reconstituted solution for injection. Health care professionals are advised to immediately stop dispensing all products from the affected lots specified above. No other lots are affected by this recall. Ertapenem injection is indicated for the treatment of moderate-to-severe infections including intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, urinary tract infections, and pelvic infections. More information is available at FDA MedWatch. Boxed Warning for Anaphylaxis Added to Omalizumab (Xolair) Prescribing Information A new boxed warning has been added to the prescribing information for omalizumab (Xolair, Genentech, Inc). The US Food and Drug Administration (FDA) had requested that Genentech add a boxed warning in February because of the risk for anaphylaxis. See eMedicine Recalls and Alerts February 21, 2007. Anaphylaxis may occur after the first dose but may also occur beyond one year of regular treatment. The onset of anaphylaxis caused by omalizumab may be delayed for 24 hours or longer. Because of the risk for anaphylaxis, omalizumab should only be administered in a health care setting, where professionals can treat life-threatening anaphylaxis using the appropriate medications and equipment. Following each omalizumab injection, patients should be observed under direct medical supervision before going home. A medication guide has also been developed to inform patients of risks and to help them understand signs and symptoms that require immediate medical attention. More information is available at FDA MedWatch. FDA Investigates Death of Patient With Cystic Fibrosis and Inhaled Colistimethate The United States Food and Drug Administration (FDA) has issued a health advisory concerning the possible connection between inhaled colistimethate and the death of a patient with cystic fibrosis (CF). Colistimethate is FDA-approved for treatment of acute or chronic infections caused by sensitive strains of certain gram-negative bacilli, particularly sensitive strains of Pseudomonas aeruginosa that are a significant problem for patients with CF and for patients with neutropenia and/or immune system compromise. Use as a liquid intended for inhalation via nebulizer is an off-label indication; however, in patients with CF, colistimethate is often mixed with sterile water for injection to form a solution immediately before inhalation via nebulizer. Once mixed with sterile water and a buffer, spontaneous hydrolysis occurs, causing colistimethate to form colistin, the bioactive compound. Polymyxin E1, a component of colistin, is toxic to lung tissue. Premixing colistimethate into an aqueous solution and storing it for longer than 24 hours results in increased concentrations of colistin in solution and increases the potential for lung toxicity. In this circumstance, the lyophilized powder of colistimethate was reconstituted and dispensed by a pharmacy as prescribed in premixed unit dose ready-to-use vials. Once colistimethate is reconstituted, the product breaks down into other chemicals that can damage lung tissue. More information is available at FDA MedWatch. Kawasaki Disease – Link to Vaccine Unclear The prescribing information for rotavirus vaccine (RotaTeq by Merck) has been updated to include information regarding the observation of Kawasaki disease during phase 3 clinical trials and postmarketing surveillance. Six cases of Kawasaki disease were reported during the phase 3 clinical trial. Five cases of Kawasaki disease were reported in 36,150 infants who received the rotavirus vaccine and one case was reported in 35,536 infants who received placebo. Three cases of Kawasaki disease have been reported to the Vaccine Adverse Event Reporting System (VAERS) since the vaccine was licensed on February 3, 2006. No known cause-and-effect relationship between the administration of rotavirus vaccine or any other vaccine and the occurrence of Kawasaki disease has been established. The cases reported to date are not more frequent than what could be expected to occur by coincidence. The US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) will continue to monitor the safety of rotavirus vaccine and all vaccines and encourage that all severe adverse events, including any additional cases of Kawasaki disease, be reported to VAERS. Kawasaki disease is a serious, but uncommon, illness in children with an unknown etiology. It is characterized by an acute febrile vasculitic syndrome that affects the lymph nodes, skin, mouth, and heart. For more information regarding Kawasaki disease, see the second link provided below. More information is available at FDA MedWatch. For additional information: http://www.emedicine.com/ped/topic1236.htm Long Weekend Dietary Supplement Recalled A nationwide recall has been issued for the dietary supplement Long Weekend, a product sold through mail orders and retailers throughout the United States, Puerto Rico, Canada, the United Kingdom, Russia, and China. The recall was prompted because Long Weekend was found to contain undeclared tadalafil, a drug approved by the US Food and Drug Administration (FDA) to treat male erectile dysfunction (ED). Tadalafil is known to interact with nitrates found in some prescription drugs (eg, nitroglycerin) and may lower blood pressure to dangerous levels. Long Weekend is not approved by the FDA; therefore, the safety and effectiveness of this product is unknown. Consumers should discontinue use of Long Weekend and consult their health care provider about approved treatments for ED. More information is available at FDA MedWatch. Proper Intravenous Sterile Technique Emphasized for Propofol The US Food and Drug Administration (FDA) has informed health care providers that several groups of patients have experienced chills, fever, and body aches shortly after the administration of propofol (Diprivan) for sedation or general anesthesia. Multiple vials and several lots of propofol used in patients who experienced these symptoms were tested, and no evidence has suggested that the propofol vials or the prefilled syringes used were contaminated with bacteria or endotoxins. Propofol is an intravenous sedative-hypnotic agent indicated for induction and maintenance of anesthesia or sedation. Propofol is available as an oil-in-water emulsion. The potential for bacterial contamination can be minimized by using propofol vials and prefilled syringes within 6 hours of opening. Each vial should be used for one patient only. Patients who develop fever, chills, body aches, or other symptoms of acute febrile illness shortly after propofol administration should be evaluated for bacterial sepsis. Careful handling and aseptic technique are essential in avoiding bacterial contamination of intravenous products. Failure to use aseptic technique when handling propofol has resulted in microbial contamination that has resulted in fever, infection, sepsis, life-threatening illness, and death. For more information, see the prescribing information for propofol provided in the second link below. More information is available at FDA MedWatch. For additional information: http://www.fda.gov/cder/foi/label/2007/019627s045lbl.pdf Class I Recalled Issued for Troponin-1 Immunoassay A class I recall has been issued for Architect Stat Troponin-1 Immunoassay. The assay is used to diagnose myocardial infarction in people with chest pain. A small number of clinical laboratories reported inconsistent or invalid test results at the lower levels of troponin-1 detection (ie, <0.1 ng/mL). Falsely elevated or falsely decreased results at and near this low level were observed, making diagnosis difficult to interpret and thereby affecting patient treatment. Laboratories are advised to be cautious when reporting results at or near the lower limit of detection and to advise physicians ordering the tests about the possibility of inaccurate test results at those levels. More information is available at FDA MedWatch. Class 1 Recall Issued for CustomCornea LASIK Algorithm for Myopathy A class I recall has been issued for Alcon Refractive Horizons LADAR6000 Excimer Laser System for CustomCornea algorithm for myopia with astigmatism (M3) and myopia without astigmatism (A7). This system is used for LASIK and wavefront-guided LASIK treatment for the reduction or elimination of mild-to-moderate nearsightedness (myopia) and farsightedness (hyperopia) with or without astigmatism or for mixed astigmatism. The recall was prompted because use for myopia with and without astigmatism caused corneal abnormalities (central islands) and decreased visual sharpness (visual acuity) in patients. These central islands may not be correctable with lasers, and the decrease in visual acuity may not be correctable with glasses or contact lenses. A Class I recall is issued when a drug or device has a reasonable probability to cause serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. Similac Special Care Premature Infant Formula With Iron Recalled A nationwide recall has been issued for Similac Special Care Ready-to-Feed Premature Infant Formula with Iron (2 ounce, 24 calories/fluid ounce). The formula is specifically used for premature infants following hospital discharge. The recall was issued because the affected lots do not contain as much iron as indicated on the label. The recall affects 3 lots distributed in the United States between November 2006 and May 2007. The recall is limited to stock code number 59582 with lot numbers 46815D5, 47847D5, or 52023D5 printed on the outside carton and case and the lot numbers 44427X8, 4427X81, or 50005X8 printed on the bottom of the bottles. No other liquid or powdered Similac infant formulas are affected. More information is available at FDA MedWatch. Contact Lens Solution Recalled A recall has been issued for Complete MoisturePlus Multipurpose Contact Lens Solution manufactured by Advanced Medical Optics. The solution is used for soft contact lenses. The United States Centers for Disease Control and Prevention (CDC) identified an association between Complete MoisturePlus Multipurpose Contact Lens Solution and reports of a rare but serious eye parasitic infection, Acanthamoeba keratitis. Acanthamoeba keratitis has been known to cause vision loss, and, in some patients, a corneal transplant is required. The infection affects otherwise healthy people who wear contact lenses. Acanthamoeba keratitis infections are estimated to occur in about 2 of every 1 million contact lens users in the United States each year. In a multistate investigation conducted by the CDC to assess a recent increase in Acanthamoeba keratitis infections, the risk for infection was discovered to be at least 7 times greater for consumers who used Complete MoisturePlus Solution versus those who did not. Additional information regarding these results is available at the CDC Web site in the second link provided below. Consumers who possess the solution may call the company at (888) 899-9183. Consumers should stop using the solution, discard all partially used or unopened bottles, and replace their lenses and storage container. More information is available at FDA MedWatch. For additional information: http://www.cdc.gov/ncidod/dpd/parasites/acanthamoeba/index.htm FDA Halts Marketing of Unapproved Guaifenesin Products The United States Food and Drug Administration (FDA) is taking action against drug manufacturers marketing unapproved guaifenesin timed0release products. Guaifenesin is an expectorant that is commonly used for cough and cold symptoms. Approximately 20 firms make timed-released guaifenesin products that have not undergone FDA review and as a result are considered unapproved drugs. Immediate release forms of guaifenesin are not affected. Timed-release drugs require FDA approval because the FDA must ensure that the product releases its active ingredients safely and effectively, sustaining the intended effect over the entire time in which the product is intended to work. To date, only Adams Respiratory Therapeutics has obtained FDA approval for timed-release guaifenesin products (600 milligrams and 1200 milligrams) under the trade names of Mucinex and Humibid. These include over-the-counter products containing guaifenesin alone (Mucinex, Humibid), with the decongestant pseudoephedrine (Mucinex-D), and with the cough suppressant dextromethorphan (Mucinex-DM). More information is available at FDA MedWatch. Class I Recall Issued for All EnDura Products A Class I recall has been issued for all EnDura No-React Dural Substitute (EnDura) products. These products are manufactured by Shelhigh Inc and distributed by Integra. The recall was prompted by a notification from the United States Food and Drug Administration (FDA) that cited manufacturing concerns including sterility. All EnDura products that may remain from the first shipment date by Integra in 2003 to present are affected by the recall. A Class I recall is issued when a drug or device has a reasonable probability to cause serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. Boxed Warning Requested by FDA for Gadolinium-Based Contrast Agents The US Food and Drug Administration (FDA) has requested that prescribing information for gadolinium-based contrast agents be updated to include a boxed warning regarding the risk of nephrogenic systemic fibrosis (NSF). The FDA has evaluated reports of the association between gadolinium-based contrast agents and NSF since June 2006. Please refer to previous eMedicine Alerts from June 8, 2006, and January 2, 2007. The updated prescribing information describes the risk for NSF following exposure to gadolinium in patients with acute or chronic severe renal insufficiency (ie, glomerular filtration rate [GFR] <30 mL/min/1.73 m2) and in patients with any acute renal dysfunction caused by hepatorenal syndrome or experienced during the perioperative liver transplantation stage. Gadolinium-based contrast media should be avoided in these patients unless diagnostic information is vital and is not able to be attained using non–contrast-enhanced MRI. Gadolinium-based contrast agents approved for use in MRI include gadopentetate dimeglumine (Magnevist), gadobenate dimeglumine (MultiHance), gadodiamide (Omniscan), gadoversetamide (OptiMARK), and gadoteridol (ProHance). For more information regarding NSF, see the second link provided below. More information is available at FDA MedWatch. For additional information: http://www.emedicine.com/derm/topic934.htm Cases of Fatal Renal Failure and Cytopenias Reported With Deferasirox (Exjade) Prescribing information for deferasirox (Exjade by Novartis) had been changed to include adverse events of acute renal failure and cytopenias (eg, agranulocytosis, neutropenia, thrombocytopenia). Some of the cases of renal failure and cytopenias resulted in death. Deaths from renal failure were most often reported in patients with advanced stages of hematologic disorders and with multiple comorbidities. The relationship of these adverse events to deferasirox treatment is uncertain. Most of the patients experiencing these adverse events also had preexisting hematologic disorders that are frequently associated with bone marrow failure. Additionally, cases of leukocytoclastic vasculitis, urticaria, and hypersensitivity reactions, including anaphylaxis and angioedema, were reported. Deferasirox is indicated for chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients aged 2 years or older. Recommended monitoring parameters include measuring baseline serum creatinine before initiating deferasirox, and then monthly thereafter. Patients who are at increased risk of complications, have preexisting renal conditions, are elderly, have comorbid conditions, or are receiving nephrotoxic drugs should be monitored weekly for the first month, then monthly thereafter. Consider dose reduction, interruption, or discontinuation for elevated serum creatinine level. Monitor urine protein level monthly. Blood counts should also be monitored regularly, and treatment should be interrupted in patients who develop unexplained cytopenia. More information is available at FDA MedWatch. Meta-analysis Raises Question Regarding Increased Myocardial Infarction Risk With Rosiglitazone (Avandia) The United States Food and Drug Administration (FDA) is alerting patients and health care professionals of rosiglitazone (Avandia by GlaxoSmithKline) potentially causing an increased risk of myocardial infarction (MI) and heart-related deaths. Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity. The drug is highly selective and a potent agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing blood glucose concentrations and reducing hyperinsulinemia. GlaxoSmithKline recently provided the FDA with a meta-analysis containing 42 randomized, controlled clinical trials that compared rosiglitazone to either placebo or other antidiabetic therapies in patients with type 2 diabetes. Nissen and Wolski, authors of the meta-analysis, suggest that short-term (ie, approximately 6-months duration) treatment with rosiglitazone may increase MI risk and other heart-related adverse events by 30-40% compared with placebo or other antidiabetic therapy. The meta-analysis was published online today in the New England Journal of Medicine with an accompanying editorial (see second link provided below). The article will appear in the June 14, 2007, issue of The New England Journal of Medicine. Other published and unpublished data from long-term clinical trials of rosiglitazone have not demonstrated this risk. An interim analysis of data from the RECORD trial (a large, ongoing, randomized open label trial) and unpublished reanalyses of data from DREAM (a previously conducted placebo-controlled, randomized trial) provide contradictory evidence regarding rosiglitazone’s risks. Additionally, rosiglitazone and other potent PPAR-gamma agonists have been shown to increase the incidence of edema (see link to Avandia’s prescribing information provided below). Diabetic patients are already at an increased risk of heart disease. Patients currently taking rosiglitazone, particularly those known to have underlying heart disease or those at high risk for MI, should discuss and evaluate available treatment options for their type 2 diabetes with their physician. The FDA has not yet confirmed meta-analysis results and will convene with an FDA Advisory Committee to further analyze the significance of the risk in the context of other studies. More information is available at FDA MedWatch. For additional information: http://www.nejm.org   http://us.gsk.com/products/assets/us_avandia.pdf Citrated Caffeine Powder Recalled A nationwide recall has been issued for 3 lots of purified citrated caffeine powder manufactured by Spectrum. The lots affected by the recall include TS0225, UK0821, and V11203. Complaints of suboptimal potency initiated the recall. Citrated caffeine is a cerebral and respiratory stimulant used primarily to treat apnea in premature infants. Following administration, caffeine blood levels were found to be significantly lower than would be expected. Respiratory depression associated with apnea of prematurity is unlikely to respond to subtherapeutic caffeine blood levels. Customers should examine their inventory, discontinue compounding and dispensing the product, quarantine the affected lots, and call Spectrum to arrange to return the product for credit or replacement. Contact information for Spectrum Customer Service is listed in the link provided below. More information is available at FDA MedWatch. Shark Cartilage Capsules Recalled A nationwide recall has been issued for 3 lots of Shark Cartilage Capsules manufactured in 2004 by NBTY Inc. The capsules were distributed to consumers through mail orders, Internet orders, and retail stores throughout the United States. The recall was issued because of possible contamination with Salmonella bacteria. Salmonella is known to cause serious and sometimes fatal infections, particularly in young children, frail or elderly individuals, or those who are immunocompromised. Otherwise healthy individuals infected with Salmonella typically have symptoms that include fever, diarrhea, nausea, vomiting, or abdominal pain. In rare instances, Salmonella may cause sepsis that leads to severe infections (eg, infected aneurysms, endocarditis, arthritis). Shark cartilage is considered an alternative agent, and its proposed actions include analgesia, anti-inflammatory, and antiangiogenesis. No illnesses have been reported. The recall was issued following routine product testing. Tests on additional batches did not show evidence of contamination. The product can be returned to the place of purchase for a full refund. Specific products included in the recall are listed in the link provided below. More information is available at FDA MedWatch. True Man and Energy Max Products Illegal and Possibly Harmful The United States Food and Drug Administration (FDA) has alerted consumers and health care professionals of the dangers associated with use of True Man or Energy Max products promoted and sold as dietary supplements throughout the United States. These products are promoted as enhancing sexual performance and as treatment of erectile dysfunction (ED). They are illegal drug products that contain potentially harmful, undeclared ingredients. The undeclared ingredients may interact with nitrates found in some prescription drugs, such as nitroglycerin, and may lower blood pressure to dangerous levels. Both products contain either a thione analog of sildenafil, the active ingredient in Viagra, or a piperadino analog of vardenafil, the active ingredient in Levitra. Both Viagra and Levitra are FDA-approved products for the treatment of ED. The FDA has not approved True Man and Energy Max; therefore, the safety and effectiveness of these products are unknown. Consumers should discontinue use of these products and consult their health care professional about approved treatments for ED. More information is available at FDA MedWatch. OxyContin Manufacturer Pays Fine of $700 Million for Felony Misbranding The United States Food and Drug Administration (FDA) announced that the Purdue Frederick Company has plead guilty to a felony count of misbranding and will pay a fine exceeding $700 million for criminal charges and civil liabilities in connection with several illegal schemes to promote, market, and sell oxycodone (OxyContin). Oxycodone is a potent narcotic analgesic manufactured by Purdue Frederick. A long-term investigation by the FDA’s Office of Criminal Investigations (OCI) discovered the manufacturer's sales force was trained to make false claims about the product to health care professionals, thereby, misbranding OxyContin by illegally promoting the drug as being less addictive, less subject to abuse, and less likely to cause tolerance and withdrawal than other pain medications. These practices falsely promote the product and may cause health risks for consumers. More information is available at FDA MedWatch. FDA Warns Manufacturers and Pharmacists of Glycerin Contaminant The United States Food and Drug Administration (FDA) has issued a warning about using glycerin contaminated with diethylene glycol (DEG) for compounding medications. DEG is poisonous. DEG is used in antifreeze and as a solvent. Glycerin is a sweetener that is commonly used in liquid over-the-counter and prescription drug products. At this time, the FDA does not believe that the US supply of glycerin is contaminated with DEG, although contamination of glycerin from other countries over the past several years has caused human deaths. Because of the severe toxicity that DEG imparts, the FDA emphasizes the importance of testing glycerin for contamination. The FDA has supplied industry with guidelines recommending testing methods and other control measures to identify DEG contamination before using glycerin for manufacture or preparation of pharmaceuticals. More information is available at FDA MedWatch. Troponin I Reagent Pack Recalled A nationwide recall has been issued for Vitros Immunodiagnostic Products Troponin I Reagent Pack (manufactured by Ortho-Clinical Diagnostics). Lot numbers affected by the recall include 3151 and 3170. The recall was initiated after a small number of clinical laboratories reported shifts in troponin I quality control results. These results detected the potential for false-negative troponin I results at very low levels. Troponin I is typically ordered with other cardiac tests to detect heart attack or injury to the heart muscle. A false-negative test result indicates that a heart attack or heart muscle injury has not occurred, when in fact it has. Lots affected by the recall were distributed to clinical laboratories within and outside the United States between January and March 2007. Laboratories should immediately discontinue using any affected lots and notify health care professionals who ordered the test in recent weeks. More information is available at FDA MedWatch. ApothéCure’s Compounded Injectable Colchicine Recalled An immediate recall has been issued for all strengths, sizes, and lots of colchicine injection compounded by ApothéCure that have been sold within the last year. The recall was prompted by recent deaths associated with the use of compounded injectable colchicine 0.5 mg/mL in 4-mL vials with the lot number 20070122@26. If you have this product, immediately discontinue use and return any remaining product to the company. More information is available at FDA MedWatch. FDA Proposes Warning for All Antidepressants Regarding Suicidality in Young Adults The United States Food and Drug Administration (FDA) has proposed that manufacturers of all antidepressant medications update the existing black box warning within the product prescribing information to include risks of suicidal thinking and behavior in young adults aged 18-24 years during the first 1-2 months of treatment. The proposed labeling also includes information that scientific data did not show this increased risk in adults older than 24 years and that suicidality risk decreases in older adults (ie, >65 y) on antidepressants. Individuals currently taking prescribed antidepressant medications should not discontinue their medication; they should contact their health care professional if they have questions. Manufacturers of antidepressant medications will have 30 days to submit their revised product labeling and revised Medication Guides to be reviewed by the FDA. More information is available at FDA MedWatch. Multiple Web Sites Suspected of Providing Counterfeit Prescription Drugs The United States Food and Drug Administration (FDA) is reminding consumers and health care professionals of the risk of purchasing prescription drugs from Internet Web sites. The FDA has received information showing that 24 Web sites may be involved in distributing counterfeit prescription drugs. The Web sites are apparently related to one another and are suspected of being operated from outside the United States. In recent months, 3 circumstances have occurred where consumers obtained counterfeit versions of orlistat (Xenical) 120-mg capsules (a prescription drug for weight loss by Hoffmann-LaRoche) from 2 different Web sites. Instead of receiving Xenical, consumers received sibutramine (Meridia by Abbott Laboratories), which is another prescription drug for weight loss. Although Meridia is also indicated for weight loss, it is an entirely different molecular entity and works by a different pharmacologic action than Xenical. Meridia is a schedule IV narcotic that acts by inhibiting norepinephrine, serotonin, and dopamine reuptake in the CNS. Xenical acts by binding gastric and pancreatic lipases, thereby blocking fat hydrolysis and absorption. Meridia should not be used in certain patient populations because it may interact with a variety of drugs (eg, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors) and may increase blood pressure and/or pulse rate. Other samples of drug products obtained from 2 of the Internet orders contained no active drug, only talc and starch; they displayed a valid Roche lot number for Xenical, but an incorrect expiration date. Consumers should be suspicious if unable to contact the Web site pharmacy by phone, if prices are dramatically lower than the competition, or if a prescription from their doctor is not required. Consumers are urged to review the FDA Web page (see second link provided below) for information prior to making purchases of prescription drugs from Web site providers. The Web sites from which the counterfeit drugs were obtained are listed in the link to the FDA provided below. More information is available at FDA MedWatch. For additional information: http://www.fda.gov/buyonline FDA Issues Permanent Injunction Against PharmaFab The US Food and Drug Administration (FDA) announced the entry of a Consent Decree of Permanent Injunction against PharmaFab Inc, its subsidiary, PFab LP, and two company officials, to stop the illegal manufacture and distribution of prescription and over-the-counter drug products. The products are deemed illegal because they are not produced according to the required current good manufacturing practice (CGMP) and many also lack required FDA approval. The consent decree requires the defendants to destroy certain illegal drugs, and bars them from distributing all drugs until they obtain required FDA approval and fully comply with CGMP. Compliance with CGMP is necessary to ensure that drugs have the requisite safety, identity, strength, quality, and purity. PharmaFab is a major contract manufacturer and distributor of more than 100 different prescription and over-the-counter drug products, including cough and cold products, ulcer treatments, and postpartum hemorrhage products. Consumers who have products manufactured by PharmaFab should consult with their physician. Some of the affected products are listed in the link provided below. More information is available at FDA MedWatch. ResMed Continuous Positive Air Pressure (CPAP) Generators Recalled A worldwide recall has been issued for ResMed Continuous Positive Air Pressure (CPAP) S8 flow generators. The generators are used for treatment of obstructive sleep apnea. The recall was issued because of the potential for the power supply connector to short circuit. ResMed is working with its distribution partners globally to provide a replacement device to patients who have an affected S8 flow generator. Patients may continue to use their S8 flow generators until they receive a replacement device; however, they should discontinue use if any signs of electrical failure (eg, intermittent power, cracking sounds, sparking, charred smell) occur. Supplemental oxygen should not be used with a recalled device. Patients using supplemental oxygen should immediately contact their home health care provider for a replacement. Approximately 300,000 SI models manufactured between July 2004 and May 15, 2006, are affected by the recall. Serial number ranges that are included in the recall are listed below. 20040285613 to 20060269563 20060275728 to 20060276751 20060277160 to 20060277415 20060281672 to 20060281991 20060283424 to 20060283743 20060284896 to 20060285445 20060287568 to 20060290823 20060292360 to 20060294694 20060312361 to 20060312597 20060318692 to 20060319459 20060325074 to 20060327794 20060330588 to 20060331043 More information is available at FDA MedWatch. Tracheoesophageal Fistula in Small-Cell Lung Cancer Treated With Bevacizumab (Avastin) New information has been released regarding the development of tracheoesophageal (TE) fistula with bevacizumab (Avastin by Genentech Inc) use for lung and esophageal cancers. A recent multicenter, nonrandomized, single-arm phase II trial in patients with limited-stage small-cell lung cancer (SCLC) combined chemotherapy and radiation plus bevacizumab. Two confirmed serious adverse events of TE fistula (one fatal) were reported in the first 29 patients enrolled in this study. A third, fatal event (upper aerodigestive tract hemorrhage and death of unknown cause), was also reported, in which TE fistula was suspected but not confirmed. All 3 events occurred during the bevacizumab maintenance phase of the study and appeared as persistent esophagitis. Limited data exist in the published literature regarding rate of TE fistula in patients with limited-stage SCLC, but it is estimated to be less than 1%. The incidence of TE fistula observed in this trial to date exceeds this rate. Additionally, 6 other cases of TE fistula have been reported in other lung and esophageal cancer studies using bevacizumab and chemotherapy alone or with concurrent radiation treatment. Bevacizumab is not FDA-approved for the treatment of SCLC. The current prescribing information includes a description of gastrointestinal tract fistula formation in patients with colorectal cancer and other types of cancer treated with bevacizumab. The bevacizumab prescribing information will be revised to include more detailed information regarding the incidence of all cases of fistula. More information is available at FDA MedWatch. Fluoroquinolones No Longer Recommended for Gonorrhea Treatment in US The Centers for Disease Control and Prevention (CDC) has announced that fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the US. The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP), which showed in 2006, the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001. The data were published in the April 13, 2007, issue of the Morbidity and Mortality Weekly Report (see first link provided below). The CDC has recommended fluoroquinolones (eg, ciprofloxacin, ofloxacin, levofloxacin) as first-line treatments of gonorrhea since 1993; however, over the past several years, as QRNG cases increased steadily, the CDC advised that they were not recommended for treating gonorrhea in various locations and populations. Fluoroquinolones were not recommended as treatment in Hawaii (2000), then California (2002), and most recently, in homosexual men nationwide (2004). Options for treating gonorrhea are now limited to cephalosporin antibiotics. More information and updated guidelines for sexually transmitted diseases can be found at the CDC’s antibiotic-resistant gonorrhea Web site (see second link provided below). For additional information: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5614a3.htm   http://www.cdc.gov/std/gonorrhea/arg/ FDA Seizes Implantable Medical Devices from Shelhigh Inc The US Food and Drug Administration (FDA) investigators and US Marshals have seized all implantable medical devices from Shelhigh Inc (Union, NJ) because of significant deficiencies in the company's manufacturing processes. The deficiencies that were found may compromise the safety and effectiveness of the products, particularly their sterility. The products include pediatric heart valves and conduits, surgical patches, dural patches, annuloplasty rings, and arterial grafts. The tissue-based devices are used in many surgical settings, including open heart surgery in adults, children, and infants; they are also used to repair soft tissue during neurosurgery and abdominal, pelvic, and thoracic surgery. Critically ill patients, pediatric patients, and immunocompromised patients may be at greatest risk from the use of these devices. Medical devices manufactured by Shelhigh include the following: Shelhigh Pericardial Patch Shelhigh No-React Pericardial Patch Shelhigh No-React PneumoPledgets Shelhigh No-React VascuPatch Shelhigh No-React Tissue Repair Patch/UroPatch Shelhigh Pulmonic Valve Conduit No-React Treated Shelhigh No-React Dura Shield Shelhigh BioRing (annuloplasty ring) Shelhigh No-React EnCuff Patch Shelhigh No-React Stentless Valve Conduit Shelhigh Internal Mammary Artery Shelhigh Gold perforated patches Shelhigh Pre Curved Aortic Patch (Open) Shelhigh NR2000 SemiStented aortic tricuspid valve Shelhigh BioConduit stentless valve Shelhigh NR900A tricuspid valve Shelhigh MitroFast Mitral Valve Repair System Shelhigh BioMitral tricuspid valve Shelhigh Injectable Pulmonic Valve System More information is available at FDA MedWatch. Premature Battery Depletion Prompts ICDs and CRT-Ds Worldwide Recall A recall has been issued for certain models of Contak Renewal 3 and 4, Vitality, and Vitality 2 implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-Ds). The ICDs and CRT-Ds are manufactured by Guidant Corporation (Cardiac Rhythm Management division of Boston Scientific Corp). The recall was initiated because of faulty capacitors within the affected ICDs and CRT-Ds. The faulty capacitors may malfunction, leading to premature battery depletion. The battery depletion may reduce the time between when the elective replacement indicator signals battery replacement and the end of battery life to less than 3 months. As of March 30, 2007, Boston Scientific confirmed 19 adverse events with the Guidant devices, of which most were due to premature battery depletion. No serious injuries or deaths were reported. Although the current recall is similar to a recall of pacemakers and ICDs in 2006, the failure modes and patient outcomes for this recall differ. Patients with one of the recalled devices should contact their health care provider regarding the next steps to take. The recall includes about 73,000 ICDs and CRT-Ds that were distributed worldwide. The following device models are affected by the recall in the US. To check if models not listed below are affected by the recall, please refer to second link provided below. Contak Renewal 3 HE CRT-Ds (Models H177 and H179) Contak Renewal 3 CRT-Ds (Models H170 and H175) Vitality 2 DR ICDs (T165) Vitality 2 VR ICDs (T175) Vitality AVT ICDs (A155) Vitality DS DR ICDs (T124) Vitality EL Dr ICDs (T135) More information is available at FDA MedWatch. Potent CYP1A2 Inhibitors Contraindicated With Tizanidine (Zanaflex) The prescribing information for tizanidine (Zanaflex) has been changed to include new information regarding drug interactions. Tizanidine is indicated for muscle spasticity caused by spinal cord injury. Recent studies have found that when tizanidine was coadministered with fluvoxamine (Luvox) or ciprofloxacin (CYP1A2 inhibitors), tizanidine’s serum concentration was significantly increased and hypotensive and sedative effects were potentiated. Use of fluvoxamine or ciprofloxacin is now contraindicated with tizanidine. Coadministered with other CYP1A2 inhibitors such as zileuton (Zyflo), other fluoroquinolones (eg, levofloxacin), antiarrhythmic agents (eg, amiodarone), cimetidine (Tagamet), famotidine (Pepcid), oral contraceptives, acyclovir (Zovirax), or ticlopidine (Ticlid) should also be avoided. More information is available at FDA MedWatch. Granular Psyllium Products Deemed Unsafe by FDA The US Food and Drug Administration (FDA) has issued a final ruling stating OTC granular-based bulk laxatives containing psyllium are not generally recognized as safe and effective and are misbranded. This latest ruling follows incidents of esophageal obstruction associated with use of the granular dosage form of psyllium laxatives. These adverse incidents continue despite efforts promoting safe use through label warnings and directions to take with plenty of fluids and not to exceed dosage recommendations. This final order does not apply to psyllium-containing laxative products in other dosage forms (eg, powders, tablets, wafers). Manufacturers will be allowed time to reformulate the granular-based psyllium products to other dosage forms. More information is available at FDA MedWatch. Griseofulvin Oral Suspension (Grifulvin V) Recalled A nationwide recall has been issued for griseofulvin oral suspension (Grifulvin V by Ortho Dermatological and Patriot Pharmaceuticals). The recall was initiated because of 2 reports of glass fragments found in bottles of the liquid formulation. Griseofulvin is a prescription medication used to treat ringworm and other fungal infections. Consumers should contact the pharmacy where they purchased griseofulvin to determine if they have the product that has been recalled and direct medical questions to their healthcare professional. Lot numbers affected by the recall can be viewed at the second link provided below. More information is available at FDA MedWatch. For additional information: http://www.aboutgrifulvin.com./recall.asp#lot Combivir Bottles With Counterfeit Labels Contain Ziagen GlaxoSmithKline and the US Food and Drug Administration (FDA) have been informed of an apparent third-party tampering that used counterfeit labels for the combination product of lamivudine and zidovudine (Combivir). The counterfeit labels resulted in the misbranding of abacavir (Ziagen) as lamivudine and zidovudine (Combivir). Both medications are used as part of combination regimens to treat HIV-positive infection. Two 60-count misbranded bottles of Combivir Tablets contained 300-mg tablets of Ziagen. The counterfeit labels identified are Lot No. 6ZP9760 with expiration dates of April 2010 and April 2009. The incident appears to be isolated and limited in scope to one pharmacy in California. Pharmacists should immediately examine the contents of each bottle of Combivir in their pharmacy to confirm that the bottles contain the correct medication. More information is available at FDA MedWatch. FDA Enforces Withdrawal of Trimethobenzamide Suppositories The US Food and Drug Administration (FDA) has notified companies selling unapproved suppositories containing trimethobenzamide to cease manufacturing and distribution. These products are used to treat nausea and vomiting in adults and children. The products have been marketed under various names, including Tigan, Tebamide, T-Gen, Trimazide, and Trimethobenz. Drugs containing trimethobenzamide in suppository form lack evidence of effectiveness. This action does not affect oral capsules and injectable products containing trimethobenzamide that have been approved by the FDA. Consumers who currently use trimethobenzamide suppositories or have questions or concerns should contact their healthcare professional. Alternative products approved to effectively treat nausea and vomiting are available in a variety of forms. This announcement is part of the FDA’s initiative to ensure that marketed drugs in the US are approved and meet efficacy and safety standards. More information is available at FDA MedWatch. Tegaserod (Zelnorm) Withdrawn From Market Because of Cardiovascular Risks The United States Food and Drug Administration (FDA) has issued a Public Health Advisory announcing the withdrawal of tegaserod (Zelnorm) from the market. Tegaserod is indicated for short-term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation. The market withdrawal was prompted by the analysis of safety data pooled from 29 clinical trials involving more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, heart attacks, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients and placebo by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Thirteen patients treated with tegaserod (0.1%) had serious and life-threatening cardiovascular adverse effects; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication. Patients taking tegaserod should contact their healthcare professional to discuss treatment alternatives and seek emergency medical care if they experience severe chest pain, shortness of breath, sudden onset of weakness or difficulty walking or talking, or other symptoms of a heart attack or stroke. Health care professionals should assess their patients and transition them to other therapies as appropriate. For patients whom no other treatment options are available, the benefits of tegaserod treatment may outweigh the chance of serious adverse effects. The FDA is considering allowing limited access to tegaserod through a special program or the possibility of reintroducing the drug to the market through a special access program. More information is available at FDA MedWatch. Pergolide Withdrawn From US Market Companies that manufacture and distribute pergolide (Permax and generic equivalents) have announced they will withdraw the drug from the US market. Pergolide is a dopamine agonist (DA) used with levodopa and carbidopa to manage the signs and symptoms of Parkinson disease. Two recently published studies showed that some patients with Parkinson disease treated with pergolide developed cardiac valve regurgitation compared with patients who did not receive the drug. These two studies confirm earlier studies that also describe this heart valve damage. The studies were published in the New England Journal of Medicine (Schade R, Andersohn F, Suissa S, et al. N Engl J Med 2007;356(1):29-38, and Zanettini R, Antonini A, Gatto G, et al. N Engl J Med2007;356(1):39-46). The abstracts for these studies are in the 2nd and 3rd links provided below. It is important not to abruptly stop pergolide. Health care professionals should assess their patient's need for DA therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. More information is available at FDA MedWatch. For additional information: http://content.nejm.org/cgi/content/abstract/356/1/29   http://content.nejm.org/cgi/content/abstract/356/1/39 DermaFreeze365 Products Recalled Because of Bacterial Contamination A recall has been issued for all lots of DermaFreeze365 Instant Line Relaxing Formula and DermaFreeze365 Neck and Chest products. The recall was prompted because certain lots tested positive for Pseudomonas aeruginosa bacteria. The bacteria may cause serious eye infections, urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gastrointestinal infections, and a variety of systemic infections. Patients who have severe burns, cancer, AIDS, or other immunosuppressive disease are particularly vulnerable. The product is often applied topically around the eye, and inadvertent application in the eye could result in serious eye infections and, in rare circumstances, possible blindness. More information is available at FDA MedWatch. FDA Urges Consumers Not to Buy Isotretinoin (Accutane) Over Internet The United States Food and Drug Administration (FDA) has launched a special Web page to warn about the dangers of buying isotretinoin (Accutane) or generic isotretinoin versions (eg, Amnesteem, Claravis, Sotret) online. Isotretinoin is a drug approved for the treatment of severe acne that does not respond to other forms of treatment. If the drug is improperly used, it can cause severe adverse effects, including birth defects. Serious psychological problems (eg, mood changes, depression, suicidality) have also been reported with isotretinoin use. The Web page will appear in online search results for isotretinoin. The Web page warns that the drug should only be taken under the close supervision of a physician or a pharmacist and provides links to helpful information. The new Web page is in addition to special safeguards put in place by the FDA and manufacturers of isotretinoin to reduce the risks of the drug, including a risk management program called iPLEDGE. The aim of iPLEDGE is to ensure that women using isotretinoin do not become pregnant and that women who are pregnant do not use isotretinoin. More information is available at FDA MedWatch. For additional information: http://www.fda.gov/buyonline/accutane   http://www.fda.gov/cder/drug/infopage/accutane/default.htm Mislabeled Denervation Probes Prompt Class I Recall A Class I recall has been issued for Smith & Nephew, Inc, Radiofrequency Denervation Probes. The probes are used with the Smith & Nephew Electrothermal 20S Spine System indicated to relieve chronic pain. The product was incorrectly labeled as a sterile item. The probes are reusable and must be sterilized before the initial use and resterilized before each subsequent use. The mislabeled probes could result in infections, associated infection risk, organ failure, and/or death. A Class I recall is issued when a drug or device has a reasonable probability to cause serious adverse health risks, including death, to some users. The following are included in this recall. Part number 7210270 associated with lot numbers 602549 602550 602846 602847 Part number 7210271 associated with lot numbers 602541 602542 602556 602557 602558 602559 602560 602561 602562 602848 602849 602999 Part number 7210272 associated with lot numbers 602543 602570 602571 602850 603000 More information is available at FDA MedWatch. Linezolid -Associated Mortality Increased With Gram-Negative Infections New safety concerns have emerged from a recent clinical study about linezolid (Zyvox). An open-label, randomized trial compared linezolid to vancomycin, oxacillin, or dicloxacillin for treatment of intravascular catheter-related bloodstream infections including those with catheter-site infections. Patients treated with linezolid had a higher chance of death than patients treated with any comparator antibiotic, and the chance of death was related to the type of organism causing the infection. Patients infected with gram-positive organisms had no difference in mortality according to their antibiotic treatment; however, in patients treated with linezolid, mortality was higher in those who were infected with gram-negative organisms alone, in those who were infected with both gram-positive and gram-negative organisms, or in those who had no infection when they entered the study. Linezolid is not approved for the treatment of catheter-related bloodstream infections, catheter-site infections, or infections caused by gram-negative bacteria. If infection with gram-negative bacteria is known or suspected, appropriate therapy should be started immediately. Linezolid is approved for the treatment of vancomycin-resistant Enterococcus faecium infections; nosocomial pneumonia; community-acquired pneumonia; uncomplicated skin and skin structure infections; and complicated skin and skin structure infections (without concomitant osteomyelitis), including diabetic foot infections. More information is available at FDA MedWatch. Recalled Supplements Contain Tadalafil (Cialis) Analogue A nationwide recall has been issued for supplement products sold under the names Rhino Max (Rhino V Max, by Cosmos Trading, Inc) and V.MAX (by Barodon SF). Lab analysis by the United States Food and Drug Administration (FDA) found the products contained aminotadalafil, an analogue of tadalafil (Cialis), an FDA-approved drug used to treat erectile dysfunction (ED). The FDA states that this poses a threat to consumers because aminotadalafil 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. Consumers who have any of these products in their possession should stop using it immediately and contact their physician if they experienced any problem that may be related to taking this product. More information is available at FDA MedWatch. Changes Requested for Prescribing Information of Sedative-Hypnotic Drugs The United States Food and Drug Administration (FDA) has requested that the prescribing information for sedative-hypnotic drugs that are indicated to help induce and/or maintain sleep, strengthen their warnings concerning potential risks. These risks include severe allergic reactions (eg, anaphylaxis, angioedema) and complex sleep-related behaviors, which may include sleep-driving (ie, driving while not fully awake after ingesting a sedative-hypnotic, with no memory of the event), making phone calls, or preparing and eating food. In addition to the revisions to the prescribing information, the FDA has also requested that each product manufacturer send letters to health care providers regarding the new warnings and develop Patient Medication Guides to inform consumers about risks and advise them of precautions that can be taken. More information is available at FDA MedWatch. Erythropoiesis Stimulating Agents—New Boxed Warning New safety information for erythropoiesis-stimulating agents (ESAs) has prompted changes to the prescribing information including a new boxed warning, updated warnings, and changes to the dosage and administration sections. The changes apply to all ESAs (ie, darbepoetin alfa [Aranesp], epoetin alfa [Epogen, Procrit]). Four new studies in patients with cancer using ESAs found a higher chance of serious and life-threatening adverse effects or death. These research studies were evaluating an unapproved dosing regimen, a patient population for which ESAs are not approved, or a new unapproved ESA. Because ESAs have similar mechanisms of action, the United States Food and Drug Administration (FDA) believes the new warnings apply to all ESAs and is re-evaluating how to safely use this product class. The FDA has published a public health advisory describing information for patients, important study results, and information for physicians to consider when prescribing ESAs. Patients should be informed of the following. A higher chance of death and an increased rate of tumor growth were reported in patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain hemoglobin levels >12 g/dL. A higher chance of death was reported and no fewer blood transfusions were received when ESAs were given to patients with cancer and anemia not receiving chemotherapy. A higher chance of death was reported and an increased number of blood clots, strokes, heart failure, and heart attacks was reported in patients with chronic kidney failure when ESAs were given to maintain hemoglobin levels of more than 12 g/dL. A higher chance of blood clots was reported in patients who were scheduled for major surgery and given ESAs. ESAs are not approved for treatment of the symptoms of anemia, such as fatigue in patients with cancer, surgical patients and patients with HIV. Important study results include the following. Patients with chronic kidney failure had an increased number of deaths and of non-fatal heart attacks, strokes, heart failure, and blood clots when ESAs were adjusted to maintain higher red blood cell levels (hemoglobin more than 12 g/dL). Patients with head and neck cancer receiving radiation therapy had faster tumor growth when ESAs were adjusted to maintain hemoglobin levels higher than 12 g/dL. Patients with cancer not receiving chemotherapy died sooner and had no fewer blood transfusions when ESAs were given according to the dosing recommendations for cancer patients receiving chemotherapy. Patients scheduled for orthopedic surgery who received ESAs to reduce blood transfusions during and after surgery had more blood clots than those not given an ESA. Physicians who prescribe ESAs should consider the important study results above and the following information. Adjust the dose of ESA to maintain the lowest hemoglobin level necessary to avoid the need for transfusions. Monitor patients’ hemoglobin levels to ensure they do not exceed 12 g/dL. Understand that ESAs are given to decrease the chances of receiving transfusions. Understand that ESAs have not been shown to improve the outcomes of chemotherapy treatment (eg, better tumor shrinkage, delay in tumor growth, longer time for survival). Consider both the risks of transfusions and those of ESAs when deciding to prescribe an ESA. Understand that ESAs should not be given to treat the symptoms of anemia, including shortness of breath, dizziness, fatigue, low energy, or poor quality of life. FDA-approved uses of ESAs Treatment of anemia in patients with chronic kidney failure, Treatment of patients with cancer whose anemia is caused by chemotherapy Treatment in patients with HIV whose anemia is caused by zidovudine (AZT) Reduction of the number of blood transfusions in patients scheduled for major surgery (except heart surgery) For detailed information of recent warnings leading to these changes, see related eMedicine Recalls and Alerts from November 17, 2006, January 27, 2007, and February 16, 2007. More information is available at FDA MedWatch. Pioglitazone and Fracture Risk Takeda, the manufacturer of pioglitazone-containing products (Actos, ACTOplus met, Duetact), has recently completed an analysis of the clinical trial database of pioglitazone. The analysis results showed more reports of fractures in female patients taking pioglitazone than those taking other diabetes therapies or placebo. Most of the reported fractures were in the distal upper limb (ie, forearm, hand, wrist) or distal lower limb (ie, foot, ankle, fibula, tibia). More than 8100 patients were in the pioglitazone-treated groups, and more than 7400 patients were in the comparator-treated groups. The duration of pioglitazone treatment was up to 3.5 years. This corresponds to almost 12,000 patient-years exposure per group. The calculated incidence for fracture was 1.9 fractures per 100 patient-years in the pioglitazone-treated group and 1.1 fractures per 100 patient-years in the comparator-treated group. The explanation for this finding is currently not known. None of the pioglitazone studies in the analyzed database were designed to study effects on bone, but incidents of fracture were collected as adverse events. A recently published study (A Diabetes Outcome and Progression Trial [ADOPT]) also observed an increase risk for fractures in women taking a different thiazolidinedione (rosiglitazone [Avandia]). For more information, see eMedicine Recalls and Alerts from February 20, 2007. Health care professionals should consider the risk of fracture when initiating or treating female patients with type 2 diabetes mellitus with pioglitazone. More information is available at FDA MedWatch. Study Treating Idiopathic Pulmonary Fibrosis With Interferon Gamma-1b Terminated Early The INSPIRE clinical trial to treat idiopathic pulmonary fibrosis (IPF) with interferon gamma-1b (Actimmune by InterMune) has been halted because interim analysis did not show beneficial results. The trial compared survival in patients receiving interferon gamma-1b or placebo. The results revealed that 14.5% of patients treated with interferon gamma-1b died compared with 12.7% of patients treated with placebo. Interferon gamma-1b is not FDA-approved to treat IPF; however, some patients with IPF may be receiving interferon gamma-1b as an off-label drug. More information is available at FDA MedWatch. Class I Recall for Automatic External Defibrillators (AEDs) Defibtech, LLC, and the United States Food and Drug Administration (FDA) have issued a class I recall for Lifeline and ReviveR automatic external defibrillators (AEDs). The recall affects 42,000 Lifeline and ReviveR AEDs with software versions 2.002 or earlier. The AEDs have been distributed worldwide. AEDs are used to treat cardiac arrest. The defibrillator delivers a shock to the heart to restore normal heart rhythm. Prior to delivering the shock, the device analyzes the patient’s heart rhythm to determine if a shock is appropriate. The recall was prompted by inaccuracy of the self-test software, which may allow a self-test to clear a detected low battery condition. The operator may be unaware of the low battery and the device may not deliver a defibrillation shock, resulting in resuscitation failure. Defibtech is aware of 3 circumstances of malfunction reported by users. The company has provided a maintenance procedure that can be used to verify functionality of the device until the free software upgrade has been installed, thereby allowing continued temporary use of the AED. The devices were distributed to schools, fire and EMS, businesses, health clubs, and hospitality companies. A Class I recall is issued when a drug or device has a reasonable probability to cause serious adverse health risks, including death, to some users. More information is available at FDA MedWatch. ReNu MultiPlus Contact Lens Solution Recalled A global recall has been issued for 12 lots of Bausch & Lomb’s contact lens solution, ReNu MultiPlus, because of elevated trace iron levels. As a result, a potential loss of effectiveness may result before the product’s 2-year expiration date. No reports of serious adverse events associated with the affected lots have been received. Bausch & Lomb believe virtually all the affected product, manufactured about a year ago, have already been used by consumers. Twelve lot numbers are included in the recall. The recalled lots all carry the expiration date “2008 – 03” on the bottle. Consumers who have lots affected by the recall may check the company’s web site provided below or contact consumer affairs at (866) 259-8255 to arrange a replacement or refund. GC6030 GC6037 GC6038 GC6045 GC6048 GC6052 GC6061 GC6063 GC6072 GC6073 GC6080 GC6085 More information is available at FDA MedWatch. Salivart Oral Moisturizer Recalled A nationwide recall has been issued for Salivart Oral Moisturizer (by Gebauer Company). Some lots do not meet specifications for aerobic bacteria and mold. Use of the affected lots may cause nausea, vomiting, or diarrhea. Customers who have the recalled product should stop using the product and dispose of it immediately and call Gebauer Company Customer Service (800) 321-9348. Lot numbers affected by the recall Lot Number Pattern Expiration Date Initial Ship Date 06AA001 06-08 09-11-06 06AA002 06-08 10-05-06 06AA003 06-08 10-26-06 06AA004 07-08 11-16-06 06AA005 07-08 12-14-06 06AA006 10-08 01-10-07 More information is available at FDA MedWatch. FDA Halts Illegal Drugs for Migraine Headaches The Food and Drug Administration (FDA) has contacted 20 companies that are marketing unapproved drug products containing ergotamine tartrate. Ergotamine is used to treat vascular headaches, including migraines. Eight manufacturers and 12 distributors have received a warning from the FDA that they are subject to further enforcement action if they do not stop manufacturing and distributing these products. The companies have 15 days to respond and 60 days to cease manufacturing. In addition to marketing these products without FDA approval, most of the companies receiving warning letters have omitted critical warnings from their drugs’ prescribing information regarding the potential for serious, possibly fatal, interactions with certain other drugs. The 5 marketed, approved versions of ergotamine-containing products have updated their labeling to include a box warning (the strongest agency warning) against using ergotamine when also taking potent CYP 3A4 inhibitors, including some antifungal agents, protease inhibitors, and certain antibiotics. This interaction can pose serious and life-threatening ischemia, including death and gangrene. Most unapproved versions of the drug do not carry these warnings. Patients with questions regarding their ergotamine product should contact their physician or pharmacist. A list of the companies affected by this warning can be viewed in link provided below. More information is available at FDA MedWatch. FDA Publishes Recommendations for Endoscope Washer and Disinfector The US Food and Drug Administration (FDA) has published a public health notice regarding endoscope washer and disinfector systems. Please see eMedicine Recalls and Alerts from February 7, 2007, regarding the alert. FDA recommendations and guidelines are outlined in the link provided below. More information is available at FDA MedWatch. HBV Treated With Entecavir (Baraclude) Linked to HIV Resistance in HIV/HBV Coinfected Patients Not Receiving HAART Bristol-Myers Squibb has revised the prescribing information for entecavir (Baraclude). The revised labeling is the result of a case report in which a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during entecavir treatment of chronic hepatitis B virus (HBV) infection in an HIV/HBV coinfected patient who was not simultaneously receiving highly active antiretroviral therapy (HAART). There have been 3 reported cases of HIV/HBV coinfected patients not receiving HAART in whom a 1-log10 has been noted while receiving entecavir as chronic HBV treatment. Current HIV treatment guidelines recommend entecavir as an option for treatment of HBV in HIV/HBV coinfected adult patients not qualifying for HAART (see second link provided below). Entecavir has not been evaluated in HIV/HBV coinfected patients who were not simultaneously receiving effective HIV treatment. Health care professionals are advised that when considering therapy with entecavir in an HIV/HBV coinfected patient not receiving HAART, the risk of developing HIV resistance cannot be excluded based on current information. Entecavir is a nucleoside analogue that is not active against HIV and is indicated to treat chronic hepatitis B virus infections in adults. This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naive and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease and on more limited data in adult subjects with HIV/HBV coinfection who have received prior lamivudine therapy. More information is available at FDA MedWatch. Increased Incidence of Acute Rejection in Heart Transplant Recipients with Mycophenolate and Sirolimus Combination Therapy A higher than expected incidence of acute rejection in heart transplant recipients has been observed when patients are switched from calcineurin inhibitors (eg, tacrolimus, cyclosporine) in combination with mycophenolate mofetil (CellCept) to sirolimus (Rapamune) in combination with mycophenolate mofetil. This observation has led to the termination of the clinical trial, the Heart Spare the Nephron (STN). The study found that, when switched from calcineurin inhibitors (CNI) at 12 weeks post heart transplantation, an increased incidence of grade IIIA acute rejection was observed. The intent of the Heart STN clinical trial was to investigate whether renal function impairment could be avoided when CNI therapy was withdrawn and sirolimus was initiated. All patients received corticosteroids in addition to the other antirejection agents. Fifteen patients were randomized to 1 of 2 study arms. All patients were initiated on mycophenolate mofetil, a CNI, and corticosteroids. At 12 weeks post transplantation, 8 patients remained on the initial regimen. Of the 7 patients randomized to the sirolimus, mycophenolate mofetil, and corticosteroid arm, 4 experienced a grade IIIA rejection within 5 weeks of discontinuing CNI therapy. Three of the 4 rejection episodes occurred at one center in the United States. Three of these patients responded well to treatment with corticosteroids, and the fourth patient recovered after experiencing hemodynamic compromise. No cases of graft loss occurred. No similar episodes of rejection occurred in patients receiving the calcineurin-based regimen (ie, CNI, mycophenolate mofetil, corticosteroids). More information is available at FDA MedWatch.