Special Alerts

Gemtuzumab: Voluntary Market Withdrawal - June 2010

Pfizer Inc, in conjunction with the U.S. Food and Drug Administration (FDA), is voluntarily withdrawing gemtuzumab (Mylotarg®) from the U.S. market after results from a recent post-approval clinical trial failed to demonstrate a clinical benefit. The trial, which was designed to determine if there was a benefit to adding gemtuzumab to chemotherapy, also demonstrated an increased number of deaths in patients receiving gemtuzumab, compared to those receiving chemotherapy alone. Additionally, postmarketing data have shown an increased incidence of a serious and potentially fatal liver condition, veno-occlusive disease (VOD).

Healthcare providers should inform all patients receiving gemtuzumab of the potential safety risk. Patients who are currently receiving gemtuzumab may complete their therapy following consultation with their healthcare provider. Gemtuzumab will not be commercially available to new patients. Any future gemtuzumab use in the U.S. will require a submission of an investigational new drug application to the FDA.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation....

Angiotensin II Receptor Blockers (ARBs) and Cancer Risk - June 2010

McNeil Consumer Healthcare has expanded previous recalls to include specific lots of certain additional OTC products. For additional information and a full list of the recalled product lots, please refer to http://www.mcneilproductrecall.com.

Consumers may also contact the manufacturer at 1-888-222-6036.

Angiotensin II Receptor Blockers (ARBs) and Cancer Risk - June 2010

A meta-analysis of angiotensin II receptor blockers (ARBs) was conducted assessing effect of ARBs on the incidence of new cancers, with a secondary outcome assessing cancer-related mortality (Sipahi, 2010). The analysis involved publicly available data from 9 randomized controlled trials, each with follow up of =12 months and =100 patients. The ARBs included in the analysis were candesartan, losartan, valsartan, and telmisartan. It is postulated that the renin-angiotensin aldosterone system may have a role in the regulation of cell proliferation, tumor growth and angiogenesis; ARBs could thereby have an effect on the risk of new cancer by antagonizing the renin-angiotensin system. While not able to extract an exact risk of cancer for each ARB, data for telmisartan, which most patients in the meta-analysis had received, demonstrated a risk of new cancers (relative risk [RR] 1.07, 95% CI 1.00-1.14; p=0.05). The data for losartan, which included a single trial, did not demonstrate a significant risk for cancers in general, however, the data did demonstrate a significant risk of lung cancer (RR 2.41, 95% CI 1.23-4.71; p = 0.01). While data for new cancers was not available for candesartan, mortality due to cancer was significantly higher in one clinical trial (2.3% vs 1.6%, p=0.038). Although further investigation is warranted, the authors conclude that the meta-analysis demonstrated an increased risk (modest) in the occurrence of new cancer, with a statistically significant increase in the risk for lung cancer. It is unknown whether or not other ARBs (eprosartan, irbesartan, or olmesartan) are associated with a similar risk.

At this point, patients should not stop taking their ARB in light of this information unless told to do so by their healthcare professional.

Vitamin D Supplements (Liquid Formulations): Potential for Dosing Errors - June 2010

The U.S. Food and Drug Administration (FDA) is alerting healthcare providers and consumers of the potential for dosing errors with liquid vitamin D preparations (eg, cholecalciferol and ergocalciferol) when given to infants. Some manufacturers provide droppers with liquid vitamin D products and, in some cases, the droppers could potentially allow for overdose in infants. Excess vitamin D may be harmful to infants, resulting in nausea, vomiting, constipation, abdominal pain, loss of appetite, polydipsia, polyuria, muscle weakness, muscle/joint pain, confusion, and fatigue. Serious events such as renal damage may also occur. The FDA has advised manufacturers providing droppers to assure that the droppers are clearly marked to easily provide 400 international units. Additionally, for products intended for infants, the FDA recommends that accompanying droppers deliver no more than 400 international units per dose.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Olmesartan: Study Suggesting Possible Increased Risk of Death in Type 2 Diabetics - June 2010

The U.S. Food and Drug Administration (FDA) is alerting healthcare providers on the ongoing safety review of olmesartan and its potential to increase the risk of death when used for blood pressure management in patients with type II diabetes.

The FDA will be evaluating data from two studies: ROADMAP (The Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study) and ORIENT (The Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial). Both studies were randomized, double-blind, placebo-controlled trials consisting of type II diabetic patients receiving olmesartan therapy to slow the development of kidney disease. An unexpected finding in both trials was an increased number of deaths due to cardiovascular events (eg, heart attack, stroke) in patients receiving olmesartan compared to placebo. In ROADMAP, cardiovascular deaths occurred in 15 patients receiving olmesartan compared to 3 patients receiving placebo. In ORIENT, cardiovascular deaths occurred in 10 patients receiving olmesartan compared to 3 patients receiving placebo.

The FDA has not concluded that olmesartan increases the risk of death and believes that the benefits of its use outweigh the potential risks. Angiotensin II receptor blockers have previously been evaluated in studies involving patients with a high risk for cardiovascular events. There have been no reports of an increased risk for cardiovascular-related deaths in these trials. Some of these studies have also indicated that angiotensin II receptor blockers are useful treatments for certain patients at high risk for cardiovascular events. Therefore, patients should continue olmesartan therapy unless otherwise directed by a healthcare professional.

Any suspected adverse events should be promptly reported to MedWatch at 800-332-1088 or http://www.fda.gov/medwatch.

Further information may be found at http://www.fda.gov/Safety/MedWatch...

Mold Contamination of Metronidazole, Ondansetron, and Ciprofloxacin Intravenous Products - Updated June 2010

The U.S. Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) are warning healthcare professionals to prohibit use of all lots of metronidazole, ondansetron, and ciprofloxacin I.V. bags manufactured by Claris Lifesciences Limited. These products are sold under the following labels: Claris, Sagent Pharmaceuticals, Pfizer, and West-Ward Pharmaceuticals.

Health Canada has issued a similar warning to Canadian practitioners regarding all lots of ciprofloxacin 2 mg/mL I.V. bags (100 and 200 mL) manufactured by Claris and distributed in Canada by BioSyent Pharma Inc. The Canadian packaging for these products bears both the BioSyent and Claris names.

Concerns of floating materials in these products, including evidence of mold (Cladosporium spp) contamination, have prompted the recall of these products by Claris. Clinicians are urged to discontinue use of these specific products and carefully monitor any patients who may have received them for signs of infection. In the U.S., any suspected adverse events should be promptly reported to MedWatch at 800-332-1088 or http://www.fda.gov/medwatch. In Canada, suspected adverse events should be promptly reported to BioSyent Pharma Inc, at 888-439-0013 or Canada Vigilance Program at 866-234-2345.

For more information, healthcare professionals may refer to the following websites:

U.S.: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety...

Canada: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2010/ciprofloxacin_nth-aah-eng.pdf

Gammagard Liquid: Market Withdrawal of Certain Lots Due to Adverse Events Reported - June 2010

Baxter BioScience and the Food and Drug Administration (FDA) are notifying healthcare professionals of a voluntary market withdrawal of 2 lots of Gammagard Liquid due to an increased frequency of reports of allergic reactions associated with the affected lots.

Customers should contact Baxter BioScience for Urgent Market Withdrawal instructions.

For information regarding the withdrawal, including the lots affected, refer to http://www.fda.gov/BiologicsBloodVaccines...

Varenicline: Canadian Product Labeling Updated, Health Canada Issues Notice - June 2010

Pfizer Canada, in conjunction with Health Canada, has issued a "Dear Healthcare Professional" letter informing Canadian practitioners of recent updates to the varenicline Canadian product monograph. The Canadian labeling has been updated with:

• A Boxed Warning related to neuropsychiatric adverse events
• Warnings of rare reports of hypersensitivity reactions (eg, angioedema) and serious dermatologic reactions (eg, Stevens-Johnson syndrome, erythema multiforme)
• Addition of an "Information for Patients" section which provides advice to clinicians on sharing information with patients before and during therapy
• New dosing options (0.5-1 mg twice daily).

As a result of postmarketing case reports of neuropsychiatric events (eg, loss of consciousness, seizures, dizziness), patients should be advised to refrain from potentially dangerous activities (eg, driving, operating heavy machinery) until they know how varenicline therapy might affect them. Patients should also be advised to discontinue varenicline treatment immediately with onset of neuropsychiatric symptoms or atypical behavior, or if they experience signs/symptoms of severe skin/hypersensitivity reactions. Caregivers should be advised to monitor patients for such symptoms/reactions.

Further information may be found at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2010/champix_2_hpc-cps-eng.pdf

Mold Contamination of Metronidazole, Ondansetron and Ciprofloxacin Intravenous Products - June 2010

The U.S. Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) are warning healthcare professionals to prohibit use of all lots of metronidazole, ondansetron and ciprofloxacin I.V. bags manufactured by Claris Lifesciences Limited. These products are sold under the following labels: Claris, Sagent Pharmaceuticals, Pfizer, and West-Ward Pharmaceuticals. Concerns of floating materials in these products, including evidence of mold (Cladosporium spp.) contamination, have prompted the recall of these products by Claris. Clinicians are urged to discontinue use of these specific products and carefully monitor any patients who may have received them for signs of infection. Any suspected adverse events should be promptly reported to MedWatch at 800-332-1088 or http://www.fda.gov/medwatch.

For more information, U.S. healthcare professionals may refer to the following website: http://www.fda.gov/Safety/MedWatch/SafetyInformation...

PediaCare® OTC Products: Voluntary Recall of Certain Products - June 2010

Blacksmith Brands, in conjunction with the U.S. Food and Drug Administration (FDA), has issued a voluntary and precautionary recall of all lots of four PediaCare® children's products distributed solely in the United States: PediaCare® Multi-Symptom Cold, PediaCare® Long Acting Cough, PediaCare® Decongestant, and PediaCare® Allergy and Cold. The affected lots were manufactured by McNeil Consumer Healthcare at a facility in Fort Washington, PA. This facility was recently cited by the FDA for failure to meet good manufacturing practices, resulting in a similar recall of several McNeil Consumer brands of infant's and children's OTC products. The plant has been temporarily shut down due to these violations.

Consumers who have purchased the recalled products are advised to discontinue their use and discuss alternative treatment options with their healthcare provider. Consumers may also contact the manufacturer at 888-474-3099 or at http://www.blacksmithbrands.com.

Further information including a complete listing of products affected by this recall may be found at http://www.fda.gov/Safety/Recalls/ucm214005.htm.

Orlistat: Liver-Related Adverse Events and Ongoing Safety Review - Revised May 2010

The U.S. Food and Drug Administration (FDA) announced completion of their review of liver-related adverse events reported with orlistat. The FDA has identified 13 total reports of severe liver injury associated with orlistat (12 foreign reports with Xenical®; 1 U.S. report with Alli™). At the present time, a causal association of severe liver injury with orlistat has not been established. However, due to the serious nature of severe liver injury, the FDA has approved a revised label for Xenical® and Alli™ which includes safety information about these rare cases of severe liver injury reported with the use of orlistat.

In August 2009, the FDA announced the safety review of orlistat. The review was prompted by 32 reports of serious liver-related adverse events submitted to the FDA between 1999 and October 2008. Liver injury was commonly reported as jaundice, weakness, and abdominal pain, and included 6 cases of liver failure; 30 of the 32 reports cases occurred outside of the U.S.

Although a definite relationship has not been established, the FDA is recommending that healthcare professionals weigh the benefits of weight loss with the potential risks associated with orlistat before prescribing or recommending orlistat to their patients. Patients currently receiving therapy should continue taking orlistat as directed. However, patients should stop use of orlistat and report any signs/symptoms associated with liver injury (eg, fatigue, fever, jaundice, brown urine, nausea, vomiting, abdominal pain) to a healthcare professional.

For more information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Possible Increased Risk of Fractures (Hip, Wrist, and Spine) with Proton Pump Inhibitor (PPI) Use - May 2010

The U.S. Food and Drug Administration (FDA) is revising all prescription and over-the-counter labels for proton pump inhibitors (PPI) with information regarding an increase in the risk of fractures (hip, wrist, and spine). This information is based on several epidemiologic studies. The greatest risk for these fractures was in patients who received high doses or used them for ≥1 year. The majority of the patients in the epidemiologic studies were ≥50 years of age with the risk of fractures being limited to this age group.

The FDA recommends that healthcare providers continue to prescribe, and patients continue to use these products as described within their labeling. In addition, healthcare providers should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition. Patients who continue to receive PPIs and who are at risk for osteoporosis, should receive vitamin D and calcium supplementation and have their bone status monitored and managed according to current practice standards. Patients should not stop taking their proton pump inhibitor unless told to do so by their healthcare provider.

For more information, U.S. healthcare professionals may refer to the following website: http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Tramadol: Prescribing Information Changes - May 2010

Ortho-McNeil-Janssen Pharmaceuticals, Inc and the U.S. Food and Drug Administration (FDA) have notified healthcare professionals of changes previously made to the Warnings section of the prescribing information for tramadol (Ultram®) and tramadol/acetaminophen (Ultracet®). A risk of suicide exists for patients taking tramadol who are also addiction-prone and/or taking tranquilizers or antidepressant drugs. In addition, the labeling also warns of interactions with alcohol and drugs of abuse; misuse, abuse, and diversion; and the risk of overdose.

For more information, U.S. healthcare professionals may refer to the following FDA website: http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Thyrogen®: Potential Foreign Particle Contamination - Updated May 2010

On May 24, 2010, the U.S. Food and Drug Administration (FDA) agreed to allow Genzyme to produce enough Thyrogen® to meet the needs of U.S. patients for whom the FDA deems the drug to be medically necessary. Genzyme may only distribute the drug to those customers (ie, distributors and wholesalers) who sign a Certificate of Procedures Related to Medical Necessity. This certificate states that the customer agrees to distribute the product with a Dear Healthcare Provider Letter describing the terms of medical necessity. To help identify patients who meet the criteria of medical necessity for Thyrogen®, the FDA has developed specific criteria. To access these criteria, the healthcare professional is referred to the following website: http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm213008.htm.

Previously, Genzyme and the FDA had issued a notice to healthcare professionals regarding the potential contamination of certain lots of Thyrogen® (lot numbers beginning with the letter "A" [eg, Lot A12345]). Particulate matter (eg, stainless steel fragments, non-latex rubber from the vial stopper, and fiber-like material from the manufacturing process) had been discovered in some products. Because thyroid hormone withdrawal, an alternative treatment modality to the use of Thyrogen®, may not be suitable for all patients, the FDA had decided to allow the continued marketing of Thyrogen®; though several reconstitution and administration recommendations were made and/or emphasized to reduce the likelihood of a patient receiving contaminated product. Healthcare providers were advised to (in addition to current recommendations in the drug labeling):

• Visually inspect the powder in the vial for particulate matter prior to reconstitution.
• Visually inspect the solution following reconstitution for particulate matter.
• Do not administer products with visualized particulate matter.
• Monitor patients for adverse effects following administration.

Further information regarding the previous FDA alert may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation....

Natalizumab: Health Canada Issues Update Regarding Incidence of Progressive Multifocal Leukoencephalopathy - May 2010

Health Canada has issued a "Dear Healthcare Professional" letter alerting clinicians that the risk of developing progressive multifocal leukoencephalopathy (PML) with natalizumab (Tysabri®) therapy increases with an increasing duration of therapy. As of April 6, 2010, 46 confirmed cases of PML have been reported worldwide. In patients receiving >24 infusions, the incidence of PML is 1.59 per 1000 patients (95% CI 1.11-2.21) versus ~1 per 1000 patients observed in clinical trials. Following 24 natalizumab infusions, the risks and benefits of continuing therapy should be re-evaluated with the patient. Experience with natalizumab therapy >36 months is limited and the risk for PML can not be reliably estimated.

The Canadian product monograph and consumer information have been updated with this most recent PML information. Patients receiving natalizumab in Canada must be enrolled in the Tysabri Care Program™. This program provides information regarding prescribing, administration and monitoring of patients receiving natalizumab therapy.

For additional information, refer to the following website:

Canada: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2010/tysabri_3_hpc-cps-eng.pdf

Maalox® Liquid OTC Products: Potential for Medication Errors - Updated May 2010

The U.S. Food and Drug Administration (FDA) and Health Canada, have independently issued warnings to their respective healthcare providers and consumers regarding serious medication errors that have occurred with Maalox® products containing bismuth subsalicylate. Bismuth subsalicylate is found in Maalox® Total Relief (U.S.) and Maalox® Multi Action (Canada) and due to similarities in labeling, name, and/or packaging, consumers have inadvertently used these products as antacids, instead of traditional Maalox® liquid antacid products containing aluminum hydroxide, magnesium hydroxide, and simethicone. Bismuth subsalicylate may cause bleeding and should not be used in children or teens recovering from a viral infection, pregnant women during the third trimester, patients with a salicylate allergy, a history of a bleeding disorder, gastrointestinal ulcer disease, taking anticoagulants, antiplatelet agents (eg, clopidogrel), NSAIDS, and/or oral antidiabetic medications.

When consulting with patients/consumers, healthcare professionals are encouraged to refer to Maalox® products by their full names or by the active ingredient name(s). Healthcare providers and consumers should check all labels of Maalox® products to ensure the appropriate product is selected. In the U.S., the manufacturer of Maalox® products has agreed to remove the name "Maalox" from their Maalox® Total Relief (bismuth subsalicylate) product, revise the product labeling to help distinguish the active ingredients, set-up an educational program to inform healthcare providers and consumers of the differences in Maalox® products, and monitor safety and adverse event reports associated with Maalox® products. The renamed Maalox® Total Relief product is not expected to be available until September 2010.

In Canada, proposed changes by the manufacturer include a new name for Maalox® Multi Action and a new product label design to better differentiate it from other Maalox® liquid products. The planned changes are expected to be phased in during 2010.

Further information may be found at the following websites:

U.S.: http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Canada: http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/maalox_hpc-cps-eng.php

Rotavirus Vaccination: FDA Updates Recommendations - May 2010

The U.S. Food and Drug Administration (FDA) has updated recommendations regarding the use of rotavirus vaccines (Rotarix®, RotaTeq®). After reviewing laboratory findings from their respective manufacturers (GSK, Merck), as well as its own laboratories, the FDA has determined it is safe to resume the use of Rotarix® rotavirus vaccine and to continue the use of RotaTeq® rotavirus vaccine. The FDA had previously suspended use of Rotarix® while it further investigated the presence of porcine circovirus DNA found in the vaccine. Subsequently, fragments of DNA from porcine circovirus 1 (PCV1) and porcine circovirus 2 (PCV2) were identified in RotaTeq®. In updating the recommendations, the FDA notes the following:

- It has no evidence that PCV1 or PCV2 poses a safety risk to humans

- Neither PCV1 or PCV2 are known to cause infection or illness in humans.

- Both vaccines have strong safety records.

- Known vaccine benefits outweigh theoretical risks.

The FDA is working with the manufacturers to continue to investigate the findings of PCV in rotavirus vaccines and to update the prescribing information and patient information. The FDA is reminding healthcare professionals to discuss with parents/caregivers the PCV DNA findings and the lack of evidence regarding the potential threat to human safety.

Health Canada also recently issued notice to its citizens and healthcare professionals and is reviewing information regarding the presence of PCV DNA in rotavirus vaccines. Though not announcing specific recommendations regarding use of rotavirus vaccines, the regulatory agency is emphasizing their relative safety and known benefits. Further communication from the regulatory agency will be forthcoming.

Further information may be found at the following websites:

U.S.:

http://www.fda.gov/Safety/MedWatch/Safety...

http://www.fda.gov/BiologicsBloodVaccines/Vaccines...

Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_69-eng.php

Eltrombopag: Portal Venous Thromboses Reported - May 2010

GlaxoSmithKline (GSK) and the U.S. Food and Drug Administration (FDA) notified healthcare professionals of an increased risk of portal venous thrombosis found through an interim analysis of a ongoing trial. The ELEVATE study was conducted to evaluate the safety and efficacy of eltrombopag (75 mg daily for 14 days) in reducing platelet transfusions in thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures. Six patients (4%) in the eltrombopag group and one (1%) in the placebo group experienced a thrombotic event of the portal venous system. Five of the six patients treated with eltrombopag had platelet counts >200,000/mm3 at the time the event occurred. GSK terminated the study to conduct a comprehensive analysis of the study data. Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.

For additional information and a link to the full prescribing information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Rivastigmine: Serious Adverse Events with Transdermal Patch; Health Canada Issues Warning - May 2010

Novartis Canada, in consultation with Health Canada, has issued a "Dear Healthcare Professional" letter to Canadian practitioners, regarding post-market reports of rivastigmine overdose and serious adverse events (including fatalities) due to medication errors/improper use of rivastigmine (Exelon®) transdermal patches. A total of 129 cases (including 2 fatalities) of medication errors/improper use of Exelon® patches have been reported worldwide as of July 31, 2009. In Canada, 3 cases have been reported as of February 28, 2010.

Reported overdoses were most frequently associated with failure to remove an existing patch prior to applying a new patch and application of more than 1 patch at the same time. Patients, caregivers, and/or healthcare providers have been involved in these reported errors. Symptoms reported in association with rivastigmine overdose include respiratory depression, seizures, hypertension, hallucinations, nausea/vomiting/diarrhea, sweating, salivation. Syncope and/or bradycardia may also occur.

Healthcare professionals are being reminded of the importance of proper use and application of Exelon® patches. The manufacturer is also updating the Canadian product monograph, placing an emphasis on the following safety information:

- Prior to initiating therapy, healthcare providers should instruct patients and caregivers on proper use of rivastigmine patches and the need for strict adherence to these instructions.

- Application of only 1 patch per day to intact, healthy skin on the upper arm or chest, or upper or lower back

- After 24 hours, existing patch must be removed prior to applying a new patch to a different skin location.

- Patches should not be cut into pieces.

- In case of overdose, all rivastigmine patches should be immediately removed and the patient evaluated by a physician; no further rivastigmine patches should be applied for the following 24 hours.

Further information may be found at http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2010/exelon_hpc-cps-eng.pdf

GnRH Agonists: FDA Evaluating Possible Increased Risk of Diabetes and Cardiovascular Disease - May 2010

The U.S. Food and Drug Administration (FDA) has issued a notice regarding an ongoing safety review of gonadotropin-releasing hormone (GnRH) agonists (eg, goserelin, leuprolide) for the treatment of prostate cancer and a possible increased risk of diabetes and cardiovascular disease. The FDA is evaluating preliminary data from one randomized, controlled clinical trial, as well as several observational studies. Some of these studies have shown a small, but statistically significant increased risk of diabetes and/or cardiovascular disease in men receiving GnRH agonist therapy versus men receiving alternative therapy for prostate cancer. While acknowledging several limitations to some study designs, the FDA has not concluded that GnRH agonists increase the risk for diabetes and/or cardiovascular diseases in men with prostate cancer.

While the FDA continues to evaluate information as it becomes available, healthcare practitioners are encouraged to:

- Follow prescribing recommendations for GnRH agonists

- Carefully weigh known benefits/risks of GnRH agonists when determining appropriate treatment for prostate cancer

- Monitor patients receiving GnRH agonist therapy for diabetes/cardiovascular events

- Manage cardiovascular risk factors (blood pressure, weight, cholesterol, blood sugar, smoking) according to current clinical practice

Though GnRH agonists may be used in women and children, there are no known comparable studies evaluating this same risk in either of these populations.

Further information may be found at http://www.fda.gov/Drugs/DrugSafety...

Promethazine Injection: Canadian Labeling Updated; Health Canada Issues Notice - April 2010

Health Canada has issued a notice to the Canadian public and healthcare professionals regarding recent updates to the Canadian product monograph for promethazine injection. Labeling revisions include strengthened warnings against use in children <2 years of age and appropriate routes of administration to avoid severe tissue injury.

Further information may be found at the following website: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_58-eng.php

Propylthiouracil-Induced Hepatic Failure - April 2010

As an update to the June, 2009 notice of increased risk of hepatic failure with use of propylthiouracil, the U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the labeling. Since the June report, 2 additional cases (1 adult, 1 child) of acute liver injury have been identified, although neither were fatal.

The new warning highlights the risk of acute hepatic injury and recommends reserving use of propylthiouracil for those who cannot tolerate other treatments (methimazole, radioactive iodine, or surgery). Due to the occurrence of birth defects associated with methimazole use during the first trimester, propylthiouracil may be the treatment of choice during and just before the first trimester of pregnancy. As part of the Risk Evaluation and Mitigation Strategy (REMS), the FDA is requiring that a Medication Guide be given to every patient filling a prescription for propylthiouracil to understand the known benefits and risks of this medication.

Additional information can be found at http://www.fda.gov/Drugs/DrugSafety...

FDA Advisory: Phase Out of MDI Inhalers Containing CFCs - April 2010

Heparin: New USP Standards and Potency Issues - Updated April 2010

In October 2009, the U.S. Food and Drug Administration (FDA) alerted healthcare providers of a change to the United States Pharmacopeia (USP) monograph for heparin. Effective October 1, 2009, a new reference standard for heparin and a new test to determine potency were established to address heparin contamination problems encountered in 2007-2008. The new monograph also harmonized the USP unit with the WHO international standard (IS) unit (ie, international unit). At that time, the FDA estimated a reduction in potency of approximately 10% for heparin marketed in the United States under this new standard. The FDA is now reporting that the original estimation of an approximate 10% reduction in anticoagulant activity has been validated in laboratory studies.

Healthcare providers should be aware that the reduction in potency of heparin products manufactured and tested according the new USP monograph may cause some patients to require more heparin to achieve and maintain a desired level of anticoagulation. Consideration of this reduction in potency is necessary when making dosing decisions. The impact of this change in potency should be less significant when heparin is administered by subcutaneous injection due to low and variable bioavailability.

The FDA has requested that all manufacturers differentiate (from "old" heparin products) heparin products manufactured by the new standards. The labels of products manufactured according to the new standard will have an "N" in the lot number or following the expiration date. Additionally, products manufactured by Hospira may be identified by the number "82" or higher (eg, 83, 84) at the beginning of their lot numbers.

Finally, the FDA summarizes important clinical recommendations to consider during this time of transition to heparin made according to the new USP standards:

- There will be simultaneous availability of heparin manufactured by the "old" and "new" USP standards. These products have differences in potency. Consider not using the "old" and "new" heparin products interchangeably, separating supplies, and/or exhausting any "old" heparin supplies prior to transitioning to the "new" product.

- Consider the reduction in potency when utilizing heparin in situations when aggressive anticoagulation is necessary to treat or prevent life-threatening thrombosis.

- More frequent or intensive aPTT or ACT monitoring may be required.

- The FDA-approved labeling (including dosing) for heparin has not changed. Heparin dosing should always be individualized according to the patient-specific clinical situation. Appropriate clinical judgment is essential in determining heparin dosage.

For additional information, refer to the following websites:

http://www.fda.gov/Drugs/DrugSafety...

www.usp.org

Propofol Shortage - April 2010

Due to the ongoing shortage of propofol, the Food and Drug Administration (FDA) has temporarily authorized the reintroduction of an international propofol 1% product, Fresenius Propoven 1%, into the U.S. market. Clinicians should note that, in addition to the contraindications listed within the FDA-approved labeling, Fresenius Propoven 1% is also contraindicated in patients who are allergic to peanuts.

Additional information may be found at http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm207290.htm

Levodopa, Carbidopa, and Entacapone (Stalevo®): FDA Evaluating Trial Suggesting an Increased Risk for Prostate Cancer - March 2010

The U.S. Food and Drug Administration (FDA) has announced that it is conducting an on-going review of data obtained from a long-term clinical trial in patients with Parkinson's disease suggesting a possible increased risk of prostate cancer in patients treated with levodopa/carbidopa/entacapone (Stalevo®). The double-blind, randomized, parallel group trial, Stalevo Reduction in Dyskinesia Evaluation - Parkinson's Disease (STRIDE-PD), was designed to evaluate the time to onset of dyskinesia in patients receiving Stalevo® compared to patients receiving levodopa/carbidopa. However, an increased incidence of prostate cancer was observed in the 245 male patients receiving Stalevo® (3.7%, 95% CI: 1.69% to 6.86%) compared to the 222 male patients receiving levodopa and carbidopa (0.9%). The reported odds ratio for prostate cancer occurring in males taking Stalevo® was 4.19 (95% CI: 0.90 to 19.63). The treatment duration was 2.6-4 years (mean duration: 2.7 years). Of note, other clinical trials, primarily with shorter treatment durations, have not shown an increased risk of prostate cancer in patients treated with Stalevo®. The FDA has not made any new recommendations or reached any conclusions about the use of Stalevo®.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Rho(D) Immune Globulin Intravenous (Human): Addition of Boxed Warning - Updated March 2010

Cangene Corporation and Baxter Healthcare Corporation have released a "Dear Healthcare Professional" letter regarding the addition of a boxed warning to the WinRho® SDF (Rho[D] immune globulin intravenous [human]) prescribing information. The labeling update was prompted by reports of fatal cases of intravascular hemolysis (IVH) in patients receiving WinRho® SDF for immune thrombocytopenic purpura (ITP). The boxed warning was added to the U.S. product labeling earlier this year. Health Canada, in conjunction with Cangene Corporation, has now issued a similar letter to Canadian practitioners regarding important updates to the Canadian labeling.

IVH can lead to clinically compromising anemia and multisystem organ failure (including acute respiratory distress syndrome). There have been serious complications reported including severe anemia, disseminated intravascular coagulation and acute renal insufficiency/failure. Patients >65 years of age with comorbidities are more likely to experience complications from hemolysis, including fatal outcomes. Neither the U.S. boxed warning nor Canadian labeling update apply to patients receiving WinRho® SDF for the suppression of Rh isoimmunization.

For further information, refer to the following websites:

U.S.: http://www.fda.gov/downloads/BiologicsBloodVaccines...

Canada: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/winrho_2_nth-aah-eng.pdf

Moxifloxacin: Rare Risk of Hepatic Injury; Health Canada Issues Notice - March 2010

Health Canada has issued a notice to Canadian healthcare professionals and citizens regarding a safety-related update to moxifloxacin (Avelox®) Canadian labeling. Following a safety review, Health Canada has concluded that moxifloxacin may be associated with a risk for rare but potentially serious hepatic injury (including hepatic failure). Patients receiving moxifloxacin therapy are advised to discontinue use and contact their healthcare provider immediately with onset of abdominal pain, signs of jaundice (yellowing of eyes and skin), loss of appetite, pale-colored stools, or severe itching.

Further information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_42-eng.php

Rotavirus Vaccination: Temporary Suspension of Rotarix® Use in the U.S. - March 2010

Due to detection of extraneous viral components, the U.S. Food and Drug Administration (FDA) is recommending temporary suspension of immunizations with Rotarix® rotavirus vaccine. DNA components from porcine circovirus 1 (PCV1) have been detected in Rotarix® rotavirus vaccine. Further testing has determined that PCV1 components have been present in Rotarix® rotavirus vaccine since the early development process, including during clinical trials. PCV1 is not known to cause human illness. While there is no evidence that the Rotarix® rotavirus vaccine poses a safety risk at this time, the suspension is recommended as a precautionary measure while the FDA pursues further information regarding the extraneous components. The FDA recommends healthcare providers retain supplies of Rotarix® rotavirus vaccine until further recommendations are made, expected in approximately 4-6 weeks.

Preliminary testing of a second vaccine available for immunization against rotavirus, RotaTeq®, has not detected PCV1 components, and therefore immunization recommendations with RotaTeq® are unaffected. Most children vaccinated for rotavirus in the U.S. have received RotaTeq®. If an infant has received one dose of Rotarix® rotavirus vaccine, the Centers for Disease Control (CDC) advises to complete the immunization series with 2 doses of RotaTeq® rotavirus vaccine.

Additional information may be found at http://www.fda.gov/Safety/MedWatch/Safety...

Simvastatin and Increased Risk of Myopathy - March 2010

The Food and Drug Administration (FDA) is notifying healthcare professionals of the increased risk of myopathy, including rhabdomyolysis, with the use of simvastatin (Zocor®) at the highest FDA-approved dose (80 mg). To evaluate this increased risk, the FDA is reviewing new data from multiple sources, including adverse event reports, observational studies, and clinical trials, as well as the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial. Further information will be available once the FDA completes this review.

For additional information, refer to the following FDA website: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm205215.htm

Reduced Effectiveness of Clopidogrel (Plavix®) in Patients with Poor Metabolizer Status - March 2010

The U.S. Food and Drug Administration (FDA) has added a Boxed Warning to the prescribing information for clopidogrel. Patients with defective CYP2C19 activity (eg, loss of function allele) do not effectively metabolize clopidogrel to the active metabolite and, therefore, may not exhibit adequate platelet inhibition. This may result in increased risk of myocardial infarction, stroke, and cardiovascular death.

The Boxed Warning includes the following information to:

- Warn about reduced effectiveness in patients who are poor metabolizers of clopidogrel

- Inform healthcare professionals that tests are available to identify patients with CYP2C19 loss of function alleles

- Advise healthcare professionals to consider the use of other antiplatelet medications or alternative dosing strategies in patients with poor metabolizer status. Of note, an appropriate dose regimen for patients who are poor metabolizers of clopidogrel has not been established in clinical outcome trials.

Patients should not stop taking clopidogrel in light of this information unless told to do so by their healthcare professional.

For more information, U.S. healthcare professionals may refer to the following website: http://www.fda.gov/Drugs/DrugSafety...

Fentanyl Transdermal Systems: Dose Conversion Guidelines Modified; Health Canada Issues Notice - March 2010

In conjunction with the manufacturers of Fentanyl Transdermal Systems (FTS), Health Canada has issued a notice to Canadian healthcare professionals regarding changes made to the opioid dose conversion guidelines within FTS Canadian labeling.

Healthcare professionals are reminded that dose conversion guidelines are used to convert adult patients with chronic pain from oral or parenteral opioids to FTS only and should not be used to convert FTS to other opioids due to risks of overdose and toxicity.

Further information may be found at http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/fentanyl_2_hpc-cps-eng.php

Isoniazid: Severe Liver Injury in Patients Treated for Latent Tuberculosis - March 2010

The Centers for Disease Control (CDC) recently reported the results of a national project created to monitor severe adverse events associated with the treatment of latent tuberculosis infection (LTBI). The report, published in MMWR, summarizes 17 cases of severe isoniazid-associated liver injury identified by state health departments during 2004-08, and reported via a passive surveillance system. Of the 17 patients identified (15 adults; 2 children ≤15 years of age), 5 patients required liver transplantation, including 1 child. Five of the 15 adult patients died, including 1 liver transplant patient. The adverse events were diagnosed between the second and the ninth month of isoniazid therapy in 16 of the patients.

The MMWR editors emphasize that INH-induced liver injury can occur at any age, and at any time during treatment. The report also recommends that patients be instructed to immediately discontinue isoniazid treatment at the earliest onset of liver injury (eg, nausea, vomiting, abdominal discomfort, unexplained fatigue), and follow up with a healthcare provider for further evaluation. Patients receiving isoniazid therapy for LTBI should be monitored according to American Thoracic Society (ATS)/CDC guidelines, which recommend monthly clinical monitoring, including a brief physical examination.

For additional information, please refer to http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5908a3.htm

FDA-Approved Name Change to Avoid Potential Medication Errors - March 2010

The Food and Drug Administration (FDA) has approved a name change for dexlansoprazole from the brand name Kapidex™ to Dexilant™ to avoid potential confusion with other medications. Since approval of Kapidex™ in January 2009, dispensing errors have occurred when Casodex® (bicalutamide) or Kadian® (morphine sulfate) were incorrectly dispensed in the place of the intended product, Kapidex™.

Beginning in April 2010, Takeda Pharmaceuticals will market dexlansoprazole under the new trade name, Dexilant™.

For additional information, please refer to http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm203096.htm

Saquinavir (Invirase®): Possible Association with Abnormal Heart Rhythms - February 2010

The U.S. Food and Drug Administration (FDA) is reviewing clinical trial data concerning a potentially serious cardiovascular effect from the use of saquinavir (Invirase®) in combination with ritonavir (Norvir®). According to preliminary data from a study submitted by the manufacturer of Invirase® (Roche), the use of these two drugs together may cause a dose-dependent prolongation of the QT and PR intervals. This can cause patients to be at an increased risk for torsade de pointes, heart block, or other arrhythmias.

Healthcare professionals are advised to not use saquinavir combined with ritonavir in patients with a history of QT interval prolongation, cardiomyopathy, preexisting conduction system disease, ischemic heart disease, or underlying structural heart disease. This medication combination should also be avoided in patients currently using Class IA (eg, quinidine) or Class III (eg, amiodarone) antiarrhythmic drugs or other drugs that may prolong the QT or PR interval (eg, verapamil).

The FDA's analysis of these data is ongoing, and the agency will update the public as soon as this review is complete.

For additional information, refer to http://www.fda.gov/Drugs/DrugSafety...

Rosiglitazone (Avandia®): Ongoing Review of Cardiovascular Safety - February 2010

The U.S. Food and Drug Administration (FDA) notified healthcare professionals and patients that it is reviewing primary data from the recently completed RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) study involving rosiglitazone use in patients with type 2 diabetes mellitus. This large, long-term clinical trial was designed to evaluate the cardiovascular safety of rosiglitazone, and compared 2220 patients receiving rosiglitazone (in combination with metformin or a sulfonylurea) with 2227 patients receiving metformin and a sulfonylurea. In addition to the RECORD trial, the FDA continues to review numerous published observational studies evaluating the cardiovascular safety of rosiglitazone.

Available data concerning an association between rosiglitazone and myocardial ischemia are inconclusive; however, a meta-analysis of 42 clinical trials (mean duration 6 months) involving 14,237 patients has found an association with rosiglitazone use and cardiovascular events (angina, myocardial infarction). Three other studies, including the RECORD trial, have not confirmed or excluded a similar risk.

Currently, there are no new conclusions or recommendations by the FDA regarding the use of rosiglitazone in the treatment of patients with type 2 diabetes mellitus. The FDA is reminding healthcare professionals to follow current recommendations in the drug label, including a contraindication of rosiglitazone use in patients with NYHA Class III or IV heart failure, and avoiding use in patients with symptomatic heart failure. All patients should be monitored for signs and symptoms of heart failure (rapid weight gain, difficulty breathing, and/or swelling) after initiation of treatment and after dose increases of rosiglitazone. Discontinuation or dose reduction of the medication may be warranted if these symptoms occur. Patients should understand the risks of rosiglitazone therapy, the risks/benefits of other antidiabetic medications, and the importance of compliance and proper glycemic control.

Once the FDA completes its review of data from the RECORD study, the agency will present a summary of any new and existing cardiovascular safety data on rosiglitazone at the upcoming Advisory Committee meeting in July 2010.

For additional information, refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Deferasirox (Exjade®): Product Labeling Updated, Boxed Warning Added - February 2010

Novartis Oncology, in conjunction with the U.S. Food and Drug Administration (FDA), has distributed a "Dear Healthcare Provider" letter to alert practitioners of recent changes to the prescribing information for Exjade® (deferasirox). The labeling changes include a boxed warning that deferasirox may cause renal impairment/failure, hepatic impairment/failure, and gastrointestinal hemorrhage. Fatalities have also been reported in association with these events. These events have occurred at a higher incidence in patients with high-risk myelodysplastic syndromes (MDS), underlying renal or hepatic impairment, low platelet counts (<50,000/mm3), or in patients of advanced age. Contraindications within the U.S. labeling have been also updated to include patients with creatinine clearance <40 mL/minute or serum creatinine >2 x age-appropriate ULN, patients with poor performance status and high-risk MDS or advanced malignancies, or in patients with platelet counts <50,000/mm3.

The boxed warning also includes certain laboratory monitoring requirements, including a baseline (in duplicate) and monthly serum creatinine and/or creatinine clearance. Levels should be drawn more frequently (weekly) during the first month in patients with underlying renal impairment or with risk factors for renal impairment. In addition, serum transaminases and bilirubin levels should be drawn in all patients prior to initiation, then every 2 weeks for the first month, and monthly thereafter.

Of note, other labeling changes include reports of erythema multiforme occurring during therapy, a recommendation to avoid concomitant administration of cholestyramine and deferasirox, and additional information pertaining to serious adverse events reported with deferasirox use in patients with comorbidities.

Further information may be found at

Long-Acting Beta-Agonists (LABAs): New Safety Requirements - February 2010

The U.S. Food and Drug Administration (FDA) is communicating new changes required for the use of long-acting inhaled medications, called Long-Acting Beta-Agonists (LABAs), for the treatment of asthma. These changes are based on an FDA meta-analysis conducted in 2008, the Salmeterol Multicenter Asthma Research Trial (SMART) and the Salmeterol Nationwide Surveillance study (SNS). These trials reported an increased risk of severe exacerbation of asthma symptoms, leading to hospitalization (as well as deaths) in pediatric and adult patients using LABAs for asthma treatment.

The FDA has determined that the benefits of LABAs for improvement of asthma symptoms outweigh the potential risks when used concomitantly with an asthma-controller medication (ie, inhaled corticosteroid). Therefore, to ensure safe use of LABAs the FDA is recommending the following safety measures:

- Use of single-agent LABAs is contraindicated without the use of an asthma-controller medication.

- LABAs should be used only in patients whose asthma is not adequately controlled on asthma-controller medications.

- LABAs should be used for shortest duration possible to achieve control of asthma symptoms, then discontinued if possible.

- Pediatric and adolescents requiring an LABA should use a combination product (LABA and corticosteroid) to ensure medication compliance.

A Risk Evaluation and Mitigation Strategy (REMS) will include a revised medication guide written specifically for patients, a plan to educate healthcare providers about appropriate use of LABAs, and require the manufacturers to conduct additional clinical trials further evaluating the safety of LABAs in combination with inhaled corticosteroids.

For more information, please refer to http://www.fda.gov/Drugs/DrugSafety...

Maalox® Liquid OTC Products: Potential for Medication Errors - February 2010

The U.S. Food and Drug Administration (FDA) has issued a warning to healthcare providers and consumers regarding serious medication errors that have occurred when consumers have inadvertently used Maalox® Total Relief (bismuth subsalicylate) as an antacid instead of the intended traditional Maalox® liquid antacids (Maalox® Advanced Regular Strength and Maalox® Advanced Maximum Strength) containing aluminum hydroxide, magnesium hydroxide, and simethicone. Maalox® Total Relief (bismuth subsalicylate) may cause bleeding and should not be used in children or teens recovering from a viral infection, patients with a history of a bleeding disorder, gastrointestinal ulcer disease, taking anticoagulants, clopidogrel, NSAIDS, and/or oral antidiabetic medications.

The manufacturer of Maalox® products has agreed to remove the name "Maalox" from their Maalox® Total Relief (bismuth subsalicylate) product, revise the product labeling to help distinguish the active ingredients, set-up an educational program to inform healthcare providers and consumers of the differences in Maalox® products, and monitor safety and adverse event reports associated with Maalox® products. The renamed Maalox® Total Relief product is not expected to be available until September 2010, therefore, healthcare providers and consumers should be advised to check all labels of Maalox® products to ensure the appropriate product is selected.

Further information may be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety...

Erythropoiesis-Stimulating Agents (ESAs): Updated Safety Information - February 2010

The U.S. Food and Drug Administration (FDA) is requiring that all Erythropoiesis-Stimulating Agents (ESAs) be prescribed under a Risk Evaluation and Mitigation Strategy (REMS) which includes a medication guide to explain risks to patients and caregivers, and the ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) Oncology Program. The FDA is requiring a REMS because studies have shown an increased risk of tumor growth or progression and decreased survival in patients with cancer, as well as an increased risk of cardiovascular events (eg, blood clots, heart failure, MI, stroke) with ESAs. The goal is to support informed decisions between patients and healthcare providers when weighing the risks of ESA therapy, and to mitigate the risk of decreased survival and increased risk of tumor growth in cancer patients.

Only hospitals and healthcare providers who have enrolled and completed training through Amgen's ESA APPRISE Oncology program will be allowed to prescribe and dispense ESAs to patients with cancer. Amgen will be overseeing and monitoring the program to ensure compliance with the program.

For more information, U.S. healthcare professionals may refer to the following: http://www.fda.gov/Drugs/DrugSafety...

Isotretinoin: Rare Reports of Severe Skin Reactions: Health Canada Issues Notice - February 2010

Hoffmann-La Roche Limited, in conjunction with Health Canada, has issued a "Dear Health Care Professional" letter regarding rare reports of serious skin reactions including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) in adult and pediatric patients receiving isotretinoin (Accutane™). As of November 6, 2009, 66 cases (including 2 fatalities) have been reported worldwide and although confounding factors were present with a majority of the reported cases, a causal association with isotretinoin therapy can not be ruled out.

The manufacturer will be updating the Canadian product monograph to include this important safety information. Canadian healthcare professionals are advised to closely monitor patients receiving isotretinoin therapy for severe skin reactions and to consider discontinuation of therapy if clinically indicated.

Further information may be found at http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/accutane_2_hpc-cps-eng.php.

Natalizumab: Updated Information on Progressive Multifocal Leukoencephalopathy - February 2010

The U.S. Food and Drug Administration (FDA) is alerting clinicians that the risk of developing progressive multifocal leukoencephalopathy (PML) with natalizumab (Tysabri®) use increases with the number of infusions received. As of January 21, 2010, the FDA is aware of 31 confirmed cases of PML related to the use of natalizumab for multiple sclerosis. Ten of these cases have been in the United States. PML has not been reported in patients treated for less than 12 months since remarketing of Tysabri® in 2006. There have been no postmarketing cases reported in patients receiving natalizumab for Crohn's disease (<2% of natalizumab use).

The overall worldwide cumulative rate of PML in patients receiving at least one dose is 0.5 per 1000 patients. The overall worldwide cumulative rate in patients receiving ≥12 infusions ranges from 0.8-1.3 per 1000 patients (the rate of PML observed during clinical trials was 1 per 1000 patients). There is minimal information on patients who have received 36 doses or more of natalizumab.

In addition, cases of Immune Reconstitution Inflammatory Syndrome (IRIS) have been reported in patients after discontinuing natalizumab due to PML. IRIS is a rare condition which is characterized by severe inflammation during or following immune system recovery, which can result in a decline in patient condition after return of immune function. Healthcare professionals should take the appropriate steps to monitor patients for the development of this syndrome.

The updated information on PML and IRIS has been added to the prescribing information for Tysabri® and the patient Medication Guide. The FDA believes the clinical benefits of Tysabri® continue to outweigh the risks. Patients receiving natalizumab in the United States must be enrolled in the TOUCH Prescribing Program. This program helps ensure that patients are closely monitored for signs and symptoms of PML.

For additional information, refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Olanzapine: Use in Adolescents (New Indications) - February 2010

Eli Lilly has issued a "Dear Healthcare Professional Letter" to announce important considerations when using olanzapine in adolescent patients (13-17 years of age). These include:

• Olanzapine is now FDA-approved for treatment of schizophrenia and bipolar I disorder (manic or mixed episodes) in adolescents patients.
• Clinicians should be aware that there is an increased potential for weight gain, hyperlipidemia in adolescents as compared to adults. The long-term risks associated with these adverse effects may make other drugs more appropriate for first-line use.
• Compared to adult patients, adolescents also experienced a higher incidence of increased sedation and prolactin and transaminase concentrations.

For more information, refer to the "Dear Healthcare Professional" letter at http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation....

Didanosine: Postmarketing Reports of Noncirrhotic Portal Hypertension - January 2010

The U.S. Food and Drug Administration (FDA) has alerted healthcare professionals to the potential risk of noncirrhotic portal hypertension in patients using didanosine. Complications, including hemorrhaging esophageal varices, progressive liver failure, and death, have been reported. Portal hypertension onset occurred within months to years of initiating didanosine therapy. While a causal relationship has not been established, the FDA has concluded an association exists. Healthcare professionals and patients should weigh the risks and benefits of continued therapy. The warnings and precautions section of the manufacturer's labeling has been updated to include this information.

For additional information, see http://www.fda.gov/Drugs/DrugSafety....

Rho(D) Immune Globulin Intravenous (Human): Addition of Boxed Warning - January 2010

Cangene Corporation and Baxter Healthcare Corporation have released a "Dear Healthcare Professional" letter. The purpose of this letter is to inform the healthcare community of an addition of a box warning to the WinRho® SDF (Rho[D] immune globulin intravenous [human]) prescribing information. Fatal cases of intravascular hemolysis (IVH) have been reported in patients receiving WinRho® SDF for immune thrombocytopenic purpura (ITP). IVH can lead to clinically compromising anemia and multisystem organ failure (including acute respiratory distress syndrome). There have been serious complications reported including severe anemia, disseminated intravascular coagulation and acute renal insufficiency/failure. This boxed warning does not apply to patients receiving WinRho® SDF for the suppression of Rh isoimmunization.

For more information, refer to the "Dear Healthcare Professional" letter at http://www.fda.gov/downloads/BiologicsBloodVaccine...

Bortezomib: Dosage in Hepatic Impairment - January 2010

Takeda Oncology, in conjunction with the U.S. Food and Drug Administration (FDA), recently alerted healthcare professionals about revisions made to the Velcade® (bortezomib) prescribing information. These revisions provide initial dosage adjustment recommendations in patients with moderate-to-severe hepatic impairment. Information pertaining to the safety of dose adjustments in this patient population has also been added. The revisions inform that bortezomib is metabolized by liver enzymes and that drug exposure is increased in moderate or severe hepatic impairment presenting the need for a decrease in the initial dose and careful monitoring for related toxicities.

This labeling update has been previously incorporated into this monograph.

For additional information and a link to the full prescribing information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation...

Sibutramine: Preliminary Safety Information from the SCOUT Trial - Updated January 2010

The Food and Drug Administration (FDA) has notified healthcare providers of preliminary findings from the Sibutramine Cardiovascular OUTcomes Trial (SCOUT). SCOUT is a double-blind, placebo-controlled postmarketing study conducted in obese or overweight subjects who are also at an increased risk of cardiovascular events. It is intended to determine if weight management with sibutramine would decrease cardiovascular morbidity and mortality in this patient population. Sibutramine is currently FDA approved for the management of weight loss in obese patients with a body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 in the presence of other risk factors such as hypertension, diabetes, and/or dyslipidemia. In addition, patients enrolled into the SCOUT study were ≥55 years of age who also had cardiovascular disease (CVD; eg, history of coronary artery disease, peripheral arterial occlusive disease, stroke) and/or type 2 diabetes mellitus (T2DM) with additional risk factors (controlled hypertension, dyslipidemia, diabetic nephropathy, or who smoke). Important cardiovascular exclusions of the trial were 1) heart failure symptoms greater than NYHA Class II, 2) uncontrolled hypertension/tachycardia, 3) recent history of cardiovascular events.

Preliminary analysis of the study data has shown that sibutramine-treated patients with a history of CVD are at an increased risk for cardiovascular events. In patients with a history of CVD alone, 10.1% of sibutramine-treated patients experienced a cardiovascular event compared to 8.3% of placebo-treated patients (p=0.151). In patients who, in addition to CVD, also had a history of T2DM, 13.9% of sibutramine-treated patients vs. 11.9% of placebo-treated patients experienced a cardiovascular event (p=0.023).

In light of these additional contraindications, healthcare providers should re-evaluate the appropriateness of sibutramine therapy in their patients. A complete review by the FDA of the full study report, expected to be submitted by the sponsor in March 2010, is forthcoming.

Refer to the following FDA website for additional information: http://www.fda.gov/Safety/MedWatch/SafetyInformation...

McNeil Consumer Healthcare OTC Products: Voluntary Recall - January 2010

McNeil Consumer Healthcare has expanded a previous recall to include specific lots of certain additional OTC products. For information on returning the recalled products, contact McNeil Consumer Healthcare at (800) 222-6036.

For additional information and a link to the full list of recalled products and lot numbers, please refer to http://www.fda.gov/Safety/Recalls/ucm197746.htm.

Gadoversetamide: Updated Safety Information, Health Canada Issues Notice - January 2010

Tyco Healthcare/Covidien, in conjunction with Health Canada, has issued a "Dear Health Care Professional" letter regarding important safety information and upcoming labeling changes to the gadoversetamide (Optimark®) Canadian product monograph. Due to its reported association with onset of nephrogenic systemic fibrosis (NSF) in some renally-impaired patients, use of gadoversetamide is now contraindicated in patients with acute or chronic severe renal insufficiency (GFR <30 mL/minute/1.73m2) or acute renal insufficiency (regardless of severity) due to hepatorenal syndrome or during the perioperative liver transplantation period. Additionally, use in children <2 years of age is not recommended due to unknown effects on immature renal function.

Further information may be found at http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/optimark_hpc-cps-eng.php

Tylenol® Arthritis Pain Caplet: Voluntary Recall - December 2009

McNeil Consumer Healthcare, in conjunction with the U.S. Food and Drug Administration (FDA), has announced a voluntary recall on all lots of Tylenol® Arthritis Pain Caplets (100-count bottles with red EZ-OPEN cap). Consumer reports of a mildew-like odor were associated with reports of temporary and minor adverse effects, including abdominal pain, diarrhea, nausea, and vomiting. Trace amounts of a chemical (2,4,6-tribromoanisole) were found to cause the unusual smell of the caplets; health effects of this chemical are not well studied, however use of the affected products should be discontinued. Tylenol® Arthritis Pain Caplets are expected to be reintroduced by January 2010.

For information on returning the recalled Tylenol® Arthritis Pain Caplets, contact McNeil Consumer Healthcare at (800) 222-6036.

For additional information and a full list of recalled lot numbers, please refer to http://www.fda.gov/Safety/Recalls/ucm195690.htm

Shortage of Propofol and Authorization of International Propofol Product - December 2009

The U.S. Food and Drug Administration (FDA) has authorized the importation of an international propofol 1% product, Fresenius Propoven injection, to alleviate the critical shortage of propofol injection. Fresenius Propoven 1% is manufactured by Fresenius Kabi AG, the parent company of APP Pharmaceuticals, in facilities that are in compliance with FDA manufacturing standards. The importation of the international product will be allowed until the U.S. manufacturers are capable of meeting market demands. According to the FDA, Fresenius Propoven 1% is a clinically acceptable substitute for other U.S.-marketed generic propofol 1% products.

The FDA is recommending that Fresenius Propoven 1% be used according to U.S. approved indications (despite differences in the package insert for the international product). APP Pharmaceuticals has also distributed a "Dear Healthcare Professional" letter to alert practitioners of the differences between the Fresenius Propoven 1% formulation and label, and the U.S. propofol products. A portion of the key differences are as follows:

• Fresenius Propoven 1% is contraindicated in patients with soy or peanut allergies.
• Fresenius Propoven 1% contains both medium-chain triglycerides and long-chain triglycerides, in contrast to the U.S.-marketed propofol products which contain only long-chain triglycerides. Nevertheless, as with all lipid formulations, caution is recommended in patients with fat metabolism disorders or those receiving total parenteral nutrition (TPN).
• Fresenius Propoven 1% does not contain an antimicrobial component. Strict aseptic technique should always be used during handling of any propofol product. Fresenius Propoven vials are for single-use administration only; unused vials should be discarded immediately following use. Product drawn into syringes should be discarded after 6 hours.
• Fresenius Propoven 1% barcode may not be recognized in U.S. institutions employing barcode scanning systems. Alternative procedures should be followed to verify correct drug products prior to patient administration.

Please refer to the APP "Dear Healthcare Professional" and the FDA for a complete summary of the recommendations and labeling differences at http://www.fda.gov/Drugs/Drug...

CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated December 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Prompt empiric treatment is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Prompt empiric treatment is recommended for patients who are at higher risk for influenza-related complications (eg, children <2 years of age, adults ≥65 years, pregnant women and women up to 2 weeks postpartum [including after pregnancy loss], immunosuppressed patients [of any age], patients <19 years of age receiving long-term aspirin therapy, persons [of any age] with disorders that may alter respiratory function or increase risk for aspiration [eg, cognitive dysfunction, seizure disorders, spinal cord injuries] and persons [of any age] with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, endocrine, or metabolic disorders). Morbidly obese (BMI ≥40) and obese persons may be at increased risk for hospitalization and death due to 2009 H1N1 influenza infection (studies pending). This patient population frequently has other underlying conditions that increases their risk of influenza complications. Carefully evaluate morbidly obese and obese patients for underlying conditions and empirically treat as indicated.

(3) Prompt empiric treatment is recommended for patients with progressive, severe, or complicated illness due to suspected or confirmed influenza (regardless of age or previous health). Progressive illness is defined as signs/symptoms of more severe disease (eg, chest pain, dyspnea, tachypnea, unexplained oxygen desaturation) in addition to typical symptoms (eg, fever, cough, muscle pain, chills, headache). Severe or complicated illness is characterized by signs/symptoms consistent with an acute lower respiratory tract disease (eg, hypoxia requiring supplemental oxygen, abnormal chest radiograph, mechanical ventilation), signs of CNS involvement (encephalitis, encephalopathy), manifestations of low blood pressure (shock, organ failure), myocarditis or rhabdomyolysis or invasive secondary bacterial infection.

(4) Treatment (when indicated) with oseltamivir or zanamivir should be started without delay (within 48 hours of illness onset). Early initiation is more likely to provide benefit; treatment initiated >48 hours of illness onset has shown some benefit in hospitalized patients. Peramivir, an intravenous neuraminidase inhibitor, is an investigational agent that was made available under an Emergency Use Authorization (EUA) for the treatment of hospitalized patients with 2009 H1N1 influenza meeting the established EUA criteria for use. Concomitant antibiotic therapy may also be considered in patients (due to the potential for concurrent bacterial coinfections [usually Staphylococcus or Streptococcus sp]).

(5) Healthcare providers should not wait for laboratory confirmation of influenza prior to initiating empiric antiviral therapy. Therapy should be started as soon as possible regardless of the diagnostic test used (eg, rapid influenza test or real-time reverse transcriptase-polymerase chain reaction [rRT-PCR] assay). A negative rapid influenza diagnostic test result does not rule out infection and patients should still be considered for treatment.

(6) Early recognition of illness and treatment (when indicated) is preferred over chemoprophylaxis for healthy vaccinated persons. A history of vaccination does not rule out the possibility of influenza; treatment recommendations are the same for vaccinated patients as unvaccinated patients.

(7) Treatment is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications, but antiviral treatment may be considered based on clinical judgment.

(8) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in close contacts of a person with suspected or confirmed influenza:

- Persons at higher risk of influenza complications

- Healthcare and public health workers or first responders

- Pregnant women

(9) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period (1 day before fever through 24 hours after fever ends). Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, workplace, school, camp, or other setting.

(10) Alternatively, the CDC emphasizes that early antiviral treatment is also an option to chemoprophylaxis after a suspected exposure. Close contacts (with risk factors for complications) or healthcare personnel with occupational exposures can be counseled as to the early signs and symptoms of influenza and advised to immediately contact their healthcare provider if signs or symptoms develop. This approach (signs and symptom education/prompt treatment) is also recommended and preferred by the CDC in healthy vaccinated patients (including healthcare workers) after a suspected exposure.

(11) Oseltamivir or zanamivir treatment or prophylaxis to control outbreaks of 2009 H1N1 influenza in nursing homes and other long-term care facilities is recommended (similar to recommendations used for seasonal influenza outbreaks in these settings). Antiviral chemoprophylaxis may also be considered for outbreak control in other closed or semi-closed settings (eg, correctional facilities).

(12) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Only rare cases of oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, seasonal influenza A is commonly resistant to oseltamivir, but is typically susceptible to zanamivir, rimantadine, and amantadine. At present, since very few seasonal influenza A viruses have circulated in the U.S., oseltamivir or zanamivir is appropriate for influenza treatment. If oseltamivir-resistant seasonal influenza A viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal influenza A virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/guidance/

http://www.cdc.gov/h1n1flu/recommendations.htm (updated by CDC December 7, 2009)

http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

Diclofenac and Hepatic Effects - December 2009

Endo Pharmaceuticals, Novartis, and the U.S. Food and Drug Administration (FDA) notified healthcare providers of the potential for liver function test elevations with use of any diclofenac-containing product. Cases of drug-induced hepatotoxicity, including hepatic failure resulting in death or requiring transplantation, have been reported Healthcare providers should monitor transaminase levels periodically in those patients receiving long-term therapy. The majority of patients had liver enzyme abnormalities detected in the first 1-2 months of therapy, but abnormalities can occur at anytime throughout the treatment course. Optimal monitoring intervals are not known, but within 4-8 weeks after initiation may be advisable based upon clinical trials and postmarketing experience.

If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, abdominal pain, diarrhea, dark urine), diclofenac sodium should be discontinued immediately.

Additional information can be found at http://www.fda.gov/downloads/Safety...

Valproic Acid and Derivatives: Risk of Birth Defects - December 2009

The U.S. Food and Drug Administration (FDA) has issued a reminder to healthcare professionals and patients about the increased risk of neural tube defects (1 in 20 babies born exposed to valproic acid and derivatives compared to ~1 in 1500 not exposed), as well as, other major birth defects (eg, craniofacial defects, cardiovascular malformation), especially with exposure during the first 12 weeks of pregnancy. Information from the North American Antiepileptic Drug Pregnancy Registry notes a fourfold increase in congenital malformations with exposure to valproic acid monotherapy during the 1st trimester of pregnancy when compared to monotherapy with other antiepileptic drugs (AED).

Healthcare professionals should inform women of childbearing potential about these risks and consider appropriate alternatives, especially in patients using valproic acid and derivatives for conditions considered non life-threatening (ie, migraines). Patients should be encouraged to use effective contraception and to take folic acid before and during the first trimester of pregnancy if they do become pregnant. Prenatal diagnostic testing should be available to all women who become pregnant while taking valproic acid and derivatives.

Additional information may be found at: http://www.fda.gov/Safety/MedWatch/Safety...

Deferasirox (Exjade®): Ongoing Safety Review - Updated December 2009

The U.S. Food and Drug Administration (FDA) and Health Canada have independently communicated adverse event information suggesting a potentially increased risk of kidney failure, GI hemorrhage, and death in patients with myelodysplastic syndrome (MDS), particularly patients >60 years of age, treated with deferasirox. The adverse events reported are not uncommon in patients with MDS.

Neither the FDA or Health Canada have determined if patients with MDS (including older patients) receiving deferasirox are at an increased risk compared to patients without these conditions; the review is ongoing. The FDA is currently working with Novartis (the manufacturer of Exjade®) regarding any potential revisions to the prescribing information. Health Canada is also working with Novartis Canada to update the Canadian product monograph.

For more information, please refer to:

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Canada:

Desipramine (Norpramin®): Prescribing Information Updated - December 2009

Sanofi-Aventis, in conjunction with the Food and Drug Administration (FDA), has issued a "Dear Healthcare Professional" letter concerning revisions made to the product labeling for desipramine (Norpramin®). In particular, since overdose of desipramine has resulted in a higher death rate compared to other tricyclic antidepressants, the labeling advises extreme caution should be used when desipramine is prescribed to patients with a family history of sudden death, cardiac dysrhythmias, or conduction abnormalities, and that in certain patients, seizures may precede dysrhythmias and death. In addition, the overdosage section in the product labeling was also updated regarding the management of desipramine overdosage.

Additional information, including a copy of the "Dear Healthcare Professional" letter, is available at http://www.fda.gov/Safety/MedWatch/Safety...

Sibutramine: Preliminary Safety Information from the SCOUT Trial - November 2009

The Food and Drug Administration (FDA) has notified healthcare providers of preliminary findings from the Sibutramine Cardiovascular OUTcomes Trial (SCOUT). SCOUT is a double-blind, placebo-controlled postmarketing study conducted in obese or overweight subjects who are also at an increased risk of cardiovascular events. It is intended to determine if weight management with sibutramine would decrease cardiovascular morbidity and mortality in this patient population. Sibutramine is currently FDA approved for the management of weight loss in obese patients with a body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 in the presence of other risk factors such as hypertension, diabetes, and/or dyslipidemia. In addition, patients enrolled into the SCOUT study were >55 years of age who also had cardiovascular disease (eg, history of coronary artery disease, peripheral arterial occlusive disease, stroke) and/or type 2 diabetes mellitus with additional risk factors (controlled hypertension, dyslipidemia, diabetic nephropathy, or who smoke). Important cardiovascular exclusions of the trial were 1) heart failure symptoms greater than NYHA Class II, 2) uncontrolled hypertension/tachycardia, 3) recent history of cardiovascular events.

A preliminary analysis of the study data showed that cardiovascular events occurred in 11.4% of patients taking sibutramine in comparison to 10% of patients in the placebo group. Until additional information is available, these preliminary results highlight the importance of avoiding the use of sibutramine in patients with a history of coronary artery disease, heart failure, arrhythmias or stroke, as per the currently approved product labeling.

Refer to the following FDA website for additional information: http://www.fda.gov/Safety/MedWatch/Safety...

CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated November 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Empiric treatment with oseltamivir or zanamivir should be considered for patients who are at higher risk for influenza-related complications (eg, children <2 years of age, adults ≥65 years, pregnant women and women up to 2 weeks postpartum [including after pregnancy loss], immunosuppressed patients [of any age], patients <19 years of age receiving long-term aspirin therapy, persons [of any age] with disorders that may alter respiratory function or increase risk for aspiration [eg, cognitive dysfunction, seizure disorders, spinal cord injuries] and persons [of any age] with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders). Morbidly obese (BMI ≥40) and obese persons may be at increased risk for hospitalization and death due to 2009 H1N1 influenza infection (studies pending). This patient population frequently has other underlying conditions that increases their risk of influenza complications. Carefully evaluate morbidly obese and obese patients for underlying conditions and empirically treat as indicated.

(3) Any suspected influenza patient (regardless of age or previous health) with warning signs/symptoms of severe disease (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness or clinical deterioration should promptly receive empiric antiviral therapy. Antibiotic therapy may be considered due to the potential for concurrent bacterial coinfections (usually Staphylococcus or Streptococcus sp). The risk of developing severe disease is likely to be the highest in infants and children.

(4) Treatment (when indicated) should be started without delay (within 48 hours of illness onset). Early initiation is more likely to provide benefit; treatment initiated >48 hours of illness onset has shown some benefit in hospitalized patients.

(5) Healthcare providers should not wait for laboratory confirmation of influenza prior to initiating empiric antiviral therapy. Therapy should be started as soon as possible regardless of the diagnostic test used (eg, rapid influenza test or real-time reverse transcriptase-polymerase chain reaction [rRT-PCR] assay). A negative rapid influenza diagnostic test result does not rule out infection and patients should still be considered for treatment.

(6) Early recognition of illness and treatment (when indicated) is preferred over chemoprophylaxis for healthy vaccinated persons.

(7) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.

(8) Prophylaxis should be reserved for persons at high risk for influenza-related complications who have had close contact with someone likely to be infected. Alternately, the CDC emphasizes that early antiviral treatment is also an option. Close contacts (with risk factors for complications) or healthcare personnel with occupational exposures can be counseled as to the early signs and symptoms of influenza and advised to immediately contact their healthcare provider if signs or symptoms develop. This approach (signs and symptom education/prompt treatment) is also recommended by the CDC in vaccinated patients after a suspected exposure.

(9) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):

- Persons at higher risk of influenza complications and who are close contacts of a person with confirmed, probable, or suspected influenza

- Healthcare and public health workers or first responders

(10) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.

(11) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. At present, oseltamivir or zanamivir is appropriate for the treatment of 2009 H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/guidance/

http://www.cdc.gov/h1n1flu/recommendations.htm (updated by CDC October 16, 2009)

http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

CDC Interim Guidelines: Use of 23-Valent Pneumococcal Polysaccharide Vaccine During 2009 H1N1 Influenza Outbreak - Updated November 2009

The Centers for Disease Control and Prevention (CDC) has provided interim guidance on which groups should be vaccinated using the 23-valent pneumococcal polysaccharide vaccine (PPSV23) during the 2009 H1N1 influenza outbreak. Pneumococcal vaccines may be useful in preventing secondary pneumococcal infections during influenza outbreaks. Influenza predisposes patients to bacterial community-acquired pneumonia and was an important factor of illness and death associated with the 20th century influenza pandemic. Pneumococcal infections have also been an important complication among severe cases (eg, requiring hospitalization) of the current H1N1 outbreak.

The CDC's Advisory Committee on Immunization Practices (ACIP) recommends a single dose of PPSV23 be given to the following patient populations due to their increased risk of pneumococcal disease and from suffering complications arising from influenza infection:

1. All patients ≥65 years of age
2. Patients 2-64 years of age with certain high-risk condition(s):
   • Chronic cardiovascular disease (heart failure and cardiomyopathies)
   • Chronic pulmonary disease (including COPD and emphysema)
   • Diabetes mellitus
   • Alcoholism
   • Chronic liver disease (including cirrhosis)
   • Cerebrospinal fluid leaks
   • Cochlear implants
   • Functional or anatomic asplenia (including sickle cell disease and splenectomy)
   • Immunocompromising conditions (including HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome; patients receiving immunosuppressive chemotherapy, including corticosteroids; patients who have received an organ or bone marrow transplant).
   • Residents of nursing homes or long-term care facilities
3. Adults aged 19-64 years of age who smoke cigarettes or have asthma

PPSV23 vaccination, including revaccination, should continue during the present H1N1 outbreak according to current ACIP recommendations for patients with existing indications. At present, the CDC is not recommending vaccination using PPSV23 in patients without existing ACIP recommended indications.

Of note, the 7-valent pneumococcal conjugate vaccine (PCV7) is recommended for use in children <5 years of age; however, expanding the use of PCV7 to patients ≥5 years is not recommended due to the declining circulation of the 7 serotypes included in this vaccine.

Recommendations may change or be revised as more information concerning the clinical impact of the novel influenza A (H1N1) virus becomes available. For the most recent recommendations, please refer to: http://www.cdc.gov/h1n1flu/guidance/ppsv_h1n1.htm (October 26, 2009)

Update to the Labeling of Clopidogrel: Omeprazole Drug Interaction - November 2009

The U.S. Food and Drug Administration (FDA) is alerting healthcare providers to new safety information concerning the interaction between clopidogrel and the proton pump inhibitor (PPI), omeprazole (a known inhibitor of CYP2C19). New studies have demonstrated a 45% reduction in serum concentrations of the active metabolite of clopidogrel when used concurrently with omeprazole. This resulted in up to a 47% reduction in clopidogrel's antiplatelet activity. This reduction occurred when the drugs were given concurrently or if separated by 12 hours.

Other potent CYP2C19 inhibitors that would also be expected to reduce the antiplatelet activity of clopidogrel include cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine. Concurrent use of clopidogrel and these CYP2C19 inhibitors should be avoided. The level of enzyme inhibition varies within the PPI class and the effects of other PPIs on clopidogrel activity are unknown. However, since esomeprazole is an omeprazole metabolite it should also be avoided in patients receiving clopidogrel. The prescribing information for clopidogrel will be updated to reflect this interaction information.

The following are considerations for healthcare providers:

- The concurrent use of clopidogrel and omeprazole should be avoided. Patients receiving clopidogrel for MI or stroke may not receive the expected antiplatelet activity if omeprazole is used concurrently.

- Separating the time of administration of clopidogrel and omeprazole does not reduce the chance of the interaction.

- Concurrent use of cimetidine, esomeprazole, etravirine, felbamate, fluconazole, fluvoxamine, fluoxetine, ketoconazole, voriconazole and ticlopidine should also be avoided because they may also reduce clopidogrel's antiplatelet activity.

- The FDA does not have sufficient drug interaction information to provide recommendations for concurrent use of other PPIs.

- There is no evidence that H2 antagonists (other than cimetidine) interfere with antiplatelet activity of clopidogrel.

- Both cimetidine and omeprazole are available in nonprescription (OTC) forms and patients should be educated to avoid these drugs if receiving clopidogrel.

For more information, healthcare professionals may refer to the following website: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety...

Chondrolysis Reported With Continuous Intra-articular Infusions of Local Anesthetics - November 2009

The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals and patients of the recent reporting of 35 cases of chondrolysis following continuous intra-articular infusion of local anesthetics (eg, bupivacaine, chloroprocaine, lidocaine, mepivacaine, procaine, ropivacaine) via elastomeric infusion devices; some of these patients were otherwise healthy young adults. Affected patients received these agents (with and without epinephrine) for extended periods of time (eg, 48-72 hours) to control postsurgical pain, mainly following shoulder surgery. The onset of symptoms of chondrolysis occurred as early as 2 months following treatment (median: 5 months); symptoms included joint pain, stiffness, and loss of motion. More than half of these patients required repeat surgery (eg, arthroscopy, arthroplasty) as a result of the chondrolysis.

The mechanism by which the intra-arterial infusion of local anesthetics results in chondrolysis has not been identified; possible factors may include the drug, elastomeric infusion device, and/or other unknown factors. Clinicians should note that single intra-articular injections of local anesthetics have been used safely during orthopedic procedures for years without resulting in chondrolysis.

Healthcare professionals are reminded that the intra-articular administration of local anesthetics is not an FDA-approved route of administration. In addition, no infusion device, including elastomeric infusion devices, are FDA-approved for continuous intra-articular infusions. The FDA has encouraged clinicians to consult and follow the approved drug and device labeling recommendations with regard to proper administration.

In the event that a patient receives a continuous intra-articular infusion of local anesthetic, the patient should be monitored for the development of chondrolysis; symptoms may take months to develop.

Further information may be found at http://www.fda.gov/Drugs/Drug...

Myozyme®: Potential Foreign Particle Contamination - November 2009

Genzyme Corporation, in conjunction with the U.S. Food and Drug Administration (FDA), has issued a notice to healthcare professionals regarding the potential contamination of certain lots of Myozyme®; all affected products have lot numbers that begin with the letter "A" (eg, Lot A12345). The notice is due to the potential for foreign particle contamination in these lots based on the discovery of particulate matter (eg, stainless steel fragments, non-latex rubber from the vial stopper, and fiber-like material from the manufacturing process) in some products; the source has not yet been identified and <1% of products are expected to be affected. Due to the lack of FDA-approved therapeutic alternatives for Pompe disease, the FDA has decided to allow the continued marketing of Myozyme®; however, several reconstitution and administration recommendations have been made and/or emphasized to reduce the likelihood of a patient receiving contaminated product. Healthcare providers are advised to (in addition to current recommendations in the drug labeling):

• Visually inspect the powder in the vial for particulate matter prior to reconstitution.
• Visually inspect the solution following reconstitution for particulate matter.
• Do not administer products with visualized particulate matter.
• Continue to use an in-line, low protein-binding 0.2 or 0.22 micrometer filter.
• Monitor patients for adverse effects following administration.

Facilities that discover particulate matter in a vial of Myozyme® have been advised to return the affected product immediately.

Further information may be found at http://www.fda.gov/Safety/MedWatch/Safety...

Liposyn®: Voluntary Recall Due to the Presence of Particulate Matter - November 2009

Hospira, Inc, in conjunction with the U.S. Food and Drug Administration (FDA), has issued a notice to healthcare professionals regarding a voluntary recall of 85 lots of Liposyn® II (10%, 20%) and Liposyn® III (10%, 20%, 30%); all recalled products begin with the lot numbers 79 and 80. The recall is due to the presence of particulate matter in the affected lots, whose source has been identified as stainless steel equipment used in the manufacturing process. Due to the serious nature of this recall and potential health hazards, healthcare professionals are advised to closely monitor and promptly treat (if indicated) any patient who may have received an affected Liposyn® product. Facilities with existing affected inventory have been advised to quarantine and return the affected products immediately.

Further information may be found at http://www.fda.gov/Safety/Recalls/ucm189564.htm

Zanamivir (Relenza®) Inhalation Powder: Inappropriate Administration - Updated November 2009

The U.S. Food and Drug Administration (FDA) and Health Canada, in conjunction with GlaxoSmithKline (GSK), have notified their respective healthcare providers of information concerning the death of a mechanically-ventilated patient who received zanamivir (Relenza®) inhalation powder which was solubilized and administered via nebulization/mechanical ventilation. Relenza® inhalation powder is not intended to be reconstituted and is not recommended for use in any nebulizer. The death was attributed to obstruction of the ventilator; lactose contained in the powder formulation may have resulted in excessive stickiness leading to ventilator obstruction.

Relenza® inhalation powder is provided in a foil blister disk which should only be used with the Diskhaler® delivery device provided with the product and should not be otherwise manipulated. An investigational zanamivir aqueous formulation for nebulizer delivery was researched in the early development of zanamivir, but this formulation is not commercially available.

For information, please refer to

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Canada: http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/relenza_nth-aah-eng.php

Ketorolac: Voluntary Recall Due to Particulate Matter - Updated November 2009

American Regent, in conjunction with the U.S. Food and Drug Administration (FDA), has announced a voluntary recall on all lots of ketorolac injection (30 mg/mL; 1 mL and 2 mL single-dose vials). These vials may contain particulate matter and crystallization that may result in adverse effects, including pulmonary emboli or thrombosis, anaphylactic reactions, foreign body granulomas, and local irritation if administered.

On November 3, 2009, the voluntary recall was expanded by American Regent to include all lots of ketorolac injection 15 mg/mL (1 mL single-dose vials).

For information on returning the recalled ketorolac product, contact American Regent at (800) 645-1706.

For more information, please refer to the FDA Recall alert: http://www.fda.gov/Safety/MedWatch/Safety...

Exenatide and Reports of Altered Renal Function - November 2009

The U.S. Food and Drug Administration (FDA) has approved a labeling revision for exenatide (Byetta®) which includes information on postmarketing reports of altered renal function, including renal insufficiency, acute renal failure, and worsening chronic renal failure. Most patients developing altered renal function had contributing risk factors, and nearly half also experienced adverse events which could lead to volume depletion (eg, diarrhea, vomiting) and contribute to renal dysfunction. The onset to altered renal function occurred between 3 days to 2 years after exenatide initiation. Exenatide should not be used in patients with Clcr <30 mL/minute or in patients with end-stage renal disease. Use with caution in patients with renal transplantation and with exenatide initiation or dose increases in patients with moderate renal impairment (Clcr 30-50 mL/minute). Carefully monitor for the development of renal dysfunction; if suspected, evaluate appropriateness of continuing exenatide treatment.

Additional information is available at http://www.fda.gov/Safety/MedWatch/Safety...

Propofol: Presence of Particulate Matter, Health Canada Issues Notice - October 2009

Hospira Healthcare Corp, in conjunction with Health Canada, has issued a notice to Canadian healthcare professionals regarding a voluntary recall of two lots of propofol injection (lot 79834DJ and lot 79883DJ). The recall, classified as TYPE I risk, is due to the presence of particulate matter identified as stainless steel in the affected lots. Due to the serious nature of this recall and potential health hazards, healthcare professionals are advised to closely monitor and promptly treat (if indicated) any patient who may have received the affected propofol. Hospitals receiving the affected lots have been notified and instructed to quarantine and return the affected products.

Further information may be found at http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/propofol_hpc-cps-eng.php

Rituximab-Associated Progressive Multifocal Leukoencephalopathy (PML) in Rheumatoid Arthritis (RA) Patients - October 2009

Genentech, Inc and Biogen Idec, Inc, in conjunction with the U.S. Food and Drug Administration (FDA), and Hoffmann-La Roche Limited, in conjunction with Health Canada, have notified their respective healthcare professionals about a third case of PML in a rheumatoid arthritis patient. This tumor necrosis factor antagonist-naive patient developed neurologic symptoms (dysesthesias, ataxia) 4-6 months following rituximab treatment; this is the first case of rituximab-associated PML in a rheumatoid arthritis patient. Two cases had been previously reported in rheumatoid arthritis patients who had possible risk factors for PML. Healthcare providers should consider PML in any patient being treated with rituximab who presents with new neurological symptoms. Consultation with a neurologist should be considered as well as diagnostic testing (brain MRI and lumbar puncture) as clinically indicated. Discontinue rituximab treatment in patients who develop PML.

For more information, healthcare professionals may refer to the following: http://www.fda.gov/downloads/Safety/MedWatch/Safety...

Ketorolac: Voluntary Recall Due to Particulate Matter - October 2009

American Regent, in conjunction with the U.S. Food and Drug Administration (FDA), has announced a voluntary recall on all lots of ketorolac injection (30 mg/mL; 1 mL and 2 mL single-dose vials). These vials may contain particulate matter and crystallization that may result in adverse effects, including pulmonary emboli or thrombosis, anaphylactic reactions, foreign body granulomas, and local irritation if administered.

For information on returning the recalled ketorolac product, contact American Regent at (800) 645-1706.

For more information, please refer to the FDA Recall alert: http://www.fda.gov/Safety/MedWatch/Safety..

CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated October 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Empiric treatment with oseltamivir or zanamivir should be considered for patients who are at higher risk for influenza-related complications (eg, children <2 years of age, adults ≥65 years, pregnant women and women up to 2 weeks postpartum [including after pregnancy loss], immunosuppressed patients [of any age], patients <19 years of age receiving long-term aspirin therapy, persons [of any age] with disorders that may alter respiratory function or increase risk for aspiration [eg, cognitive dysfunction, seizure disorders, spinal cord injuries] and persons [of any age] with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).

(3) Any suspected influenza patient (regardless of age or previous health) with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness or clinical deterioration should promptly receive empiric antiviral therapy. Antibiotic therapy may be considered due to the potential for concurrent bacterial coinfections (usually Staphylococcus or Streptococcus sp).

(4) Treatment (when indicated) should be started without delay (within 48 hours of illness onset). Early initiation is more likely to provide benefit; treatment initiated >48 hours of illness onset has shown some benefit in hospitalized patients.

(5) Healthcare providers should not wait for laboratory confirmation of influenza prior to initiating empiric antiviral therapy. Therapy should be started as soon as possible regardless of the diagnostic test used (eg, rapid influenza test or real-time reverse transcriptase-polymerase chain reaction [rRT-PCR] assay). A negative rapid influenza diagnostic test result does not rule out infection and patients should still be considered for treatment.

(6) Early recognition of illness and treatment (when indicated) is preferred over chemoprophylaxis for healthy vaccinated persons.

(7) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.

(8) Prophylaxis should be reserved for persons at high risk for influenza-related complications who have had close contact with someone likely to be infected. Alternately, the CDC emphasizes that early antiviral treatment is also an option. Close contacts (with risk factors for complications) or healthcare personnel with occupational exposures can be counseled as to the early signs and symptoms of influenza and advised to immediately contact their healthcare provider if signs or symptoms develop.

(9) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):

- Persons at higher risk of influenza complications and who are close contacts of a person with confirmed, probable, or suspected influenza

- Healthcare and public health workers or first responders

(10) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.

(11) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/guidance/

http://www.cdc.gov/h1n1flu/recommendations.htm (updated by CDC October 16, 2009)

http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

Ceftriaxone: Update on the Warning Concerning Concomitant Use of Calcium-Containing Products - October 2009

Health Canada has issued a notice to Canadian hospitals regarding updated safety information pertaining to the use of cetriaxone and intravenous calcium-containing products. Recently in the U.S., the Food and Drug Administration (FDA) had issued a similar update regarding an interaction between ceftriaxone and intravenous calcium-containing products. Based on the results of two in vitro studies conducted in both adult and neonatal plasma, the FDA and Health Canada now state that ceftriaxone may be used concomitantly with I.V. calcium-containing products in patients >28 days of age. However, concomitant use of ceftriaxone and I.V. calcium-containing products at any time during the course of therapy is contraindicated in neonates (≤28 days). In patients >28 days of age, the following safety recommendations have also been issued and/or reiterated by both regulatory agencies:

- Ceftriaxone and I.V. calcium-containing products may be given sequentially in patients >28 days of age as long as the infusion lines are thoroughly flushed (with a compatible fluid) between infusions.

- Ceftriaxone should not be administered simultaneously with any calcium-containing solution (including parenteral nutrition) via Y-site in any patient.

- Do not reconstitute or admix ceftriaxone with calcium-containing solutions (eg, LR, Hartmann's solution).

For more information, healthcare professionals may refer to the following websites:

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Canada: http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/ceftriaxone_2_nth-aah-eng.php

Intelence™ (Etravirine): Severe Skin and Hypersensitivity Reactions - Updated October 2009

The U.S. Food and Drug Administration (FDA) and Health Canada, in conjunction with Tibotec Therapeutics, have issued "Dear Healthcare Professional" letters to their respective healthcare practitioners informing of a labeling update for etravirine (Intelence™) to include warnings of severe skin and hypersensitivity reactions. Cases of skin reactions have included Stevens-Johnson syndrome, toxic epidermal necrolysis (may be fatal), and erythema multiforme. Hypersensitivity reactions, ranging from rash and/or constitutional symptoms to occasional organ dysfunction (including hepatic failure), have been reported. Immediately discontinue etravirine with signs or symptoms of severe skin reaction or hypersensitivity. Monitor hepatic transaminases and clinical status if signs or symptoms of hypersensitivity (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia) are present. Life-threatening reaction may occur due to a delay in stopping therapy after onset of severe rash.

Additional information, including a copy of the "Dear Healthcare Professional" letters, is available at:

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Canada: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/intelence_hpc-cps-eng.php

CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated October 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Empiric treatment with oseltamivir or zanamivir should be considered for patients who are at higher risk for influenza-related complications (eg, children <2 years of age, adults ≥65 years, pregnant women and women up to 2 weeks postpartum [including after pregnancy loss], immunosuppressed patients [of any age], patients <19 years of age receiving long-term aspirin therapy, and persons [of any age] with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).

(3) Any suspected influenza patient (regardless of age or previous health) with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy. Antibiotic therapy may be considered due to the potential for concurrent bacterial coinfections (usually Staphylococcus or Streptococcus sp).

(4) Treatment (when indicated) should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit; treatment initiated >48 hours of illness onset has shown some benefit in hospitalized patients.

(5) Early recognition of illness and treatment (when indicated) is preferred over chemoprophylaxis for healthy vaccinated persons.

(6) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.

(7) Prophylaxis should be reserved for persons at high risk for influenza-related complications who have had close contact with someone likely to be infected. Alternately, the CDC emphasizes that early antiviral treatment is also an option. Close contacts (with risk factors for complications) or healthcare personnel with occupational exposures can be counseled as to the early signs and symptoms of influenza and advised to immediately contact their healthcare provider if signs or symptoms develop.

(8) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):

- Persons at higher risk of influenza complications and who are close contacts of a person with confirmed, probable, or suspected influenza

- Healthcare and public health workers or first responders

(9) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.

(10) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/guidance/

http://www.cdc.gov/h1n1flu/recommendations.htm (updated by CDC October 16, 2009)

http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

Iron Dextran (Dexferrum®): Product Labeling Updated Emphasizing Risk of Anaphylactic-Type Reactions - October 2009

The Food and Drug Administration (FDA) and American Regent are notifying healthcare professionals of recent revisions made to the prescribing information for Dexferrum® (iron dextran injection). The changes pertain to the risk of anaphylactic-type reactions, including fatalities, which have occurred with parenteral administration of iron dextran. In particular, the boxed warning has been revised to recommend administering a test dose prior to the first therapeutic dose. Fatal reactions have been reported even in patients who tolerated the test dose; therefore all patients (regardless of an uneventful test dose) should be observed for signs/symptoms of anaphylactic-type reactions. Resuscitation equipment and trained personnel should be available during administration. The labeling also identifies patients who may be at an increased risk for anaphylactic-type reactions to iron dextran therapy. These patients include those with a history of drug allergy (including multiple drug allergies) and/or those receiving a concomitant ACE inhibitor. Additionally, the labeling revision highlights the difference in chemical characteristics between iron dextran products; iron dextran products are not clinically interchangeable.

For additional information, please refer to http://www.fda.gov/Safety/MedWatch/Safety...

Heparin: American College of Chest Physicians (ACCP) Response to New Reference Standard for Heparin - October 2009

The American College of Chest Physicians convened a large group of experts in parenteral anticoagulants and thrombosis to discuss the impact of the new reference standard for heparin potency on the ACCP antithrombotic guidelines. The group decided not to revise guideline recommendations at this time, but emphasized the following:

- For therapeutic use, physicians may or may not notice that larger doses of heparin are required to achieve "therapeutic" levels of anticoagulation. Clotting tests, such as aPTT, ACT, or TCT, should be used to guide heparin infusion dosing.

- In cases where fixed doses of heparin are used with clinical monitoring but not laboratory monitoring (eg, extracorporeal circuits), increased heparin doses may or may not be required to maintain circuit patency.

- In cases where fixed doses of heparin are used without laboratory or clinical monitoring, reduced efficacy may go unnoticed. This may particularly impact those patients in whom large, weight-adjusted, fixed doses of heparin are used for the treatment of acute venous thromboembolism.

The ACCP will reconvene in 3 months to review new data and make changes if necessary. Notification of any changes will be available at http://www.chestnet.org

Sleep-Aids: Health Canada Issues Safety Alert Regarding the Risk for Complex Sleep-Related Behaviors - October 2009

Health Canada has issued an alert to both its healthcare professionals and general public regarding the use of sleep-aids (eg, temazepam, nitrazepam, flurazepam, triazolam, zopiclone) and reported complex sleep-related behaviors (cooking, eating, driving, walking, and talking while not fully awake). Patients typically did not recall the events happening afterwards.

The Canadian product labelings for the associated sleep-aids have been updated to include the reported events and to emphasize safe and appropriate use of these agents. Patients and caregivers are encouraged to be aware of possible sleep-related behaviors and report suspected events to their healthcare providers. Discontinuation of sleep-aids in patients reporting sleep-related behaviors may be necessary. Patients should consult their healthcare providers prior to discontinuing use of these agents to avoid withdrawal symptoms.

Further information may be found at:

Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2009/2009_161-eng.php

Oseltamivir Oral Suspension: Authorization of Certain Lots Beyond Expiration Date - October 2009

The Food and Drug Administration (FDA) has authorized the use of certain lots of expired oseltamivir (Tamiflu®) oral suspension to ensure availability of the product during this public health emergency. Previously in July 2009, the FDA had authorized four lots for use beyond their labeled expiration dates; however, on October 2nd, additional lots were added to the list. The lots authorized have undergone scientific testing and analysis to support their use beyond the labeled expiration date. The emergency use authorization remains in effect until April 26, 2010, unless it is terminated earlier or extended later by the Secretary of the Department of Health and Human Services (HHS).

For information regarding the authorization, please refer to http://www.fda.gov/Drugs/DrugSafety...

For the listing of the lot numbers authorized for use, please refer to http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm154962.htm

Heparin: New USP Standards and Potency Issues - October 2009

The U.S. Food and Drug Administration (FDA) is alerting healthcare providers to a change to the United States Pharmacopeia (USP) monograph for heparin. Effective October 1, 2009, there will be a new reference standard for heparin and a new test to determine potency. The new test method will more readily detect impurities in heparin products. This change is largely due to the 2007-2008 heparin contamination problem. The new monograph will also harmonize the USP unit with the WHO international standard (IS) unit (ie, international unit). However, harmonization of the standard will result in an estimated 10% reduction in potency of heparin marketed in the United States under this new standard. Manufacturing and testing procedures as defined in the new standard will decrease the potential for heparin contamination and assure production of high quality product.

Healthcare providers should be aware that the reduction in potency of heparin products manufactured and tested according the new USP monograph may cause some patients to require more heparin to achieve and maintain a desired level of anticoagulation. Consideration of this reduction in potency is necessary when making dosing decisions. The impact of this change in potency should be less significant when heparin is administered by subcutaneous injection due to low and variable bioavailability.

The FDA has requested that all manufacturers differentiate (from currently available heparin products) heparin products manufactured by the new standards. The labels of products manufactured according to the new standard will have an "N" in the lot number or following the expiration date. Additionally, products manufactured by Hospira may be identified by the number "82" or higher (eg, 83, 84) at the beginning of their lot numbers. Manufacturers will not start shipping heparin prepared according to new standard until October 8, 2009, or possibly later.

Finally, the FDA summarizes important clinical recommendations to consider during this time of transition to heparin made according to the new USP standards:

• There will be simultaneous availability of heparin manufactured by the "old" and "new" USP standards. These products will have potential differences in potency.
• Consider potential reduction in potency when utilizing heparin in situations when aggressive anticoagulation is necessary to treat or prevent life-threatening thrombosis.
• More frequent or intensive aPTT or ACT monitoring may be required.
• The FDA-approved labeling (including dosing) for heparin has not changed. Heparin dosing should always be individualized according to the patient-specific clinical situation. Appropriate clinical judgment is essential in determining heparin dosage.

The FDA is working with heparin manufacturers to study the impact of this variation in potency and will report results as they become available.

For additional information, refer to the following websites:

http://www.fda.gov/Drugs/DrugSafety...

www.usp.org

Oseltamivir (Tamiflu®): Potential Dosing Errors With Liquid Formulation; Health Canada Issues Warning - September 2009

Health Canada has issued a warning to the Canadian public regarding dosing errors associated with the liquid formulation (powder for oral suspension) of oseltamivir (Tamiflu®) reported in the U.S. to the Food and Drug Administration (FDA). In both Canada and the U.S., the dosing device provided within the approved packaging is calibrated in milligrams (mg). In the reported cases, the product labeling included instructions for dosing in milliliters (mL), causing patient and/or caregiver confusion and incorrect dosing.

It is advised that when the manufacturer provided oral syringe is dispensed, patient instructions should be provided based on milligram dosage (not mL or teaspoon). When labeling instructions are provided in mL, pharmacies should replace the manufacturer provided delivery device with one calibrated in mL. Patients should always be provided with a measuring device calibrated the same way as their labeled instructions and instructed on correct dosing and administration. Consumers with questions regarding the proper use of this product are advised to consult their healthcare provider.

Health Canada will be notifying its healthcare professionals with regards to this important safety information.

Further information may be found at:

Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2009/2009_158-eng.php

U.S.: http://www.fda.gov/downloads/Safety/MedWatch/Safety...

Children's and Infants' Tylenol® Products: Recall Due to Potential Manufacturing Problems - September 2009

McNeil Consumer Healthcare, in conjunction with the U.S. Food and Drug Administration (FDA), has issued a voluntary, cautionary recall of certain lots of Children's and Infants' Tylenol® manufactured between April and June 2008. The manufacturer states that one of the inactive ingredients did not meet internal testing requirements and the gram-negative bacteria Burkholderia cepacia was detected. The contaminated material was not used in the final product and the finished product did meet all specifications. Parents and caregivers should be advised to contact their healthcare providers if they have concerns. If an affected product is found, contact McNeil Customer Care Center at 1-800-962-5357 to receive a coupon for a new bottle.

For additional information and a full list of the recalled product lots, please refer to:

http://www.tylenolprofessional.com/assests/TYLENOL_Letter_091809/pdf

http://www.fda.gov/Safety/MedWatch/Safety...

Deferasirox (Exjade®): Ongoing Safety Review - September 2009

The U.S. Food and Drug Administration (FDA) is communicating adverse event information suggesting a potentially increased risk of kidney failure, GI hemorrhage, and death in patients with myelodysplastic syndrome (MDS), particularly patients >60 years of age, treated with deferasirox. The adverse events reported are not uncommon in patients with MDS.

The FDA has not determined if patients with MDS (including older patients) receiving deferasirox are at an increased risk compared to patients without these conditions; the review is ongoing. The FDA is currently working with Novartis (the manufacturer of Exjade®) regarding any potential revisions to the prescribing information.

For more information, please refer to: http://www.fda.gov/Safety/MedWatch/Safety...

Sitagliptin and Acute Pancreatitis - September 2009

The Food and Drug Administration (FDA) is notifying health care providers that cases of acute pancreatitis have been reported in patients using sitagliptin (Januvia™) or sitagliptin in combination with metformin (Janumet™). Between October 2006 and February 2009, 88 cases of acute pancreatitis (including two cases of hemorrhagic or necrotizing pancreatitis) have been reported to the FDA's Adverse Event Reporting System (AERS). Although 51% of the cases were also associated with risk factors for developing pancreatitis (eg, diabetes, high cholesterol, high triglycerides, obesity), the FDA believes there may be an association with sitagliptin use. Pancreatitis occurred within 30 days of starting sitagliptin or sitagliptin with metformin in 21% of the cases. In 53% of these patients, pancreatitis resolved once sitagliptin was discontinued. The FDA is working with the manufacturer to update the product labeling. They are also recommending that healthcare professionals monitor for the development of pancreatitis (with initiation or dosage increases), and discontinue sitagliptin or sitagliptin in combination with metformin if pancreatitis is suspected. Patients currently taking sitagliptin or sitagliptin with metformin should not discontinue the medication; however, they should notify their prescriber if experiencing symptoms which may be associated with acute pancreatitis, such as persistent severe abdominal pain, anorexia, nausea, and vomiting.

For additional information, refer to the following FDA website: http://www.fda.gov/Drugs/DrugSafety...

SCDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated September 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Empiric treatment with oseltamivir or zanamivir should be considered for patients who are at higher risk for influenza-related complications (eg, children <2 years of age, adults ≥65 years of age, pregnant women, immunosuppressed patients (of any age), patients <19 years of age receiving long-term aspirin therapy, and persons (of any age) with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).

(3) Any suspected influenza patient (regardless of age or previous health) with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.

(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.

(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.

(6) Prophylaxis should be reserved for persons at high risk for influenza-related complications who have had close contact with someone likely to be infected. Alternately, the CDC emphasizes that early antiviral treatment is also an option. Close contacts (with risk factors for complications) or healthcare personnel with occupational exposures can be counseled as to the early signs and symptoms of influenza and advised to immediately contact their healthcare provider if signs or symptoms develop.

(7) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):

- Persons at higher risk of influenza complications and who are close contacts of a person with confirmed, probable, or suspected influenza

- Healthcare and public health workers or first responders

(8) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.

(9) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/recommendations.htm (updated by CDC September 22, 2009)

http://www.cdc.gov/h1n1flu/guidance/

Note: The information below is a portion of a previous notice posted in May 2009.

The U.S. Food and Drug Administration (FDA) is recommending that all companies, U.S. states and localities, and other organizations consider keeping any oseltamivir (Tamiflu®) and zanamivir (Relenza®) that are nearing or are past the labeled expiration dates. These two medications are covered under the Emergency Use Authorization that the FDA has issued for the 2009 influenza (H1N1) outbreak. At present, the U.S. Department of Health and Human Services is evaluating options and may decide to utilize these stockpiled medications, if needed.

Any organization that decides to retain the soon-to-expire or expired zanamivir or oseltamivir should maintain the product(s) under the labeled storage requirements, and should contact the FDA's Emergency Operations Center (301-443-1240) with the amounts of antivirals in their stockpiles. The FDA is not directing this statement to individual patients with either of the antivirals in their home.

http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm154962.htm

Stolen Medication: Albuterol Inhalation Solution Unit-Dose Vials - Updated September 2009

For information on affected NDC/lot numbers, please refer to:

Notice to pharmacists concerning theft in Texas (September 10th): http://www.fda.gov/Safety/MedWatch/Safety...

Dey-issued advisory concerning theft in Florida (September 11th): http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm182091.htm

FDA advisory to consumers (September 17th): http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182846.htm

Stolen Medication: Ipratropium Inhalation Solution Unit-Dose Vials - September 2009

For information on affected NDC/lot numbers, please refer to:

Dey-issued advisory concerning theft in Florida (September 11th): http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm182091.htm

FDA consumer advisory (September 17th): http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182846.htm

Updated Recommendations for H. influenzae Conjugate Vaccine - September 2009

In August 2009, the Food and Drug Administration (FDA) approved Hiberix® (Hib-PRP-T) vaccine for use as a booster (final) dose in the Hib vaccine series. With approval of this product, the Advisory Committee on Immunization Practices (ACIP) has updated their recommendations for vaccination of children requiring catch-up vaccination.

Due to a recent shortage of Hib vaccine, the ACIP had recommended deferral of the booster (final) dose of Hib vaccine in December 1997. In June 2009, the ACIP advised healthcare providers to begin administration of the deferred dose at the child's next regularly scheduled visit. With approval of Hiberix® and adequate supplies of ActHIB® and Pentacel®, the ACIP now recommends that once feasible and when sufficient vaccine supplies are available in the office, healthcare providers begin contacting all children whose booster dose was deferred. Those children who did not receive a booster dose due to the shortage of vaccine, should receive the booster with any available Hib-containing vaccine.

For additional information, refer to the following CDC website http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a5.htm?s_cid=mm5836a5_e

Natalizumab: Updated Information on Progressive Multifocal Leukoencephalopathy - September 2009

The U.S. Food and Drug Administration (FDA) has received 13 reports of progressive multifocal leukoencephalopathy (PML) related to the use of natalizumab for multiple sclerosis since it was re-released in July 2006. Four of these cases have been in the United States. There have been no cases reported in Crohn's disease. PML has been previously reported following the use of natalizumab and its use is contraindicated in patients with a history of PML.

The risk of developing PML seems to correlate with the number of infusions. The average number of infusions in the 13 patients developing natalizumab-related PML was 25. There is minimal information on patients who have received greater than 35 doses of natalizumab.

The rate of developing natalizumab-related PML in patients who have received at least one dose remains under 1 per 1000 patients. The current rate in patients receiving at least 24 infusions ranges from 0.4-1.3 per 1000 patients.

Currently, the FDA is not recommending any changes to the natalizumab prescribing information or to the TOUCH Prescribing Program (a risk management program for natalizumab). Patients receiving natalizumab in the United States must be enrolled in the TOUCH Prescribing Program. This program helps assure that patients are closely monitored for signs and symptoms of PML.

For additional information refer to http://www.fda.gov/Drugs/Drug...

Stolen Medication: Albuterol Inhalation Solution Unit-Dose Vials - September 2009

For information on affected NDC/lot numbers, please refer to:

http://www.fda.gov/Safety/MedWatch...

http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm182091.htm

CDC Updated Interim Recommendations for the Use of Antivirals During 2009-2010 Influenza Season - Updated September 2009

The Centers for Disease Control and Prevention (CDC) has issued interim recommendations for the use of antivirals for the treatment and prevention of influenza during the 2009-2010 season. These recommendations apply to seasonal influenza and the 2009 H1N1 influenza (formerly known as novel influenza A [H1N1]). Antiviral doses and schedules for treatment or chemoprophylaxis of 2009 H1N1 influenza are the same as those recommended for seasonal influenza. Additionally, the U.S. Food and Drug Administration (FDA) has issued a temporary Emergency Use Authorization to allow the use of oseltamivir in children <1 year of age. The following is a summary of the updated interim recommendations:

(1) Treatment with oseltamivir or zanamivir is recommended in any patient hospitalized with suspected or confirmed influenza.

(2) Treatment with oseltamivir or zanamivir is generally recommended for patients who are at higher risk for influenza-related complications (eg, children <5 years of age, adults ≥65 years of age, pregnant women, immunosuppressed patients, patients <19 years of age receiving long-term aspirin therapy, and persons with chronic health conditions such as pulmonary, cardiovascular, renal, hepatic, hematologic, neurologic, neuromuscular, or metabolic disorders).

(3) Any suspected influenza patient with warning signs/symptoms (eg, dyspnea, tachypnea, unexplained oxygen desaturation) consistent with an acute lower respiratory tract illness should promptly receive empiric antiviral therapy.

(4) Treatment, when indicated, should be started without delay (within 48 hours of illness onset) and should not await laboratory confirmation. Early initiation is more likely to provide benefit.

(5) Treatment or prophylaxis is generally not required in patients with suspected influenza who present with uncomplicated febrile illness or are not at higher risk for complications.

(6) Postexposure antiviral chemoprophylaxis with oseltamivir or zanamivir may be considered in the following populations after an exposure or close contact of a person with suspected, probable, or confirmed influenza during that person's infectious period ("infectious period" is defined as 1 day before through 24 hours after fever ends):

Persons at higher risk of influenza complications

Healthcare and public health workers or first responders

(7) Chemoprophylaxis is generally not recommended if more than 48 hours has lapsed since last exposure to the infectious person, and is not indicated if the exposure did not occur during the infectious period. Chemoprophylaxis is not recommended in healthy children or adults after a potential exposure in the community, school, camp, or other setting.

(8) Currently circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Oseltamivir-resistant 2009 H1N1 viruses have been identified, most commonly observed during chemoprophylaxis or in immunocompromised patients receiving treatment for influenza. Conversely, regular seasonal influenza A (H1N1) is commonly resistant to oseltamivir, but is typically susceptible to rimantadine and amantadine. However, at present, oseltamivir or zanamivir is appropriate for the treatment of seasonal H1N1 influenza. If oseltamivir-resistant seasonal H1N1 viruses become more common or are identified in community outbreaks, zanamivir (or a combination of oseltamivir and rimantadine or amantadine) should be considered for empiric treatment of suspected oseltamivir-resistant seasonal human influenza A (H1N1) virus infection.

CDC recommendations are changing frequently as more information on antiviral susceptibilities and effectiveness becomes available. For the most recent recommendations and information from the CDC, please refer to:

http://www.cdc.gov/h1n1flu/recommendations.htm

http://www.cdc.gov/h1n1flu/guidance/

Mycophenolate Mofetil: Reports of Pure Red Cell Aplasia (PRCA); Health Canada Issues Warning - Updated September 2009

Hoffman-La Roche Limited (Roche), Roche Laboratories, Inc, and Novartis Pharmaceuticals Corporation, in conjunction with Health Canada and the Federal Drug Administration (FDA), have issued "Dear Healthcare Professional" letters regarding reports of PRCA in patients receiving mycophenolate mofetil (MMF) (CellCept®) therapy concomitantly with other immunosuppressive agents (eg, cyclosporine, corticosteroids, tacrolimus). Following oral or I.V. administration, MMF is converted to mycophenolic acid (MPA), the active ingredient of Myfortic®. As of February 2008, forty-one cases of PRCA had been reported. Following a review of the reported data, Health Canada deemed that, in a few cases, a causal relationship with mycophenolate therapy could not be ruled out. In some cases, mycophenolate dose reduction or discontinuation resulted in reversal of PRCA.

Although the mechanism is not precisely known, PRCA development may be related to immunosuppression. Symptoms may include fatigue, lethargy, and/or pallor; however, of primary concern is the risk for anemia which can range from subclinical to severe. Symptoms of severe anemia may include weakness, tachycardia, and/or dyspnea. Treatment usually involves discontinuation of the agent inducing PRCA or treatment of the underlying disease state. Prior to discontinuing mycophenolate or other immunosuppressive therapy, clinicians are advised to consider the potential contribution of the drugs to PRCA, as well as the risk for transplant rejection. The Canadian and U.S. labeling has been updated to include this safety information.

Further information may be found at:

Canada: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/cellcept_2_hpc-cps-eng.php

U.S.:

http://www.fda.gov/Safety/MedWatch/Safety...

http://www.fda.gov/Safety/MedWatch/Safety...

Leukotriene Inhibitors: Potential Association with Neuropsychiatric Events - Updated August 2009

The Food and Drug Administration (FDA) is updating healthcare professionals regarding the possible association between leukotriene inhibitor use and neuropsychiatric events including agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide) and tremor. The FDA has requested that manufacturers of leukotriene inhibitors add a precaution regarding this potential risk to the drug prescribing information. In addition, the FDA recommends that both patients and healthcare providers are aware of the potential neuropsychiatric risks of taking these medications. Patients should be encouraged to report any neuropsychiatric effects to a healthcare provider. Healthcare professionals should consider discontinuing leukotriene inhibitors if a patient exhibits or reports a neuropsychiatric symptom.

In August, the respective manufacturers updated the prescribing information for Singulair® (montelukast), Accolate® (zafirlukast), and Zyflo CR®/Zyflo® (zileuton) to include information about neuropsychiatric events.

Additional information can be found at http://www.fda.gov/Safety/MedWatch/Safety...

Intelence™ (Etravirine): Severe Skin and Hypersensitivity Reactions - August 2009

Tibotec Therapeutics, in conjunction with the U.S. Food and Drug Administration (FDA), has issued a "Dear Healthcare Professional" letter informing of a labeling update for etravirine (Intelence™) to include warnings of severe skin and hypersensitivity reactions. Cases of skin reactions have included Stevens-Johnson syndrome, toxic epidermal necrolysis (may be fatal), and erythema multiforme. Hypersensitivity reactions, ranging from rash and/or constitutional symptoms to occasional organ dysfunction (including hepatic failure), have been reported. Immediately discontinue etravirine with signs or symptoms of severe skin reaction or hypersensitivity. Monitor hepatic transaminases and clinical status if signs or symptoms of hypersensitivity (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia) are present. Life-threatening reaction may occur due to a delay in stopping therapy after onset of severe rash.

Additional information, including a copy of the "Dear Healthcare Professional" letter, is available at http://www.fda.gov/Safety/MedWatch/Safety...

Levemir®: MedWatch Alert Concerning Certain Lots of Stolen Product That May Be Dangerous - Updated August 2009

The U.S. Food and Drug Administration (FDA) is concerned that vials of stolen insulin detemir may still be on the market. Efficacy issues due to lack of proper handling and storage are causing patients to experience a lack of glucose control.

For complete information and a list of affected lot numbers, please refer to the MedWatch alert at http://www.fda.gov/Safety/MedWatch/Safety...

Orlistat: Liver-Related Adverse Events and Ongoing Safety Review - August 2009

The U.S. Food and Drug Administration (FDA) is communicating information regarding an ongoing safety review of orlistat prompted by reports of liver-related adverse events. Between 1999 and October 2008, 32 reports of serious liver injury (commonly reported as jaundice, weakness, and abdominal pain), including six cases of liver failure, were submitted to the FDA's Adverse Event Reporting System. Thirty of the 32 reports occurred outside of the United States. In addition to these reports, the FDA is reviewing other data submitted by the manufacturer regarding suspected cases of hepatic injury.

The FDA analysis is ongoing, and at present time no definite association between liver injury and orlistat has been established. The FDA is not recommending that healthcare professionals change their prescribing practices, and patients currently receiving therapy should continue taking orlistat as directed. However, patients should be encouraged to report any signs/symptoms associated with liver injury (eg, fatigue, fever, jaundice, brown urine, nausea, vomiting, abdominal pain) to a healthcare professional.

For more information, please refer to http://www.fda.gov/Safety/MedWatch/Safety..

Ibuprofen: Unapproved Topical Products - August 2009

The U.S. Food and Drug Administration (FDA) issued information for healthcare providers and consumers regarding unapproved topical combination products containing ibuprofen. Unlike oral ibuprofen products (which are FDA-approved), topical products containing ibuprofen are not FDA-approved. Safety claims for topical products containing ibuprofen have not been reviewed by the FDA.

For information, including a list of the unapproved products, please refer to: http://www.fda.gov/Safety/MedWatch/Safety...

Tumor Necrosis Factor-Alpha Blockers Associated with Malignancies and New-Onset Psoriasis - Updated August 2009

The U.S. Food and Drug Administration (FDA) has completed its previously announced analysis of Tumor Necrosis Factor-Alpha (TNF) blockers, and is alerting healthcare professionals of an increased risk of lymphomas in children and adolescents and leukemia in all patients, including adults. Health Canada has recently issued a similar alert to Canadian practitioners. The FDA analysis is an update to the June 2008 Early Communication About an Ongoing Safety Review regarding a possible association between the use of TNF blockers and the development of lymphoma and other cancers in children and young adults. In addition, as a result of a separate analysis, the FDA is also notifying healthcare professionals of an increased risk of new-onset psoriasis in all patients, including adults.

Pediatric malignancies: Forty-eight cases of malignancy were identified by the FDA in children and adolescents with the use of TNF blockers. Etanercept and infliximab were the only TNF blockers included in the analysis. Of the 48 cases, ~50% were lymphomas (eg, Hodgkin's and non-Hodgkin's lymphoma). Other malignancies such as leukemia, melanoma, and solid organ tumors were reported; malignancies rarely seen in children (eg, leiomyosarcoma, hepatic malignancies, and renal cell carcinoma) were also observed. Of note, most of these cases (88%) were receiving other immunosuppressive medications (eg, azathioprine and methotrexate); however, the role of TNF blockers in the development of malignancies in children could not be excluded. Further data regarding the incidence of these malignancies is expected from ongoing postmarketing studies and registries conducted by the TNF blocker manufacturers.

Leukemia: The FDA also reviewed 147 postmarketing reports of leukemia (including acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) in patients using TNF blockers. Average onset time to development of leukemia was within the first 1-2 years of TNF blocker initiation. Although most patients were receiving other immunosuppressive agents, the role of TNF blockers in the development of leukemia could not be excluded. The FDA concluded that there is a possible association with the development of leukemia and the use of TNF blockers.

New-onset psoriasis: In a separate analysis, the FDA reviewed 69 cases of new-onset psoriasis (including pustular, palmoplantar) occurring in patients using TNF blockers for the treatment of conditions other than psoriasis and psoriatic arthritis. Of the 69 cases, 2 were reported in children and 12 required hospitalization, the most severe outcome. Improvement was seen when the TNF blocker was discontinued. The FDA concluded that there is a possible association with new-onset psoriasis and the use of TNF blockers.

The FDA has required the manufacturers of TNF blockers to update the Boxed Warnings and the Warnings in the prescribing information as it relates to malignancies, to update the Adverse Events section to include reported cases of new-onset psoriasis, and to revise the medication guide to reflect this information. Health Canada is also working with their respective manufacturers to update the Canadian labeling with this important safety information. Patients should be monitored closely for signs and symptoms suggestive of malignancy or new-onset psoriasis, evidence of which should result in prompt discontinuation of the medication and appropriate diagnostic evaluation.

Additional information can be found at:

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2009/2009_137-eng.php

Clopidogrel (Plavix®) and Proton Pump Inhibitors (PPIs): Health Canada Issues Notice - August 2009

Health Canada, in conjunction with Sanofi-Aventis Canada Inc., and Bristol Myers Squibb Canada Co., has issued a Dear HealthCare Professional letter to Canadian practitioners regarding the potential interaction between clopidogrel (Plavix®) and proton pump inhibitors (PPIs). A similar notice had previously been issued in the U.S. by the Food and Drug Administration (FDA). Certain PPIs may inhibit the cytochrome enzyme (CYP2C19) which metabolizes clopidogrel to its active metabolite, thus potentially resulting in decreased clinical efficacy of clopidogrel.

Health Canada is recommending that healthcare providers continue to prescribe clopidogrel and patients continue taking clopidogrel as directed. Health Canada recommends against the use of drugs (including PPIs) which inhibit CYP2C19 in patients receiving clopidogrel. Prescribers should consider the risk-benefits of combination (PPI-clopidogrel) therapy as well as use of alternative gastroprotective agents. Health Canada is currently working with the manufacturers mentioned to update the Canadian product monograph with this important safety information.

Further information may be found at: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/plavix_hpc-cps-eng.php

Mycophenolate Mofetil: Reports of Pure Red Cell Aplasia (PRCA); Health Canada Issues Warning - August 2009

Hoffman-La Roche Limited (Roche) and Roche Laboratories, Inc., in conjunction with Health Canada and the Federal Drug Administration (FDA), have issued a "Dear Healthcare Professional" letter regarding reports of PRCA in patients receiving mycophenolate mofetil (CellCept®) therapy concomitantly with other immunosuppressive agents (eg, cyclosporine, corticosteroids, tacrolimus). As of February 2008, forty-one cases had been reported. Following a review of the reported data, Health Canada deemed, in a few cases, a causal relationship with mycophenolate therapy could not be ruled out. In some cases, mycophenolate dose reduction or discontinuation resulted in reversal of PRCA.

Although the mechanism is not precisely known, PRCA development may be related to immunosuppression. Symptoms may include fatigue, lethargy, and/or pallor; however, of primary concern is the risk for anemia which can range from subclinical to severe. Symptoms of severe anemia may include weakness, tachycardia, and/or dyspnea. Treatment usually involves discontinuation of the agent inducing PRCA or treatment of the underlying disease state. Prior to discontinuing mycophenolate or other immunosuppressive therapy, clinicians are advised to consider the potential contribution of the drugs to PRCA, as well as the risk for transplant rejection. The Canadian and U.S. labeling has been updated to include this safety information.

Further information may be found at:

Canada: http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/cellcept_2_hpc-cps-eng.php

U.S.: http://www.fda.gov/Safety/MedWatch/Safety...

Dextroamphetamine and Amphetamine Recall Due to Exceeded Weight Requirement ) - August 2009

Barr Laboratories, Inc. has issued a voluntary recall of dextroamphetamine and amphetamine 20 mg tablets, 100 count bottle, lot number 311756. This lot may contain tablets that exceed weight requirements, potentially resulting in supratherapeutic doses. Possible adverse effects associated with a supratherapeutic dose include cardiovascular, neurologic, psychiatric and gastrointestinal reactions. The affected lot was distributed between 6/11/09 and 6/16/09. Patients are instructed to discontinue use of this lot and return it to their pharmacy. Wholesalers and retailers should cease distribution of all medication from this lot only.

For additional information, please refer to http://www.fda.gov/Safety/MedWatch/Safety...

Omalizumab (Xolair®): Interim Findings From Ongoing Safety Review (EXCELS Study) - August 2009

The U.S. Food and Drug Administration (FDA) and Health Canada have issued independent communication to their respective healthcare professionals regarding interim safety findings from an ongoing observational trial titled Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS) involving ~5000 patients treated with omalizumab and ~2500 patients not receiving omalizumab. Preliminary findings suggest an increased risk of cardiovascular (eg, arrhythmias, cardiomyopathy, ischemic heart disease, heart failure, pulmonary hypertension), cerebrovascular, and thromboembolic adverse events in patients treated with omalizumab compared to those not receiving omalizumab. The primary objective of the trial is to assess long-term safety (5 years) of omalizumab in patients ≥12 years of age with moderate-to-severe persistent asthma and a positive skin/blood test for an aeroallergen.

At this time, the FDA and Health Canada are not recommending patients discontinue omalizumab therapy or recommending any changes to the current prescribing information for Xolair®. Analysis of this preliminary safety data is ongoing and neither regulatory agency has reached any conclusions at this time. The final results from the EXCELS trial are not expected until 2012.

For more information, healthcare professionals may refer to the following websites:

U.S.: http://www.fda.gov/Safety/MedWatch/SafetyInfor...

Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2009/2009_129-eng.php

Oral Sodium Phosphate Products: Health Canada Issues Updated Safety Information - August 2009

Health Canada has issued a "Dear Health Care Professional" letter regarding updated safety information associated with the use of oral sodium phosphate bowel cleansing agents. In Canada, over-the-counter (OTC) oral sodium phosphate products are now indicated for laxative use only and are no longer indicated for purgative use. Manufacturers of these products have revised or are working to revise the labeling, which will no longer include instructions for purgative use.

Further information may be found at http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2009/oral_sodium_phos_hpc-cps-eng.php

Tumor Necrosis Factor-Alpha Blockers Associated with Malignancies and New-Onset Psoriasis - August 2009

The U.S. Food and Drug Administration (FDA) has completed its previously announced analysis of Tumor Necrosis Factor-Alpha (TNF) blockers, and is alerting healthcare professionals of an increased risk of lymphomas in children and adolescents and leukemia in all patients, including adults. This analysis is an update to the June 2008 Early Communication About an Ongoing Safety Review regarding a possible association between the use of TNF blockers and the development of lymphoma and other cancers in children and young adults. In addition, as a result of a separate analysis, the FDA is also notifying healthcare professionals of an increased risk of new-onset psoriasis in all patients, including adults.

Pediatric malignancies: Forty-eight cases of malignancy were identified by the FDA in children and adolescents with the use of TNF blockers. Etanercept and infliximab were the only TNF blockers included in the analysis. Of the 48 cases, ~50% were lymphomas (eg, Hodgkin's and non-Hodgkin's lymphoma). Other malignancies such as leukemia, melanoma, and solid organ tumors were reported; malignancies rarely seen in children (eg, leiomyosarcoma, hepatic malignancies, and renal cell carcinoma) were also observed. Of note, most of these cases (88%) were receiving other immunosuppressive medications (eg, azathioprine and methotrexate); however, the role of TNF blockers in the development of malignancies in children could not be excluded. Further data regarding the incidence of these malignancies is expected from ongoing postmarketing studies and registries conducted by the TNF blocker manufacturers.

Leukemia: The FDA also reviewed 147 postmarketing reports of leukemia (including acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) in patients using TNF blockers. Average onset time to development of leukemia was within the first 1-2 years of TNF blocker initiation. Although most patients were receiving other immunosuppressive agents, the role of TNF blockers in the development of leukemia could not be excluded. The FDA concluded that there is a possible association with the development of leukemia and the use of TNF blockers.

New-onset psoriasis: In a separate analysis, the FDA reviewed 69 cases of new-onset psoriasis (including pustular, palmoplantar) occurring in patients using TNF blockers for the treatment of conditions other than psoriasis and psoriatic arthritis. Of the 69 cases, 2 were reported in children and 12 required hospitalization, the most severe outcome. Improvement was seen when the TNF blocker was discontinued. The FDA concluded that there is a possible association with new-onset psoriasis and the use of TNF blockers.

The FDA has required the manufacturers of TNF blockers to update the Boxed Warnings and the Warnings in the prescribing information as it relates to malignancies, to update the Adverse Events section to include reported cases of new-onset psoriasis, and to revise the medication guide to reflect this information. Patients should be monitored closely for signs and symptoms suggestive of malignancy or new-onset psoriasis, evidence of which should result in prompt discontinuation of the medication and appropriate diagnostic evaluation.

Additional information can be found here.

Botulinum Toxin Types A and B: Name Changes and Revisions to Prescribing Information - August 2009

On July 31, 2009, the U.S. Food and Drug Administration (FDA) approved the following revisions to the prescribing information of licensed botulinum toxin products, including the newest botulinum toxin type A, Dysport™, which was granted FDA approval in April 2009:

• A Boxed Warning regarding the risk of potentially life-threatening spread of toxin effect from the local injection site.
• A Risk Evaluation and Mitigation Strategy (REMS) which includes a medication guide to explain risks to patients and caregivers.
• The established drug names of the botulinum toxin products have been changed to emphasize the potency differences and the lack of interchangeability among the products (see below). Clinical doses expressed in units cannot be compared or converted from one product to the next. Of note, the marketed trade names and the product formulations have not changed for these products.

For more information, U.S. healthcare professionals may refer to the following:

• http://www.fda.gov/Safety/MedWatch/...
• http://www.fda.gov/Drugs/DrugSafety/...

Colchicine: FDA Approved Oral Product (Colcrys™) and Safety Issues Associated With Colchicine Use - July 2009

The Food and Drug Administration (FDA) has approved an oral colchicine product, Colcrys™, for the treatment of familial Mediterranean fever (FMF) and acute gout flares. Prior to the approval of Colcrys™, colchicine had been available as an unapproved medication without FDA-approved prescribing information. In addition, the FDA is also notifying healthcare professionals of two new safety concerns associated with colchicine involving drug interactions and the safety of doses historically used in the treatment of acute gout.

The FDA analyzed safety data from published literature, pharmacokinetic and drug interaction studies, as well as previously reported adverse events, and discovered cases of fatal colchicine toxicity in certain patients. The cases occurred in patients receiving concomitant medications that interact with colchicine, such as clarithromycin (despite receiving standard therapeutic doses of colchicine). These reports suggest a role of concomitant medications which affect the gastrointestinal absorption and/or hepatic metabolism of colchicine in the development of toxicity (particularly in patients with renal or hepatic impairment).

In addition, the FDA analysis of safety and efficacy data of colchicine in acute gout revealed that a substantially lower dose of colchicine (total cumulative dose: 1.8 mg) demonstrated efficacy compared to the higher dose (total cumulative dose: 4.8 mg) traditionally used. There were also fewer adverse events reported with the lower dose.

In light of the safety issues, the FDA is recommending that colchicine not be used concurrently with P-glycoprotein (P-gp) or strong CYP3A4 inhibitors in patients with renal or hepatic impairment, and a dose reduction or interruption of colchicine therapy be considered in those patients without renal or hepatic impairment. A medication guide has also been developed for patient distribution.

For additional information, please refer here.

Mecasermin Rinfabate (Iplex™): Updated Supply Information and Postponement of Phase II Clinical Trial in ALS Patients - July 2009

Insmed, Inc, the manufacturer of mecasermin rinfabate (Iplex™), has announced it will cease supplying Iplex™ to any new patient due to their extremely limited inventory. In addition, Insmed will postpone the initiation of the Phase II clinical trial for amyotrophic lateral sclerosis (ALS) patients previously announced with the U.S. Food and Drug Administration (FDA) in March 2009. Insmed no longer has the capability to manufacture the medication and has determined it must conserve the current inventory to ensure the existing patients (~70 patients worldwide) continue to receive therapy. In the U.S., there are 12 patients with access to Iplex™ through a single-patient IND application approved by the FDA. Insmed believes there is sufficient inventory to supply the existing patients for no more than 24 months.

Insmed intends to analyze data collected from the use of Iplex™ in various indications, including myotonic muscular dystrophy and ALS, to determine the possibility of future clinical trials and explore manufacturing options with third party manufacturers, if feasible.

Iplex™ is a combination of recombinant human insulin-like growth factor 1 (rhIGF-1) and human insulin-like growth factor-binding protein-3 (rhIGFBP-3). Iplex™ was FDA approved in 2005 for the treatment of severe growth failure in children with primary IGF-1 deficiency (primary IGFD), or with growth hormone (GH) deletion who have developed neutralizing antibodies to GH, but has not been currently marketed for that indication due to a court order related to patent infringement.

Additional information can be found at:

http://investor.insmed.com/releasedetail.cfm?ReleaseID=399059

http://www.fda.gov/Drugs/ResourcesForYou/HealthProfessionals/ucm118117.htm

Fosamprenavir: Health Canada Issues Notice Regarding Possible Risk For Myocardial Infarction - July 2009

GlaxoSmithKline Inc, in conjunction with Health Canada, has issued a "Dear HealthCare Professional" letter regarding a possible risk for myocardial infarction (MI) in adult patients with human immunodeficiency virus (HIV) receiving fosamprenavir (Telzir®). Data recently reported from a nested case-control study, linked cumulative fosamprenavir exposure to an increased risk of MI (OR = 1.55 per additional year of exposure [95% CI, 1.20-1.99]). Previously, the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study identified a possible association between MI and the use of protease inhibitors.

Protease inhibitor therapy can increase serum lipids. Therefore, clinicians are reminded to evaluate cholesterol and triglyceride levels prior to initiation and periodically during fosamprenavir therapy. Physical signs of fat distribution (associated with combination antiretroviral therapy), as well as modifiable risk factors for cardiovascular disease (eg, smoking, diabetes, hypertension), should also be evaluated and addressed as appropriate.

Health Canada is working with the manufacturer to incorporate this important safety information within the fosamprenavir Canadian product monograph.

Additional information may be found here.

Omalizumab (Xolair®): Interim Findings From Ongoing Safety Review (EXCELS study) - July 2009

The U.S. Food and Drug Administration (FDA) is communicating information regarding interim safety findings from an ongoing observational trial titled Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS) involving ~5000 patients treated with omalizumab and ~2500 patients not receiving omalizumab. Preliminary findings suggest an increased risk of cardiovascular (eg, arrhythmias, cardiomyopathy, ischemic heart disease, heart failure, pulmonary hypertension), cerebrovascular, and thromboembolic adverse events in patients treated with omalizumab compared to those not receiving omalizumab. The primary objective of the trial is to assess long-term safety (5 years) of omalizumab in patients ≥12 years of age with moderate to severe persistent asthma and a positive skin/blood test for an aeroallergen.

At this time, the FDA is not recommending patients discontinue omalizumab therapy or recommending any changes to the current prescribing information for Xolair®. The FDA's analysis of this preliminary safety data is ongoing and the FDA has not reached any conclusions at present. The final results from the EXCELS trial are not expected until 2012.

For more information, healthcare professionals may refer to the following website http://www.fda.gov/Safety/MedWatch/SafetyInformation/Sa...

Acetaminophen Concentrated Drops (16 ounce) Recall Due to Potential For Overdosing - July 2009

Brookstone Pharmaceuticals, with awareness of the U.S. Food and Drug Administration (FDA), has issued a voluntary recall of all lots of concentrated acetaminophen drops (80 mg/0.8 mL) in 16 ounce bulk containers. The manufacturer states this is a cautionary measure to minimize confusion between this bulk container of the concentrated acetaminophen preparation and the bulk container of the regular strength acetaminophen liquid preparations (160 mg/15 mL), and to limit the risk of potential dosing errors.

For additional information, please refer to http://www.fda.gov/Safety/MedWatch/...

Immunosuppressant Drugs: Risk of Opportunistic Infections - July 2009

The U.S. Food and Drug Administration (FDA) is alerting healthcare professionals of updated labeling requirements to emphasize an increased risk for opportunistic infections (eg, activation of latent viral infections, including BK virus-associated nephropathy) in patients treated with certain immunosuppressant agents. The labeling changes will be required for cyclosporine (Neoral®, Sandimmune®), mycophenolate (Cellcept®, Myfortic®), and sirolimus (Rapamune®). This risk has been previously reported and reflected in the prescribing information for tacrolimus (Prograf®). Analyses of the FDA's Adverse Event Reporting System (AERS) has shown an association between BK virus-associated nephropathy and immunosuppressant drug use (primarily in renal transplant patients) which can lead to renal allograft loss. Patients should be monitored for this risk and early intervention is essential. Immunosuppressant therapy adjustments should be considered in patients who develop BK virus-associated nephropathy.

For additional information, refer to the following FDA website: http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety...

Propoxyphene-Containing Products and Fatal Overdose - July 2009

The Food and Drug Administration (FDA) is requiring the manufacturers of propoxyphene to strengthen product labeling, emphasizing the risk of fatal overdose with its use. Manufacturers will be required to update their boxed warnings and also to develop medication guides which would be provided to patients with every new or refilled prescription. This action is being taken in response to concerns that propoxyphene may be more lethal in overdose (accidental or intentional) when compared to other pain medications.

The FDA is also requiring the manufacturers of propoxyphene products to conduct safety studies which will asses the effects of higher than recommended doses of propoxyphene on the heart. Additional safety studies (including a study of propoxyphene in the elderly) are being planned or are under consideration.

Propoxyphene has been available in the United States since 1957 for the treatment of mild-to-moderate pain. Because the FDA considers propoxyphene to be effective at recommended doses, it is not proposing that propoxyphene be removed from the U.S. market at this time. However, additional regulatory action may be taken based on the results of the proposed safety studies.

Healthcare providers should be aware of the risk of fatal overdose when prescribing propoxyphene and carefully review patient histories when considering an appropriate pain medication.

For additional information, refer to the following FDA website: http://www.fda.gov/Safety/MedWatch/...

Smoking Cessation Aids (Bupropion and Varenicline): Boxed Warnings and Medication Guides Highlighting Neuropsychiatric Risks Required by the Food and Drug Administration (FDA) - July 2009

The U.S. Food and Drug Administration (FDA) has announced it will require manufacturers to add a black box warning and provide a medication guide regarding the previously reported association between varenicline or bupropion use and neuropsychiatric adverse effects. Reports of postmarketing events temporally associated with these medications (including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide) continue to be collected and reviewed by the FDA. Events may occur in patients without a history of psychiatric disease and may also be difficult to diagnose due to similarities to typical symptoms of nicotine withdrawal including irritation, depression, insomnia, and anxiety.

Healthcare professionals should instruct patients to stop taking these medications and contact a healthcare provider if neuropsychiatric symptoms occur. Family members or friends who notice any changes in behavior (especially suicidal thoughts or behavior) of patients using these medications should inform the patient, and recommend they discontinue the medication and call a healthcare professional.

For additional information, see http://www.fda.gov/Drugs/DrugSafety/Postmarket...