NEW DRUG APPROVALS

By Shamna

Eleven New Cancer Drugs

Axitinib ( Inlyta, Pfizer) is used to treat patients with advanced renal cell carcinoma who have not responded to other therapies. It was approved in the United States in January and in Europe in September.

Vismodegib ( Erivedge, Genentech) is used to treat patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and to treat patients whose cancer has metastasized. It was approved in the United States in January.

Pertuzumab ( Perjeta, Roche) is used to treat patients who have HER2-positive metastatic breast cancer and to treat patients who have not received any previous HER2-trageted therapy or chemotherapy in combination with trastuzumab ( Herceptin) and docetaxel. It was approved in the United States in June and was just recommended for approval in Europe.

Carfilzomib ( Kyprolis, Onyx Pharmaceuticals) is used to treat patients whose multiple myeloma has progressed despite at least 2 previous therapies, including bortezomib ( Velcade, Millennium Pharmaceuticals) and an immunomodulatory agent. It was approved in the United States in July.

Ziv-aflibercept ( Zaltrap) is used to treat patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen, in combination with the FOLFIRI regimen (5-fluorouracil, leucovorin, and irinotecan). The drug was approved for colorectal cancer in the United States in August. In November 2011, an ophthalmic solution ( Eylea) was approved for use in age-related macular degeneration.

Enzalutamide (Xtandi, Astellas/Medivation) is used to treat men with metastatic castration-resistant prostate cancer who previously received docetaxel. It was approved in the United Stated in August.

Regorafenib ( Stivarga, Bayer) is used to treat patients with metastatic colorectal cancer that has progressed despite standard treatment. It was approved in the United States in September.

Bosutinib ( Bosulif, Pfizer) is used to treat patients with chronic myeloid leukemia who have developed resistance or tolerance to previous therapy with tyrosine kinase inhibitors. It was approved in the United States in September.

Omacetaxine mepesuccinate ( Synribo, Teva Pharmaceuticals) is used to treat patients with chronic myeloid leukemia who have progressed after treatment with at least 2 tyrosine kinase inhibitors. It was approved in the United States in October.

Cabozantinib ( Cometriq, Exelixis) is used to treat patients with metastatic medullary thyroid cancer, which accounts for about 4% of all of thyroid cancers. It was approved in the United States in November.

Ponatinib ( lclusig, Ariad) is used to treat patients with chronic myeloid leukemia or Philadelphia-chromosome-positive acute lymphoblastic leukemia who are resistant to other therapies, and in those who carry T315I mutations. It was approved in the United States in December.

Three Other Approvals

The FDA approved another 3 agents for use in cancer patients this year, either for supportive care or for imaging.

Glucarpidase ( Voraxaze, BTG International) is used to treat patients with high levels of methotrexate in their blood due to renal impairment. It metabolizes methotrexate and leads to a rapid and sustained reduction of methotrexate blood levels. It was approved in the United States in January.

Tbo-filgrastim ( Neutroval, Sicor Biotech), a colony-stimulating factor, is used to increase the production of neutrophils in cancer patients with nonmyeloid malignancies who are receiving chemotherapy drugs that cause severe neutropenia. It was approved in the United States in August.

Choline C 11 injection (manufactured and distributed by the Mayo Clinic PET Radiochemistry Facility in Rochester, Minnesota) is an imaging agent used in positron emission tomography scanning to detect recurrent prostate cancer. These scans are performed in men who have elevated prostate-specific antigen levels after previous treatment for prostate cancer. It was approved in the United States in September.

Targeted Agents

In its annual report, the American Society of Clinical Oncology notes that nearly all of the new drugs are targeted agents, designed to block the activity of specific proteins involved in tumor growth.

That report highlights the fact that vismodegib has a novel mechanism of action, and is the first approved drug to target the Hedgehog signaling pathway, which plays an important role in tissue growth and repair. Vismodegib, currently marketed for basal cell skin cancer, is also being investigated in clinical trials of patients with colorectal, stomach, and pancreatic cancers.

FDA Panel Split on Telavancin for Nosocomial Pneumonia

Nov 30, 2012

SILVER SPRING, Maryland — A federal advisory panel has given qualified support for the use of telavancin in the treatment of patients with nosocomial pneumonia (NP) resulting from susceptible isolates of gram-positive organisms.

The US Food and Drug Administration (FDA) Anti-Infective Drugs Advisory Committee members split the vote, with 9 voting no and 6 yes, in answering whether they believe overall that the data support the efficacy and safety of the proposed indication for telavancin, but they subsequently voted 13 to 2 in favor of more limited use of the drug in certain seriously ill patients with NP for whom other alternatives are not suitable.

Telavancin is an intravenous lipoglycopeptide drug that has bactericidal activity against gram-positive bacteria. Manufactured under the name Vibativ by Theravance Inc, it has been licensed by the FDA since September 2009 for the treatment of complicated skin and skin structure infections. In October of that year, it was approved for the treatment of NP in the European Union.

However, in the United States, the FDA has twice rejected Theravance's new drug application for the NP infection indication. The first time, in November 2009, the FDA cited concerns about missing mortality data and whether the participants in the company's studies met guideline-based criteria for NP (chest X-ray plus 2 clinical features).

In November 2010, the FDA published new guidelines for the development of drugs to treat NP, which recommended noninferiority in 28-day all-cause mortality as a study endpoint rather than noninferiority in test-of-cure to an active comparator drug (vancomycin, in this case). It also recommended that companies conduct at least 2 randomized controlled studies.

Theravance's original new drug application for telavancin was based on 2 randomized, double-blind, active-controlled, parallel-group, multinational trials of identical design. The first, study 0015, was conducted in 22 countries and enrolled 761 patients, including 31% from the United States. The other, study 0019, enrolled 771 patients in 29 countries, with 14% from the United States. Patients were randomly assigned to receive either telavancin or vancomycin treatment for 7 to 10 days.

The test-of-cure endpoint, assessed by physician determination of the resolution of clinical signs and symptoms of NP, was noninferior to vancomycin overall, with an overall cure rate of about 60% with both, and telavancin was superior to vancomycin in certain analyses, including those with NP caused by Staphylococcus aureus, said Steven Barriere, PharmD, from Theravance.

However, after the new guideline was published, the FDA denied telavancin's NP indication a second time because only study 0019, and not study 0015, met the newly specified endpoint criteria of a 10% noninferiority margin in all-cause mortality for the patients who had at least 1 baseline gram-positive pathogen.

Difficulties Interpreting the Data

A major problem for the advisory panel in analyzing the data was that although the 2 trials were designed to be identical, they differed significantly in certain baseline characteristics, including the proportion of patients with a history of diabetes (31% in study 0015 vs 21% in study 0019), chronic renal failure (9% vs 4%, respectively), and baseline creatinine clearance less than 50 mL/minute (36% vs 27%), according to FDA medical reviewer Benjamin Lorenz, MD.

Mathai Mammen, MD, PhD, from Theravance, presented pooled data for the 2 trials. All-cause mortality at 28 days was 24% with telavancin vs 22% for vancomycin, which is a statistically insignificant difference. However, according to Dr. Lorenz, noninferiority was not demonstrated in study 0015, which showed a trend toward increased all-cause mortality with telavancin.

In Dr. Mammen's analysis, the increased mortality was primarily seen among patients with creatinine clearance values less than 30 mL/minute, and he said the product label would include guidance for using serum creatinine levels to guide therapy. (The label currently includes dose adjustments for patients with creatinine clearance values lower than 50 mL/minute.)

The committee struggled with the statistical interpretation of much of the efficacy and safety data, given the limitations of studies using both types of endpoints. The FDA had turned away from the use of the test-of-cure endpoint because of the inability to precisely determine efficacy for active comparators such as vancomycin, which must be used for ethical reasons, said Edward Cox, MD, director of the Office of Antimicrobial Products at the FDA.

Noninferiority for all-cause mortality was chosen instead because it is a more definitive endpoint for which there are data in the population being studied. However, that endpoint is also problematic in very sick populations with high overall mortality rates. Use of other endpoints is being explored, Dr. Cox said.

Support for Use with Restrictions

Most panel members agreed that telavancin should only be approved for NP caused by methicillin-resistant S aureus and not methicillin-susceptible S aureus or Streptococcus pneumonia, for which other agents are available. Several members also advised limiting the drug's use to patients with creatinine clearance levels above 30 or 50 mL/minute.

Matthew Goetz, MD, chief of infectious diseases at the Veterans Affairs Greater Los Angeles Healthcare System in California, said he voted no to the first question primarily out of concern for the renal data. "As a clinician I can't predict whose creatinine clearance will decrease over time," he said. He subsequently voted yes for more limited use.

Judith Voynow, MD, professor of pediatrics in the Division of Pulmonary Medicine at Duke University in Durham, North Carolina, voted yes to both questions with the caveat that it should be indicated for staph and not strep infections, and with the renal status restrictions. "These are very sick patients, mortality rates are high, and I thought that under the right circumstances this may be a useful drug in this population."

Peter Katona, MD, clinical professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, said he voted no on the first question because he was disturbed by the fact that the FDA's rules had changed midstream and that the mortality data were therefore derived post hoc.

"I feel very strongly that when you start a study and you have predesignated endpoints, you really don't want to deviate from that if you can at all help it. Once you open the window to deviate from what you originally intended to do, it opens up a Pandora's box of things that may not serve us well," he said. However, he also voted yes for more limited use.

Wallace Kemper Alston, MD, professor of medicine in the Infectious Disease Unit at the University of Vermont, Burlington, voted yes to both questions. "Of all these applications I've listened to over the years, I think this one ended up the most muddled, but I don't think that's necessarily the fault of telavancin. It speaks to the fact that this is a very heterogeneous, very difficult diagnosis to make. It's very hard to assess a cure."

He concluded, "In my heart of hearts, I think telavancin would probably cure [methicillin-resistant S aureus] pneumonia at least as well as vancomycin and that the problems we're encountering have to do with the unknowns surrounding trial design for nosocomial pneumonia and not the drug itself."

FDA Okays 4-Strain Seasonal Influenza Vaccine

The US Food and Drug Administration (FDA) today (Dec 17,2012) approved a new 4-strain influenza vaccine for adults and children aged 3 years and older to help prevent disease caused by the seasonal influenza virus subtypes A and B contained in the vaccine.

Fluarix Quadrivalent (GlaxoSmithKline) is the first intramuscular vaccine to offer protection against 4 influenza strains, the company said.

Currently-administered trivalent (3-strain) influenza vaccines help guard against the 2 A virus strains most commonly occurring in humans and the B strain expected to be predominant in a given year, the company noted in a statement.

However, since 2000, 2 B influenza virus strains (Victoria and Yamagata) have cocirculated to varying degrees each influenza season. Various degrees of mismatch have occurred between the B strain included in trivalent vaccines and the B strain that actually circulated, causing an increased risk for influenza-related morbidity across all age groups.

The new 4-strain vaccine continues to help protect against the 2 A strains and also adds coverage against a second B strain.

"Trivalent influenza vaccines have helped protect millions of people against flu, but in 6 of the last 11 flu seasons, the predominant circulating influenza B strain was not the strain that public health authorities selected," Leonard Friedland, MD, vice president and director of clinical and medical affairs at GlaxoSmithKline North America Vaccine Development, said in a statement.

"Fluarix Quadrivalent will help protect individuals against both B strains and, from a public-health standpoint, can help decrease the burden of disease," he concluded.

The company said the vaccine will be available in time for the 2013-2014 influenza season. The company added it will also fulfill orders for its trivalent vaccines.

Fluarix Quadrivalent is not currently approved or licensed in any country outside of the United States.

Hepatitis C Responds Better to Triple Antiviral Therapy

Sustained virological response (SVR) rates for the most common chronic hepatitis C virus (HCV) infection may be "substantially higher" if newer triple-therapy regimens are administered compared with the standard dual-therapy approaches, according to a study published online November 26 in the Annals of Internal Medicine.

Roger Chou, MD, from the Oregon Health & Science University in Portland, and colleagues assessed 458 full-text studies identified through multiple databases and published between 1947 and 2012. The publications included randomized trials of antiviral treatments and cohort studies on clinical outcomes and SVR after antiviral treatment.

No study, however, assessed comparative clinical effectiveness of antiviral treatments because of the long time course for HCV complications to develop. The researchers instead used SVR rates as a surrogate endpoint because SVR after antiviral treatment "appears to be associated with improved clinical outcomes."

Dual therapy with pegylated interferon combined with ribavirin became the standard HCV treatment in the early 2000s, and the US Food and Drug Administration approved the antiviral agents boceprevir and telaprevir in 2011 for chronic HCV genotype 1; this genotype accounts for about 75% of HCV infection cases in the United States.

"Understanding the comparative effectiveness of antiviral regimens is critical for making informed treatment decisions for HCV infection," the researchers write. Their review focuses on comparative effectiveness for treatment-naive patients and on whether effectiveness varies according to clinical and demographic characteristics. They used "the absence of detectable HCV RNA in the serum six months after the end of a course of therapy" as their definition for SVR.

The researchers found that in 2 clinical trials (n = 1097 and 520) that evaluated the triple therapy of boceprevir, pegylated interferon alfa-2b, and ribavirin compared with dual therapy without boceprevir for HCV genotype 1, the triple therapy was associated with a greater likelihood for SVR than dual therapy alone (pooled relative risk [RR], 1.8 [95% confidence interval (CI), 1.6 - 2.1]; I ², 0%; pooled absolute increase, 31 percentage points [95% CI, 23 - 39 percentage points]).

They also found that 3 trials (n = 189 - 250) concluded that a 24-week triple therapy regimen including telaprevir, pegylated interferon, and ribavirin was associated with a greater likelihood of SVR compared with a 48-week dual therapy without telaprevir (pooled RR, 1.5; 95% CI, 1.3 - 1.8; I ², 0%).

The review includes many other findings. For example, in trials comparing dual therapy of ribavirin plus pegylated interferon alfa-2a (180 μg/kg/week) with alfa-2b (1.5 μg/kg/week), alfa-2b was associated with a lesser likelihood of SVR than alfa-2a (pooled RR, 0.87 [95% CI, 0.80 - 0.95]; I ², 27%; pooled absolute difference, 8 percentage points [95% CI, 3 - 14 percentage points]).

"Across all antiviral regimens, absolute treatment response rates across regimens are lower in older patients, black patients, and patients with higher baseline viral load, genotype 1 infection, or more advanced fibrosis," the researchers write.

Limitations include that their analysis is based only on English-language articles and that pooled estimates based on a small number of trials should be interpreted cautiously.

The researchers conclude, "The relative ineffectiveness of dual therapy for genotype 1 infection has led to ongoing efforts to identify more effective treatments. Recent trials found triple therapy with boceprevir or telaprevir superior to dual therapy, with SVR rates approaching the 70–80 percent observed in trials of dual therapy for genotype 2 or 3 infection. This has important implications for treatment as well as for screening, since screening benefits depend in part on the effectiveness of available treatments."

This study was supported by the Agency for Healthcare Research and Quality. The authors have disclosed no relevant financial relationships.

FDA Approves Signifor

FDA Approves Signifor, a New Orphan Drug for Cushing’s Disease

December 14, 2012 -- The U.S. Food and Drug Administration today approved Signifor (pasireotide diaspartate) injection for the treatment of Cushing’s disease patients who cannot be helped through surgery.

Cushing’s disease is caused by over-production of cortisol, a hormone made by the adrenal glands. A tumor in the pituitary gland leads to overstimulation of the adrenal gland, which results in excess cortisol production. Cortisol regulates many important functions in the body, including response to stress and injury. Patients with Cushing’s disease may have increased weight, glucose intolerance or diabetes, high blood pressure, easy bruising, and increased risk for infections.

“Although surgery tends to be first line therapy to treat Cushing’s disease, Signifor is a new treatment option for patients when surgery hasn’t worked or isn’t an option,” said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research.

The safety and effectiveness of Signifor were evaluated in a clinical trial of 162 Cushing’s disease patients. Trial participants were randomly chosen to receive one of two dose levels of Signifor over a six-month treatment period. Some patients who safely responded to the medication where allowed to continue treatment. Signifor resulted in decreased cortisol levels as measured in urine collected over a 24-hour period. This reduction was seen as early as one month after starting treatment. About 20 percent of patients in the clinical trial were able to reduce urine cortisol levels into the normal range.

Signifor caused increases in blood sugar levels, which could be detected as early as two weeks after starting treatment. Continued treatment caused or worsened diabetes in some patients; therefore, patients need to be carefully monitored for this side effect and be treated appropriately with anti-diabetic therapies, including insulin.

The FDA is requiring three postmarketing studies for Signifor: a clinical trial to assess high blood sugar (hyperglycemia) management; a long-term prospective observational cohort study (registry) of patients with Cushing’s disease treated with Signifor; and focused safety monitoring for reports of serious hyperglycemia, acute liver injury, and adrenal insufficiency.

Signifor is administered under the skin (subcutaneously) twice daily, and will be dispensed with a Medication Guide, including instructions for patients and caregivers that describe the risks and adverse reactions people should be mindful of when using the product.

The most common adverse reactions observed in the clinical trial included hyperglycemia, diarrhea, nausea, abdominal pain, and gallstones.

Signifor is manufactured by Novartis Pharma Stein AG, Stein, Switzerland.

Source: FDA

Posted: December 2012

FDA Approves Raxibacumab

FDA Approves Raxibacumab to Treat Inhalational Anthrax

December 14, 2012 -- The U.S. Food and Drug Administration today approved raxibacumab injection to treat inhalational anthrax, a form of the infectious disease caused by breathing in the spores of the bacterium Bacillus anthracis. Raxibacumab also is approved to prevent inhalational anthrax when alternative therapies are not available or not appropriate.

Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis that can cause massive and irreversible tissue injury and death. A monoclonal antibody is a protein that closely resembles a human antibody that identifies and neutralizes foreign material like bacteria and viruses. Anthrax is a potential biological terrorism threat because the spores are resistant to destruction and can be easily spread by release in the air.

The FDA granted raxibacumab fast track designation, priority review, and orphan product designation. The drug demonstrated the potential to fill an unmet medical need, has the potential to provide safe and effective treatment where no satisfactory alternative therapy exists, and is intended to treat a rare disease, respectively.

Raxibacumab is the first monoclonal antibody approved under the FDA’s Animal Efficacy Rule, which allows efficacy findings from adequate and well-controlled animal studies to support FDA approval when it is not feasible or ethical to conduct trials in humans. In this case, because inhalational anthrax is a rare and lethal disease, it is not possible to conduct adequate efficacy trials in humans.

“In addition to antibiotics, raxibacumab will be a useful treatment to have available should an anthrax bioterrorism event occur,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research. “Although antibiotics are approved to prevent and treat anthrax infection, raxibacumab is the first approved agent that acts by neutralizing the toxins produced by B. anthracis.”

Raxibacumab’s effectiveness for inhalational anthrax was demonstrated in one study in monkeys and three studies in rabbits. All animals were administered aerosolized B. anthracis spores, and efficacy was determined by survival at the end of the studies. Animals received varying doses of raxibacumab, placebo or antibiotics normally used to treat anthrax.

More animals treated with raxibacumab lived compared to animals treated with placebo. Sixty-four percent of animals in the monkey study and 44 percent of animals in one rabbit study receiving the 40 milligrams per kilogram dose of raxibacumab survived exposure to anthrax, compared with none in the placebo groups. All surviving animals developed toxin-neutralizing antibodies. Another study in rabbits showed that 82 percent of animals treated with antibiotics and raxibacumab survived exposure to anthrax compared with 65 percent of animals receiving antibiotic treatment alone.

The safety of raxibacumab was evaluated in 326 healthy human volunteers. Common side effects included rash, extremity pain, itching and drowsiness.

Raxibacumab was developed by Rockville, Md.-based Human Genome Sciences, in conjunction with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority. Human Genome Sciences has since been acquired by GlaxoSmithKline.

Source: FDA

Posted: December 2012

FDA Approves Iclusig

December 14, 2012 - The U.S. Food and Drug Administration today approved Iclusig (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases.

Iclusig is being approved more than three months ahead of the product’s prescription user fee goal date of March 27, 2013, the date the agency was scheduled to complete review of the drug application. The FDA reviewed the Iclusig drug application under the agency’s priority review program, which provides for an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.

Iclusig blocks certain proteins that promote the development of cancerous cells. The drug is taken once a day to treat patients with chronic, accelerated, and blast phases of CML and Ph+ ALL whose leukemia is resistant or intolerant to a class of drugs called tyrosine kinase inhibitors (TKIs). Iclusig targets CML cells that have a particular mutation, known as T315I, which makes these cells resistant to currently approved TKIs.

“The approval of Iclusig is important because it provides a treatment option to patients with CML who are not responding to other drugs, particularly those with the T315I mutation who have had few therapeutic options,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “Iclusig is the third drug approved to treat CML and the second drug approved to treat ALL this year, demonstrating FDA’s commitment to approving safe and effective drugs for patients with rare diseases.”

The FDA approved Bosulif (bosutinib) in September 2012 and Synribo (omacetaxine mepesuccinate) in October 2012 to treat various phases of CML. Marqibo (vincristine sulfate liposome injection) was approved in August 2012 to treat Philadelphia chromosome negative ALL.

Iclusig is being approved under the agency’s accelerated approval program, which provides patients earlier access to promising new drugs while the company conducts additional studies to confirm the drug’s clinical benefit and safe use. The therapy is being granted an orphan product designation because it is intended to treat a rare disease or condition.

Iclusig’s safety and effectiveness were evaluated in a single clinical trial of 449 patients with various phases of CML and Ph+ ALL. All participants were treated with Iclusig.

The drug’s effectiveness was demonstrated by a reduction in the percentage of cells expressing the Philadelphia chromosome genetic mutation found in most CML patients, major cytogenetic response (MCyR). Fifty-four percent of all patients and 70 percent of patients with the T315I mutation achieved MCyR. The median duration of MCyR had not yet been reached at the time of analysis.

In accelerated and blast phase CML and Ph+ ALL, Iclusig’s effectiveness was determined by the number of patients who experienced a normalization of white blood cell counts or had no evidence of leukemia (major hematologic response or MaHR). Results showed:

· 52 percent of patients with accelerated phase CML experienced MaHR for a median duration of 9.5 months;

· 31 percent of patients with blast phase CML achieved MaHR for a median duration of 4.7 months; and

· 41 percent of patients with Ph+ ALL achieved MaHR for a median duration of 3.2 months.

Iclusig is being approved with a Boxed Warning alerting patients and health care professionals that the drug can cause blood clots and liver toxicity. The most common side effects reported during clinical trials include high blood pressure, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.

Iclusig is marketed by ARIAD Pharmaceuticals, based in Cambridge, Mass. Bosulif is marketed by New York City-based Pfizer, and Synribo is marketed by Frazer, Pa.-based Teva Pharmaceuticals. Marqibo is marketed by Talon Therapeutics Inc. based in South San Francisco, Calif.

Source: FDA

Posted: December 2012

FDA Approves Varizig

December 21, 2012 -- The U.S. Food and Drug Administration has approved Varizig for reducing the severity of chicken pox (varicella zoster virus) infections in high risk individuals when given within four days after exposure.

Varizig is a varicella zoster immune globulin preparation. Varicella zoster virus (VZV) causes chickenpox in children and shingles in adults. Varizig is the only FDA approved immune globulin for VZV after exposure available in the United States. It was designated as an orphan drug by the FDA and received a priority review.

Most people in the United States have immunity to VZV from vaccination or from having had chickenpox during childhood. However, people without immunity to VZV who are exposed to the virus may experience severe infections that are sometimes fatal.

People most at risk include children or adults with weakened immune systems, pregnant women, and infants exposed during pregnancy or after birth. Occasionally, healthy people without immunity to VZV may contract severe infections. Antiviral treatments are not always effective and cannot be used in some cases.

“This approval fills an unmet need by providing a treatment to lower the risk of severe, potentially fatal varicella infections in vulnerable patients,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research.

Varizig is an antibody preparation manufactured from plasma of healthy donors with high anti-VZV antibody levels. The donated plasma comes from FDA-licensed collection facilities in the United States and Canada. Varizig is administered in two or more injections, depending on the weight of the recipient, within 96 hours after exposure. Varizig is approved for immuno-compromised children and adults, newborns, pregnant women, premature infants, children less than a year old, and adults with no immunity to VZV.

Varicella zoster immune globulin (VZIG) has been shown to lower the risk of severe infections if given soon enough after exposure. An earlier FDA-licensed VZIG was removed from the U.S. market by the manufacturer in 2006, and Varizig has only been available under an investigational expanded access protocol during the licensing process.

In studies Varizig was shown to be comparable to VZIG and was as effective as VZIG in preventing infection during pregnancy. Data on Varizig collected from individuals treated under the expanded access protocol showed a low rate of severe VZV infection in susceptible individuals compared with the rate in untreated individuals.

The studies also showed that Varizig is safe for its intended use, with the most common side effects being pain at the injection site and headache.

Varizig is manufactured by Cangene Corporation in Winnipeg, Canada.

Source: FDA

FDA Approves Gattex

FDA Approves Gattex to Treat Short Bowel Syndrome

December 21, 2012 -- The U.S. Food and Drug Administration today approved Gattex (teduglutide) to treat adults with short bowel syndrome (SBS) who need additional nutrition from intravenous feeding (parenteral nutrition).

SBS is a condition that results from the partial or complete surgical removal of the small and/or large intestine. Extensive loss of the small intestine can lead to poor absorption of fluids and nutrients from food needed to sustain life. As a result, patients with SBS often receive parenteral nutrition.

Gattex is an injection administered once daily that helps improve intestinal absorption of fluids and nutrients, reducing the frequency and volume of parenteral nutrition. It is the third FDA-approved drug to treat adults with SBS receiving nutritional support. Zorbtive (somatropin) and Nutrestore (glutamine) were approved in 2003 and 2004, respectively.

“Today’s approval expands the available treatment options for patients with this life-threatening condition,” said Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Because Gattex may cause other serious health conditions, it is critical that patients and health care professionals understand the drug’s potential and known safety risks.”

Patients treated with Gattex have a potential increased risk of developing cancer and abnormal growths (polyps) in the intestine, obstructions in the intestine, gallbladder disease, biliary tract disease and pancreatic disease. To ensure that the benefits of Gattex outweigh the potential risks, the drug is being approved with a Risk Evaluation and Mitigation Strategy, consisting of a communication plan and training for prescribers.

Gattex’s safety, efficacy and tolerability were evaluated in two clinical trials and two extension studies. Patients in the trials were randomly assigned to receive Gattex or a placebo.

The clinical trials were designed to measure the number of patients who achieved at least 20 percent reduction in the volume of weekly parenteral nutrition after 20 and 24 weeks of treatment (clinical response). Forty-six percent and 63 percent of patients treated with Gattex achieved clinical response, versus 6 percent and 30 percent of patients treated with placebo.

The trials also measured the mean reduction in the volume of parenteral nutrition (liters per week) after 24 weeks of treatment. Results showed a mean reduction in parenteral nutrition of 2.5 L/week and 4.4 L/week in Gattex-treated patients, compared with 0.9 L/week and 2.3 L/week in placebo-treated patients.

The extension studies followed patients treated with Gattex in the clinical trials for an additional 28 weeks. Patients experienced a 4.9 L/week and 5.2 L/week mean reduction in parenteral nutrition after one year of continuous Gattex treatment. Six patients in the extension studies were weaned off parenteral nutrition while on Gattex.

The most common side effects of Gattex identified in clinical trials were abdominal pain, injection site reactions, nausea, headaches, abdominal distension and upper respiratory tract infection.

To study Gattex’s long-term safety, the FDA is requiring a postmarket study of SBS patients treated with the drug in a routine clinical setting to further evaluate the drug’s potential increased risk to cause colorectal cancer and other conditions. Patients in this study will be followed for at least 10 years.

Gattex is marketed by Bedminster, N.J.-based NPS Pharmaceuticals. Zorbtive is marketed by EMD Serono, based in Rockland, Mass. and Nutrestore is marketed by Torrance, Calif.-based Emmaus Medical Inc.

Source: FDA

FDA Approves Bivigam

FDA Approves Biotest's Bivigam, an Intravenous Immune Globulin (Human), 10% Liquid

DREIEICH, Germany and BOCA RATON, Fla., Dec. 20, 2012 /PRNewswire/ -- Biotest AG announced today that Biotest Pharmaceuticals Corporation received approval for BIVIGAM™ for the treatment of patients with Primary Humoral Immunodeficiency (PI) from the U.S. Food and Drug Administration (FDA). BIVIGAM is the first polyspecific intravenous immune globulin manufactured in the U.S. by Biotest Pharmaceuticals Corporation (BPC) at its Boca Raton, Florida facility. This product is being produced for patients in the United States, and the company plans to begin commercial shipments shortly.

Prof. Dr. Gregor Schulz , CEO of Biotest AG, said: "Biotest has made a significant commitment in the U.S. to bring a new immune globulin to individuals with primary immunodeficiency. We have invested over $50 million to create a state-of-the-art facility and have expanded our U.S. capabilities from plasma collection to protein purification and product distribution. BPC will eventually produce up to 1.5 million grams (= 1.5 tons) of BIVIGAM in the U.S. facility. We look forward to providing this therapy to patients in the U.S. This will be another milestone in Biotest's long legacy of providing immune globulin products to patients around the globe."

The U.S. IVIG market is the largest in the world and Biotest's entry into this market fulfills the company's longstanding vision of being a significant global participant. Biotest formed BPC as a U.S. subsidiary in 2007, with the purchase of Nabi Biopharmaceuticals' biologics strategic business unit, which included a plasma protein plant and plasma collection centers. Today's approval represents a sales potential of $100 million for BPC.

Marcia Boyle , President & Founder of the Immune Deficiency Foundation, a national patient organization for persons with primary immunodeficiency diseases, commented, "We commend Biotest for its significant commitment and investment in the development of BIVIGAM. Its launch provides a new product to our community, helping to assure continued access to this lifesaving therapy for people who live with primary immunodeficiency diseases. We welcome BIVIGAM as a valuable option to help members of our community live healthy and productive lives."

The BIVIGAM pivotal clinical study successfully achieved its primary endpoints for safety, efficacy and tolerability, and the results were recently published in the Journal of Clinical Immunology (Wassermann RL, Church JA, Stein M, et al. Safety, efficacy and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeficiency. Journal of Clinical Immunology).
(See Open access at http://dx.doi.org/10.1007/s10875-012-9656-5).

BIVIGAM is a sugar-free, glycine stabilized intravenous immune globulin that was approved by the FDA December 19, 2012 and is available in 50 mL (5 gram) and 100 mL (10 gram) tamper-evident vials. The product uses a label with an integrated hanger and the packaging material is latex free. For Full Prescribing Information and more information about the product, the indication and additional services, please visit www.BIVIGAM.com.

For ordering information, please contact customer support at 1.800.458.4244 and select Option 1.

Disclaimer
This document contains forward-looking statements on overall economic development as well as on the business, earnings, financial and assets position of Biotest AG and its subsidiaries. These statements are based on current plans, estimates, forecasts and expectations of the company and are thus subject to risks and elements of uncertainty that could result in significant deviation of actual developments from expected developments. The forward-looking statements are only valid at the time of publication. Biotest does not intend to update the forward-looking statements and assumes no obligation to do so.

About Biotest AG
Biotest is a provider of pharmaceutical and biotherapeutic drugs. With a value added chain that extends from pre-clinical and clinical development to worldwide sales, Biotest has specialized primarily in the areas of application of clinical immunology, haematology and intensive medicine. In its Plasma Protein portfolio Biotest develops and markets immunoglobulins, coagulation factors and albumins based on human blood plasma. These are used for diseases of the immune and haematopoietic systems. Biotest also researches into the clinical development of monoclonal antibodies, including in the indications of rheumatoid arthritis and cancer of plasma cells. Biotest has more than 1.600 employees worldwide. The preference shares of Biotest AG are listed in the SDAX on the Frankfurt stock exchange.

www.biotest.de

FDA Approves Adasuve

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipolar I Disorder in Adults

MOUNTAIN VIEW, Calif., Dec. 21, 2012 /PRNewswire/ -- Alexza Pharmaceuticals, Inc. announced today that the U.S. Food and Drug Administration (FDA) approved Adasuve (loxapine) Inhalation Powder 10 mg for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Adasuve combines Alexza's proprietary Staccato^® delivery system with the antipsychotic drug, loxapine. The Staccato system is a hand-held inhaler that delivers a drug aerosol to the deep lung that results in rapid systemic delivery and absorption of a drug. See below for Important Safety Information about Adasuve, including Boxed Warnings.

"The approval of Adasuve is an important event in the treatment of agitation. Adasuve is the first approved non-injectable therapy for the acute treatment of agitation in adults with schizophrenia and bipolar I disorder. As noted in the consensus guidelines for Best Practices in the Evaluation and Treatment of Agitation, we believe that the ability to deliver medications rapidly and non-invasively will be important for patients and the professionals who care for them," said Thomas B. King, President and CEO of Alexza. "This is a landmark day for Alexza and we are proud of our accomplishments in developing this unique product. We project that Adasuve will be available for commercial launch early in the third quarter of 2013."

"The data we have seen from the Adasuve Phase 3 clinical trials in patients with schizophrenia and bipolar I disorder are compelling," said Michael Lesem, MD, Executive Medical Director, Claghorn-Lesem Research Clinic, Houston, TX and a principal investigator in the Adasuve clinical trials. "I believe that Adasuve represents an important new and much needed therapeutic option in treating agitation patients who will benefit from a non-coercive therapeutic intervention that works quickly to relieve their symptoms."

The FDA approval is based on a clinical data package involving more than 1,600 patients and subjects. In two Phase 3 trials, Adasuve was found to be effective in the acute treatment of agitation in adults with schizophrenia or bipolar I disorder. In these two studies, Adasuve 10 mg met the primary efficacy endpoint, with statistically significant reductions in agitation as compared to placebo at the two-hour post-dose time point, as well as the principal secondary endpoint. Of note, Adasuve exhibited rapid effects in agitated patients, with statistically significant reductions in agitation apparent starting at 10 minutes following administration of a dose versus placebo^1,2.

As part of the Adasuve development program, Alexza identified a risk of bronchospasm in certain asthma and chronic obstructive pulmonary disease (COPD) patients following dosing with Adasuve. It is important to note that Adasuve can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. Adasuve will be available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS (described below).

Adasuve Partial Prescribing Information (U.S.)
Please click here for Full Prescribing Information, including Boxed WARNINGS, or visitwww.Adasuve.com .

INDICATIONS AND USAGE

Adasuve is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Efficacy was demonstrated in 2 trials in acute agitation: one in schizophrenia and one in bipolar I disorder.
Limitations of Use: Adasuve must be administered only in an enrolled healthcare facility.

IMPORTANT SAFETY INFORMATION

WARNING: BRONCHOSPASM and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS.

Bronchospasm:

· Adasuve can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest

· Adasuve is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS

· Administer Adasuve only in an enrolled healthcare facility that has immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation)

Increased Mortality in Elderly Patients with Dementia-Related Psychosis:

· Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Adasuve is not approved for the treatment of patients with dementia-related psychosis

CONTRAINDICATIONS:

Adasuve is contraindicated in patients with the following:

· Current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), or other lung disease associated with bronchospasm

· Acute respiratory signs / symptoms (e.g., wheezing)

· Current use of medications to treat airways disease, such as asthma or COPD

· History of bronchospasm following Adasuve treatment

· Known hypersensitivity to loxapine and amoxapine

WARNINGS AND PRECAUTIONS:

· Neuroleptic Malignant Syndrome : May develop in patients treated with antipsychotic drugs. Discontinue treatment

· Hypotension and Syncope : Use with caution in patients with known cardiovascular or cerebrovascular disease

· Seizure : Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold

· Potential for Cognitive and Motor Impairment : Use caution when driving or operating machinery

· Cerebrovascular Adverse Reactions : Increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis treated with antipsychotic drugs

ADVERSE REACTIONS:
The most common adverse reactions (incidence ≥ 2% and greater than placebo) in clinical studies in patients with agitation treated with Adasuve were dysgeusia, sedation, throat irritation

Adasuve will be available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Adasuve REMS. Adasuve should only be administered in a healthcare facility enrolled in the Adasuve REMS program that has immediate access on-site to equipment and personnel trained to manage acute bronchospasm, including advanced airway management (intubation and mechanical ventilation). In addition to product labeling, Alexza developed the Adasuve REMS with the purpose of mitigating the risk of bronchospasm. The Adasuve REMS includes a communication plan and an "elements to assure safe use" of the product, including provisions designed to ensure that Adasuve will only be dispensed in healthcare settings that are enrolled in the Adasuve REMS program.

With the Adasuve NDA approval, Alexza also has several post-approval requirements, including a large observational clinical trial designed to gather patient safety data based on the real-world use of Adasuve, as well as a clinical program addressing the safety and efficacy of Adasuve in agitated adolescent patients.

About Agitation Associated with Schizophrenia and Bipolar I Disorder
Agitation is a serious medical problem that can present in a number of psychiatric disorders, including schizophrenia and bipolar I disorder. Of the estimated 3.2 million patients treated for schizophrenia or bipolar I disorder in the U.S.³, about 90% suffer from agitation in their lifetime⁴, due to the natural course of underlying disease or non-compliance with chronic medication. Patients average 11 to 12 episodes of agitation each year⁵.

Agitation episodes may escalate unpredictably and, in some cases, necessitate chemical or physical restraint to relieve the individual's distress and to protect care providers and others in close proximity. Rapid, effective and safe intervention is key to returning the agitated person to a less agitated state.

About Alexza Pharmaceuticals, Inc.
Alexza is a pharmaceutical company focused on the research, development and commercialization of novel, proprietary products for the acute treatment of central nervous system conditions. Alexza's technology, the Staccato system, vaporizes unformulated drug to form a condensation aerosol that, when inhaled, is designed for rapid systemic drug delivery through deep lung inhalation. (Click here to see an animation of how the Staccato system works.)

Adasuve^® (Staccato loxapine) is Alexza's lead therapeutic program. Grupo Ferrer Internacional, S.A is Alexza's commercial partner for Adasuve in Europe, Latin America, Russia and the Commonwealth of Independent States countries. Alexza filed its Adasuve Marketing Authorization Application with the European Medicines Agency (EMA) in October 2011. In December 2012, Alexza received a positive opinion from the EMA's Committee for Medicinal Products for Human Use recommending the approval of Adasuve in the European Union for the rapid control of mild-to-moderate agitation in adult patients with schizophrenia or bipolar disorder. Patients should receive regular treatment immediately after control of acute agitation symptoms. The European Commission is now expected to grant marketing authorization for Adasuve in all 27 European Union Member States, plus Iceland, Lichtenstein and Norway. A decision is expected from the European Commission in the first quarter of 2013.

For more information about Alexza, the Staccato system technology or the Company's development programs, please visit www.alexza.com. For more information about Adasuve, please visit www.Adasuve.com. Adasuve^® and Staccato^® are registered trademarks of Alexza Pharmaceuticals, Inc.

Safe Harbor Statement
This news release contains forward-looking statements that involve significant risks and uncertainties. Any statement describing the Company's expectations or beliefs is a forward-looking statement, as defined in the Private Securities Litigation Reform Act of 1995, and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of developing and commercializing drugs, including the ability for Alexza to effectively and profitably commercialize Adasuve in the US, the impact and risks of the Adasuve post-marketing studies and Risk Evaluation and Mitigation Strategy (REMs) on the commercialization of Adasuve the adequacy of the Company's capital to support the Company's operations and the Company's ability to raise additional funds and the potential terms of such potential financings. The Company's forward-looking statements also involve assumptions that, if they prove incorrect, would cause its results to differ materially from those expressed or implied by such forward-looking statements. These and other risks concerning Alexza's business are described in additional detail in the Company's Annual Report on Form 10-K for the year ended December 31, 2011 and the Company's other Periodic and Current Reports filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

References:

1. Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, Spyker DA, Kehne JH and Cassella JV. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011 Jan;198(1):51-8.

2. Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, Spyker DA, Kehne JH and Cassella JV. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord. 2012 Feb;14(1):31-40.

3. Alexza data on file (Calculation: from NIMH prevalence; Saha 2005; Merikangas K. Lifetime and 12-month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2007. 64(5):543-552.)

4. Alexza data on file (primary market research among caregivers of patients with schizophrenia (95% have agitation) and bipolar patients (87% have agitation))

5. Alexza data on file (primary market research among caregivers of patients with schizophrenia (have an average of 12 agitation episodes per year) and bipolar patients (have an average of 11 agitation episodes per year))

SOURCE Alexza Pharmaceuticals, Inc.

CONTACT: Thomas B. King, President and CEO, +1-650-944-7634, tking@alexza.com; or Karen L. Bergman and Michelle Corral, BCC Partners, +1-650-575-1509 or +1-415-794-8662, kbergman@bccpartners.com or mcorral@bccpartners.com

Web Site: http://www.alexza.com

Posted: December 2012

DRUG RECALLS

Carboplatin Injection by Hospira: Recall - Visible Particulate Matter Identified

December 15, 2012

ISSUE: Hospira, Inc. is further informing the general public about a previously communicated voluntary user-level recall of three lots of Carboplatin Injection due to visible particulates identified during a retain sample inspection. Findings have identified the particles as Carboplatin crystals. If particulate matter from crystallization is injected into a patient, it may potentially become lodged in and obstruct blood vessels, potentially causing local infarction, thromboembolism and vasculitis. Chronically, following sequestration, granulomatous formation in the lungs is possible.

BACKGROUND: Carboplatin Injection is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. Carboplatin Injection is indicated for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with Cisplatin.

RECOMMENDATION: Anyone with an existing inventory should stop use and distribution, quarantine the product immediately, and call Stericycle at 1-877-650-8362 between the hours of 8am and 5pm EST, Monday through Friday, to arrange for the return of the product.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety

Protandim by LifeVantage Corporation: Recall - Possible Metal Fragments in Product

December 7, 2012

ISSUE: LifeVantage Corporation announced a voluntarily recall of Protandim, the Nrf2 Synergizer dietary supplement. The Company is taking this action due to the possible inclusion of small metal fragments in the final product. The fragments were originally discovered in batches of turmeric extract, an ingredient in Protandim that was purchased from a third party supplier.

BACKGROUND: Protandim is packaged in a cylindrical blue bottle and contains thirty caplets per bottle. The potentially affected Protandim lot numbers were distributed in the United States and Japan between July and November 2012. See the Press Release for affected lot numbers. Lot numbers are located on the left side of the product label when looking at the front of the label, directly above the RFID scan bar.

RECOMMENDATION: Consumers who have received bottles of Protandim from the lot numbers identified are encouraged to cease use of such product. The Company will immediately reach out to potentially affected consumers.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

[12/05/2012 - Press Release - LifeVantage Corp]

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Qualitest Hydrocodone Bitartrate and Acetaminophen Tablets 10 mg/500 mg: Recall - Potential for Oversized Tablets

December 7, 2012

ISSUE: Qualitest, a subsidiary of Endo Health Solutions, issued a voluntary nationwide recall for 101 lots of Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/500 mg. Bottles from the affected lots may contain tablets that have a higher dosage of acetaminophen, and as a result, it is possible that consumers could take more than the intended acetaminophen dose.

Unintentional administration of tablets with increased acetaminophen content could result in liver toxicity, especially in patients on other acetaminophen containing medications, patients with liver dysfunction, or people who consume more than 3 alcoholic beverages a day.

Taking a higher dose of hydrocodone than intended could result in an increase in the severity or frequency of side effects, such as sedation or respiratory depression, particularly in patients who are elderly, have severe kidney or liver impairment, or are also taking interacting medications, for example other sedating medications or certain antidepressants.

BACKGROUND: Hydrocodone bitartrate and acetaminophen 10mg/500 mg tablets are indicated for the relief of moderate to moderately severe pain.

The affected lots, were distributed between Feb. 20, 2012 and Nov. 19, 2012 to wholesale distributors and retail pharmacies nationwide.

See Press Release for a list of affected lot numbers.

RECOMMENDATION: Consumers who have the affected lots should contact Qualitest at 1-800-444-4011. Consumers who are unsure if they have the affected lot numbers or have any concerns about their product should consult their pharmacy or health care professional.

Pharmacists and wholesalers are asked to check their inventories for the affected lots, segregate any material from the lots, and to contact MedTurn at 1-800-967-5952 for instructions on product return. Pharmacies that received the affected lots will receive a copy of this press release with their recall notification information to be prominently posted in the pharmacy area.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

FDA Pulls One Generic Form of Wellbutrin Off the Market

WEDNESDAY Dec. 5, 2012 -- People taking the antidepressant Wellbutrin now have one less option for a generic version of the drug.

In October, the U.S. Food and Drug Administration recommended that generic Wellbutrin, or bupropion, made by Impax Laboratories and distributed by Teva Pharmaceuticals, be taken off the market, and Impax and Teva have agreed to stop shipping the drug.

The decision is based on an FDA study that found that the extended release (XL) form of bupropion -- Budeprion XL -- at the 300 milligram (mg) dose was not bioequivalent to brand-name Wellbutrin XL at the same dose, suggesting that it may not be as safe and effective.

The study was published Dec. 5 in the New England Journal of Medicine.

Four other manufacturers make bupropion XL in 300 mg tablets, and patients can still get their prescription filled with these products.

"The other four generic versions of 300 mg extended-release bupropion tablets are not affected by FDA's recent announcement," said FDA spokesperson Sandy Walsh.

Although the agency stated that lack of bioequivalence might only apply to the Impax/Teva product because of its unique formulation, the agency is requesting that the other four manufacturers submit bioequivalence data to the agency by March 2013.

"This kind of result puts a cloud over all of the generic XL [forms of bupropion]," said Dr. David Hellerstein, a professor of psychiatry at Columbia University Medical Center, in New York City.

Companies including Impax/Teva also make a bupropion XL in 150-mg tablets, which are also not affected by the FDA decision.

But even before the FDA decision, Hellerstein avoided any kind of generic bupropion XL. "Patient would complain that generic XL is not the same as brand-name XL -- it wears off sooner, it has more side effects," he said. "I tell patients not to go to XL unless you're committed to taking brand name."

For patients who want a less expensive generic, he recommends sustained release (SR) because there does not seem to be a clinical difference between the brand name and generic versions in that form. SR has to be taken twice a day, while XL is taken once a day.

"If it were me and I could afford it and/or my insurance company allowed me to take it, I would err on the side of caution and take the brand name until the generics were proven at the higher doses to be bioequivalent," said Dr. Sheldon Preskorn, a professor of psychiatry at University of Kansas School of Medicine-Wichita.

The FDA decided to study the bioequivalence of bupropion XL 300 mg made by Impax/Teva to the brand-name counterpart because of adverse events that had been reported to the agency since the generic was approved in 2006.

"The adverse event reports we got included loss of antidepressant effect and, in some instances, worsening of depression symptoms, following a switch from the brand name to a generic product," Walsh said.

Some patients also reported that adverse effects associated with bupropion, including headache, fatigue and anxiety, got worse after switching to Impax/Teva's generic version, Walsh added.

About half of these patients said their depressive symptoms and adverse events improved after switching back to Wellbutrin XL 300 mg, according to the FDA.

"Relapsing of major depression is not inconsequential," Preskorn said. "Major depression causes problems with social functioning, work performance and some level of a suicide risk."

For the bioequivalence study, the FDA measured the level of Wellbutrin and bupropion XL 300 mg in the blood of 24 healthy adult volunteers over the course of the day after taking the medications.

The FDA requires the level of generic drug absorbed in the blood to be, on average, within 80 and 125 percent of the level of the brand-name version. However the range of absorption of bupropion XL was only between 77 and 96 percent of the level of Wellbutrin.

The difference in blood concentration between Wellbutrin and bupropion in this study could explain the clinical difference in safety and effectiveness, Preskorn said. "If the concentration is substantially lower or higher, then your concern would be reduced efficacy or greater likelihood of off-target effects," he said.

Although it is unclear why only the generic XL in 300-mg tablets and not in 150-mg tablets, or only the Impax/Teva version of the 300-mg tablets, would lack bioequivalence, it could be because higher doses of the drug have trouble dissolving in the gastrointestinal tract, Preskorn said.

The FDA approved the generic versions of Wellbutrin XL based on the studies demonstrating bioequivalence at the lower, 150-mg dose.

Typically the FDA recommends that makers of generic drugs test the blood concentration of the drug at the highest dose and then extrapolate bioequivalence data for the lower doses based on these findings.

However, in the case of bupropion, the FDA granted a waiver to companies to test the lower dose because of concern that the higher dose could cause seizures in the volunteers, Walsh wrote.

Either way, extrapolating information about safety and efficacy from one dose is usually appropriate, said Dr. Sidney Wolfe, director of the health research group at Public Citizen, a nonprofit consumer advocacy organization based in Washington, D.C.

"For most drugs, there is such a wide difference between the amount that works and the amount that causes trouble that checking out every single dose is not necessary," he said.

However bupropion might be an exception. Ever since it entered the market in 1985, it was known there was a fine line between antidepressant effect and seizure risk, Wolfe said. The FDA knows which drugs have this type of narrow therapeutic window, and for them it might have been better to check out all the doses, he added.

More information

To learn more about depression and treatments, visit the U.S. National Institute of Mental Health.

Posted: December 2012

Libigrow, Libigrow XXXtreme, Blue Diamond, Blue Diamond Platinum, Mojo Nights, Mojo Nights Supreme, And Casanova: Recall - Undeclared Ingredients Sulfoaildenafil and Thioaildenafil

[Posted 12/18/2012]

ISSUE: Performance Plus Marketing, Inc. Issues a Voluntary Nationwide Recall of Libigrow, Libigrow XXXtreme, Blue Diamond, Blue Diamond Platinum, Mojo Nights, Mojo Nights Supreme, and Casanova because they contain undeclared Sulfoaildenafil and Thioaildenafil. Sulfoaildenafil and thioaildenafil are close in structure to sildenafil and are expected to possess a similar pharmacological and adverse event profile. This poses a threat to consumers because sildenafil may interact with nitrates found in some prescription drugs such as nitroglycerin and may lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take nitrates.

BACKGROUND: These products are marketed as a dietary supplement sexual enhancer for men. The product was sold to distributors and retail stores nationwide and via internet sales.

RECOMMENDATION: Consumers should not consume these products return them immediately to the place of purchase for a full refund. Consumers should contact their physician if they have experienced any problems that may be related to taking these products.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Zicam Extreme Congestion Relief Nasal Gel: Recall - Contamination With Burkholderia Cepacia

ISSUE: Matrixx Initiatives notified the public of a recall of one lot of Zicam Extreme Congestion Relief nasal gel. Burkholderia cepacia was found in a single sample of the product taken from the affected lot. The problem was detected during a routine review at the manufacturing facility. Tests on additional samples from the same lot have shown no evidence of the organism.

Burkholderia cepacia poses little medical risk to healthy individuals. However, Burkholderia cepacia in a nasal spray could cause upper airway colonization and secondarily lead to respiratory infections in individuals with a compromised immune system or those with chronic lung conditions, such as cystic fibrosis. The organism is resistant to many antibiotics and may be difficult to eradicate in this sensitive population if an infection occurs.

The affected lot is 2J23, Expiration 09/15.

BACKGROUND: The product is a non-drip liquid nasal gel used as a nasal decongestant and is packaged in a 0.5 oz. spray bottle contained in an outer carton, bearing NDC number 62750-005-10. The product was distributed to retailers nationwide throughout the United States.

RECOMMENDATION: Matrixx is notifying its distributors and retail customers by FEDEX letter and by phone and is arranging for return of all recalled products. Consumers that have the affected lot of Zicam Extreme Congestion Relief nasal gel should stop using the product and contact Matrixx. See the Press Release for additional information.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

LABEL EXPANSION

FDA Expands Zytiga’s Use for Late-Stage Prostate Cancer

December 10, 2012 -- The U.S. Food and Drug Administration today expanded the approved use of Zytiga (abiraterone acetate) to treat men with late-stage (metastatic) castration-resistant prostate cancer prior to receiving chemotherapy.

The FDA initially approved Zytiga in April 2011 for use in patients whose prostate cancer progressed after treatment with docetaxel, a chemotherapy drug. Zytiga is a pill that decreases the production of male sex hormone testosterone.

In prostate cancer, testosterone stimulates prostate tumors to grow. Drugs or surgery are used to reduce testosterone production or to block testosterone’s effects. Some men have castration-resistant prostate cancer, meaning the prostate cancer cells continue to grow even with low levels of testosterone.

“Today’s approval demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

The FDA reviewed Zytiga’s application for this new indication under the agency’s priority review program. The program provides for an expedited six-month review for drugs that may offer major advances in treatment or provide a treatment when no adequate therapy exists.

Zytiga’s safety and effectiveness for its expanded use were established in a clinical study of 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Participants received either Zytiga or a placebo (sugar pill) in combination with prednisone.

The study was designed to measure the length of time a patient lived before death (overall survival) and the length of time a patient lived without further tumor growth as assessed by imaging studies (radiographic progression-free survival, or rPFS).

Patients who received Zytiga had a median overall survival of 35.3 months compared with 30.1 months for those receiving the placebo. Study results also showed Zytiga improved rPFS. The median rPFS was 8.3 months in the placebo group and had not yet been reached for patients treated with Zytiga at the time of analysis.

The most common side effects reported in those receiving Zytiga include fatigue, joint swelling or discomfort, swelling caused by fluid retention, hot flush, diarrhea, vomiting, cough, high blood pressure, shortness of breath, urinary tract infection, and bruising.

The most common laboratory abnormalities included low red blood cell count; high levels of the enzyme alkaline phosphatase, which can be a sign of other serious medical problems; high levels of fatty acids, sugar, and liver enzymes in the blood; and low levels of lymphocytes, phosphorous and potassium in the blood.

Zytiga is marketed by Horsham, Pa.-based Janssen Biotech Inc.

Source: FDA

Posted: December 2012

FDA Expands Tamiflu's Use to Treat Children Younger Than One Year

December 21, 2012 -- The U.S. Food and Drug Administration today expanded the approved use of Tamiflu (oseltamivir) to treat children as young as 2 weeks old who have shown symptoms of flu for no longer than two days.

The drug is not approved to prevent flu infection in this population. In addition, the safety and efficacy of Tamiflu to treat flu infection has not been established in children younger than 2 weeks old.

Tamiflu was approved in 1999 to treat adults infected with flu who have shown symptoms for no longer than two days. It has since been approved to treat flu in children ages 1 year and older who have shown symptoms of flu for no longer than two days, and to prevent flu in adults and children ages 1 year and older.

Although there is a fixed dosing regimen for patients 1 year and older according to weight categories, the dosing for children younger than 1 year must be calculated for each patient based on their exact weight. These children should receive 3 milligrams per kilogram twice daily for five days. These smaller doses will require a different dispenser than what is currently co-packaged with Tamiflu.

“Pharmacists must provide the proper dispenser when filling a prescription so parents can measure and administer the correct dose to their children,” said Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “Parents and pediatricians must make sure children receive only the amount of Tamiflu appropriate for their weight.”

Tamiflu is the only product approved to treat flu infection in children younger than 1 year old, providing an important treatment option for a vulnerable population. According to the Centers for Disease Control and Prevention (CDC), children younger than 2 years are at higher risk for developing complications from the flu, with the highest rates of hospitalization in those less than 6 months of age.

The FDA expanded the approved use of Tamiflu in children younger than 1 year based on extrapolation of data from previous study results in adults and older children, and additional supporting safety and pharmacokinetic studies sponsored by both the National Institutes of Health and Roche Group, Tamiflu’s manufacturer.

Pediatric legislation permits efficacy to be extrapolated from previous study results in adults and older children if the illness being studied and the effects of the drug are sufficiently similar in adult and pediatric patients. Data on how the drug is metabolized in the body (pharmacokinetic data) indicated a dose of 3 mg/kg twice daily provided concentrations of Tamiflu similar to those observed in older children and adults, and is expected to provide similar efficacy in this very young age group.

Almost all of the 135 pediatric patients enrolled in the two safety studies had confirmed flu. Results from these studies showed the safety profile in children younger than 1 year was consistent with the established safety profile of adults and older children. The most common side effects reported with Tamiflu use in this age group include vomiting and diarrhea. Although not seen in the new studies, rare cases of severe rash, skin reactions, hallucinations, delirium, and abnormal behavior have been reported.

The FDA monitors drugs for side effects and believes reporting side effects is important. Health care professionals and patients should report any side effects associated with Tamiflu’s use to FDA’s MedWatch program.

Tamiflu is not a substitute for early, annual flu vaccination, as recommended by the CDC’s Advisory Committee on Immunization Practices. CDC recommends all persons aged 6 months and older receive an annual flu vaccine.

Tamiflu is distributed in the United States by South San Francisco-based Genentech, a member of the Roche Group.

Source: FDA

DRUG SAFETY COMMUNICATION

Xyrem (sodium oxybate): Warning Against Use With Alcohol or Drugs Causing Respiratory Depression

FDA reminded healthcare professionals and patients that the combined use of Xyrem(sodium oxybate) with alcohol or central nervous system (CNS) depressant drugs can markedly impair consciousness and may lead to severe breathing problems (respiratory depression). The use of alcohol with Xyrem is a new contraindication added to the Xyrem label, which already contraindicates its use with insomnia drugs. The use of Xyrem with other CNS depressant drugs such as opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, general anesthetics, and muscle relaxants should generally be avoided.

The use of Xyrem along with these products or other CNS depressants increases the risk of breathing problems that may lead to loss of consciousness, coma, and death.

BACKGROUND: Xyrem (sodium oxybate) is FDA-approved to reduce attacks of muscle weakness (cataplexy) and treat daytime sleepiness in patients with narcolepsy. Sodium oxybate, the active ingredient of Xyrem, is also known as gamma-hydroxybutyrate (GHB). GHB is a known drug of abuse that has been associated with central nervous system (CNS) adverse events, including death. Even at recommended doses, Xyrem can cause confusion, depression, and other neuropsychiatric events.

RECOMMENDATION: Healthcare professionals are urged to follow the dosing recommendations, contraindications, and boxed warning in the updated Xyrem drug label and to avoid drug combinations that raise the risk of respiratory depression and death. Patients taking Xyrem should not drink alcohol or take insomnia drugs. See the FDA Drug Safety Communication for a Data Summary.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Chantix (Varenicline): Safety Communication - Updated Safety Review On The Risk of Cardiovascular Adverse Events

ISSUE: FDA is informing the public about the results of a large, combined analysis (called a meta-analysis) of clinical trials that compared patients who received the smoking cessation drugChantix (varenicline) to patients who received a placebo (an inactive treatment). A higher occurrence of major adverse cardiovascular events (a combined outcome of cardiovascular-related death, nonfatal heart attack, and nonfatal stroke) was observed in patients using Chantix compared to placebo. These events were uncommon in both the Chantix and placebo groups, and the increased risk was not statistically significant, which means it is uncertain whether the excess risk for the Chantix group was due to the drug or due to chance.

BACKGROUND: Chantix is a prescription medicine used to help adults quit smoking that works by blocking the effects of nicotine (from smoking) on the brain. FDA first notified the public about a possible increased risk of cardiovascular adverse events with Chantix in its June 2011 Drug Safety Communication (DSC). FDA required the manufacturer of Chantix to conduct the meta-analysis to further evaluate the cardiovascular safety of the drug, and believes it is important to let health care professionals and patients know about the results of this study. The meta-analysis findings of cardiovascular risk are similar to the findings in the smoking cessation clinical trial of patients with stable cardiovascular disease that was described in FDA’s June 16, 2011 DSC. The Warnings and Precautions section of the Chantix label has been updated to include the results of the meta-analysis.

RECOMMENDATION: Health care professionals are advised to weigh the risks of Chantix against the benefits of its use. It is important to note that smoking is a major risk factor for cardiovascular disease, and Chantix is effective in helping patients to quit smoking and abstain from it for as long as one year. The health benefits of quitting smoking are immediate and substantial.

Patients taking Chantix should contact their health care professional if they experience new or worsening symptoms of cardiovascular disease, such as chest pain, shortness of breath, calf pain when walking, or sudden onset of weakness, numbness, or difficulty speaking. Patients should also contact their health care professional if they have any questions or concerns about Chantix.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

December 12, 2012

FDA Drug Safety Communication: Important Change to Heparin Container Labels to Clearly State the Total Drug Strength

Safety Announcement

[12-06-2012] The U.S. Food and Drug Administration (FDA) is notifying health care professionals, caregivers, and patients about a change to the container and carton labels for heparin products, which are blood-thinning agents that prevent the formation of blood clots.

Facts about heparin

· A blood thinner that works by decreasing the clotting ability of the blood

· Used to prevent blood clots from forming in people who have certain medical conditions or who are undergoing certain medical procedures that may increase the chance that clots will form

· Used to stop the growth of clots that have already formed in the blood vessels and to prevent blood clots from forming in catheters that are left in veins over a period of time

This label change will require manufacturers of Heparin Lock Flush Solution, USP and Heparin Sodium Injection, USP to clearly state the strength of the entire container of the medication followed by how much of the medication is in 1 milliliter (mL). These modifications will eliminate the need for health care professionals to calculate the total amount of heparin medication in a product containing more than 1 mL, thereby reducing the risk of miscalculations that may result in medication errors.

FDA supports the United States Pharmacopeia (USP)* proposal to revise the labeling section of USP monographs for Heparin Lock Flush Solution, USP and Heparin Sodium Injection, USP to clearly state the total drug strength on the label. This will ensure that labels for heparin products comply with USP’s general requirements for all small-volume injectable products, which currently display the total drug content.

Health care professionals, caregivers, and patients should be aware that that there will be a transition period before and after the official implementation date on May 1, 2013, during which both the current heparin container labels and the revised heparin container labels will be available in the marketplace. To minimize the potential for medication errors, users should consider separating the supplies of “current” and “revised” labeled heparin, and use all of the supplies of the “current” heparin before using products with the “revised” container label.

*USP is a scientific nonprofit organization that develops standards for the identity, strength, quality, and purity of drugs and drug ingredients marketed in the U.S. These standards are published in USP’s official compendia, U.S. Pharmacopeia and National Formulary.

Current and Revised Heparin Labels

Current Heparin Label

Revised Heparin Label

The proposed revision to the labeling sections in the heparin monographs will require the labels to comply with the USP standards for injectable medications, specifically USP 35 -NF 30 General Chapter <1> Injections section.

The following formats are those FDA considers acceptable for heparin vials and syringes that contain more than 1 mL:

The strength per total volume should be the primary and prominent expression on the principal display panel of the label, followed in close proximity by strength per mL enclosed by parentheses.

Example 1:

50,000 USP units per 10 mL
(5,000 USP units per mL)

Example 2:

50,000 USP units/10 mL
(5,000 USP units/mL)

The following format is acceptable for contents of less than 1 mL:

The strength per fraction of a mL should be the only expression of strength.

100 USP units/0.5 mL

Strength per single mL should be expressed as mg/mL, not mg/1 mL.

5,000 USP units/mL

Additional Information for Patients and Caregivers

· Always ask your health care professional to look at the label on the heparin container and to check the dose and volume to be administered.

· Contact your health care professional if you have any questions or concerns about heparin.

· Report medication errors or side effects from the use of heparin to FDA’s MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.

Additional Information for Health Care Professionals, Hospitals, and Pharmacies

· To minimize the potential for medication errors, hospitals and pharmacies may wish to consider separating the supplies of “current” and “revised” labeled heparin and exhausting the supplies of the “current” heparin before transitioning to products with the “revised” label.

· Always look at the label on the heparin vial being dispensed and counsel the patient or caregiver on how to administer the correct dose.

· Report medication errors or adverse events involving heparin to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of this page.

Additional Background Information

In 2003, the United States Pharmacopeia’s (USP) Safe Medication Use Expert Committee became aware of medication errors involving the expression of strength in the labeling for all injectable products. Containers labeled with the strength per mL were often misunderstood as the total drug content, which could result in dosing errors with serious consequences to patients. To address this safety issue, the USP Parenteral Products?Industrial Expert Committee approved the new “Strength and Total Volume for Single- and Multiple-Dose Injectable Drug Products” section of the USP General Chapter <1> Injections in 2007, and the text became official on February 1, 2009. General Chapter <1> requires that the strength per total volume should be the primary and prominent expression of strength on the principal display panel of the label, followed in close proximity by strength per mL enclosed by parentheses. Container labels that have already been changed to state the strength per total volume have had no reported medication errors.

Since 2009, concerns have arisen about the conflict in labeling requirements between the Heparin Sodium Injection and Heparin Lock Flush Solution monographs and the General Chapter <1> Injections section on “Strength and Total Volume for Single- and Multiple-Dose Injectable Drug Products.” The labeling requirement in the current heparin monographs states that the label must reflect only strength per mL, except it also allows for single-dose vials to be labeled additionally to indicate the total drug content. To address this conflict, USP has proposed revising the labeling section of the heparin monographs to ensure that the heparin container labels comply with the USP General Chapter <1> Injections section.

The proposed revision to the labeling sections in the heparin monographs will require the container labels to comply with the USP 35 -NF 30 General Chapter <1> Injections section that reads in part:

“[T]he strength per total volume should be the primary and prominent expression on the principal display panel of the label, followed in close proximity by strength per mL enclosed by parentheses. For containers holding a volume of less than 1 mL, the strength per fraction of a mL should be the only expression of strength. Strength per single mL should be expressed as mg/mL, not mg/1 mL.”

The official implementation date for the USP Heparin Lock Flush Solution and USP Heparin Sodium Injection monographs is May 1, 2013. Manufacturers are expected to have revised their heparin labels accordingly by that time. A transition period will occur during which both the current heparin container labels and the revised heparin container labels will appear in the marketplace.

FDA Drug Safety Communication: Updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products

Safety Announcement

[12-4-2012] The U.S. Food and Drug Administration (FDA) is notifying health care professionals that the 32 mg, single intravenous (IV) dose of the anti-nausea drug Zofran (ondansetron hydrochloride) will no longer be marketed because of the potential for serious cardiac risks. This dose has been removed from the Zofran drug label. FDA is now working with the manufacturers of all 32 mg dose ondansetron injectable products (brand and generic) to voluntarily recall them from the market. These drugs are sold pre-mixed in solutions of either dextrose or sodium chloride in plastic containers (See Table 1).

A previous Drug Safety Communication (DSC), issued on June 29, 2012², communicated that the 32 mg, single IV dose should be avoided due to the risk of a specific type of irregular heart rhythm called QT interval prolongation, which can lead to Torsades de Pointes, an abnormal, potentially fatal heart rhythm.

The 32 mg, single IV dose had been used to prevent chemotherapy-induced nausea and vomiting. As stated in the previous DSC, FDA continues to recommend the intravenous regimen of 0.15 mg/kg administered every 4 hours for three doses to prevent chemotherapy-induced nausea and vomiting. If the calculated weight-based dose were to exceed 16 mg, the potential for prolonged QT interval would be greater; therefore, no single intravenous dose should exceed 16 mg. In addition, oral dosing of ondansetron³ remains effective for the prevention of chemotherapy-induced nausea and vomiting. At this time, there is not enough information available for FDA to recommend an alternative single IV dose regimen.

FDA anticipates these products (see Table 1, below) to be removed from the market through early 2013. FDA does not anticipate that removal of the 32 mg intravenous dose of ondansetron currently sold as pre-mixed injections will contribute to a drug shortage of IV ondansetron, as the 32 mg dose makes up a very small percentage of the current market. According to sales distribution data, ondansetron IV 32 mg premixed bags accounted for less than 1% of ondansetron IV sales (vials, bags, etc.) from the manufacturers to retail and non-retail channels of distribution in the 12-month period ending in June 2012.¹

Table 1. List of ondansetron products to be voluntarily withdrawn from the U.S. market

Generic name	Sponsor	Application Number
Ondansetron Hydrochloride Injection, USP premix in Intravia Plastic Container	Baxter Healthcare Corporation	NDA 021915
Ondansetron Hydrochloride and Dextrose in Plastic Container	Hospira	ANDA 077348
Ondansetron Hydrochloride and Dextrose in Plastic Container	Teva	ANDA 077480
Ondansetron Hydrochloride and Dextrose in Plastic Container	Bedford Labs	ANDA 078291
Ondansetron Hydrochloride and Dextrose in Plastic Container	Claris Lifesciences	ANDA 078308

Reference

1. Source: IMS Health, IMS National Sales Perspectives™. July 2011-June 2012. Extracted Nov 2012.

FDA: Don't Use Pradaxa Blood Thinner in Patients With Artificial Heart Valves

THURSDAY Dec. 20, 2012 -- The blood thinner Pradaxa should not be used to prevent stroke or blood clots in patients with mechanical heart valves, the U.S. Food and Drug Administration said in a warning issued Wednesday.

As the agency noted, a clinical trial in Europe was halted recently because patients taking Pradaxa (dabigatran) were more likely to suffer strokes, heart attacks and clots forming on their mechanical heart valves than patients who were taking the older blood thinner warfarin.

Patients in the study who were taking Pradaxa also had more bleeding after valve surgery, the agency said.

Doctors should immediately switch patients with a mechanical heart valve who are taking Pradaxa to another medication, the FDA said. The use of Pradaxa in patients with heart valve replacements made of natural biological tissue has not been evaluated and cannot be recommended, the agency added.

The message for patients is that anyone who has received any type of heart valve replacement and is taking Pradaxa should talk to their doctor as soon as possible to determine the most appropriate type of blood thinner (anticoagulant) to take, the FDA said.

Consultation with a physician is crucial, agency officials said, because stopping anticoagulant drugs without seeking advice from their doctor first can increase the risk of blood clots and stroke.

Pradaxa is approved to treat patients with a common heart rhythm disorder called atrial fibrillation. It is not approved to treat patients with atrial fibrillation caused by heart valve problems, the FDA said.

More information

The American Heart Association has more about heart valves.

Posted: December 2012

Reumofan Plus Dietary Supplement Relabeled and Sold as “WOW”: Public Warning - Undeclared Drug Ingredients

ISSUE: The U.S. Food and Drug Administration (FDA) is warning the public that the potentially harmful dietary supplement product Reumofan Plus is being relabeled and sold under the name “WOW.” The product is being marketed to treat arthritis, muscle pain, osteoporosis, bone cancer, and other conditions. FDA laboratory analysis confirmed that “WOW” contains the same prescription drug ingredients that are in Reumofan Plus, including dexamethasone (a corticosteroid), diclofenac sodium (a non-steroidal anti-inflammatory drug), and methocarbamol(a muscle relaxant). These ingredients have the potential to cause serious injury.

BACKGROUND: FDA warned the public of the harm of Reumofan Plus on June 1, 2012, and again on August 21, 2012. Since June, FDA has received dozens of adverse event reports, many of them serious, from consumers who used Reumofan Plus. The reports include liver injury, severe bleeding, corticosteroid withdrawal syndrome, adrenal suppression, stroke, and even death.

Reumofan Plus and “WOW” products are sold on various websites, includingwww.gonepainfree.com andwww.browerent.com. The products are manufactured by Riger Naturals S.A. In addition to websites selling “WOW,” FDA has become aware that various websites, including www.reumofanusa.com, owned by Reumofan USA, LLC, continue to sell Reumofan Plus even after previous FDA warnings. Please see the link to the FDA public warning for product photos.

RECOMMENDATION: Consumers currently taking or who have taken Reumofan Plus or “WOW” should immediately consult a health care professional. Health care professionals are urged to ask their patients about the use of Reumofan Plus, “WOW,” and other similar products marketed as dietary supplements when patients present with unexplained symptoms that suggest NSAID toxicity, psychiatric changes, or the use or abrupt discontinuation of corticosteroids.
Additionally, health care professionals should evaluate patients who have used Reumofan Plus and/or WOW for drug and disease interactions involving diclofenac, methocarbamol, and corticosteroids, and consider whether a corticosteroid taper regimen may be appropriate.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of Reumofan Plus products and “WOW” to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.

Incivek (telaprevir) In Combination with Drugs Peginterferon Alfa and Ribavirin (Incivek combination treatment): Drug Safety Communication - Serious Skin Reactions

ISSUE: FDA received reports of serious skin reactions, some fatal, in patients taking the hepatitis C drug Incivek (telaprevir) in combination with the drugs peginterferon alfa and ribavirin (Incivek combination treatment). Some patients died when they continued to receive Incivek combination treatment after developing a worsening, or progressive rash and systemic symptoms (symptoms affecting the entire body).

See the FDA Drug Safety Communication Data Summary section for additional information.

FDA is adding a boxed warning to the Incivek drug label stating that Incivek combination treatment must be immediately stopped in patients experiencing a rash with systemic symptoms or a progressive severe rash.

BACKGROUND: Incivek is a hepatic C virus NS3/4A protease inhibitor indicated in combination with peginterferon alfa and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including patients who have cirrhosis, are treatment-naïve, or who have been previously received interferon-based treatment.

RECOMMENDATIONS: Make sure your patients know that rash may occur with Incivek combination treatment, and explain the signs and symptoms of severe skin reaction and when to seek care.

If serious skin reactions occur, all three components of Incivek combination treatment, including peginterferon alfa and ribavirin, must be immediately discontinued, and the patient should receive urgent medical care. Consideration should also be given to stopping any other medications that may be associated with serious skin reactions.

· Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

· Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Updated CVD Risks With Varenicline: FDA

BETHESDA, Maryland — The US Food and Drug Administration (FDA) issued new information this week warning physicians that the smoking-cessation aid varenicline (Chantix, Pfizer) may increase the risk of cardiovascular events in adults with cardiovascular disease [1]. In a new meta-analysis, a higher number of major adverse cardiovascular events, a combined end point that included cardiovascular mortality, nonfatal MI, and nonfatal stroke, were observed among those treated with varenicline.

Event rates were low and not statistically significant when compared with placebo. "However, the data were analyzed many different ways and consistently showed a higher occurrence of events in patients using Chantix, which makes it seem more likely that it is related to the drug and not purely a chance finding," states the FDA.

In the full meta-analysis of 15 studies, 0.31% of 4190 patients treated with varenicline had a major adverse cardiovascular event vs 0.21% of 2812 patients treated with placebo.

In 2011, the varenicline label was changed to warn physicians and patients about a potential increased risk of cardiovascular events with the drug. The label has now been updated with the new information. The meta-analysis was requested by the FDA after a 700-patient study showed an increased risk of adverse cardiovascular events with varenicline. Like the meta-analysis, the study showed a trend toward a higher number of major adverse cardiovascular events among those treated with varenicline.

The drug label warns physicians that while varenicline is effective in helping patients with cardiovascular disease quit smoking, it is also associated with a small increased risk of cardiovascular adverse events in this patient population. The FDA is advising physicians to "weigh the known benefits of Chantix against the potential risks of its use in smokers with cardiovascular disease" and report adverse events to the MedWatch program.

GENERAL INFORMATIONS

Most Coughs Don't Respond to Antibiotics, Study Confirms

TUESDAY Dec. 18, 2012 -- Commonly prescribed antibiotics don't help cure most coughs in adults, new research confirms.

Patients with a cough or bronchitis are often prescribed antibiotics, and previous studies have had conflicting results about their effectiveness. For this study, researchers randomly assigned more than 2,000 adults complaining of a cough to take either the antibiotic amoxicillin for a week or an inactive placebo.

Overall, the antibiotic was no more effective at relieving symptoms or their duration than the placebo, the study found. The findings also held among people who were older than 60.

"The main message here is that antibiotics are usually not necessary for respiratory infections, if pneumonia is not suspected," said Dr. Philipp Schuetz of the Kantonsspital Aarau in Switzerland.

"Only a few patients benefit from antibiotics and these may be identified with new blood tests for bacterial infections," said Schuetz, who wrote an editorial accompanying the study. "Physicians and patients should generally refrain from antibiotic use, yet, if they feel unsure, the blood test helps them to further minimize risks."

Study participants were 18 and older and had sought treatment for an acute cough -- meaning they'd had the cough for less than a month -- which is one of the most common illnesses seen by primary care doctors. There was no reason to suspect that any of them had the lung infection pneumonia, which is treated with antibiotics.

Participants took the antibiotic three times daily for seven days. While they had no better recovery than those taking the dummy pills, they were more likely to report side effects such as nausea, rash and diarrhea, according to the study, published online Dec. 19 in The Lancet Infectious Diseases.

That said, more people in the placebo group did experience new or worsening symptoms, but this did not occur frequently enough to justify treating everyone with antibiotics. Thirty people would need to be treated with antibiotics to prevent one person from developing new or worsening symptoms, the study found.

The study is the largest to date that shows antibiotics do not help treat lower-respiratory infections, the researchers say.

Indiscriminate use of antibiotics may also pose risks, Schuetz said. "The main risk from antibiotics is related to direct side effects such as severe diarrhea," he said. "The other risk relates to emergence of multi-resistant bacteria, which on a population level are a threat to society as antibiotics may not work properly."

Dr. Len Horovitz, a pulmonologist at Lenox Hill Hospital in New York City, said that many patients beg for antibiotics to nip a cold in the bud. "This is not how it works," he said. "Viruses such as the common cold do not respond to antibiotics."

So what does work? "Comfort care, such as more sleep, drinking lots of fluids, and using a humidifier at night," he said. "If you have a cough or lower respiratory tract infection, go to the doctor and let him examine you." The doctor can take a culture of any mucus that comes up with the cough to see if there is a bacteria present, he explained.

"Getting antibiotics for a dry cough without taking a culture is doing a disservice," he said. "There is no benefit and there may be a slight risk."

More information

Learn more about the common cold, at the U.S. Centers for Disease Control and Prevention.

Posted: December 2012

Treating Kidneys With Radio Waves May Ease Tough-to-Control Hypertension

MONDAY Dec. 17, 2012 -- For patients whose high blood pressure cannot be controlled despite taking several medications, a short burst of radio waves at the nerves around the kidneys may do the trick, a small new study says.

The treatment was effective for at least six months. The findings could be a significant step in treating people with resistant hypertension, which is a major risk factor for heart attack and stroke, the researchers said.

The technique -- called catheter-based renal denervation -- is minimally invasive. In it, doctors use a catheter inserted through the artery in the groin, which sends radio waves burning away nerve tissue around the arteries that feed the kidneys.

The procedure destroys nerves that help control and filter salt in the body and may be overactive in patients with high blood pressure. The U.S. Food and Drug Administration has not yet approved its use.

The study was funded by medical device maker Medtronic. The findings were published Dec. 17 in the journal Circulation.

"This is a very promising approach for managing medication-resistant hypertension," said Dr. Gregg Fonarow, a spokesman for the American Heart Association and professor of cardiology at the University of California, Los Angeles.

"High blood pressure is a major contributor to heart attack, stroke, heart failure, and [kidney] failure," said Fonarow, who was not involved in the study. "Despite the availability of a number of effective medications, many patients with hypertension have not achieved adequate control of their blood pressure. There is thus an important, but currently unmet, need for additional therapies to effectively control hypertension."

For the study, an international team lead by Dr. Murray Esler, professor and senior director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia, assigned 35 patients to renal denervation and compared them to 47 patients who had already had the procedure.

All the patients suffered from drug-resistant hypertension. Their systolic blood pressure -- the top number in a blood-pressure reading -- remained dangerously high at 160 millimeters of mercury (mmHg) or above despite having taking three or more drugs to control blood pressure, the researchers noted.

Esler's team found that more than 83 percent of those who had denervation treatment before had a drop in systolic blood pressure of at least 10 mmHg after six months and almost 79 percent maintained the reduction at 12 months.

The 35 patients in this phase of the study had similar results to the initial group. Almost 63 percent of these patients saw a reduction in systolic blood pressure of 10 mmHg or more six months after treatment.

Fonarow noted: "In all, reductions in systolic blood-pressure levels on the order of 25 to 30 mmHg were achieved and maintained without any loss in efficacy."

The procedure is safe as well as effective, the study authors said.

"Participants' kidneys were not damaged or functionally impaired," Esler said in a journal news release. "We also found no ill effects on long-term health from the procedure."

Whether this technique might be useful in treating less severe high blood pressure hasn't yet been tested. If it is applicable, it could mean patients need not take blood-pressure drugs, Esler suggested.

Another expert, however, said that scenario is likely overoptimistic.

"Hypertension is a hard disease to treat because there are so many things that go into getting blood pressure under control," said Dr. Varinder Singh, an interventional cardiologist at Lenox Hill Hospital in New York City. "There's lifestyle and diet, there is getting to the right doses of medications, there are adherence issues. So anything that will help patients get their goals is exciting."

Even with this technique, people will most likely still have to take blood-pressure medications, Singh said. "You may have to take less medication and you may have to take lower doses of medication, but we all expect that patients will still have to take some medication," he said.

Singh also noted that although this procedure is used in other countries it is not yet approved in the United States.

Fonarow added: "While this study demonstrates that renal denervation provides sustained reduction of blood pressure up to one year and appears safe, additional studies with longer-term follow-up are needed."

According to the American Heart Association, more than 78 million adults in the United States have high blood pressure, which is blood pressure higher than 140/90 mmHg.

Among these adults, about 9 percent have resistant hypertension, which means that even taking three or more medications to control their blood pressure, it remains higher than 140/90 mmHg.

More information

To learn more about hypertension, visit the U.S. National Library of Medicine.

Posted: December 2012

Vitamin D Levels Linked to Daytime Sleepiness

FRIDAY Dec. 14, 2012 -- A strong but complicated association exists between vitamin D levels and daytime sleepiness, and race is a major factor, according to a small new study.

The study included 81 sleep clinic patients who were eventually diagnosed with a sleep disorder. Most of the patients were found to have obstructive sleep apnea. People with obstructive sleep apnea experience repeated breathing interruptions while they sleep.

The patients' levels of daytime sleepiness were assessed and blood samples were taken to measure their vitamin D levels.

Among patients with normal vitamin D levels, progressively higher levels of daytime sleepiness were associated with progressively lower levels of vitamin D, the investigators found.

Among patients with vitamin D deficiency, an association between vitamin D levels and daytime sleepiness was seen only in black patients. But in these patients, higher vitamin D levels were associated with higher levels of daytime sleepiness, according to the study published online Dec. 15 in the Journal of Clinical Sleep Medicine.

"While we found a significant correlation between vitamin D and sleepiness, the relationship appears to be more complex than we had originally thought," principal investigator Dr. David McCarty said in a news release from the American Academy of Sleep Medicine.

"It's important to now do a follow-up study and look deeper into this correlation," he added.

This study is the first to demonstrate a significant association between vitamin D levels and sleepiness, according to the researchers. They said it makes sense that race would affect this relationship because darker skin is a known risk factor for low vitamin D levels. This is because the body makes vitamin D, sometimes called the "sunshine" vitamin, when the skin is directly exposed to the sun.

While the study found an association between daytime sleepiness and vitamin D blood levels, it did not prove a cause-and-effect relationship.

Blood Cancer Patients May Benefit From New Transplant Technique

WEDNESDAY Dec. 12, 2012 -- Researchers who have multiplied umbilical cord-blood cells in the laboratory say their technique might improve recovery for patients needing blood stem cell transplants to treat a blood cancer.

Their approach, still in the experimental stage, involves expanding normal blood cells from donated cord blood in conditions similar to those in bone marrow. This greatly enlarges the supply needed for transplant. And because umbilical cord blood is more easily matched in patients than donor bone marrow, the recovery period is safer and shorter, the researchers said.

"Since our very first patients, we had a very strong signal [of success]," said Dr. Marcos de Lima, who led the study while at the University of Texas M.D. Anderson Cancer Center in Houston.

"Recipients of cord-blood transplants are less likely to have some of the complications with the same degree of matching with bone marrow transplants. So if we can be less picky with the matching, immediately our inventory is bigger," said de Lima, now a professor of medicine at Case Western Reserve University School of Medicine in Cleveland.

For the study, scientists at M.D. Anderson multiplied blood cells from one of two cords transplanted into 31 patients suffering from blood-borne cancers such as leukemia, lymphoma and myeloma. Compared to 80 patients receiving a standard double-cord blood transplant, these patients established a normal blood supply faster and were more likely to survive 100 days post-transplant.

The study is published Dec. 13 in the New England Journal of Medicine.

Each year more than 100,000 cases of blood, bone marrow and lymph node cancers are diagnosed in the United States, and more than 50,000 people die from these cancers, according to the U.S. Centers for Disease Control and Prevention. For many of these patients, the only chance of a cure lies in stem cells retrieved from bone marrow, peripheral blood or umbilical cord transplants, which can re-establish a normal blood supply after diseased cells are destroyed by chemotherapy and/or radiation.

The blood stem cells can develop into any type of blood cell -- white, red or platelets.

But only about 25 percent of those needing a blood stem cell transplant have a matching donor, which can complicate or sabotage the patient's recovery. While cord blood is more easily matched genetically, de Lima said, even two cords provide far fewer cells needed by adult recipients than bone marrow or peripheral blood donations.

In the lab, de Lima and his colleagues took blood from one of the two donated umbilical cords and expanded it on a bed of so-called mesenchymal precursor cells, which in the bone marrow serve to grow a healthy blood supply.

The amount of time it took for the expanded cord blood cells to "engraft" -- or firmly establish -- in patients was significantly quicker than in the comparison group, leading to less risk of complications from low numbers of white blood cells and platelets, which fight infection and control bleeding, respectively.

One expert welcomed the findings.

"Cord blood and transplant doctors have been trying over the years to increase the number of stem cells in test tubes, and those methods have slowly been developing. This report is the first important study where this is not only feasible but practical," said Dr. Kanti Rai, a hematologist/oncologist with the North Shore-LIJ Health System in New Hyde Park, N.Y. "If this methodology can become reproducible in other people's hands ... then it opens a whole new opportunity for cancer patients."

Stressing that the results need to be duplicated in late-stage trials, de Lima refused to speculate how the new cord blood expansion method might affect cure rates.

"What we're offering folks is a less toxic [treatment] and hopefully a transplant that would be safer, with a shorter stay in the hospital," he said. "I hope it may one day improve the so-called cure rates simply because more people will survive this initial [period]."

Avastin Shows No Benefit for Earlier Colon Cancer: Study

TUESDAY Dec. 11, 2012 -- Adding the pricey cancer drug Avastin to standard chemotherapy for earlier-stage colon cancer does not extend patients' lives, a new clinical trial finds.

Avastin, known generically as bevacizumab, is approved in the United States to treat advanced-stage colon cancer that has spread to distant sites in the body -- what doctors call metastatic cancer.

Other research has shown that adding Avastin to standard drugs can extend those patients' lives by a few months.

The new trial was set up to see whether the drug could also help patients with earlier-stage cancer, explained lead researcher Dr. Carmen Allegra, chief of hematology and oncology at the University of Florida, in Gainesville.

He and his colleagues found no evidence that the expensive drug -- priced at around $5,000 per month -- kept patients in remission longer or lengthened their lives.

Doctors not involved in the study said it added to evidence that Avastin is of no use to patients with earlier-stage, curable colon cancer.

"I think it's time to move on," said Dr. Jennifer Obel, a medical oncologist with the NorthShore University Health System in suburban Chicago.

The study, reported online Dec. 10 in the Journal of Clinical Oncology, included 2,673 patients who'd had surgery for stage 2 or stage 3 colon cancer -- meaning the tumor was either confined to the colon or had spread no farther than the lymph nodes.

All of the patients were getting "adjuvant," or follow-up, chemotherapy to hopefully take care of any remaining tumor cells and cut the odds of a recurrence.

Allegra's team randomly assigned half of the patients to receive six months of standard chemotherapy -- a three-drug regimen of fluorouracil, leucovorin and oxaliplatin. The other half received that therapy, plus Avastin for one year.

In the end, the addition of Avastin made no difference in survival: About three-quarters of patients in each group were in remission three years later. And five years out, just over 80 percent in each group were still alive.

The findings are similar to those of another trial reported this month, called AVANT, that found Avastin did not help stage 3 colon cancer patients.

"There's no evidence to suggest that this drug should be given in the adjuvant setting," said Dr. Frank Sinicrope, a professor of medicine and oncology at the Mayo Clinic in Rochester, Minn.

Avastin is one of a group of newer, so-called "targeted" cancer drugs -- meaning they interfere with specific proteins that help cancer cells grow and spread. Avastin blocks the formation of blood vessels that feed a tumor's growth and spread. Added to chemotherapy drugs -- which fight tumor cells directly -- Avastin can prolong the lives of people with advanced colon cancer.

No one knows for sure why the drug doesn't benefit people with earlier-stage colon cancer. But Allegra said the same situation has been seen with another "targeted" cancer drug: Erbitux (cetuximab).

He also said the experience with that medication, and now Avastin, raises questions about how drugs for stage 2 and 3 colon cancer are developed.

The current "paradigm," Allegra said, is to first test new drugs in patients with metastatic colon cancer. Only if the drugs show benefit in those trials are they moved to studies of patients with earlier-stage colon cancer.

Mayo's Sinicrope noted that in the past, that's worked.

Often, he said, chemotherapy drugs that have worked for metastatic colon cancer have turned out to work for earlier-stage disease, too. But that has not been the case when it comes to the targeted therapies like Erbitux and Avastin.

"We can't just grab the drug that works in the metastatic setting and cross our fingers that it will work in the adjuvant setting," Sinicrope said.

For patients with colon cancer, he said it's important to remember that if you hear of a new drug that's supposed to be effective for advanced cancer, that doesn't mean it works for everyone.

"Different stages of disease are different biologically, and need to be treated differently," Sinicrope said.

NorthShore's Obel said researchers need a better understanding of the biology of earlier-stage colon cancer, to develop therapies specifically for it. On the other hand, existing therapies are pretty good: "Many of our patients are cured," Obel said.

That's especially true with stage 2 colon cancer, which can often be treated with surgery alone, Obel noted.

She added that the current study is "a very good example of why we need rigorous clinical trials."

"What if doctors just said, 'Well, [Avastin] works for metastatic cancer,' and decided to give it to patients with early-stage disease?" Obel said. "This is an expensive drug that causes side effects, and before you give iy

Consider Weight When Choosing Blood Pressure Meds: Study

THURSDAY Dec. 6, 2012 -- Taking a patient's weight into account when choosing blood pressure medications might help prevent strokes, heart attacks and death, a new study suggests.

Lean and obese people react differently to different blood pressure medications, said the researchers, who believe their findings could change the way high blood pressure (hypertension) is treated.

"Unexpectedly, people who have high blood pressure and are fat actually have a better prognosis than people who have high blood pressure and are thin," said lead researcher Dr. Michael Weber, a professor of medicine at Downstate Medical Center of the State University of New York in New York City.

"You can now choose blood pressure medication as a means of compensating for this difference between obese and thin people, so that it's possible to treat everybody with a medicine that maximizes the outcome regardless of how much you weigh," he said.

Weber recommends starting all patients with high blood pressure on a class of drugs called calcium channel blockers, regardless of weight. One such drug is Norvasc (amlodipine).

Although diuretics, which reduce excess water in the body, are effective in obese patients, they can harm thin patients, and should be relegated to a third-line therapy, Weber said.

Obese people respond better to diuretics, Weber explained, because their hypertension is often caused by a combination of excess weight, too much fluid and too much salt. Thin hypertensive patients, he said, may have underlying circulatory problems that are causing their high blood pressure and placing them at increased risk for cardiovascular disease.

For the study, published in the Dec. 6 online edition of The Lancet, Weber's group analyzed data on more than 11,000 individuals in an international high blood pressure trial.

That trial compared treatment with a diuretic and Lotensin (benazepril), which is known as an ACE inhibitor, with a regimen of Lotensin plus the calcium channel blocker Norvasc.

The goal of the study was to see which combination better controlled high blood pressure in people at high risk for heart disease and to see if weight had an effect on blood pressure control.

Participants were grouped into three categories -- normal weight, overweight and obese -- based on their body mass index (BMI). BMI is a body fat calculation based on height and weight.

Normal-weight people taking the diuretic fared the worst, the investigators found. This group was 68 percent more likely to have a heart attack, stroke or die than obese patients taking a diuretic.

People taking the Lotensin-Norvasc combination did well regardless of weight, they found. This drug duo reduced stroke, heart attack and death by 43 percent in normal-weight people and 24 percent in overweight people, according to the study.

Among obese people, both drug regimens worked well with no significant differences between them, the researchers found.

However, some doctors argue against giving obese patients diuretics.

"We disagree that diuretics are a reasonable choice for the obese patient," said Dr. Franz Messerli, a cardiologist and director of the hypertension program at St. Luke's-Roosevelt Hospital and Columbia University College of Physicians and Surgeons in New York City.

Obesity is a reason not to use diuretics, he said. Diuretics should be used only when certain types of heart disease, including heart failure, exist, said Messerli, co-author of an accompanying journal editorial.

In obese patients, diuretics can trigger poor blood sugar control and gout, Messerli said.

Messerli agreed that calcium channel blockers should be first-line treatment for all patients with high blood pressure whether they are fat, thin or in between.

Dr. Gregg Fonarow, a spokesman for the American Heart Association and a professor of cardiology at the University of California, Los Angeles, said the study findings may be an example of the "obesity paradox." This theory holds that obesity is a well-established risk factor for developing hypertension, heart disease and heart failure, while "among individuals with established hypertension, coronary heart disease, and heart failure, obesity has been unexpectedly associated with lower cardiovascular event rates and mortality."

These new findings suggest that an individual's BMI should be considered when selecting anti-hypertensive medications, he said.

"Treatment with calcium channel blockers appears preferable to treatment with diuretics in non-obese men and women with hypertension," Fonarow said.

The study was funded by Novartis Pharmaceuticals, maker of Lotensin.

More information

For more information on high blood pressure, visit the American Heart Association.

Posted: December 2012

Sedatives May Raise Pneumonia Risk

WEDNESDAY Dec. 5, 2012 -- People taking the widely prescribed sedatives known asbenzodiazepines may be putting themselves at greater risk for developing pneumonia, British researchers report.

Moreover, they may also face an increased risk of dying from the disease, the investigators added. Benzodiazepines such as Halcyon, Librium, Valium and Xanax are commonly prescribed for anxiety, epilepsy, muscle spasm and insomnia.

"Our study calls into question the safety of benzodiazepine drugs in the context of infection," said study author Dr. Robert Sanders, a senior clinical research associate at the Wellcome Department of Imaging Neuroscience at the Institute of Cognitive Neuroscience at University College London.

"While further study is required, this initial analysis suggests that benzodiazepine exposure may increase the risk of developing pneumonia or dying from pneumonia," he said.

Sanders hopes this study prompts more research, including randomized, controlled trials and cohort studies. A randomized, controlled study is one in which people are randomly assigned to different groups: one group receives the treatment and the other does not receive the treatment (the "control" group).

The report was published online Dec. 5 in the journal Thorax.

For the study, Sanders' team analyzed the medical records of patients whose data was included in the Health Improvement Network database.

Specifically, they looked at almost 5,000 patients diagnosed with pneumonia between 2001 and 2002. The researchers compared those patients with more than 29,500 patients who didn't have pneumonia.

Patients with pneumonia typically had suffered pneumonia before, along with other serious illnesses such as heart attack, depression and psychosis. In addition, they were also more likely to smoke, the study authors noted.

Sanders' team compared the use of benzodiazepines in both groups. They also looked at the use of zopiclone (Imovane), which although not a benzodiazepine acts like one.

The findings indicated that benzodiazepines were associated with a 54 percent increased risk of developing pneumonia. This was also true for zopiclone, the researchers added.

Specifically, diazepam (Valium), lorazepam (Ativan) and temazepam (Restoril) were associated with an increased risk of pneumonia, according to the report.

The risk was not associated with the benzodiazepine chlordiazepoxide (Librium), the authors noted.

Further analysis found that the risk of dying within a month after being diagnosed with pneumonia was 22 percent higher among people taking benzodiazepines. The risk of dying was 32 percent higher within three years after diagnosis, the researchers found.

These risks of dying were linked to diazepam, chlordiazepoxide, lorazepam and temazepam, they noted.

About 2 percent of people in the United Kingdom and the United States have used benzodiazepines for a year or more; among the elderly, however, one in 10 use these drugs, the study authors pointed out.

Benzodiazepines have also been linked to an increased risk of infections and death from blood poisoning in critically ill patients, according to background information in the study.

Although these results do not prove a cause-and-effect link between these drugs and an increased risk of pneumonia or death from pneumonia, they should be studied further, the researchers said.

One expert offered a possible explanation for how these drugs may raise the risk of pneumonia.

"I am not surprised by the finding at all," said Dr. Len Horovitz, an internist and pulmonologist at Lenox Hill Hospital in New York City. "Benzodiazepines are sedative/hypnotics."

People take them as tranquilizers during the day or to sleep at night, Horovitz said. "They are often taken with alcohol, even though patients know not to. They depress the respiratory system and they are cough suppressants," he explained.

If the cough reflex is suppressed, there is going to be a high rate of pneumonia in the population in the study, Horovitz said.

Horovitz advises not using these drug as sleep aids. "You can use something that isn't a benzodiazepine, like Ambien or Lunesta, or melatonin if you are trying to be natural about it," he said. "Benzos are a band-aid on anxiety or a panic attack, they are not the answer."

More information

For more on benzodiazepines, visit the U.S. National Library of Medicine.

Posted: December 2012

Is a Breath Test for Colon Cancer Possible?

WEDNESDAY Dec. 5, 2012 -- If colon cancer screening was as easy as taking a breath, more people might do it. Now, a small pilot study suggests such a test could be developed.

The study, of 78 people with and without colon cancer, found that those with the disease tended to have a distinct pattern of chemicals in their breath. And when researchers analyzed the study participants' breath samples, they correctly identified the colon cancer patients 76 percent of the time.

The findings, reported online Dec. 5 in the British Journal of Surgery, sound good. But if you're waiting for your doctor to offer such a test, don't hold your breath.

"It's an interesting concept, but this is in the very early stages," said Dr. Durado Brooks, director of prostate and colorectal cancers for the American Cancer Society.

"There's no way to tell if this would work in the general population," said Brooks, who was not involved in the research.

What's more, he added, there are already several good ways to catch colon cancer -- or, even better, precancerous growths called polyps, which can then be removed before a tumor develops. Yet about 40 percent of Americans who should be getting screened are not.

"Colon cancer is a highly preventable disease," Brooks said. "And I would encourage the four out of 10 people who are not taking advantage of the existing screening tools to talk with their doctor."

The idea of using a breath test to catch cancer is not new: Researchers are looking into breath tests for detecting a number of cancers, including lung and breast tumors. It's all based on studies showing that breath samples from cancer patients tend to have a distinguishing pattern of so-called volatile organic compounds (VOCs).

When it comes to colon cancer, people already have several options for screening, which for most adults should begin at age 50 -- or possibly earlier if you are at higher-than-normal risk.

The choices include a yearly stool test that looks for hidden blood, or either of two invasive tests that scope the colon: sigmoidoscopy every five years, along with stool testing every three years; or colonoscopy every 10 years.

But many people are turned off by those tests.

So Dr. Donato Altomare and colleagues at the University Aldo Moro in Bari, Italy, decided to test the feasibility of a breath test.

Analyzing breath samples from 37 patients with colon cancer and 41 healthy middle-aged adults, the researchers found 15 VOCs that seemed to differ between the two groups.

They then used a statistical model to see if certain VOC patterns separated the colon cancer patients from the healthy participants. In the end, the researchers were able to correctly identify the cancer patients 76 percent of the time.

But, Brooks pointed out, that also means the breath test was wrong about one-quarter of the time.

There's no way of knowing how well such a screening test would work in the real world -- including how many people might wrongly get a positive result and undergo needless invasive tests to follow up, Brooks said.

Another big question, he added, is whether breath analysis could pinpoint people with colon polyps.

"One of our goals in screening is to detect polyps, not cancer," Brooks said. "This study doesn't address that."

Altomare's team acknowledges that there is a lot of work left to do. It's still unclear which breath chemicals should be measured, or what statistical method is best for weeding out cases of colon cancer.

Brooks said it would be nice to have a very simple, accurate screening test -- whether that means a breath test or blood or urine tests. Yearly stool tests are simple and cheap, but people often don't want to do them.

"We're always searching for simpler things to do," Brooks said. But for now, he added, "this study raises many more questions than answers."

Posted: December 2012

Antidepressants May Lead to Fewer Seizures in People With Epilepsy

MONDAY Dec. 3, 2012 -- Besides helping to boost mood, antidepressants may also reduce seizure frequency for people with epilepsy, a new study suggests.

The study, to be presented Monday at the annual meeting of the American Epilepsy Society in San Diego, included patients who were prescribed one of two types of antidepressants -- selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). These types include drugs such asCelexa, Paxil, Prozac and Zoloft, among others.

Researchers led by Dr. Ramses Ribot, of Rush University Medical Center in Chicago, tracked changes in mood and anxiety levels for 100 people with epilepsy at three and six months after the start of antidepressant therapy.

Improvement or remission of symptoms was seen in 86 percent of patients, the investigators found.

The antidepressants tested "do not appear to worsen seizure frequency and yield a good therapeutic response independently of seizure frequency," Ribot said in a society news release. "Our studies also suggest these antidepressants may actually have an anti-seizure effect in patients with frequent seizures," he added.

The researchers said the findings should be of interest to doctors who treat people with epilepsy, but the results need to be confirmed in further studies.

One epilepsy expert said the findings are reassuring for doctors and patients.

"This study provides additional support for the safety and effectiveness of antidepressant medications in patients with epilepsy and comorbid [co-existing] depression," said Dr. Orrin Devinsky, director of the Comprehensive Epilepsy Center at NYU Langone Medical Center in New York City.

He explained that, in rare cases in the past, SSRIs and SSNIs have been linked to a lowering of the threshold at which epileptic seizures might occur.

"This has unfortunately led many psychiatrists and neurologists to avoid the use of these medications in epilepsy patients," Devinsky said. "However, the findings of Ribot and colleagues provide clear support that depressed patients with epilepsy should be treated with effective doses of these medications. Further, these medications can improve depression and quality of life and, in many patients, reduce seizure frequency."

While the study found an association between antidepressant use and reduced seizure activity, it did not prove a cause-and-effect relationship.

Findings presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about epilepsy.

Posted: December 2012

Common Diabetes Drug Shows Promise as Ovarian Cancer Treatment

MONDAY Dec. 3, 2012 -- Ovarian cancer may join a growing list of malignancies that seem to be slowed by a commonly prescribed diabetesdrug.

Ovarian cancer patients who were takingmetformin at the time of their diagnosis survived longer than patients who weren't on the drug, a new study by Mayo Clinic researchers shows.

Metformin goes by the brand name Glucophage and is derived from French lilacs. It's typically prescribed to lower blood sugar levels in people with type 2 diabetes but has shown promise as a potential anticancer agent in recent prostate, colon, pancreas, brain and breast cancer studies, as well as in lab experiments with ovarian cancer cells.

The new research, published online Dec. 3 in the journal Cancer, was a retrospective study where the scientists evaluated the medical records of ovarian cancer patients who had received their cancer diagnosis between 1995 and 2010. Sixty-one patients were taking metformin at the time of their cancer diagnosis while 178 patients -- the control group -- weren't on the medication.

The scientists reported that 67 percent of the women using metformin had not died within five years of their diagnosis, while only 47 percent of the control group had survived that long.

Overall, patients taking metformin were 3.7 times more likely to survive throughout the study than those who did not take it, the researchers said.

"Our study demonstrated improved survival in women with ovarian cancer that were taking metformin," said Dr. Sanjeev Kumar, a Mayo Clinic gynecologic oncology fellow, who also noted that the scientists took into account each patient's body mass index, cancer severity, type of chemotherapy they were taking and surgery quality.

Dr. Pamela Soliman, an associate professor in the department of gynecologic oncology at the University of Texas M.D. Anderson Cancer Center in Houston, said, "Even after controlling for all of those factors, there still showed a benefit for metformin."

Soliman was not involved with the study, but has conducted similar research in endometrial cancer cells. "This is good first evidence that maybe metformin will have a benefit to patients with ovarian cancer," she said. "There's information to gain, but I think more studies need to be done."

Scientists are still trying to better understand why metformin improves cancer outcomes. Kumar and colleagues said in the lab they have shown that if you feed ovarian cancer cells metformin, they stop dividing. In patients with diabetes, it lowers blood sugar levels and increases insulin sensitivity, two factors associated with cancer growth. Still, more research is needed to understand the biological mechanism at play, Kumar said.

According to the American Cancer Society, about 22,280 women are newly diagnosed with ovarian cancer each year, and about 15,500 die from the disease annually.

Many patients may wonder if the drug could help curb their cancer, Kumar said, but he advised that it's too early for doctors to start prescribing metformin as an ovarian cancer treatment.

"We don't have sufficient evidence that patients with ovarian cancer should be on metformin. This is a study that forms a hypothesis, but patients should wait until large-scale randomized trials are conducted," Kumar said.

Study co-author Dr. William Cliby, a professor of obstetrics and gynecology at the Mayo Clinic, said if a cancer patient develops prediabetes or diabetes after diagnosis, using metformin is an option, though. "If you have patients who are borderline diabetic and they could use a diabetic agent, in that case, this study indicates there might be a benefit."

More information

For more on ovarian cancer, go to the American Cancer Society.

Posted: December 2012

Increased Mortality With Digoxin in AF

LEXINGTON, Kentucky — The use of digoxin in patients with atrial fibrillation (AF) is being called into question, with the publication of a new study suggesting it is associated with a significant increase in all-cause mortality [1].

The study, a propensity-adjusted analysis of the AFFIRM trial that controlled for multiple comorbidities, was published online on November 27, 2012 in the European Heart Journal. It found an overall 41% increase in all-cause mortality in patients taking digoxin vs those not taking digoxin. The increase in all-cause mortality was consistently observed in men and women and in patients with and without underlying heart failure.

Senior author Dr Claude Elayi (University of Kentucky, Lexington) explained to heart wire that the use of digoxin has previously been associated with an increased risk of death in AF patients, but it has not been known whether this is because it tends to be used in sicker patients.

A major randomized trial of digoxin in heart failure (the DIG trial) showed an overall neutral effect on mortality, although death was increased in patients taking high-dose digoxin. However, hospitalizations for heart failure were reduced, and the consensus is that digoxin is beneficial in heart failure, Elayi noted.

"We would really like to see a similar randomized trial of digoxin in AF patients, but it is unlikely to ever be done, so we have tried to get the information from a large existing study, correcting the data for biases with complex statistical models.

"And the magnitude of the effect seen is so high--an increase in mortality of 41% in patients on digoxin--that even if we haven't corrected for some of the biases, I don't think it would account for the results we saw."

Elayi believes these results should make doctors think hard about whether to prescribe digoxin for AF patients, especially if they don't also have heart failure. "I'm not saying we should never use digoxin again in AF patients, more that we have to think carefully about it."

Different Advice Dependent on Heart Failure

He suggests that if patents have AF and heart failure, it is still reasonable to use digoxin. "Theoretically, digoxin should be the perfect drug for patients with both conditions, as it slows the heart rate, which is needed in AF, and we know from the DIG trial that it has benefits in heart failure. But I would caution that low doses should be used and blood levels should be carefully monitored, as digoxin can interact with many different drugs."

Digoxin's time as a first-line agent in AF patients without heart failure is over.

But Elayi now advises against use of digoxin in AF patients without heart failure. "In this group, the only benefit of digoxin is to slow the heart rate, which many other drugs can do better and more safely. So I would advise against using digoxin in such patients, unless beta blockers or calcium antagonists are not appropriate, maybe because of low blood pressure. And again, if it is used, stick to low doses with careful monitoring."

Elayi estimates that 30% to 50% of AF patients are currently taking digoxin, more in some developing countries. "It is extensively used across the planet, perhaps a bit less in the US and Europe. I hope this study will bring some warnings that digoxin's time as a first-line agent in AF patients without heart failure is over."

Nissen: Findings Raise Safety Concerns

A press release issued by the University of Kentucky quotes Dr Steve Nissen (Cleveland Clinic, OH), who was not involved in the study, as saying: "These findings raise important concerns about the safety of digoxin, one of the oldest and most controversial heart drugs. Although considered obsolete by some authorities, digoxin is still widely used. A thorough review by the FDA is warranted to determine whether regulatory action is needed, including stronger warnings about the use of digoxin in patients with atrial fibrillation" [2].

A thorough review by the FDA is warranted.

The AFFIRM trial randomized 4060 patients (39% women) to rhythm control or rate control. Overall, 2816 patients (69.4%) received digoxin within six months of randomization and/or during the study. Heart failure was present in 26% of patients.

After propensity scoring and multivariable Cox proportional models were applied, digoxin was associated with an increase in all-cause mortality, cardiovascular mortality, and arrhythmic mortality.

Hazard Ratio (95% CI) for Death on Digoxin in AF Patients

Outcome	HR (95% CI)	p
All-cause mortality	1.41 (1.19–1.67)	0.001
CV mortality	1.35 (1.06–1.71)	0.016
Arrhythmic mortality	1.61 (1.12–2.30)	0.009

Because in a post hoc analysis of the DIG trial there appeared to be a gender difference in the effect of digoxin, with a greater increase in mortality among women taking the drug compared with men, the effect of gender was closely observed in the current study. However, no gender interaction was seen in the AFFIRM data, with both men and women showing significantly increased overall mortality with digoxin use.

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Tuesday, January 1, 2013

NEW DRUG APPROVALS

FDA Approves Raxibacumab

FDA Approves Iclusig

FDA Pulls One Generic Form of Wellbutrin Off the Market

Libigrow, Libigrow XXXtreme, Blue Diamond, Blue Diamond Platinum, Mojo Nights, Mojo Nights Supreme, And Casanova: Recall - Undeclared Ingredients Sulfoaildenafil and Thioaildenafil

FDA Drug Safety Communication: Important Change to Heparin Container Labels to Clearly State the Total Drug Strength

Safety Announcement

Additional Information for Patients and Caregivers

Additional Information for Health Care Professionals, Hospitals, and Pharmacies

Additional Background Information

FDA Drug Safety Communication: Updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products

Safety Announcement

Table 1. List of ondansetron products to be voluntarily withdrawn from the U.S. market

Reference

Treating Kidneys With Radio Waves May Ease Tough-to-Control Hypertension

Vitamin D Levels Linked to Daytime Sleepiness

Blood Cancer Patients May Benefit From New Transplant Technique

Avastin Shows No Benefit for Earlier Colon Cancer: Study

Consider Weight When Choosing Blood Pressure Meds: Study

Sedatives May Raise Pneumonia Risk

Is a Breath Test for Colon Cancer Possible?

Antidepressants May Lead to Fewer Seizures in People With Epilepsy

Common Diabetes Drug Shows Promise as Ovarian Cancer Treatment

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