Avandia Continues to Face Scrutiny: Biotech's Latest Mishaps

GlaxoSmithKline’s (GSK) diabetes drug Avandia is once again under regulatory scrutiny—this time it’s in Europe where the European Medicines Agency met to discuss whether Avandia should continue to be marketed. The agency in a press statement said that no final decision has been made about the drug.

It said it has further questions for GSK before deciding whether and what action needs to be taken. A final decision is expected by September 23. The meeting took place as a controversy erupted in the United Kingdom over a recommendation made at the end of July by the UK Commission on Human Medicines, according to TheHeart.Org. The commission unanimously voted that Avandia should be withdrawn. Though it informed the Medicines and Healthcare Products Regulatory Agency, the agency responsible for licensing drugs in the United Kingdom, its decision was not made public. Instead the agency sent letters to doctors restating safety information about the drug and suggesting they consider alternatives. Because the drug was approved by the European Medicines Agency, only it can revoke the license for the drug.

Roche said it halted dosing of patients in a late-stage trial of its experimental diabetes drug taspoglutide because side effects including nausea and vomiting resulted in many participants in the study to drop out of it, Bloomberg reported. The company is trying to determine what caused the side effects and see if it can reformulate the medication to reduce the risk, a spokeswoman told Bloomberg. Because a large number of patients dropped out of the study, the company said it would be difficult to determine whether the drug is effective.

Genzyme is laying off an undisclosed number of staff as part of a restructuring first announced in May, Reuters reported. The company said the move was unrelated to Sanofi-Aventis’ efforts to acquire the company. Genzyme has 12,800 employees. It offered no estimates on how much it expects to save through the restructuring.

Shares of Idenix Pharmaceuticals (IDIX) plummeted after the U.S. Food and Drug Administration ordered the company to halt a mid-stage study of two experimental hepatitis C drugs. Three healthy volunteers testing a combination of the drugs IDX184 and IDX320 showed elevated liver enzyme levels in a routine post-study safety test, the Cambridge, Massachusetts company says. Although liver function returned to nearly normal levels in all three subjects, the FDA placed a clinical hold on the study until it can discuss the results and other relevant data with Idenix. Idenix shares fell to $3.18 from $5.99 on the day it was announced. On top of that punishment, the hold will also likely make Idenix's ongoing search for an outside partner to advance its hepatitis C program more difficult. [see story].

U.S.-based Valeant Pharmaceuticals International and Canada’s Biovail plan to eliminate about 25 percent of their combined workforce once a merger is completed between the two companies, Reuters reported. The company’s said they expect to save more than $300 million through cost synergies with more than $200 million being realized in 2011. The companies have a combined workforce of about 4,400.

Marc Tessier-Lavigne, Genentech’s (DNA) executive vice president of research and chief scientific officer, is leaving the biotech to become president of Rockefeller University in New York, Reuters reported. The departure of Tessier-Lavigne, the second highest executive in research at Genentech, is one of the most significant executive changes since Roche acquired Genentech last year. He takes on his new post in early 2011.

U.S. Food and Drug Administration is requiring that certain contrast agents used in magnetic resonance imaging carry new warnings on their labels about the risk of a rare and potentially fatal condition known as nephrogenic systemic fibrosis, if the drug is administered to certain patients with kidney disease.

Nephrogenic systemic fibrosis or NSF is a condition involving the formation of excess fibrous connective tissue in the skin, joints, eyes, and internal organs. Symptoms of NSF can include scaling, hardening and tightening of the skin, red or dark patches on the skin, and stiffness. NSF may lead to death, especially if it involves body organs. The order pertains to gadolinium-based contrast agents or GBCAs.

The agency said three of the GBCAs—Magnevist, Omniscan, and Optimark— will be described as inappropriate for use among patients with acute kidney injury or chronic severe kidney disease. All GBCA labels will emphasize the need to screen patients to detect these types of kidney dysfunction before administration.

GBCAs are intravenous drugs used to help detect abnormalities of body organs, blood vessels, and other tissues through MRI. Magnevist is marketed by Bayer Healthcare, Omniscan by GE Healthcare, and Optimark by Covidien (COV).

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New Drug-Interaction Warnings for All HIV Protease Inhibitors

Package inserts for all of the approved protease inhibitors (PIs) used to treat HIV have been updated to reflect important drug-drug interactions, according to an April 27 e-mail announcement from the U.S. Food and Drug Administration.

Drug-drug interactions are a common obstacle among people living with HIV receiving antiretroviral therapy. This is especially true for those using PIs, widely known for their ability to compete with other medications for enzymes that regulate drug levels in the body. This can elevate blood levels of one or more drug, ultimately increasing the risk of side effects; it can also reduce blood levels of medications and reduce the effectiveness of treatment.

Among the important interactions to be added to all PI package inserts include those involving Revatio (slidenafil), Uroxatral (alfuzosin), Advair and Serevent (both contain salmeterol), Tracleer (bosentan), Adcirca (tadalafil) and colchicine.

Revatio, a version of the erectile dysfunction medication sildenafil, is prescribed to treat pulmonary arterial hypertension. It is contraindicated among people living with HIV using PIs, meaning that the drug should not be used under any circumstances.

Tracleer and Adcirca are also used to treat pulmonary arterial hypertension and should be used cautiously. According to the FDA, their doses may need to be adjusted when combined with protease inhibitors. The agency also warns against using Tracleer with the PI Reyataz (atazanavir) if a Norvir (ritonavir) booster is not also included.

Advair and Serevent are frequently prescribed to help manage symptoms of asthma, chronic obstructive pulmonary disease (COPD) and sometimes seasonal allergies. They should not be combined with protease inhibitors.

Uroxatral, used to treat benign prostatic hyperplasia (BPH) in men, is also contraindicated among people using HIV protease inhibitors.

Colchicine, a natural produce derived from the Colchicum genus of plant, is used to treat gout and familial Mediterranean fever. Depending on the PI used, dose adjustments may be necessary. Additionally, colchicine should be avoided among those who take PIs and have a history of either liver (hepatic) or kidney (renal) impairment.

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Children overdosed during Pfizer drug study

In the article titled “Pharmaceutical injury alert: FDA slams Pfizer with warnings for deadly clinical trials,” posted on April 23, 2010, it was incorrectly reported that participants of a drug trial died. Twenty-six pediatric patients received overdoses of a psychiatric drug in 2006, and three more overdoses occurred in 2007; the overdoses did not result in any fatalities.

The U.S. Food and Drug Administration (FDA) issued Pfizer a warning letter, stating they have failed to rectify its testing procedures, which resulted in overdoses in over two-dozen patients during a company trial of Geodon. Several children experienced tremors, restless legs and other complications as a result of the overdoses, as reported by Reuters.

The letter, which was released on Tuesday, April 20, 2010, states that Pfizer was not properly monitoring physicians who were testing the experimental medication. Pfizer said in a statement that only 10 of the overdoses were caused by physician error, and the rest were probably because of patient error.

A new warning letter was prompted after a July 2009 inspection found that the drug maker was still failing to follow its own rules for safely conducting a study. A Pfizer spokeswoman pointed out, “Pfizer has communicated with the FDA about our conduct of clinical trials and, over the next two weeks, will provide an outline of new and existing processes for preventing similar issues with Pfizer clinical trials.”

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FDA warns Procter & Gamble over Vicks products with vitamin C

The U.S. Food and Drug Administration sent a warning letter Friday to Procter & Gamble Co. saying the company was illegally marketing two Vicks cold and flu medicines containing vitamin C.

The FDA said the single-dose combinations of drug and dietary ingredients in Vicks DayQuil Plus Vitamin C and Vicks Nyquil Plus Vitamin C cannot be marketed legally because they have not been proven safe and effective.

The agency also said it had previously determined that there was insufficient data to show vitamin C is safe and effective in preventing or treating the common cold.

The FDA said it allows some over-the-counter drugs to be marketed without agency approval, but that the two Vicks products did not comply with its rules and first must be evaluated and approved under the FDA's new drug approval process.

A spokeswoman for the Cincinnati consumer products company said in an e-mail message that the FDA warning was "not new news" and was similar to a letter earlier this month that the FDA indicated had been posted to its Web site due to an internal error.

"It's also not about the safety or quality of the Vicks NyQuil or DayQuil brands," wrote Kate DiCarlo. "We believe we are marketing within FDA guidelines and regulations, and we'll continue to work closely with the FDA to resolve any concerns."

Shares of P&G, the world's largest consumer products maker, slid $1.46, or 2.5 percent, to $58.08 in afternoon trading.

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New Standard Reduces Heparin Potency

Beginning next week, heparin shipped to hospitals and pharmacies will be about 10% less potent than that currently available, a change that is likely to have clinical implications when the drug is administered as a bolus IV dose, the FDA said today.

The loss in potency is the result of new manufacturing controls -- including a new reference standard for the drug's unit dose -- adopted by United States Pharmacopeia (USP), a nonprofit standards-setting organization.

The FDA has known for months that the reference standards for heparin would change, but learned only three weeks ago that the change would reduce potency, said John K. Jenkins, MD, director of the office of new drugs, at the FDA's Center for Drug Evaluation and Research.

The difference in potency, which is estimated at about 10% per labeled unit, is unlikely to affect subcutaneous administration because there is a wide range of bioavailability when heparin is administered by that route, he said.

Jenkins said the new standard has been in the works since 2007, when contamination of heparin resulted in hundreds of severe allergic reactions and deaths as well as widespread recalls and shortages.

When USP circulated the new drug monograph for comment during the spring and summer, "there was little concern about clinical significance," but as manufacturers began making heparin using the new standard, one of the companies discovered the difference in potency and informed the FDA, Jenkins said.

The FDA then contacted other manufacturers and confirmed that the reduced potency was observed by all drugmakers using the new reference standard.

At that point, the FDA contacted USP to determine if the rollout of the new standard could be delayed until in vitro and in vivo testing could confirm the exact potency range.

But by then, it was too late. The four makers of heparin -- APP, Hospira, Baxter, and B. Braun -- had all retooled their manufacturing processes to make the drug based on the new standard, which takes effect today.

The best that the FDA could manage was an agreement to delay shipment of the new heparin until Oct. 8, Jenkins said.

To differentiate "new" from "old" heparin once supplies hit the shelves, the four manufacturers have agreed to special labeling on the new product.

Three companies -- APP, the largest manufacturer, which markets heparin in vials; Baxter, which sells the drug in IV bags; and B. Braun, which also markets heparin in IV bags -- have all agreed to add the letter "N" next to the lot number or expiration date on labels of "new" heparin.

The fourth manufacturer -- Hospira which markets heparin in intravenous bags, vials, and syringes -- said it will identify the new heparin with a unique numbering system.

Meanwhile, the FDA is cooperating with the companies to conduct both in vitro and in vivo testing to determine the exact extent of the potency difference. The in vitro tests should be completed in a few weeks, but "animal tests will take longer," said Jenkins. He estimated the in vivo results would be available in less than two months.

But even with those test results, the FDA may not require changes in heparin labeling because dosing of the drug has always been a matter of "individual monitoring of patients" to determine the anticoagulant effect.

Regardless of potency, Jenkins said, heparin should continue to be dosed based on results of patient monitoring.

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FDA - Ibuprofen Pain Relief Gels Are Unproven

A new tougher Food and Drug Administration (FDA) is issuing another crackdown – this time on creams that claim to relieve pain because they contain ibuprofen, among other active ingredients.

A number of Ibuprofen ointments or creams claim they are safer than pills because they do not cause stomach ulcers. The FDA says there has been no research supporting that claims and that the over-the-counter products are unapproved.

"These companies have an obligation to demonstrate to the FDA that their products are safe and effective, and they have failed to do so," said Deborah Autor, director of FDA's office of compliance.

The FDA says companies must submit an application for new drug approval.

Eight companies have received warning letters from the FDA to stop marketing the drugs, among them, Tennessee-based Wonder Laboratories, New Mexico-based Meditrend and Alabama-based Progressive Emu Inc.

Progressive Emu says it has already responded to the FA and removed all claims off of its labels.

Other companies cited are: Colorado-based Biocentric Laboratories, Wisconsin-based Core Products International, Florida-based Geromatrix Health Products, New Jersey-based MEKT LLC, and Texas-based Ridge Medical Products.

Ibuprofen is available in tablet form such as Advil, as a pain reliever.

As part of a more regulatory-conscious FDA, chief Margaret Hamburg has issued a number of enforcement actions against companies that make unsubstantiated claims or sell dangerous products. Last month makers of supplements that contain metabolic steroids were told to pull their products from the market.

And in June, consumers were warned that the cold remedy, Zicam Cold, can permanently damage the sense of smell, while the FDA has also told dozens of Web sites to stop making phony swine flu remedies,

Source : www.injuryboard.com

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Patients Are Reminded of Aspirin’s Risks

Cheap, ubiquitous aspirin has long been known for health benefits from basic pain relief to heart attack prevention. But after a new study this week provided tantalizing evidence suggesting that aspirin might increase survival chances for colorectal cancer patients, experts were quick to warn that the drug, a medicine cabinet staple, also had its risks.

“If I were on a desert island, one of the drugs I would choose to have with me, hands down, maybe No. 1, is aspirin,” said Dr. John A. Baron, a professor of medicine at Dartmouth Medical School. “It’s a fascinating, wonderful drug, a great drug. But it is a real drug, and it has side effects.”

Both Dr. Baron and other medical experts cautioned against starting a daily regimen of aspirin without consulting a physician, because of the risks of gastrointestinal bleeding, and the potential risk for hemorrhagic strokes, or bleeding in the brain.

“Aspirin is a drug that been with us a little over 100 years, and we continue to learn impressive and important things about its potential benefits,” said Dr. Otis Brawley, medical director of the American Cancer Society. “But it is a double-edged sword.”

The study found that patients with colorectal cancer who were regular aspirin users had a much better chance of surviving than non-users, and were almost one-third less likely to die of the disease, while those who began using aspirin for the first time after the diagnosis cut their risk of dying by almost half.

Earlier studies had shown that people who took aspirin regularly were less likely to develop tumors of the colon, but the new study, published in The Journal of the American Medical Association, is the first to have found that patients who had colorectal cancer and took aspirin survived longer.

One colon cancer expert who commented on the recent study called it “remarkable” and “revolutionary.” But then his patients started seeking advice, and he was more circumspect.

“It’s one thing to talk philosophically,” said the expert, Dr. Alfred I. Neugut, an oncologist from the College of Physicians and Surgeons at Columbia University who wrote an enthusiastic editorial on the study in this week’s Journal of the American Medical Association. “But this is only one study. To know that it’s true, it needs to be repeated. Every experiment needs to be repeated once.”

The new study was not a controlled clinical trial, where patients are randomly assigned to receive either a particular treatment or a placebo. That kind of study is considered the gold standard for determining clinical recommendations in medicine, but it is also far more expensive and cumbersome. Observational studies, like this new one, can be weaker or misleading.

One clinical trial is under way in Asia, where the National Cancer Center of Singapore is enrolling 2,660 patients with nonmetastatic disease in Hong Kong, India, Indonesia and Singapore, who will continue their treatment and be randomly assigned to either get aspirin or a placebo daily for up to three years, according to the National Cancer Institute Web site.

Most colorectal cancer tumors are positive for cyclooxygenase-2, or COX-2, an enzyme that is not expressed in a healthy colon but flares up under certain circumstances. The enzyme appears to be involved in fueling abnormal cell growth and contributing both to the development and spread of the cancer, said Dr. Andrew T. Chan, the author of the new study.

Aspirin’s anti-cancer property is believed to be linked to its action as a COX-2 inhibitor.

A clinical trial of another COX-2 inhibitor, celecoxib, which has the brand name Celebrex, is in the planning stages and will be enrolling patients early next year, Dr. Chan said. Although more is known about aspirin’s effects on preventing colorectal polyps and tumors than other cancers, some studies have also hinted that aspirin could reduce the risk of developing breast, lung and prostate cancers, which are also associated with inflammation, Dr. Brawley said.

“It seems like — and we’re still talking in theory in some instances here — there is a relationship between inflammation and cancer in certain tumors,” Dr. Brawley said. “And these drugs appear to be beneficial because they are anti-inflammatory, and they inhibit inflammation by inhibiting COX-1 and COX-2.”

The new colorectal cancer study found not only that patients who took aspirin regularly after a diagnosis of colorectal cancer had a better chance of survival than those who did not, but also that those who had tumors that overexpressed the COX-2 enzyme were particularly responsive to the aspirin.

Dr. JoAnn E. Manson, chief of preventive medicine at Brigham and Women’s Hospital, which is affiliated with Harvard Medical School, warned about the risks of using even small doses of aspirin on a daily basis, saying that in a large women’s health study, half doses of baby aspirin were associated with a 40 percent increase in serious gastrointestinal bleeds that required transfusions.

But, she acknowledged, patients who already have colorectal cancer may feel they do not have the luxury of waiting for additional results.

“I don’t think everyone should be running out and taking aspirin,” she said, “But there may be some patients who would benefit from it at this point; and if they talk with their doctors they may learn they’re reasonable candidates, and some of them may not be in a position to wait.”

Source : www.nytimes.com

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TNF blockers raise cancer risk in kids

Blockbuster prescription drugs used to treat rheumatoid arthritis and other conditions can increase the risk of potentially deadly cancer in children and teenagers, U.S. health regulators said Tuesday in ordering stronger warnings on such medications.

The Food and Drug Administration, which urged greater caution with so-called TNF blockers last September, said an analysis of 48 reported cancer cases in children using the drugs "showed an increased risk of cancer, occurring after 30 months of treatment on average."

Eleven of the reported cases were fatal, the FDA said.

Anti-TNF drugs include Johnson & Johnson's Simponi or golimumab and its Remicade or infliximab; Abbott Laboratories ' Humira or adalimumab; UCB SA's Cimzia or certolizumab pegol; and Amgen Inc and Wyeth's Enbrel or etanercept.

Rheumatoid arthritis is an autoimmune disease that can strike young people, causing pain, stiffness and swelling.

It affects about 20 million people worldwide.

The drugs are used to treat other inflammatory conditions, including the bowel disorder known as Crohn's disease.

TNF (tumor necrosis factor) blockers make billions of dollars for manufacturers, but it is unclear how much they earn specifically from sales for children and teens. Not all of the drugs are approved for use in children for all related conditions.

Last year, Abbott's Humira earned $4.5 billion worldwide, while Amgen and Wyeth's Ebrel earned $1.2 billion. J&J's Remicade had 2008 sales of $3.7 billion. Its newer drug, Simponi, was approved earlier this year. UCB's Cimzia, launched in 2008, had about $14.4 million in global sales.

The drugs already carry the strongest warnings possible about the risk of possible serious infections. A new caution about cancer in younger patients will be added to the so-called "black box", the FDA said.


EVALUATING THE CANCER RISK

The FDA said in a statement on its website that its year-long analysis of the increased cancer risk in children showed about half the 48 cases involved lymphoma, which targets the immune system.

Rates for cancer cases with J&J's Remicade "were consistently higher compared to expected background rates for lymphomas and all malignancies," the FDA said. Cancer rates for lymphoma were also higher for Amgen and Wyeth's Enbrel, but rates for all cancers were similar to background rates, the FDA said.

The FDA did not calculate cancer rates for Abbott's Humira and UCB's Cimzia "because of minimal use in pediatric patients." J&J's Simponi was not approved at the time of the time of the analysis.

The FDA said it had "identified new safety information related to the occurrence of leukemia and new-onset psoriasis" that would also be included on the drugs' labeling.

An Abbott spokeswoman said the company would follow the regulator's new warning guidance.

"We will comply with FDA's guidance regarding labeling changes for the anti-TNF class and will continue to monitor the data to ensure patients and physicians have the information they need to make decisions about treatment," Abbott spokeswoman Raquel Powers said.

The FDA said it had reviewed 147 reports of leukemia in adults and children using TNF blockers, including 30 deaths.

While rheumatoid arthritis patients may already be at greater risk for the white blood cell cancer, "there is a possible association between treatment with TNF blockers and the development of leukemia in all patients treated with these drugs," the FDA said.

The FDA also reviewed 69 cases of psoriasis and said it found a possible link between the skin disorder and use of TNF blockers.

Brian Kenney, a spokesman for Johnson & Johnson's Centocor Ortho Biotech Inc unit, which makes Remicade and Simponi, said the company would work with the FDA to adopt the new warnings.

Amgen and Wyeth also said in a statement that they would revise their product warnings and continue evaluating risks and benefits of Enbrel.

Source : www.forbes.com

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FDA Approves New Botox Black Box Warning, Drug Name Changes

The FDA has signed off on a new “black box” warning for Botox and other botulinum toxic drug products, and has approved generic name changes to avoid potential pharmacy errors that could result in life-threatening injuries.

New black box warnings and medication guides were announced on August 3 for Botox, Botox Cosmetic, Myobloc and Dysport, which was recently approved in April 2009.

The stronger warnings were first ordered in April due to the risk that Botox side effects could cause potentially life-threatening problems similar to botulism if the products spread from the area of injection to other parts of the body. Most of these Botox problems have occurred when the injections are given off-label, particularly for treatment of muscle spasticity in children with cerebral palsy.

The drugs contain small quantities of the botulinum toxin, which is the bacteria associated with the development of botulism, a muscle paralyzing conditon.

To avoid confusion for doctors and pharmacies, the FDA also approved generic name changes for the three products. Botox and Botox Cosmetic, manufactured by Allergan, have changed their generic names from Botulinum Toxin Type A to onabotulinumtoxinA. Myobloc, manufactured by Solstice Neurosciences, has changed its generic name from Botulinum Toxin Type B to rimabotulinumtoxinB. The recently approved Dysport maintains the generic name abobotulinumtoxinA.

Although Botox is the most commonly known of the products for its cosmetic uses to remove wrinkles, the drugs are also approved to treat a variety of conditions, such as crossed eyes, excess sweating, involuntary blinking of the eye, contractions of neck and shoulder muscles and cervical dystonia.

The FDA issued a public health warning in February 2009 about the potential risk of serious injury or death from Botox, particularly among children with cerebral palsy who are often given much larger doses off-label. Although the FDA has not approved such uses, many disabled children have been given the injections, as the toxin prevents muscles from involuntarily contracting, helping to alleviate stiff, jerky and difficult movements commonly associated with cerebral palsy.

According to a 2008 report released by the consumer advocacy group Public Citizen, at least 180 adverse event reports have been received by the FDA, which revealed that patients treated with Botox or Myobloc showed symptoms such as aspiration pneumonia, difficulty swallowing or muscle weakness. As the toxin spreads from the injection site, it has been associated with symptoms like weakness, blurred vision, drooping eyelids, slurred speech, dry mouth, partial paralysis, respiratory distress and death.

No definitive serious reports of distant spread of the toxin have been associated with dermatologic use of Botox or Botox Cosmetic at the recommended doses, according to the FDA. In addition, no reports have been associated with Botox when used at approved doses for eyelid twitches or crossed eyes.

Several Botox lawsuits have been filed against Allergan, Inc. on behalf of people who allege that severe or fatal injuries were caused by treatments used for a variety of purposes. It has been alleged that Allergan actively promoted Botox for uses that were not approved by the FDA and failed to warn about the potential risks.

Source : www.aboutlawsuits.com

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Long-used pain pills to carry new warnings

Propoxyphene, better known by long-used brand names Darvon and Darvocet, may stay on the market, but must carry a new, stronger version of the Food and Drug Administration's most serious warnings to consumers and physicians. Products containing propoxyphene, an opiate used to treat mild to moderate pain, will now carry more stringent warnings about the dangers of taking more than the recommended dose, the FDA announced today.

The agency also announced that it has ordered studies on the risk of dangerous cardiac side effects associated with Darvon and related pain medications, as well as on the extent of their use in the elderly -- a population for which propoxyphene is considered to be problematic and less effective than newer, safer drugs.

Propoxyphene's dangers most recently came to light in February 2006, when the group Public Citizen petitioned the FDA to remove the drug from the market. The FDA said today that while it may take further action against the pain drug after studies have been completed, it would allow its continued sale, with the strengthened "black-box" warnings.

The decision came as the agency also considers the advice of one of its own advisory panels, which recently recommended banning further sale of several other widely prescribed opiate pain medications -- those that include acetaminophen, among them Vicodin and Percocet.

Propoxyphene was found to have been associated with roughly 2,110 deaths in the United States between 1981 and 1999, and during the same period was found in autopsies to have been implicated in 5.6% of drug-related deaths in the U.S. Public Citizen had sued the FDA in June of last year for failing to rule on its 2006 petition, prompting the FDA to act this week.

Source : latimesblogs.latimes.com

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Zicam, the FDA and Homeopathy

The FDA just warned consumers to stop using certain Zicam Cold Remedy products designed to be used in the nose. The agency said it has received more than 130 reports of loss of smell associated with the use of the products, which are available without a prescription.

The warning letter the agency sent to Matrixx Initiatives, which sells Zicam, illuminates a corner of the health-care world we don’t often mention on the blog: homeopathy.

According to this explainer from the National Institutes of Health, homeopathy is based on “giving extremely small doses of substances that produce characteristic symptoms of illness in healthy people when given in larger doses.” (The active ingredient in Zicam is a form of zinc.)

The NIH says that individual studies of homeopathy have had varying results, but adds that “systematic reviews have not found homeopathy to be a definitively proven treatment for any medical condition.”

Zicam is marketed as a “homeopathic medicine.” As the FDA’s warning letter makes clear, “many homeopathic drug products are manufactured and distributed without FDA approval.” But, the letter adds, the agency can intervene when there’s evidence a homeopathic drug may pose a risk to consumers. That’s what it’s doing in this case.

The warning letter to Matrixx says that, because of the possible risks, the FDA will enforce its standard new-drug approval requirements for the intranasal Zicam products. That means Matrixx will have to demonstrate to the FDA’s satisfaction that “based on adequate and well-controlled clinical investigations … [the] product is safe and effective for each of its intended uses.”

Update: Matrixx posted a statement that said the products are safe and don’t cause loss of smell. The company called the FDA action “unwarranted” and said it is “in the process of determining its response.” The affected products accounted for about 40% of the company’s net sales, the statement said.

Source : blogs.wsj.com

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FDA Flags Psychiatric Risks Of Asthma Drugs

New labels on popular asthma drugs like Merck's Singulair must highlight language about suicidal behavior, depression and anxiety seen in a small number of patients, federal regulators said Friday.

After 15 months of investigation, the Food and Drug Administration said Merck & Co. Inc., AstraZeneca and Cornerstone Therapeutics will have to raise label warnings about psychiatric problems reported by a handful of patients taking their drugs.

"Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications," the FDA said in a posting to its Web site.

A spokeswoman for Merck said the language already appears in Singulair's label, but will be raised to the "precautions" section. It's now listed in a section about various side effects reported by patients.

"We've been working with the FDA since Singulair came to market and every time we update the label it's in cooperation with them," said Merck spokeswoman Pamela Eisele.

Singulair was Whitehouse Station, N.J.-based Merck's best-selling product last year, with U.S. sales of $3.5 billion.

A spokesman for London-based AstraZeneca said new labeling on its drug would only mention two psychiatric problems: depression and insomnia.

A spokesman for Cary, N.C.-based Cornerstone Therapeutics had no immediate comment Friday evening.

FDA regulators last spring began reviewing a handful of reports about mood changes, suicidal behavior and suicide in patients who had taken Singulair. The agency also launched probes into other drugs in the class, including AstraZeneca PLC's Accolate and Cornerstone Therapeutics Inc.'s Zyflo.

Earlier this year, the agency said company studies of the three drugs did not show an increased risk of suicidal behavior, though they were not designed to detect such problems. An FDA spokeswoman said Friday the agency is monitoring ongoing reports of suicide and other psychiatric problems among patients.

"We did move this language to the 'precautions' section to highlight that we're continuing to see these things," said FDA spokeswoman Karen Riley.

The exact language of the labeling updates has not been released, but the FDA said it could mention a slew of psychiatric problems, including: "agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior -- including suicide -- and tremors."

In general, the FDA has started notifying the public earlier about possible safety issues with drugs after the agency came under fire for acting too slowly on drugs like Merck's painkiller Vioxx, which was removed from the market in 2004 because it doubled the risk of heart attack and stroke.

Source : www.wdsu.com

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Liver Transplant Drug Linked to Increased Risk of Death

Liver transplant patients who were treated with the drug sirolimus (also called Rapamune) following surgery appear to be at increased risk of death, the Food and Drug Administration is warning.

New clinical trial data suggests that stable liver transplant patients who were switched from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to treatment with sirolimus were more likely to die or suffer severe adverse reactions, the FDA said.
The clinical trial was conducted by Wyeth, the maker of sirolimus. Wyeth submitted the results of the study to the FDA on March 25, 2009, officials said. The trial compared stable liver transplant patients who were switched from a CNI-based therapy to sirolimus to patients who remained on the CNI-based regimen.

The FDA is advising transplant physicians and patients about the clinical trial findings and continuing to examine the study data. The agency may decide to order changes to the labeling of the drug to further warn users and their doctors of the risk of mortality, officials said.

The FDA also issued the following recommendations on how physicians should handle sirolimus treatment:

• Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants.

• The safety and the efficacy of sirolimus as an immunosuppressant have not been established in liver or lung transplant patients. This information is in the Boxed Warning of the sirolimus label.

• The current Boxed Warning of sirolimus indicates that the use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

• Therapeutic drug monitoring is recommended for all patients receiving sirolimus.

• Therapeutic drug monitoring should not be the sole basis for adjusting sirolimus therapy. Careful attention should be paid to clinical signs and symptoms, tissue biopsy findings, and laboratory parameters.

• Patients unable to take the tablets should be prescribed the sirolimus oral solution and instructed in its use.

• Patients should be counseled that sirolimus is to be taken by mouth, once a day, consistently and with or without food.

• Sirolimus tablets should not be crushed, chewed or split.

Source : www.attorneyatlaw.com

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Study highlights new drug risk in pregnancy

Pregnant women who use cocaine or heroin while taking methadone to beat their addiction may weaken their placenta, opening the door to dangerous infections that could further harm an unborn baby, researchers said on Thursday.

Their study in a laboratory found that exposure to either of the drugs in the presence of methadone -- used to wean people off narcotics -- harmed the placenta and allowed other dangerous substances through the organ's protective barrier.

"As the consumption of illegal drugs, especially cocaine, is increasing in many countries, our results ... may improve the practical management in monitoring pregnant women," Antoine Malek of Zurich University Hospital and colleagues reported.

"More toxic substances or bacteria and viruses may cross the placenta and harm the fetus."

The placenta is an organ rich in blood vessels that develops in the lower part of the womb during pregnancy. It transfers oxygen and nutrients from the mother to the fetus and is expelled after birth.

The researchers collected placentas from uncomplicated pregnancies after caesarean section from a group of volunteers. Experiments showed that while the drugs did not increase the transfer of methadone, they did allow other toxic substances or bacteria to seep through.

The findings, published in BioMed Central's Reproductive Biology and Endocrinology, suggest this somehow compromises the protective barrier function of the placenta, the researchers said.

Source : in.reuters.com

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New Warning on Hormone Replacement

Hormone therapy taken by women to counter the effects of menopause can increase the risk of dying from lung cancer, researchers reported here on Saturday.

The findings represent the latest black mark against a therapy already being used much more sparingly than it once was. But researchers said the new data should serve as a caution to women who did continue to take hormones not to smoke.

“We shouldn’t be using both combined hormone therapy and tobacco at the same time,” said Dr. Rowan Chlebowski of the Harbor-U.C.L.A. Medical Center in California and lead author of the study, which was presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Chlebowski said there was one avoidable lung cancer death over eight years for every 100 women who both smoked and took hormone therapy.

The new analysis used data from the Women’s Health Initiative study, in which women took either Prempro, a drug combining estrogen and progestin, or a placebo. The study was discontinued in 2002 after it was found that the hormone therapy increased the risk of breast cancer.

The new analysis looked specifically at lung cancer for the five and a half years that the women took either the drug or the placebo and for more than two years afterward.

There were 96 cases of non-small-cell lung cancer, the most common type of the disease, among the roughly 8,000 women who used hormone therapy, compared with 72 cases among the nearly equal number who took the placebo. That difference was not statistically significant, meaning it could have occurred by chance.

But there were 67 deaths from lung cancer among the hormone users versus 39 among those who took the placebo, a result that was statistically significant.

Among smokers, 3.4 percent of hormone users died from lung cancer, compared with 2.3 percent of those who got the placebo. Among women who never smoked, 0.2 percent of hormone users died from lung cancer, compared with 0.1 percent of those who got the placebo.

Dr. Otis Brawley, the chief medical officer of the American Cancer Society, said he was not convinced that the results were not due to chance, given that there was a meaningful difference in deaths but not in number of cases.

In another study presented here, researchers reported that the drug Avastin showed signs that it could help prevent the recurrence of colon cancer, but the effect wore off after patients stopped taking it.

Avastin, which blocks the flow of blood to tumors, has been a best-selling cancer drug that is used for late-stage cancers. But the new study, involving 2,700 patients, looked at whether the drug could be given earlier, immediately after a colon tumor was removed by surgery. The idea was to keep cancer from coming back and effectively “cure” the patient.

Genentech, the manufacturer of the drug, announced in April that the drug had failed to prevent recurrence, though it provided no details at that time.

The data released here on Saturday showed that after three years, 77.4 percent of those who received a year of Avastin along with six months of standard chemotherapy were alive and disease free. That compared with 75.5 percent of those who got the chemotherapy alone, an insignificant difference.

After only the first year, however, when patients were taking Avastin, 94.3 percent of those who got the drug were cancer-free and alive compared with 90.7 percent of those who got chemotherapy alone, a difference that was statistically significant.

“It was effective, but that efficacy disappeared after the year in which bevacizumab was given,” said Dr. Norman Wolmark, chairman of the group of researchers, sponsored by the National Cancer Institute, who conducted the trial. Bevacizumab is the generic name for Avastin.

Dr. Wolmark said the research group hoped now to conduct a trial in which the drug would be given for two or more years.

But the prospect of giving Avastin for such a long duration is already raising concerns among doctors, not least because the drug costs about $50,000 a year when used to treat colon cancer. Moreover, the majority of patients with early colon cancer are already kept from relapsing by surgery and chemotherapy alone. So Avastin might have to be given for a long time to a lot of people to prevent a relatively few relapses.

“We have to think hard about long-term chemotherapy in our patients due to the impact on quality of life and the costs,” said Dr. Jennifer C. Obel, a gastrointestinal oncologist at NorthShore University HealthSystem in Chicago. “Are we going to be giving bevacizumab for three years, four years?”

Dr. Hal V. Barron, chief medical officer for Genentech, which is now owned by the Swiss drug company Roche, said the results “suggest promise for future trials.” He said the company offered programs to help patients obtain its drugs.

Source : www.nytimes.com

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FDA Orders Label Warning for Testosterone Gels

Children can experience troubling health effects if they come into contact with topical testosterone gels used by some American men, and the U.S. Food and Drug Administration on Thursday announced that two of these preparations would now carry boxed warnings to highlight the risk.

Accidental pediatric exposures to the gels can occur when the “consumer forgets to wash their hands or forgets to cover a treated area, and then has close contact with the child, or may have not waited for their skin to dry and then picks up a child,” Dr. Dianne Murphy, the FDA’s director of the Office of Pediatric Therapeutics within the Office of the Commissioner, said during a Thursday afternoon press conference.

Over time, these exposures can lead to premature and/or abnormal development of male characteristics in both boys and girls, the FDA said.

The two affected prescription medications are AndroGel 1%, made by Solvay Pharmaceuticals, and Testim 1%, made by Auxilium Pharmaceuticals. These are currently the only topical gel drugs approved by the FDA to address an insufficient or total lack of testosterone production among men.

Men typically rub the gels onto their upper arms or shoulders, according to the FDA.

According to the FDA, in 2007, pharmacies dispensed about 1.4 million prescriptions for the most popular medication, AndroGel, and about 370,000 prescriptions for Testim.

In addition to the new warning box, manufacturers will also have to develop a medication guide “to ensure that consumers who use these products are aware about the risk to children of secondary exposure,” Murphy said.

The new requirements arose after a thorough review of eight cases, reported since December 2008, in which children — ranging from as young as nine months to as old as five years — experienced a range of adverse side effects as a result of coming into direct and repeated contact with the treated skin of an adult user of either gel.

This type of exposure triggered “inappropriate virilization” among the young patients, Murphy said, including the onset of premature male characteristics in boys and inappropriate male characteristics among girls. The effects included “inappropriate enlargement of the penis or clitoris, premature development of pubic hair, advanced bone age, increased libido, and aggressive behavior” among the eight cases analyzed, Murphy said.

In most cases, these side effects subsided after exposure ceased, the FDA said, but in certain instances, genitalia enlargement and bone age did not revert to normal. As well, some children had to undergo invasive diagnostic procedures, while in one of the eight cases, hospitalization and surgical intervention was required.

“In the cases we reviewed, the average duration of exposure was around six months to a year” before the children received medical attention, noted Dr. Mary Roberts, a medical officer in the division of metabolism and endocrinology within the FDA’s Office of New Drugs, Center for Drug Evaluation and Research (CDER). “We can’t tell you if it lasted for five minutes or five hours, but we do know the exposure did occur over a period of time.”

Murphy and her colleagues hope the new labeling requirement will encourage consumers to more closely follow the approved protocol for the use of such gels. These include avoiding application of the drugs to parts of the body not indicated as appropriate; washing hands with soap and water after every application; and covering the application site with clothing once dry.

And they added that women should not use either gel, despite the fact the agency found that about 25,000 of the AndroGel prescriptions in 2007 were, in fact, dispensed to women.

Source : news.health.com

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New warnings for Tarceva cancer drug-U.S. FDA

New warnings have been added to Genentech Inc and OSI Pharmaceutical Inc's (OSIP.O) cancer drug Tarceva about serious complications such as skin reactions and holes in the digestive tract, U.S. health regulators said on Friday.

In some cases patients have died, the U.S. Food and Drug Administration said.

The FDA said that some of the problems suggest larger possible disorders such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Genentech is a unit of Roche Holding AG (ROG.VX). (Reporting by Susan Heavey).

Source : uk.reuters.com

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F.D.A. Orders Warning Label for Botox

Botox and other similar antiwrinkle drugs must now carry the most stringent kind of warning label, the Food and Drug Administration said Thursday.

The F.D.A. issued that order the day after the agency approved a new drug, Dysport, that is expected to be the first real challenger to Botox in the United States. Like Botox, Dysport is an injectable drug derived from the paralytic agent botulinum toxin.

The F.D.A. said such drugs must carry warning labels explaining that the material has the potential to spread from the injection site to distant parts of the body — with the risk of serious difficulties, like problems with swallowing or breathing.

Requiring a drug to carry a box with bold-face risk information — a so-called black-box warning — is one of the strongest safety actions the F.D.A. can take. Black boxes are typically reserved for medications known to have serious or life-threatening risks. Antidepressants, for example, carry black boxes warning of the increased danger of suicidal thoughts and actions.

The F.D.A. said it would also require makers of injectable toxins to send doctors letters warning of their risks and to produce a medication guide to be given to patients at the time of injection.

In a conference call with reporters on Thursday, an F.D.A. official said that the problems had occurred mainly in patients who received overdoses of the drug for unapproved treatments, like limb spasticity in children with cerebral palsy.

Botulinum toxins are safe when administered for approved uses at approved doses, said Dr. Ellis F. Unger, an official at the agency’s office of new drugs.

The agency’s approval of Dysport, manufactured by Ipsen, based in Paris, portends a fierce competition in the United States toxin market of a sort that has been raging in Europe for years.

Last year, Botox had worldwide sales of about $1.3 billion, according to its maker, Allergan. Dysport had sales of $189 million, according to an earnings statement from Ipsen.

In the absence of serious competition, Allergan has been able to raise the drug’s price annually. But Dysport, which in Europe has been priced lower than Botox, has the potential to capture up to 20 percent of the market in this country, said David M. Steinberg, an analyst at Deutsche Bank.

“Many doctors have been clamoring for another option,” Mr. Steinberg said.

Injectable botulinum toxins are purified forms of the bacterial poison that causes botulism, a paralyzing disease that can be fatal. The drugs temporarily reduce or halt muscle activity.

In the last 20 years, the F.D.A. has approved Botox to treat crossed eyes, eyelid spasms, severe underarm sweating, and cervical dystonia, a neck problem that can cause severe pain and abnormal head position. Under the name Botox Cosmetic, the drug is also approved to treat frown lines.

In 2000, the agency approved a different type of the toxin, Myobloc, to treat cervical dystonia.

On Wednesday, the agency approved Dysport for frown lines and cervical dystonia.

Medicis Pharmaceutical, a company in Scottsdale, Ariz., that has the rights to sell Dysport for frown lines in the United States, said it planned to bring the drug to market within 60 days. Ipsen will market the drug in this country for the neck problem.

The new F.D.A. requirement for a black-box warning on such drugs comes 15 months after the agency received a petition from Public Citizen, a public advocacy group, calling for more substantial warnings.

In its petition, the group said that the F.D.A. had received reports of 180 serious health problems and 16 deaths connected to the injections. In a response sent to the group on Thursday, the agency said it had identified even more reports of complications, including 225 reports of problems caused by the drug spreading from the injection site to distant parts of the body.

“There would have been fewer problems caused if they had put this out a year ago," said Dr. Sidney M. Wolfe, the director of the health research group at Public Citizen.

Allergan shares fell 1.3 percent to $46.66 on Thursday, while shares of Medicis rose more than 18 percent, to $16.07.

Source : www.nytimes.com

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I.Q. Harmed by Epilepsy Drug

Pregnant women who took a popular epilepsy drug, also widely used to treat migraines, pain and psychiatric disorders, had children whose I.Q. scores were significantly lower than those whose mothers took a different antiseizure medication, a new study has found.

The drug, valproate, sold generically and under the brand name Depakote, remains the second-most-popular antiseizure medication used for epilepsy, but earlier studies found that use during pregnancy also increased the risk of developmental delays and major malformations.

The risks that other epilepsy drugs may pose are not clear, experts say. While some are likely to be safer than others, there have not been enough studies to guide patients and their doctors. About half of the women who take valproate are not epileptics.

The new study is to be published on Thursday in The New England Journal of Medicine.

Three-year-olds whose mothers had taken valproate during pregnancy had I.Q. scores that were nine points lower on average than children whose mothers had taken a different antiseizure medication, lamotrigine. The I.Q. scores of toddlers whose mothers took valproate were also lower than scores of children whose mothers took two other antiseizure medications, phenytoin and carbamazepine.

Physicians involved in the study warned that valproate should never be the first choice for use in women of childbearing age, though exceptions may be made if a woman’s epileptic seizures cannot be controlled with other available medications.

“My thought is that if I make a mistake and the patient has a breakthrough seizure, I can change the medication and switch the patient to valproate,” said Dr. Kimford J. Meador, professor of neurology at Emory University School of Medicine in Atlanta, and first author of the new report. “If I put the patient on valproate as a first choice and the baby has cognitive impairment or a malformation, I can’t repair that.”

Dr. Meador and his colleagues enrolled 303 pregnant women who were each using an antiepileptic drug and were treated at 25 epilepsy centers in the United States and Britain from October 1999 to February 2004.

Cognitive assessments were conducted in 258 2- and 3-year-olds born to 252 mothers, of whom 53 had taken valproate.

Over all, children’s I.Q. scores were strongly related to mothers’ I.Q. scores, except among the children of mothers treated with valproate, the study found.

At age 3, children exposed to valproate in utero had a mean I.Q. of 92, compared with 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, and 98 for those exposed to carbamazepine, the study found.

Some 13,000 to 21,000 babies each year are born to women with epilepsy, and the vast majority are healthy, researchers and advocates emphasized.

Experts warned that women should not stop taking valproate without talking to their doctors.

“It’s important to stress to readers that if they become frightened, they should not simply stop taking the drug, because that can be even more dangerous,” said Eric Hargis, president of the Epilepsy Foundation in Washington.

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New warning on mixing clopidogrel , stomach drugs

Heart attack patients taking the blood thinner clopidogrel (Plavix) received a strong warning today about also taking a stomach-soothing proton pump inhibitor drug, such as Nexium, Prevacid, or Prilosec, at the same time. This drug combination is routinely prescribed to patients after a heart attack to decrease the risk of stomach irritation and bleeding, but a new study suggests the stomach drugs can interfere with how Plavix works and may actually raise the risk of having another heart attack.

Plavix helps reduce the risk of blood clots that can lead to another heart attack. However, it can also be hard on the stomach and cause gastrointestinal bleeding, so patients are often prescribed proton pump inhibitors (PPIs) to help prevent this. But previous studies have suggested the PPIs reduce Plavix's protective effect. The new study, which appears in the March 4 issue of the Journal of the American Medical Association, adds to the body of evidence that shows patients taking these drugs together face an increased risk of heart attack and death.

In the study, researchers examined the records of 8,205 patients taking Plavix after suffering a heart attack or angina. More than 5,200 patients were also taking a PPI. Nearly 30% of the PPI group died or were rehospitalized for heart attack or angina, compared with 21% of the patients who did not take a PPI. Overall, patients taking a PPI had about a 25% increased risk of death or being rehospitalized.

In January a Canadian study found that patients taking Plavix and a PPI had a 40% increased risk of having a second heart attack than patients taking only Plavix. At the time, the FDA said the evidence was insufficient to pin the blame on PPIs because some studies suggested the drugs did not interfere with Plavix. The agency is currently working with the makers of Plavix, Sanofi-Aventis and Bristol-Myers Squibb, to better understand how PPIs interact with Plavix. It could take several months before those studies are finished.

In the meantime, here's what our medical consultants recommend: The overall incidence of gastrointestinal bleeding with Plavix is actually quite low. Only about 2% of patients will experience this side effect (the risk will be higher if you are also taking aspirin). To help prevent bleeding while taking Plavix, instead of taking a PPI, a better option is an older class of drugs called H2blockers, which includes nizatidine (Axid), famotidine (Pepcid), and ranitidine (Zantac). You could also try an antacid. These drugs have not been associated with dampening the protective effects of Plavix. You should also talk to your doctor about having periodic blood counts or monitoring of your stools in order to detect gastrointestinal bleeding you may not be aware of (black, tarry stools can be a sign of this, for example).

Source : blogs.consumerreports.org

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