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    <recommendedItem id="20100101_19_3278"
                     title="Investigation Reveals More Woes for Rosiglitazone"
                     score="0.012"
                     href="http://www.medpagetoday.com/Cardiology/Diabetes/tb/22050?impressionId=1284023056077"
                     
      &lt;p&gt;On July 15 -- a day after the FDA completed &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/21161&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/21161&quot; target=&quot;_blank&quot;&gt;two days of hearings&lt;/a&gt; on rosiglitazone (Avandia) -- a British advisory commission on drugs concluded that the product should be withdrawn from the market, according to an investigation conducted by &lt;em&gt;BMJ.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The Commission on Human Medicines&apos; opinion was passed on to the U.K.&apos;s regulatory authority, the Medicines and Healthcare Products Regulatory Agency (MHRA), which has now told &lt;em&gt;BMJ &lt;/em&gt; that rosiglitazone &quot;no longer has a place on the U.K. market.&quot; The evidence for increased risk of cardiovascular events outweighs any potential benefit, according to an MHRA statement given to &lt;em&gt;BMJ&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Yet six weeks after the commission submitted its recommendations on rosiglitazone, the drug is still on the market in Britain. The MHRA has yet to share its negative assessment of the drug with either physicians or patients.&lt;/p&gt;
&lt;p&gt;Instead, on July 26 it sent providers a &quot;dear doctor&quot; letter suggesting merely that it would be wise to consider alternatives to rosiglitazone, wrote Deborah Cohen, features editor at &lt;em&gt;BMJ. &lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The &lt;em&gt;BMJ &lt;/em&gt;investigation was detailed in a feature article published online today and also the subject of a BBC news report. The report appears to be the first confirmation that U.K. regulators are ready to withdraw the drug from the market.&lt;/p&gt;
&lt;p&gt;The lengthy article reveals no new information about the FDA&apos;s handling of rosiglitazone from its approval through two subsequent safety reviews, but it does give insight into the machinations of the approval process in Europe.&lt;/p&gt;
&lt;p&gt;For example, the European Medicines Agency initially rejected rosiglitazone, only to come back a year later in 2000 to approve the drug. As a condition of that approval, the EMA ordered a post-marketing study to verify the safety of the drug. That study, called RECORD, was an open-label trial that has been roundly criticized on both sides of the Atlantic for its poor design.&lt;/p&gt;
&lt;p&gt;Cohen quoted numerous sources who all pointed to the influence of the drug maker, GlaxoSmithKline (SmithKlineBeecham during the initial approval process), as the reason that the EMA reversed itself on rosiglitazone.&lt;/p&gt;
&lt;p&gt;&quot;According to Edwin Gale, a diabetologist and adviser to European regulators, in the years before rosiglitazone&apos;s approval diabetologists were also putting pressure on the regulators and clamouring to use this new class of drug. Some of this clamour was fuelled by pharmaceutical analysts touting its blockbuster potential, which at the time they said was crucial to Smithkline Beecham&apos;s future growth,&quot; Cohen wrote.&lt;/p&gt;
&lt;p&gt;Cohen also pointed out that the EMA does not publicly release names of members of advisory panels who review drugs for the EMA. By comparison, she wrote, the FDA process, often the subject of criticism in the U.S., is open and transparent.&lt;/p&gt;
&lt;p&gt;In a editorial that accompanied Cohen&apos;s article, Richard Lehman, PhD, of the University of Oxford, John S. Yudkin, MD, of University College in London, and Harlan Krumholz, MD, of Yale University, said there is plenty of blame to pass around in the rosiglitazone saga.&lt;/p&gt;
&lt;p&gt;Back in 1999, clinicians were &quot;strongly disposed to welcome a new drug for type 2 diabetes, and it was vigorously promoted to a receptive market,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Our mistake then -- and we have yet to put it right -- was that we did not demand better proof before we embarked on mass medication of a large group of patients who looked to us for advice and treatment.&quot;&lt;/p&gt;
&lt;p&gt;In a commentary, which was also published with the Cohen article, Nick Freemantle, PhD, of the University of Birmingham in England, argued that much of the controversy surrounding the thiazolidinediones can be laid at the feet of poor trial design -- so poor that critical questions were not answered.&lt;/p&gt;
&lt;p&gt;For example, regulators have been willing to permit high rates of loss to follow-up, especially in trials that rely on surrogate endpoints, a position that he contended &quot;makes no sense.&quot;&lt;/p&gt;
&lt;p&gt;And &quot;even when trials examine serious morbidity and mortality, loss to follow-up remains a problem. The RECORD trial, conducted to examine the safety of rosiglitazone and sponsored by GlaxoSmithKline in the UK, failed to follow-up survival in 127 participants (2.9%),&quot; he wrote. The loss to follow-up in RECORD meant that one could conclude that rosiglitazone &quot;was associated with either an increase or a decrease in mortality given different assumptions on the fate of those lost to follow-up.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Cohen declared no competing interests.&lt;/p&gt;&lt;p&gt;Lehman, Yudkin and Krumholz all declared they had received no support for the submitted work; no financial relationships with any organization that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.&lt;/p&gt;&lt;p&gt;Freemantle declared no support for the submitted work, but he disclosed that he has received funding for research and travel and consulting fees from Novo Nordisk, Sanofi-Aventis, Johnson &amp;amp; Johnson, and Eli Lilly.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3276"
                     title="FDA Approves New Eye Pressure Drop Formulation"
                     score="0.012"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/tb/22040?impressionId=1284023056077"
                     
      &lt;p&gt;WASHINGTON  --  The FDA approved a new formulation of the drug bimatoprost (Lumigan) in a 0.01% solution as a first-line treatment to reduce elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.&lt;/p&gt;
&lt;p&gt;Approval was based on a three-month clinical trial of patients with open-angle glaucoma or ocular hypertension, with an average baseline intraocular pressure of 23.5 mm Hg.&lt;/p&gt;
&lt;p&gt;The trial found intraocular pressure was reduced by up to 7 mm Hg with the 0.01% formulation with only one-third of the drug exposure compared with the 0.03% formulation of the same drug when the two were compared head-to-head.&lt;/p&gt;
&lt;p&gt;The drug is taken once daily as an eye drop during the evening.&lt;/p&gt;
&lt;p&gt;Bimatoprost may increase pigmentation of the iris, eyelid, and eyelashes.&lt;/p&gt;
&lt;p&gt;Patients with intraocular inflammation may exacerbate it with use of bimatoprost.&lt;/p&gt;
&lt;p&gt;The drug may cause macular edema, especially in aphakic patients, pseudophakic patients with a torn posterior lens capsule, and patients at risk for macular edema.&lt;/p&gt;
&lt;p&gt;Adverse events associated with the drug include conjuctival hyperemia, eyelash growth, and ocular pruritus.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Allergan of Irvine, Calif.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3260"
                     title="Tigecycline Label to Warn on Increased Death Risk"
                     score="0.011"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/22022?impressionId=1284023056077"
                     
      &lt;p&gt;A warning that the intravenous antibiotic drug tigecycline (Tygacil) is associated with increased risk of death, compared with other antibiotics, will be added to the product&apos;s label, the FDA said.&lt;/p&gt;
&lt;p&gt;Pooled data from 13 trials indicated a modestly increased risk of mortality in patients treated with tigecycline, the agency indicated.&lt;/p&gt;
&lt;p&gt;&quot;The increased risk was seen most clearly in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia, but was also seen in patients with complicated skin and skin structure infections, complicated intra-abdominal infections, and diabetic foot infections,&quot; said an FDA Drug Safety Communication.&lt;/p&gt;
&lt;p&gt;Tigecycline is not approved for some of those uses, the agency noted. Its approved indications are currently limited to complicated skin and skin structure infections, complicated intra-abdominal infections, and community-acquired pneumonia.&lt;/p&gt;
&lt;p&gt;Overall adjusted death rates in the 13 studies were 4.0% for tigecycline versus 3.0% for comparator antibiotics. The estimated risk difference was 0.6% (95% CI 0.1% to 1.2%), the FDA indicated.&lt;/p&gt;
&lt;p&gt;The agency has updated the Warnings and Precautions and Adverse Reactions sections of the drug&apos;s label to include information on the increased mortality risk. The FDA is also sending Dear Professional letters to providers outlining the new risk information.&lt;/p&gt;
&lt;p&gt;&quot;Alternatives to Tygacil should be considered in patients with severe infections,&quot; the agency recommended. It also called on healthcare professionals to report adverse effects associated with tigecycline to its MedWatch system.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3238"
                     title="Allergan Settles Civil and Criminal Charges"
                     score="0.01"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/Ethics/tb/21994?impressionId=1284023056077"
                     
      &lt;p&gt;Botox manufacturer Allergan will pay $375 million after pleading guilty to a misdemeanor misbranding charge related to off-label use of the cosmetic drug, a statement on the company&apos;s website said.&lt;/p&gt;
&lt;p&gt;In addition to the fine, the company agreed to pay $225 million to settle civil claims raised against it by the Department of Justice.&lt;/p&gt;
&lt;p&gt;The manufacturer came under criminal investigation from 2000 to 2005. The misbranding charge alleges that, during that time, the drug labeling did not contain complete directions for intended use, which included off-label uses for headache, pain, spasticity, and juvenile cerebral palsy.&lt;/p&gt;
&lt;p&gt;&quot;Under the Government&apos;s view, a use that the FDA has not approved (i.e., an &apos;off-label&apos; use) may be deemed &apos;intended&apos; based on written or oral statements made by the manufacturer,&quot; Allergan noted in the statement, adding that the company agreed that its marketing of the drug during the five years in question did result in those off-label uses.&lt;/p&gt;
&lt;p&gt;The drug was approved for use in treatment of flexor muscle spasms in the elbow, wrist, and fingers in adult patients in March. (See &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/18917&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/18917&quot; target=&quot;_blank&quot;&gt;FDA Okays Botox Use in Elbow, Wrist, Muscle Spasms&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Allergan filed for approval of onabotulinumtoxin A&apos;s use as a treatment for chronic migraine in 2008, but the results of that application are still pending. The company also is conducting phase III trials regarding use in patients with neurogenic and idiopathic overactive bladder, the prepared statement said.&lt;/p&gt;
&lt;p&gt;As part of the company&apos;s settlement, Allergan has entered a corporate integrity agreement that allows the company to keep its current compliance program at the cost of being subject to additional monitoring, adhering to new written standards, and engaging in auditing, training, education, reporting, independent and third-party review, and disclosure over a five-year period.&lt;/p&gt;
&lt;p&gt;Allergan is located in Irvine, Calif.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3236"
                     title="Opioid Dependence Drug Gets Okay for New Delivery Mode"
                     score="0.01"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/21990?impressionId=1284023056077"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved a new sublingual film formulation of the opioid dependence treatment combination buprenorphrine/naloxone (Suboxone).&lt;/p&gt;
&lt;p&gt;The new formulation will be released in the same 2 mg buprenorphrine/0.5 mg naloxone and 8 mg buprenorphrine/2 mg naloxone doses as the drug&apos;s sublingual tablet form.&lt;/p&gt;
&lt;p&gt;&quot;During clinical tests, Suboxone sublingual film was shown to be faster dissolving than Suboxone sublingual tablets,&quot; Shaun Thaxter, president of manufacturer Reckitt Benckiser Pharmaceuticals, said in a prepared statement.&lt;/p&gt;
&lt;p&gt;Drug approval included a risk evaluation and mitigation strategy program, which requires the company to monitor patients to determine whether potential treatment benefits outweigh potential risks, especially with accidental overdose, misuse, and abuse of the film, the brief said.&lt;/p&gt;
&lt;p&gt;The drug can be abused in ways similar to other opioids. Healthcare professionals should monitor patients for proper use, the company said in the statement.&lt;/p&gt;
&lt;p&gt;Buprenorphrine reduces patient opioid cravings and withdrawal symptoms, and also blocks the effects of other opioids. Naloxone triggers withdrawal symptoms in patients who crush and inject the drug, but has limited bioavailability when taken sublingually, and should cause no adverse events.&lt;/p&gt;
&lt;p&gt;Chronic use of the drug may result in physical dependence and a sudden or rapid decrease in dose may result in withdrawal symptoms, though the symptoms are milder and more delayed than those occurring with full opioid agonists, the brief said.&lt;/p&gt;
&lt;p&gt;Patients taking the film, particularly if injected or through other improper means and with central nervous system depressants, may experience life-threatening respiratory depression or death. Healthcare professionals should consider a reduced dose of the central nervous system depressant, the combination, or both when prescribing buprenophrine/naloxone, the statement said.&lt;/p&gt;
&lt;p&gt;Pediatric patients taking the drug may have severe, potentially fatal respiratory depression.&lt;/p&gt;
&lt;p&gt;Those taking the film should have liver function monitored before and during drug treatment.&lt;/p&gt;
&lt;p&gt;Patients who take the drug prior to use or abuse of other full agonists, such as heroin or oxycodone, may experience withdrawal symptoms due to interactions with the drug&apos;s naloxone.&lt;/p&gt;
&lt;p&gt;Healthcare professionals should only prescribe pregnant or nursing patients the drug combination if potential gain outweighs potential risk, due to possible neonatal withdrawal symptoms associated with the drug, according to the manufacturer.&lt;/p&gt;
&lt;p&gt;The drug is contraindicated in patients hypersensitive to buprenophrine or naloxone.&lt;/p&gt;
&lt;p&gt;Adverse events associated with the film include numb mouth, sore tongue, mouth redness, headache, nausea, vomiting, sweating, constipation, insomnia, pain, swelling of limbs, attention disturbance, palpitations, blurred vision, cytolytic hepatitis, jaundice, and anaphylactic shock.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>