Tamiflu-does it work

According to the CDC, this year’s flu season is pretty serious in the USA. Current data, shows that about 4.6% of patient visits to health care providers are for influenza like illnesses (ILI). Thirty states and New York City are now reporting high ILI activity; an increase from 24 states last week. Additionally, 10 states are reporting moderate levels of ILI activity. Forty-eight states reported widespread geographic influenza activity for the week of January 6-12, 2013. This increased from 47 states in the previous week. 

2013-flu-outbreak-week-03

 

Although there has been a slight drop-off in ILI visits over the past couple of weeks since the peak in early January, the CDC continues to identify this season as a “moderately severe” one, and supplies in some areas have tight supplies of the flu vaccine.  Continue reading “Tamiflu-does it work”

2012 Top Ten list for new drug approvals

pharmaceutical researchThe US Food and Drug Administration recently announced (pdf) that it had cleared 35 new drugs during 2012, of which 31 were novel therapies. This is in addition to the literally hundreds of approvals for changes in already approved drugs for changes in packaging, manufacturing, and dozens of other reasons. 

In no particular order, here are the top 10 most interesting of the approvals based on my subjective viewpoint, which includes innovativeness, seriousness of disease, and other random factors. In others, no different in importance than all those end-of-year top 10 movie lists. So here we go: Continue reading “2012 Top Ten list for new drug approvals”

Court says Freedom of Speech applies to Big Pharma Sales Reps

pills and pill bottlesIn a strange decision, the United States 2nd Circuit Court of Appeals, which has jurisdiction over  ConnecticutNew York, and Vermont, ruled that a drug sales representative who promotes “off-label” uses of a particular drug is exercising their “freedom of speech.” The Court decided in a 2-1 vote, in United States v. Caronia (pdf), that the criminal conviction of Alfred Caronia, a former sales representative for a pharmaceutical company, be vacated. The case was an appeal of the sales representative’s conviction for promoting an off-label use of the drug Xyrem, which is approved for treatment of narcolepsy. The Court stated that “we construe the FDCA as not criminalizing the simple promotion of a drug’s off-label use because such a construction would raise First Amendment concerns.”

The Court also found that the FDA allows off-label use by physicians, but “prohibits the free flow of information that would inform that outcome,” while “the government’s prohibition of off-label promotion by pharmaceutical manufacturers provides only ineffective or remote support for the government’s purpose.” The Court also ruled that it construes “the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs.”  It also stated “that the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug.” Continue reading “Court says Freedom of Speech applies to Big Pharma Sales Reps”

Massachusetts hits compounding pharmacies linked to meningitis outbreak

The fungal meningitis outbreak related to a compounding pharmacy’s production of methylprednisolone acetate for epidural injection has reached 354 cases and 25 deaths according to the CDC. As I reported earlier, the reasons for the outbreak are multifold, from lax regulation of the compounding pharmacy, which are pharmacies that mix approved drugs into new forms with additional, supposedly inert ingredients, to meet the needs of patients, to a procedure that is unsupported by clinical research, to pain management physicians who were trying to save a few dollars by using compounded drugs. 

Vials of methylprednisolone acetate from New England Compounding Center. Copyright, 2012, New York Newsday.

The New England Compounding Center (website has been replaced by a news release) is the center of attention for this outbreak, and because the FDA’s authority in regulating these types of pharmacies is limited, the state of Massachusetts has decided to step up it’s efforts in regulating, and if necessary, shutting down some of these pharmacies if they violate state and federal regulations. The New York Times has reported that Massachusetts shut down Infusion Resource in Waltham, MA, after “after a surprise inspection last week found conditions that called into question the sterility of its products, state officials said Sunday.” 

Gov. Deval Patrick ordered the state’s Board of Registration in Pharmacy to immediately begin surprise inspections of compounding pharmacies that prepare injectable sterile medications. According to the New York Times article,

There are 25 such pharmacies in Massachusetts, and Mr. Patrick has acknowledged that the state rules governing them were insufficient. Although the Food and Drug Administration can inspect compounding pharmacies and issue warnings, the agency says states have ultimate jurisdiction.

At the news conference on Sunday, Dr. Lauren Smith, the interim commissioner of the Massachusetts Department of Public Health, said the state was bringing on five additional inspectors to help with unannounced visits to compounding pharmacies. The goal is to inspect all of them by Jan. 1, she added.

A number of  public health advocates have called for increased FDA regulatory power over compounding pharmacies for many years, warning that these pharmacies are not currently subject to the FDA’s oversight on manufacturing, quality and efficacy. Thus, they are easily able to distribute products like the tainted steroids that pose serious public health risks without worrying about any type of significant oversight. Some members of Congress have already called for a criminal investigation into the meningitis outbreak.

Hopefully, Massachusetts will lead the way in fixing this issue, but this should be the FDA’s responsibility. Congress will probably have to revise or add new regulations for the FDA to really clamp down on this problem, or it will happen again.

Key citations

What is causing the fatal meningitis outbreak?

Over the past week or so, there have been numerous reports about a fungal meningitis outbreak that was traced to medicines associated with three lots of preservative-free methylprednisolone acetate produced by the New England Compounding Center.  The drug is an injectable steroid that is used for pain relief. The potentially contaminated injections were given starting May 21, 2012. Symptoms of the fungal meningitis include: fever, new or worsening headache, neck stiffness, sensitivity to light, new weakness or numbness, increasing pain, redness or swelling of the injection site. So far, 7 people in the US have died.

Because the drug is delivered via an epidural injection directly into the epidural space, any contamination can lead to a meningitis infection. In this case the steroid produced by the New England Compounding Center was contaminated with a fungus which caused the fungal meningitis. It’s important to note that unlike other types of meningitis, such as bacterial meningitis, it is not contagious. Fungal meningitis also does not have a vaccine, because it is quite rare. (Viral meningitis is less severe, and usually resolves itself without treatment.)

Data Table for Persons with Meningitis Linked to Epidural Steroid Injections, as of October 7, 2012

Continue reading “What is causing the fatal meningitis outbreak?”

GlaxoSmithKline fined $3 billion by FDA for improper marketing and unethical behavior

Recently, the US Department of Justice ordered the pharmaceutical giant, GlaxoSmithKline (GSK), to pay $3 billion in criminal and civil liabilities in the largest healthcare fraud settlement in US history. Basically, GSK was caught promoting several drugs for unapproved uses, failing to report safety data, paying kickbacks to physicians, and price reporting. Let’s look at the fraud charges one by one.

Unapproved uses (or off-label uses). By law, pharmaceutical companies are only allowed to market drugs according to what is stated in their package labeling which is approved by the FDA. Off-label uses are the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration. Physicians are legally allowed to prescribe drugs off-label (as long as it is not contraindicated), but the pharmaceutical company cannot directly or indirectly influence off-label use. In most cases, off-label use isn’t dangerous, nor is it particularly unethical.

GSK was accused of unlawfully promoting Paxil, an antidepressant, for treating patients under the age of 18, even though it lacked FDA approval for pediatric use. GSK participated in “preparing, publishing and distributing a misleading medical journal article that misreported a clinical trial of Paxil that demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy.” What was most troubling was that GSK did not balance its study with data from two other studies in which Paxil failed to demonstrate efficacy in treating depression in patients under 18. Typical of this type of marketing, GSK sponsored dinners, lunches, spas, and similar types of programs to promote the off-label use of Paxil in children. It’s also important to note that Paxil includes a “black box warning“, the strongest FDA warning for a pharmaceutical product, that states that antidepressants make increase suicidal ideation and behavior in patients under 18. Continue reading “GlaxoSmithKline fined $3 billion by FDA for improper marketing and unethical behavior”

Totally Drug-Resistant Tuberculosis in India

Totally Drug-Resistant Tuberculosis in India.

Along with HIV and malaria, tuberculosis (TB) is one of the most dangerous diseases in the world.  According to the World Health Organization, there were 8.8 million new worldwide cases of TB, along with 1.4 million deaths in 2010.  TB is difficult to treat, usually taking over six months with antibiotics that sometimes have difficult side effects.

Also, because of low patient compliance, misdiagnosis, and other issues, multi-drug resistant (MDR) and extensively drug-resistant (XDR) versions of TB can arise in a population. MDR is resistant to the first-choice drugs, requiring treatment with a larger cocktail of  one or more of the nine different “second-line” antibiotics, which are less effective, have more adverse effects, and can take much longer to effect a cure, up to 2 years or more. XDR TB is resistant to the three first-line drugs and several of the nine antibiotics usually considered as second line choices.

As the article states:

The vast majority of these unfortunate patients seek care from private physicians in a desperate attempt to find a cure for their tuberculosis. This sector of private-sector physicians in India is among the largest in the world and these physicians are unregulated both in terms of prescribing practice and qualifications. A study that we conducted in Mumbai showed that only 5 of 106 private practitioners practicing in a crowded area called Dharavi could prescribe a correct prescription for a hypothetical patient with MDR tuberculosis. The majority of prescriptions were inappropriate and would only have served to further amplify resistance, converting MDR tuberculosis to XDR tuberculosis and TDR tuberculosis.

The spread of this disease could be quicker than some other infectious disease (like HIV), because of how easily it’s spread (one patient can infect up to 15 others before diagnosis and treatment), and, of course, the lack of viable antibiotics for XDR TB.

Right now, the infection seems to be in a small subgroup of TB patients in India (and Iran) in a border region that has poor medical care.  However, given the lack of effective antibiotics means that we’re all in this together.

The interesting fact about the title of the article–the authors seem to have invented a new subset of TB, Totally Drug Resistant.

F.D.A. Restricts Use of Antibiotics in Livestock – NYTimes.com

F.D.A. Restricts Use of Antibiotics in Livestock – NYTimes.com.

Wise move on the part of the FDA.