Drug Injury Watch

Smoking Cessation Drugs Chantix, Wellbutrin, And Zyban Are Getting New "Black-Box" Warning

Will Warn About Risk Of Serious Neuropsychiatric Symptoms Including Agitation, Depression, Suicidal Thoughts, And Attempted Suicide

(Posted by Tom Lamb at DrugInjuryWatch.com)

On July 1, 2009 the FDA issued a Public Health Advisory about Chantix (varenicline) as well as Wellbutrin (bupropion) and Zyban (bupropion) which announced that these smoking cessation drugs will be getting a so-called "black-box" warning:

...highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease.

Contemporaneous with this July 1 FDA Public Health Advisory the FDA issued a news release -- "FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban" -- and a document intended primarily for relevant medical professionals -- "Information for Healthcare Professionals: Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)".

This second item had some concise and helpful background information about the history of safety issues concerning Chantix, Wellbutrin, and Zyban:

FDA first informed the public about the possibility of serious neuropsychiatric symptoms with [Chantix] in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review.  A complete history of related communications on [Chantix] and [Wellbutrin / Zyban] can be found at: Varenicline (marketed as Chantix) Information.  Since that time, information about serious neuropsychiatric symptoms in patients taking varenicline has been added to the POST-MARKETING EXPERIENCE section of the prescribing information.

As FDA received additional information the suggestion of a possible association between both varenicline and bupropion (which was evaluated as a comparator to varenicline) and serious neuropsychiatric symptoms, in both patients with and those without previous history of psychiatric illness, became more evident as its review progressed....

We will watch for corporate press releases from Pfizer (which sells Chantix) as well as GlaxoSmithKline (which sells Wellbutrin and Zyban) which might be issued to present the drug company's reaction to this FDA announcement about adding a black-box warning for neuropsychiatric side effects being added to their respective product's Package Insert, or label.

Merck's Popular Asthma Drug Singulair Associated With Suicide And Depression

FDA Has Gone From "No Link" In January 2009 To Wanting An Increased Warning About These Neuropsychiatric Events In June 2009

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 12, 2009 the FDA announced that Singulair (montelukast) as well as some other less popular leukotriene inhibitors -- Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton) -- must start to include a warning on its package insert, or label, regarding an increased risk of neuropsychiatric events including suicide and depression.

This June 2009 FDA warning about Singulair is seemingly a reversal from an earlier position taken by the FDA in January 2009 when the agency said their review of clinical trials did not suggest Merck's Singulair asthma drug caused suicide or suicidal thoughts.

For some perspective, let's look back in time to see how this Singulair - suicide link has become a very significant emerging drug-safety issue at the FDA. 

We start with a March 27, 2008 ABC News report, "Doctors Not Concerned by US FDA Probing Safety of Merck's Singulair":

The Food and Drug Administration (FDA) announced an investigation Wednesday examining a link between suicide and Merck's popular allergy and asthma drug, Singulair.

Concerns over "behavioral issues" with Singulair developed over the past year. Merck periodically updated the drug's labels to include warnings for tremors, depression and anxiety. FDA spokesperson Susan Cruzan said reports of suicides by "three or four" people who were taking Singulair prompted Merck to clarify suicide warnings on labels and patient information sheets in October 2007.

We get some additional background information from a March 27, 2008 article, "FDA Investigates Possible Suicide Link With Montelukast (Singulair)", published online by MedPage Today:

The FDA said it will probably take at least nine months for it to complete a safety review of the popular asthma and allergy drug montelukast (Singulair).

The ongoing investigation is examining a possible association between use of the drug and behavior/mood changes, suicidality (suicidal thoughts and behavior), and suicide, the agency said....

Over the past year, the maker of Singulair, Merck & Co, has updated the prescribing information and patient information for Singulair to include the following post-marketing adverse events: tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior) (October 2007), and anxiousness (February 2008).

From there we move forward to a January 14, 2009 Reuters article, "FDA says Singulair data do not suggest suicide link":

U.S. regulators on Tuesday said their review of clinical trials does not suggest Merck & Co's Singulair asthma drug or similar medicines cause suicide or suicidal thought, although the data were inadequate to draw a firm conclusion....

The agency also studied trials involving two other medicines that work by blocking inflammation-causing proteins called leukotrienes, AstraZeneca Pls's Accolate (zafirlukast) and Zyflo (zileuton) sold by Cornerstone Therapeutics Inc.

"Although these data do not suggest that [Singulair (montelukast), Accolate (zafirlukast) or Zyflo and Zyflo CR (zileuton)] are associated with suicide or suicidal behavior, these clinical trials were not designed specifically to examine neuropsychiatric events," the FDA said. "As a result, some events may not have been reported."

Concerns about a possible suicidal link have arrested sales growth of Singulair, Merck's biggest product with annual sales of almost $4.5 billion.

Then came the June 2009 announcement from FDA that there may be a link between Singulair and suicide.  From a June 12, 2009 MedPage Today article, "FDA: Leukotriene Inhibitors Associated with Suicide, Depression":

Leukotriene inhibitors must include a warning regarding increased risk of neuropsychiatric events including suicide and depression, according to the FDA.

The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.

Upon completing a review of the agents in April, the FDA found reports of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicide, suicidal ideation, and tremor associated with use of the drugs.

The FDA based its review on postmarket reports and clinical trial data submitted by the manufacturers of the drugs....

The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.

Now that the association between Singulair and neuropsychiatric events such as suicide and depression has been announced by the FDA, we expect there to be additional case reports about Singulair users experiencing these serious side effects.

As always, we encourage people with personal knowledge about serious side effects from Singulair use to submit a MedWatch report to the FDA.  We also welcome Comments, here, from people who want to share with others their side-effect experiences, or that of a family member, while using Singulair.

P.S.  Merck Statement in Response to the FDA's June 12, 2009 Communication with Updated Information on Leukotriene Inhibitors, Including SINGULAIR® (montelukast sodium) -- June 12, 2009 press release from Merck & Co., Inc.  (6/24/09)

Gardasil Vaccine Associated With 28 Deaths In 2008 According To Judicial Watch Report

This Public Interest Group Reviewed Gardasil Cases Found In FDA’s Vaccine Adverse Event Reporting System (VAERS)

(Posted by Tom Lamb at DrugInjuryWatch.com)

According to the Gardasil web site:

GARDASIL is the only cervical cancer vaccine that helps protect against 4 types of human papillomavirus (HPV): 2 types that cause 70% of cervical cancer cases, and 2 more types that cause 90% of genital warts cases.

On June 22, 2009 the public interest group Judicial Watch issued a press release regarding the Gardasil vaccine which had the following attention-getting headline and sub-headline:

New FDA Records Obtained by Judicial Watch Indicate 28 Deaths Related to Gardasil in 2008

• View Discussion Records Document 6,723 Adverse Reactions in 2008, Including 1,061 Considered "Serious" and 142 Considered "Life Threatening"

According to this June 22 press release Judicial Watch is basing their numbers on the group's review of the FDA’s Vaccine Adverse Event Reporting System (VAERS), during which they found:

...28 deaths in 2008 associated with Gardasil, the vaccination for human papillomavirus (HPV), up from 19 deaths in 2007. The total number of Gardasil-related deaths is 47 since the vaccine was approved in 2006. Overall, the FDA documented 6,723 "adverse events" related to Gardasil in 2008, of which 1,061 were considered "serious," and 142 considered "life threatening."

The June 22, 2009 Judicial Watch press release has links to the VAERS case reports for some Gardasil adverse reactions that are cited as examples.

The press release closes with this "position statement" by Judicial Watch:

"The FDA is supposed to be a guardian of public health, and yet the agency continues to turn a blind eye to what seems to be an extremely serious public health problem. The public relations push for Gardasil by Merck, politicians and public health officials needs to pause so that these adverse reactions can be further studied," said Judicial Watch President Tom Fitton. "The already serious problems associated with Gardasil seem to be getting worse. No one should require this vaccine for young children."

We would be interested in hearing about any Gardasil adverse reactions you know of, as well as your opinion about whether the Gardasil vaccine should be required for young children.  To participate in this conversation, you only need to submit a Comment, below.

Can New FDA Transparency Task Force Acheive Its Lofty Objectives?

While Need For Greater Disclosure By FDA Is Evident, Drug Maker Trade Secrets May Be Difficult Obstacle To Overcome

(Posted by Tom Lamb at DrugInjuryWatch.com)

In early June 2009 it was announced that the FDA would begin to set up a task force within the agency whose purpose is to recommend ways by which there could be more timely disclosure about FDA regulatory and safety decisions.

From a June 2, 2009 FDA press release titled "FDA Forms Transparency Task Force" we get these laudable "sound bytes":

• Health and Human Services Secretary Kathleen Sebelius: "The Transparency Task Force will give the American people a seat at the table and make the FDA more open and accountable."
• FDA Commissioner Margaret A. Hamburg, M.D.: "I have asked the Transparency Task Force to deliver recommendations to me for ways to make more information available and foster better understanding of decision-making."
• Principal Deputy Commissioner Joshua Sharfstein, M.D.: "Implementation of the Transparency Task Force’s recommendations should make agency actions and decisions, and their underlying processes and bases, more transparent to the public."

This new FDA task force, which will be chaired by Principal Deputy Commissioner Sharfstein, consists of FDA center directors as well as the associate commissioner for regulatory affairs, chief scientist, and the chief counsel at the agency.

The FDA issued a June 3, 2009 Federal Register notice regarding the formation of its new Transparency Task Force in which the agency announced a June 24, 2009 public meeting intended to solicit recommendations on how the FDA can make more available, useful, and understandable information on its activities and decisions.

The agency has also established a "temporary" blog -- simply named "FDA Transparency Blog" -- which will run for the next six months, June through November 2009.

Two leading members of the medical community who have been involved with various drug-safety issues over time -- Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, and Dr. Catherine DeAngelis, editor of The Journal of the American Medical Association -- both impliedly endorsed this move by the FDA according to a June 2, 2009 article, "Drug Agency May Reveal More Data on Actions", by New York Times (NYT) reporter Gardiner Harris. 

This same June 2 NYT article, however, points out that this new FDA task force will likely have a difficult time when it comes to the issue of any future disclosure of now secret data about drugs and devices under study:

The task will be complicated. Agency confidentiality decisions are governed by several interconnected laws, including the Federal Trade Secrets Act. Changing them would “involve more than one Congressional committee and impact thousands and thousands of companies, and thus would be an extremely difficult legislative path,” said Peter Barton Hutt, a former general counsel to the agency....

Ken Johnson, a spokesman for the Pharmaceutical Research and Manufacturers of America, said any agency plan to “disclose information about medicines during the F.D.A. review process should be carefully considered to ensure that the competitive development process remains intact to serve patients and the public health.”

According to the June 3 Federal Register notice, anyone interested in attending the June 24 public meeting -- which will be held at the National Transportation Safety Board (NTSB) Conference Center, 429 L'Enfant Plaza, SW., Washington, DC 20594 -- must register by June 17, 2009.

The Federal Register notice also provides information about how to make written and electronic comments, which must be submitted by August 7, 2009.

April 2009 FDA "Patient Safety News" Videos For Doctors Online

Covers Bowel Cleansing Agents Visicol and OsmoPrep, As Well As Methadone Overdoses, Ethex Generic Drug Recall, And Medication Errors

(Posted by Tom Lamb at DrugInjuryWatch.com)

The FDA's Patient Safety News (PSN) is a series of monthly video news shows intended primarily for doctors and other health care professionals.  Generally, this series covers significant approvals, recalls, and safety alerts for prescription drugs and medical devices.  Some of the FDA PSN videos contain footage and demonstrations relevant to protecting patients from serious side effects and other unwanted consequences.

Subjects covered in the April 2009 edition of the FDA Patient Safety News include the following:

Stronger Warnings for Bowel Cleansing Agents

FDA is announcing new safety measures for oral sodium phosphate (OSP) products used for bowel cleansing before colonoscopies and other procedures. These products are associated with acute phosphate nephropathy, a rare but serious type of kidney injury. The events have been reported with the prescription products Visicol and OsmoPrep, and also over-the-counter sodium phosphate products when they are used as bowel cleansers.

Preventing Overdoses when Using Methadone to Treat Chronic Pain

A report from the Institute for Safe Medication Practices (ISMP) lists several reasons for the serious and sometime fatal overdoses that have occurred when methadone is used to treat moderate to severe chronic pain.

ISMP points out that methadone differs from other opioids in a number of ways. For example, methadone remains in the body long after its analgesic effect has worn off. Also, a patient may not experience the full analgesic effect of methadone until 3-5 days of use, so it must be titrated more slowly than other opioids.

Ethex Corp. Expands Recall of Generic Drugs and Supplements

The generic drug company Ethex Corporation is expanding earlier recalls to now include over 60 generic drug products, including narcotics and cardiac medications, as well as several dozen prescription prenatal vitamins and iron supplements. The company is taking this action as a precautionary measure because these products may have been manufactured under conditions that didn't comply with current Good Manufacturing Practices. Certain lots of some of these products were recalled earlier because of defects such as oversized tablets.                                                   

Avoiding Medication Errors with Multiple Brand Names

The Institute for Safe Medication Practices (ISMP) recently highlighted medication errors that can occur when a drug is marketed under more than one brand name, especially when one of those names is well established.

ISMP says that health professionals can reduce the risk of errors by conducting a thorough drug history and reviewing drug information if they encounter unfamiliar product names. ISMP also suggests that health professionals encourage patients to fill their prescriptions at the same pharmacy where possible, to help avoid taking the same product under different names.

One can find more information about this April 2009 PSN edition and the series in general on the Patient Safety News section of the FDA's web site.

FDA Presents Ten Years Of Summary Statistics For Its Adverse Event Reporting System (AERS)

Information Current As Of December 31, 2008; FDA Says It Will Provide Quarterly Updates For This AERS Data

(Posted by Tom Lamb at DrugInjuryWatch.com)

In early April 2009 the FDA released its Adverse Event Reporting System (AERS) Statistics as of December 31, 2008.

From that document, found on the FDA's web site, we get this contextual information:

The Adverse Event Reporting System (AERS) contains over four million reports of adverse events and reflects data from 1969 to the present. Data from AERS are presented here as summary statistics. These summary statistics cover data received over the last ten years. These data are presented at the individual report level; some of the numbers may reflect duplicate reporting due to factors such as follow-up reports received on a case or different persons reporting on the same patient case.

This summary of AERS statistics from the FDA is presents four different ways:

Reports Received and Reports Entered into AERS by Year (1999 - 2008)

Number of Domestic (U.S.) and Foreign Reports in AERS (1999 - 2008)

Reporting by Healthcare Providers and Consumers by Year (1999 - 2008)

Patient Outcomes by Year (1999 - 2008)

The third statistical analysis, which provides some breakdown on the type of person who submitted the adverse event (AE) report to FDA -- or submitted the AE report to the manufacturer which, in turn, sent the report to FDA -- was the one that I found most interesting. 

From this third analysis, Reporting by Healthcare Providers and Consumers by Year, we learn that in 2008 about 54% of the almost 500,000 AE reports were submitted by healthcare providers.  And for the 269,765 AE reports that were made in 2008 by healthcare providers, we get this further breakdown:

• Physicians: 154,044 AE reports in 2008
• Pharmacist: 27,070 AE reports in 2008
• Other types of providers (includes nurses, dentists, etc.): 88,651 AE reports in 2008

Any person who made an AE report to the FDA and who is not documented in the report as a healthcare provider was categorized as a "consumer".  About 46% of the 2008 AE reports were made by this group of reporters.

One might also look at the first analysis, Reports Received and Reports Entered into AERS by Year, to see the general trend upward for AE reports in the the past six years.

We look forward to receiving the quarterly updates to this summary of AERS statistics from the FDA in the future.

Marcia Angell's List Of Seven Things That Should Be Done By The New FDA Leadership

Dr. Angell, Former NEJM Editor-In-Chief And Current Harvard Medical School Professor, Writes An April 2009 Editorial For The Boston Globe

(Posted by Tom Lamb at DrugInjuryWatch.com)

Marcia Angell was the first woman to serve as editor-in-chief of The New England Journal of Medicine (NEJM).  Dr. Angell currently is a senior lecturer in the Department of Social Medicine at Harvard Medical School, in Boston, Massachusetts.

In the April 6, 2009 edition of The Boston Globe there is an editorial by Dr. Angell titled, "Charting a new course at the FDA", wherein she offers a list of seven thing that she thinks would return the FDA to its rightful purpose, "to ensure that [drugs] are safe and effective."

Dr. Angell's Boston Globe editorial should be read in full by anyone with an interest in the drug oversight aspect of the FDA's work.  As a preview, I have listed below the seven things that she would like to see Margaret Hamburg -- the nominated commissioner of the FDA -- and Joshua Sharfstein -- Hamburg's principal deputy -- do at the FDA in addition to (just) being the "new leadership".

• First, Congress should repeal the Prescription Drug User Fee Act.

• Second, consultants for drug companies should no longer be permitted to serve on FDA advisory panels.

• Third, the agency should see that the post-marketing studies it mandates are actually carried out.

• Fourth, the FDA should review generic drugs as fast as brand-name drugs.

• Fifth, Congress should give the FDA the authority to require drug companies to compare new drugs with existing drugs of the same type.

• Sixth, the FDA should stop approving me-too drugs on the basis of surrogate endpoints.

• Finally, the FDA should prohibit direct-to-consumer advertising for three years after drugs are approved.

After Dr. Hamburg has been confirmed by the Senate, I hope that she and Dr. Sharfstein will heed the guidance offered in Dr. Angell's April 6, 2009 editorial. 

FDA Staffers Tell Obama There Is Frustration And Outrage Over Misdeeds Of Former Agency Officials

In April 2, 2009 Letter They State There Is "systemic corruption and wrongdoing that permeates all levels of FDA" Which Needs To End

(Posted by Tom Lamb at DrugInjuryWatch.com)

ABC News has posted on their website a slightly redacted copy of an April 2, 2009 letter by nine FDA staffers -- apparently in the FDA's Office of Device Evaluation -- to President Barack Obama. 

This scathing (and seemingly unprecedented) letter was sent just days after President Obama appointed Dr. Joshua Sharfstein to be Acting Commissioner until Dr. Margaret Hamburg is confirmed as the new FDA Commissioner, hopefully, in the near future.

Here are the first and last paragraphs of this April 2009 six-page FDA staff letter to President Obama.

Dear Mr. President:

The purpose of this letter is to draw your attention to the frustration and outrage that FDA physicians and scientists, public advocacy groups, the press, and the American people, have repeatedly expressed over the misdeeds of FDA officials. Recent press reports revealed extensive evidence of serious wrongdoing by Dr. Andrew von Eschenbach, Dr. Frank M. Torti, top FDA attorneys, Center and Office Directors, and many others in prominent positions of authority at FDA. As a result, Dr. Frank M. Torti, Acting Commissioner and the FDA’s first Chief Scientist, abruptly left the Agency. But, the many other FDA managers who have failed to protect the American public, who have violated laws, rules, and regulations, who have suppressed or altered scientific or technological findings and conclusions, who have abused their power and authority, and who have engaged in illegal retaliation against those who speak out, have not been held accountable and remain in place....

All FDA employees who are committed to public integrity, who follow the laws, rules and regulations, who use science to promote public safety and health, and who have the courage and patriotism to speak out, must be protected and must have their professional lives restored.  We ask that you accept nothing less.

The names of the nine FDA staff members who signed this letter to President Obama were redacted, i.e., blacked-out, on the version that was posted on the ABC News web site.

Consistent with the authors of this letter, I hope President Obama ensures that the new leadership of our FDA restores the agency to its rightful purpose.

FDA's "Sentinel Initiative" Project For Monitoring Medical Product Safety: March 2009 Update

Agency Publishes Notice In March 9 Edition Of The Federal Register: Seeking Public Comment On Proposed Voluntary Survey

(Posted by Tom Lamb at DrugInjuryWatch.com)

In May 2008 the FDA published a white paper, "The Sentinel Initiative - A National Strategy for Monitoring Medical Product Safety", that served to introduce and explain this new agency effort intended to to improve the post-approval monitoring of prescription drugs and medical devices.

In a brief article, "FDA Wants Better Product Monitoring", which appeared in the March 9, 2009 edition of HDM Breaking News we learned the FDA is moving forward with the Sentinel Initiative project:

The Food and Drug Administration is seeking public comment on a proposed survey to support its Sentinel Initiative for monitoring medical product safety....

The new survey is designed to identify data sources that could participate in the Sentinel Initiative. "The proposed system will enable queries of distributed data sources quickly and securely for relevant product safety information," according to a newly published FDA notice. Data will continue to be managed by its owners, and only data of organizations that agree to participate in this system will be included, the FDA says, adding assurance that strict privacy safeguards will be followed.

The FDA estimates that about 250 respondents will participate in the voluntary survey. They will include federal agencies, insurers, health information exchanges, large multi-specialty group practices, large hospital systems, pharmacies, medical societies, consumer-oriented Web sites, research networks, commercial data sets, laboratories and registries.

For those interested in learning information about this voluntary survey concerning possible Sentinel Initiative participants / sources, you can read the FDA's March 9 notice by starting at The Federal Register (FR): Main Page.

We will continue to monitor developments related this FDA Sentinel Initiative project.

FDA Warns About Rare Brain Infection PML Linked To Psoriasis Drug Raptiva

European Union Regulators, On Same Day, Recommend That Raptiva Be Withdrawn Because Its Risks Outweigh The Benefits

********************

Update: April 2009: Raptiva Recall In U.S.

On April 8, 2009 we learned that Raptiva has been recalled due to the association between Raptiva and progressive multifocal leukoencephalopathy (PML), a rare and usually fatal disease of the central nervous system.

More information about this Raptiva recall can be found in the Genentch press release and the FDA statement:

Genentech Announces Voluntary Withdrawal of Raptiva from the U.S. Market

FDA Statement on the Voluntary Withdrawal of Raptiva From the U.S. Market

We provide the history of Raptiva in a basic timeline that is part of our April 9, 2009 article about the Raptiva recall.  (4/9/09)

********************

(Posted by Tom Lamb at DrugInjuryWatch.com)

On February 19, 2009 the FDA confirmed that Raptiva (efalizumab) had been linked to three cases of progressive multifocal leukoencephalopathy (PML), a rare brain infection which causes swelling of the brain and is usually fatal. The FDA said that all the cases were reported in the last six months.

That same day, across the Atlantic, the European Medicines Agency announced it had completed its safety review of Raptiva and said the Agency’s Committee for Medicinal Products for Human Use (CHMP) had concluded that the benefits of Raptiva do not outweigh its risks.  Accordingly, they recommended that the use of Raptiva should be suspended across the European Union.

Raptiva was approved by the FDA in 2003 to treat adults with moderate to severe chronic plaque psoriasis.

From the February 19 MedWatch Alert email concerning this association between Raptiva and PML:

FDA issued a Public Health Advisory to notify healthcare professionals of three confirmed, and one possible report of progressive multifocal leukoencephalopathy (PML), a rare brain infection, in patients using the psoriasis drug Raptiva. In October 2008, the labeling for Raptiva was changed to highlight, in a Boxed Warning, the risks of life-threatening infections, including PML. In addition, FDA directed Genentech, the manufacturer of Raptiva, to develop a Risk Evaluation and Mitigation Strategy, or REMS, to ensure that patients receive risk information about Raptiva. The FDA is reviewing this latest information. The agency will take appropriate steps to ensure that the risks of Raptiva do not outweigh its benefits, that patients prescribed Raptiva are clearly informed of the signs and symptoms of PML, and that health care professionals carefully monitor patients for the possible development of PML. The Public Health Advisory provides recommendations for healthcare.  [hyperlink added]

For comparison purposes, one might want to read the European Medicine Agency’s document, "Efalizumab (Raptiva): Recommendation to suspend marketing authorisation as risks outweigh benefits".  The essence of their position can be taken from this excerpt:

Although psoriasis is a disabling condition that can cause social and psychological problems for patients, it is very rarely life-threatening. The Committee concluded that the risk of PML is unacceptable for patients taking efalizumab. They recommended that the marketing authorisation should be suspended until there is adequate new evidence to identify a group of patients in which the benefits of efalizumab outweigh its risks.

From a February 19 AP article, "FDA says 3 deaths associated with Genentech drug", we get the drug company reaction to what is happening to Raptiva in the U.S.:

"We take the risk of PML very seriously and are working diligently with the FDA to put the right plans in place that will help protect patient safety," said company spokeswoman Tara Cooper.

We will wait to see if the FDA decides to follow the lead taken by its European Union counterparts and eventually issue a Raptiva recall order, here.

P.S.  At the recommendation of Health Canada, EMD Serono Canada Inc. has suspended the marketing of Raptiva in Canada due to safety concerns, including the increased risk of developing PML.  (2/21/09)