Amercian doctors support FDA decision on Adderall

The American Association of Child & Adolescent Psychiatry (AACAP), the professional medical association dedicated to treating and improving the quality of life for children, adolescents, and families affected by mental, behavioral, or developmental disorders, seems to agree with the US FDA on Adderall recall decision, that is, sufficient data is just not there to show that the recent deaths have occured due to Adderall.

In the meantime, AACAP is advising its members that they include a thorough psychiatric and medical history in the context of a comprehensive evaluation when a child presents with symptoms for ADHD or any other disorder and discuss the newly available risks with the parents. It is also suggesting that patients be monitored more carefully.

Related articles:

Shire expects Adderall decision reversal

FDA must recall Adderall till complete risk analysis is done

Suspended marketing of Tysabri or natalizumab

FDA is issuing this public health advisory to inform patients and health care providers about the suspended marketing of Tysabri (natalizumab) due to two serious adverse events reported with its use. FDA has received a report from Biogen Idec, the manufacturer of Tysabri, of one confirmed, fatal case and one possible case of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri for multiple sclerosis (MS). Both patients were enrolled in a long-term clinical trial and had been taking Tysabri for more than two years. There have been no previous cases of PML reported in patients taking Tysabri. (Related article: Tysabri recall)

Although the relationship between Tysabri and PML is not known at this time, because of the rare, serious and often fatal nature of PML, FDA is announcing the following, effective immediately:

• Biogen Idec is voluntarily suspending marketing of Tysabri.
• Biogen Idec is suspending dosing of Tysabri in clinical trials and is notifying patients and investigators of the possible association between Tysabri and PML.
• Patients being treated with Tysabri should contact their physician to discuss appropriate alternative treatments. At this time, there are no specific diagnostic or therapeutic interventions recommended for patients who have been taking Tysabri, other than to discontinue its use. Physicians should evaluate all patients who have received Tysabri and who have signs or symptoms suggestive of PML. Any suspect cases of PML should be reported immediately to Biogen Idec or to the FDA MedWatch program
• FDA and Biogen Idec will provide further guidance should additional recommendations be deemed appropriate.

Discussions between the FDA, Biogen Idec, and scientific experts have begun in order to assess the potential association between Tysabri and PML, methods for early diagnosis of PML, and to determine whether MS patients who may be at particular risk can be identified. These discussions will be informed by the substantial amount of patient data from clinical trials expected to be obtained in the next few months, including specific assessments of patients who have received Tysabri for evidence of early-stage PML, and will be used to guide decisions regarding future marketing of Tysabri.

PML is a rare, serious, progressive neurologic disease, usually occurring in immunosuppressed patients, often resulting in irreversible neurologic deterioration and death. There is no known effective treatment for PML, although reversing immune system suppression may slow or arrest progression of the disease.

Based on information submitted to the FDA this week, neither patient described above has known risk factors for PML. Both patients received concomitant Avonex (interferon beta-1a). The use of interferons, including Avonex, has not been associated with PML. To further understand the association between Tysabri and the development of PML, Biogen Idec is reviewing all adverse events in the clinical trial database for Tysabri to determine if any of these could possibly represent cases of PML.

Tysabri received accelerated approval in November 2004 for reducing the frequency of exacerbations in patients with remitting-relapsing MS, the most common form of this disease, after one year of treatment. Tysabri when added to Avonex reduced the risk of exacerbations by 54% compared to Avonex alone. Tysabri by itself reduced the risk by 66% compared to placebo. These results represent an important and meaningful benefit for patients with MS. At the time of approval, approximately 1,100 patients with MS had received Tysabri for one year or more. Confirmatory studies were required to be carried out to show continued benefit of the drug after two years of treatment. The two cases reported here occurred in patients in the confirmatory studies. No cases of PML were observed during the clinical trials performed prior to approval of Tysabri.

Shire expects Adderall XR recall decision reversal

Health Canada's decision to recall Adderall is being met with more resistance from Shire Pharmaceuticals. The company has issued several statements arguing that Health Canada has made a wrong decision. In a statement issued, Shire says:

• Many of the patients on Adderall XR were on it because they had failed other treatments that left them with no treatment at all.
• Abruptly stopping a treatment for ADHD can lead to accidents, expulsion from school, aggression and other serious problems. Untreated ADHD places patients at significant morbidity and mortality that is well established in the literature.
• Many of these patients do not have a family doctor, or their family doctor is not familiar with alternative medication strategies.
• Health Canada assumed that the press release they provided gave doctors sufficient information to explain the risks and benefits of Adderall XR when in reality the press release left physicians completely unprepared to provide their patients with adequate understanding of their relative risks.

The company is arguing that since the FDA has refused to act, Shire must be doing something right, but not many people trust the judgment of FDA. The United States drug regulator not only failed to recall Vioxx, Celebrex, and Bextra on time, in a very bizarre turn of events it constituted a panel to review the safety of this drugs but filled it up with at least 10 doctors who have financial ties to Merck and Pfizer. No wonder, instead of a recall of either of the drugs, the panel recommended that even Vioxx (no longer on the market) be allowed to resume sales and Celebrex and Bextra continue to be sold. (Related article: Validity of FDA panel's recommendations in doubt due to conflicts of interest)

In the meantime, Reuters is quoting Shire CEO Matthew Emmens as saying that they expect that Health Canada will reverse its decision. He is encouraged by FDA's refusal to recall Adderall XR in the United States.

To make its Adderall problems worse, Shire has received a Paragraph IV Notice from Teva Pharmaceuticals USA, Inc., advising of the filing of an Abbreviated New Drug Application (ANDA) for a generic version of ADDERALL XR. The drug is protected by two patents which expire in 2018. Shire received previously Paragraph IV Notice letters from Barr Laboratories Inc., IMPAX Laboratories Inc. and Colony Pharmaceuticals Inc. relating to their ANDAs for their respective generic versions of ADDERALL XR. As previously announced, Shire has filed lawsuits in response to the Barr and IMPAX ANDA Notice letters.

Related articles:

FDA must recall Adderall XR till complete safety analysis is done

FDA leaves Adderall XR on the market in the US

FDA must recall Adderall till risks analysis is done

Recent decision by the Food & Drug Administration (FDA) not to follow Health Canada with Adderall recall in the United States has surprised many and has left Adderall patients (and parents of children who take Adderall) confused. On one hand, right across the border, Canada has banned Adderall citing the dangers of leaving the drug on the market. On the other hand, FDA has refused to do anything. In fact, according to United States Senator Grassley, the FDA tried to influence Health Canada not to recall Adderall.

Should a government agency charged with public safety do this? Should the agency risk lives of Americans just because it has close ties to the pharmaceutical industry? And should the FDA be telling other countries what to do with their regulations?

Some answers may be found if one takes a look at the Vioxx controversy in the United States. Judith Graham of Chicago Tribune has disclosed that FDA is really not doing its job of public safety. Not only is the agency not vigilant, it seems to let the pharmaceutical companies play with the lives of American people. "More than two years before Merck & Co. pulled the popular painkiller Vioxx from the market over safety concerns, federal regulators knew studies had indicated older people taking the drug were more likely to die than those in a placebo group," writes Graham. Or in other words, while Merck was driven by greed not to recall Vioxx on time, FDA was simply helping it in that mission.

Is it the same reason that FDA is not ready to recall Adderall? Does the agency suspect that it will also be forced to recall Celebrex, Bextra soon? Probably. In fact Senator Grassley has learned that the FDA did not want another recall crisis on its hand at a time when the agency is being criticized from all sides, particularly for not managing the drug approval process well and for coming up with laughable excuses for not allowing Americans to import prescription drugs from Canada.

Recommended article: FDA tries to protect Merck and Pfizer

Importing prescription drugs from Canada bill introduced

Despite overwhelming support among Americans for importing prescription drugs from Canada, President Bush has refused to do anything simply because the administration owes a lot to the pharmaceutical industry. The drugmakers contribute millions of dollars in campaign contributions, almost all of it to the Republican Party. By using the FDA and Department of Health & Human Services resources, the administration has even come up with "research" (somewhat similar to the "intelligence" on weapons of mass destruction in Iraq) that supposedly proves how dangerous it is to import drugs from Canada while we import so much else from Canada and other countries. (Related article: American doctors support importing prescription drugs from Canada)

While it is highly unlikely that any progress will be made as far as President Bush is around but still Sen. Chuck Grassley, chairman of the Committee on Finance, has introduced a bill that would make it legal for U.S. consumers to buy safe prescription drugs from other countries. Grassley joined forces with other key senatorial advocates of safe importation to introduce the bipartisan legislation. (Related article: Importing prescription drugs from Canada if you live in Rhode Island or Texas)

Grassley has been a consistent supporter of importing prescription drugs from Canada. The first reimportation vote in the U.S. Senate occurred in July 2000, on an amendment offered by Sen. Jim Jeffords of Vermont. Grassley supported the Jeffords amendment. Grassley voted a second time for reimportation of prescription drugs from Canada in July 2002, on an amendment offered by Sen. Byron Dorgan of North Dakota. Grassley voted for another Dorgan amendment when it was offered in June 2003. This legislation became part of the Senate bill to add a prescription drug benefit to Medicare, but it was eliminated in the final conference report on the bill.

"I have always considered making it legal for Americans to import their prescription drugs a free-trade issue," Grassley said. "Imports create competition and keep domestic industry more responsive to consumers. In the United States, we import everything consumers want. So why not pharmaceuticals? Today, consumers in the United States pay 60 to 112 percent more for brand-name prescription drugs than consumers in other countries. (Related article: Drug price controls in other countries not responsible for higher prices in America)

"If Americans could legally access prescription drugs outside the United States, then drug companies would be forced to re-evaluate their pricing strategy. The pharmaceutical industry would no longer be able to gouge American consumers by making them pay more than their fair share of the high cost of research and development. With this new legislation, we’re moving ahead together to get the job done." (Related article: Drug prices can be reduced if pharmaceutical companies want)

Grassley introduced his own legislation in the last Congress – the Reliable Entry for Medicines at Everyday Discounts through Importation with Effective Safeguards Act of 2004, or the REMEDIES Act. This time, he combined forces with importation legislation sponsors Sen. Byron Dorgan, Democrat of North Dakota, and Sen. Olympia Snowe, Republican of Maine, and others including Sen. Ted Kennedy, Democrat of Massachusetts, to introduce the Pharmaceutical Market Access and Drug Safety Act. House members are introducing a companion bill.

Grassley said the new, combined bill builds upon and improves last year’s bills:

• It tears down the trade barriers that Congress put up in 1991.
• It provides legalized access to lower-priced drugs through importation.
• It addresses safety concerns by providing the Food and Drug Administration with the necessary resources and authority to implement a safe and effective program.
• To make sure that drug makers don’t interfere with legalized importation, the legislation includes non-discrimination provisions to be enforced by the Federal Trade Commission.

Recommended article: Pharmaceutical business model in the US is failing

Adderall XR recall likely as Health Canada acts

Health Canada, the Canadian drug regulatory agency, has suspended the sale of Adderall XR in the Canadian market. Adderall XR is a controlled release amphetamine used to treat patients with Attention Deficit Hyperactivity Disorder (ADHD). The Canadian action was based on U.S. post-marketing reports of sudden deaths in pediatric patients.

The Food and Drug Administration (FDA), the drug regulatory agency in the United States says that while it is aware of Health Canada’s decision to suspend sales. FDA has been in close consultation with the Canadian authorities regarding the basis for their action. FDA does not feel that any immediate changes are warranted in the FDA labeling or approved use of this drug based upon its preliminary understanding of Health Canada’s analyses of adverse event reports and FDA’s own knowledge and assessment of the reports received by the agency.

It is important to point out that drug agencies in other countries are generally independent unlike the United States where the FDA collects user fees from the drug industry and is staffed with drug industry insiders at this time. FDA has been widely criticized in failing to recall Vioxx that has resulted in as many as 140,000 Americans injured.

Adderall XR is approved in the United States for the treatment of adults and pediatric patients 6 years of age and older with ADHD, and Adderall, the immediate-release formulation of the drug, is approved for pediatric patients with ADHD. The Food and Drug Administration (FDA) has been aware of these post-marketing cases, and evaluated the risk of sudden death with Adderall prior to approving the drug for treatment of ADHD in adults last year.

Of 12 total cases, five occurred in patients with underlying structural heart defects (abnormal arteries or valves, abnormally thickened walls, etc.), all conditions that increase the risk for sudden death. Several of the remaining cases presented problems of interpretation, including a family history of ventricular tachycardia, association of death with heat exhaustion, dehydration and near-drowning, very rigorous exercise, fatty liver, heart attack, and type 1 diabetes mellitus. One case was reported three to four years after the event and another had above-toxic blood levels of amphetamine. The duration of treatment varied from one day to 8 years. The number of cases of sudden deaths reported for Adderall is only slightly greater, per million prescriptions, than the number reported for methylphenidate products, which are also commonly used to treat pediatric patients with ADHD.

The FDA statement says that it is continuing to evaluate these and other post-marketing reports of serious adverse events in children, adolescents, and adults being treated with Adderall and related products. When one considers the rate of sudden death in pediatric patients treated with Adderall products based on the approximately 30 million prescriptions written between 1999 and 2003 (the period of time in which these deaths occurred), it does not appear, FDA argues, that the number of deaths reported is greater than the number of sudden deaths that would be expected to occur in this population without treatment. For this reason, the FDA has not decided to take any further regulatory action at this time. However, because it appeared that patients with underlying heart defects might be at increased risk for sudden death, the labeling for Adderall XR was changed in August 2004 to include a warning that these patients might be at particular risk, and that these patients should ordinarily not be treated with Adderall products.

Related articles: FDA failed to act in the case of mercury in vaccines

FDA's role in the case of Prozac not admirable

Merck knew about risks of Mercury

A Los Angeles Times article today reports that Merck, a leading manufacturer of prescription drugs, knew the overuse of mercury in their vaccines posed a dangerous health threat to children. (Related article: Merck also knew that Vioxx was dangerous but continued to sell it)

As cited by the article, a 1991 memo issued by Merck said that 6-month-old children who received their shots on schedule would get a mercury dose up to 87 times higher than guidelines for the maximum daily consumption of mercury from fish.

The memo, issued eight years before the FDA acknowledged the overuse of mercury in vaccines, goes on to discuss safety concerns and at one time states that the large use of mercury in their vaccines presents a "perception of hazard."

A number of parent and advocacy groups have been fighting for the removal of mercury in vaccines. Lujene Clark, president of NoMercury.org, has led the fight to ban mercury in vaccines in numerous states. California and Iowa passed bans in 2004.

Just last month, senate bill "S.3" was introduced to prevent such bans. If passed, not only would the bill remove states' rights, it would further protect pharmaceutical companies like Merck from vaccine-related litigation. "Because drug companies like Merck are so easily protected by certain friends on the Hill, they have no incentive to reveal such findings or right the wrong that's been done," says parent Wendy Fournier. "It is astounding that memos like this remain hidden and corporations that are supposed to be the benchmark of safety, end up covering up the dangers." (Related article: President Bush wants to to take away the rights of American people to file class action lawsuits against drugmakers)

S.3, introduced by Senator Bill Frist, is the fifth piece of legislation the Senator has tried to pass on behalf of vaccine-makers. Parents believe that the bill, and any vaccine-oriented legislation introduced by Frist, will impede efforts to uncover even more important documents that could ultimately explain what happened to millions of American children. According to opensecrets.org, a public service watchdog, Senator Frist has received hundreds of thousands of dollars in campaign contributions from pharmaceutical companies since 1997.

A full disclosure of Merck's findings in 1991 may have prevented millions of children from dangerous exposure to mercury, a known neurotoxin. Numerous studies, including a first-phase study by the Centers for Disease Control (CDC), have linked the mercury-based preservative to neurodevelopmental disorders including autism. According to the CDC, autism now affects 1 in 166 children. Some reports cite that the rise in autism and ADHD correlates with the dangerous rise in use of mercury that Merck knew of almost 15 years ago.

As of 2005, mercury remains in a handful of vaccines including flu shots recommended for infants and pregnant women.

Recommended link: Merck abandoned Vioxx study after side effects feared