FDA Drug Safety Communication:

Risk of Oral Clefts in Children Born to Mothers Taking Topamax (topiramate)

The U.S. Food and Drug Administration (FDA) is informing the public of new data that show that there is an increased risk for the development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with Topamax (topiramate) during pregnancy.

The benefits and the risks of topiramate should be carefully weighed when prescribing this drug to women of childbearing age, particularly for conditions not usually associated with permanent injury or death. Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered for these patients. If the decision is made to use topiramate in women of childbearing age, effective birth control should be used. Oral clefts occur in the first trimester of pregnancy before many women know they are pregnant.

Topiramate was previously classified as a Pregnancy Category C drug, which means that data from animal studies suggested potential fetal risks, but no adequate data from human clinical trials or studies were available at the time of approval. However, because of new human data that show an increased risk for oral clefts, topiramate is being placed in Pregnancy Category D. Pregnancy Category D means there is positive evidence of human fetal risk based on human data but the potential benefits from use of the drug in pregnant women may be acceptable in certain situations despite its risks.

Additional Topamax (topiramate) Information for Patients

• If you take topiramate during pregnancy, there is a higher risk that your baby will develop a cleft lip and/or cleft palate. Oral clefts happen early in pregnancy, before many women even know they are pregnant. For this reason, women of childbearing age should talk to their healthcare professionals about other treatment options.
• Women of childbearing age who do decide to take topiramate and are not planning a pregnancy should use effective birth control (contraception) while taking topiramate. Women should talk to their healthcare professionals about the best kind of birth control to use while taking topiramate.
• Before you start topiramate, you should tell your healthcare professional if you are pregnant or are planning to become pregnant. Healthcare professionals may discuss other treatment options with you.
• You should tell your healthcare professional right away if you become pregnant while taking topiramate. You and your healthcare provider should decide if you will continue to take topiramate while you are pregnant.
• Topiramate should not be stopped without talking to a healthcare professional, even in pregnant women. Stopping topiramate suddenly can cause serious problems. Not treating epilepsy during pregnancy can be harmful to women and their developing babies.
• If you become pregnant while taking topiramate, you should talk to your healthcare professional about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect additional information about the safety of antiepileptic drugs during pregnancy.
• Topiramate passes into breast milk, but its effects on developing babies remain unknown. You should talk to your healthcare professional about the best way to feed your baby if you take topiramate.
• You should report any side effects you experience to the FDA MedWatch program using the information in the “Contact Us” box at the bottom of the page.
• You should read the Medication Guide when picking up a prescription for topiramate. It will help you understand the potential risks and benefits of this medication.

Additional Information on Topamax (topiramate) for Healthcare Professionals

• You should inform women of childbearing age of the increased risk for oral clefts when topiramate is used in the first trimester of pregnancy.
• You should weigh the benefits and risks of topiramate when prescribing this drug to women of childbearing age, particularly when treating a condition not usually associated with permanent injury or death. Alternative medications that have a lower risk of oral clefts and other adverse birth outcomes should be considered. Healthcare professionals should discuss the relative risks and benefits of appropriate alternative therapies.
• If the decision is made to prescribe topiramate to women of childbearing age, healthcare professionals should recommend use of effective contraception for women who are not planning a pregnancy, keeping in mind the potential for a decrease in hormonal exposure and a possible decrease in contraceptive efficacy when using estrogen-containing birth control with topiramate.
• You should inform patients of the North American Antiepileptic Drug (NAEED) Pregnancy Registry and encourage patients who become pregnant to enroll by calling 1-888-233-2334.
• You should report adverse events involving topiramate to the FDA MedWatch program, using the information in the “Contact Us” box at the bottom of the page.

Data Summary on Topamax (topiramate)

Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry indicate an increased risk of oral clefts in infants exposed to topiramate monotherapy during the first trimester of pregnancy. The prevalence of oral clefts was 1.4% compared to a prevalence of 0.38% – 0.55% in infants exposed to other antiepileptic drugs (AEDs), and a prevalence of 0.07 % in infants of mothers without epilepsy or treatment with other AEDs. The relative risk of oral clefts in topiramate-exposed pregnancies in the NAAED Pregnancy Registry was 21.3 as compared to the risk in a background population of untreated women (95% Confidence Interval:7.9 – 57.1). The UK Epilepsy and Pregnancy Register reported a similarly increased prevalence of oral clefts (3.2 %) among infants exposed to topiramate monotherapy, a 16-fold increase in risk compared to the risk in their background population (0.2%).

The benefits and the risks of topiramate should be carefully weighed when prescribing this drug for women of childbearing age, particularly when topiramate is considered for a condition not usually associated with permanent injury or death. Appropriate alternative treatment should be considered. Inform women of childbearing age of the increased risk for having a baby with an oral cleft if they become pregnant while using topiramate.

Cleft lip and cleft palate range from a small notch in the lip to a groove that runs into the roof of the mouth and nose, possibly leading to problems with eating, talking and ear infections. Surgery is often used to close the lip and palate. With treatment, most children with cleft lip or palate do well.³

1. U.S. National Library of Medicine. National Institutes of Health. Topiramate monograph.
2. SDI, Vector One^®: National (VONA) and Total Patient Tracker (TPT). January 2007-December 2010.
3. U.S. National Library of Medicine. National Institutes of Health. Cleft Lip and Palate health topic.

Speak to a Topamax Lawyer about a Topamax Lawsuit

If you took Topamax (topiramate) or any other anti-seizure drug during pregnancy and your child was born with a cleft palate, cleft lip or any other congenital cranio-facial birth defect, we encourage you to contact a Topamax Litigation Attorney at our law firm immediately. It may be too late to recover from all of the devastating effects of Topamax but an experienced products liability pharmaceutical lawsuit lawyer at the Willis Law Firm can assist you in legal action against Johnson & Johnson (JNJ) and Ortho-McNeil Pharmaceutical LLC, the makers of Topamax. You are not alone. Join other birth defect victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

The U.S. Consumer Product Safety Commission (CPSC) is advising parents and caregivers to be cautious when using infant slings for babies younger than four months of age. In researching incident reports from the past 20 years, CPSC identified and is investigating at least 14 deaths associated with sling-style infant carriers, including three in 2009. Twelve of the deaths involved babies younger than four months of age.

Slings can pose two different types of suffocation hazards to babies. In the first few months of life, babies cannot control their heads because of weak neck muscles. The sling’s fabric can press against an infant’s nose and mouth, blocking the baby’s breathing and rapidly suffocating a baby within a minute or two. Additionally, where a sling keeps the infant in a curled position bending the chin toward the chest, the airways can be restricted, limiting the oxygen supply. The baby will not be able to cry for help and can slowly suffocate.

Many of the babies who died in slings were either a low birth weight twin, were born prematurely, or had breathing issues such as a cold. Therefore, CPSC urges parents of preemies, twins, babies in fragile health and those with low weight to use extra care and consult their pediatricians about using slings.

Two months ago, the Commission added slings to the list of durable infant products that require a mandatory standard. Additionally, CPSC staff is actively investigating these products to determine what additional action may be appropriate. Until a mandatory standard is developed, CPSC is working with ASTM International to quickly complete an effective voluntary standard for infant sling carriers.

CPSC recommends that parents and caregivers make sure the infant’s face is not covered and is visible at all times to the sling’s wearer. If nursing the baby in a sling, change the baby’s position after feeding so the baby’s head is facing up and is clear of the sling and the mother’s body. Parents and caregivers should be vigilant about frequently checking their baby in a sling.

ev3 Endovascular, Inc. and the FDA notified healthcare professionals of a Class I Recall of the Trailblazer Support Catheter. This device may crack near the radiopaque marker band. This may result in serious patient injury, including insufficient oxygen supply to the tissues, damage to blood vessels, heart attack, limb amputation, unplanned surgery, and/or death. See the recall notice below for a listing of affected model and lot numbers, manufactured from September 11, 2009 through September 29, 2009 and distributed from September 21, 2009 through October 27, 2009.

New USP Standards for Heparin Products Will Result in Decreased Potency
Adjustments may be Needed to Achieve Desired Anticoagulant Effect in Some Patients
New Heparin to Ship Starting October 8

The U.S. Food and Drug Administration today alerted health care professionals to a change in heparin manufacturing that is expected to decrease the potency of the common anti-clotting drug.

To ensure the quality of heparin and to guard against potential contamination, the United States Pharmacopeia (USP), a nonprofit standards-setting organization, adopted new manufacturing controls for heparin. These changes include a modification of the reference standard for the drug’s unit dose.

Manufacturers in the United States label the amount of heparin included in their products based on USP standards. The changes adopted by the USP for the heparin unit dose match the World Health Organization’s International Standard (IS) unit dose definition that has been in use in Europe for many years. The revised USP reference standard and unit definition for heparin is about 10 percent less potent than the former USP unit.

A unit is the measure of a drug’s activity in the body. For heparin, a unit dose is the measure of the drug’s ability to block the blood’s natural clotting ability (anticoagulation). Heparin’s potency is determined by the dose of the drug required to produce a specific level of anticoagulation.

Manufacturers for the U.S. market have begun to make heparin using the new USP standard. While the USP manufacturing controls take effect Oct. 1 for production, the FDA has asked that they not ship this new product to customers until Oct. 8, 2009, or later. The delay will give health care providers and facilities time to learn about the changes and to make adjustments to their pharmacy procedures and dosing practices, according to John Jenkins, M.D. director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

“Although the FDA-approved labeling for heparin has not changed, including the recommended doses, it is essential that health care professionals be aware of the potential difference in potency between the old and new vials of heparin when administering the drug,” said Jenkins.

Four companies market heparin in the United States. APP, the largest manufacturer, markets heparin in vials; Hospira markets heparin in intravenous bags, vials, and syringes; Baxter markets heparin in intravenous bags, and B. Braun markets heparin in intravenous bags. The FDA has asked that all manufacturers identify their new products to help pharmacies and health care professionals differentiate it from the former product.

Prescription and over–the–counter medicines available in the United States must generally meet USP’s public standards, when such standards exist. The revised standards for heparin are contained in a new USP monograph.

The monograph was revised, in part, in response to a 2007- 2008 incident of heparin contamination involving a manufacturing step in China. The contaminated heparin was associated with deaths and other adverse events in the United States. The monograph was changed to include a test for the contaminant.

FDA Issues Early Communication about Ongoing Safety Review of Orlistat.
Weight loss drug review includes both prescription drug Xenical and OTC drug Alli.

The U.S. Food and Drug Administration announced today that it is reviewing adverse event reports of liver injury in patients taking the weight loss drug orlistat, marketed as the prescription drug Xenical and the over-the-counter medication Alli.

Between 1999 and 2008, the FDA received 32 reports of serious liver injury in patients taking orlistat. Of those cases, 27 reported hospitalization and six resulted in liver failure. Thirty of the adverse events occurred outside the United States. The most commonly reported adverse events included yellowing of the skin or whites of the eyes (jaundice), weakness, and stomach pain.

The FDA is reviewing additional data submitted by orlistat manufacturers on suspected cases of liver injury, and the issue has been discussed at the FDA’s Center for Drug Evaluation and Research Drug Safety Oversight Board.

“The issues here are complex, but FDA has benefited from the input of the Board, including comments from representatives from three FDA Centers and several other Agencies in the Department of Health and Human Services,” said Steven Osborne, M.D., executive director of the Board.

The FDA’s analysis of these data is ongoing, and no definite association between liver injury and orlistat has been established at this time. Consumers taking Xenical should continue to take it as prescribed, and those using over-the-counter Alli should continue to use the product as directed.

For more information on the Early Communication about the ongoing safety review please read: Orlistat (Marketed as Alli and Xenical) Safety Review. The Early Communication is a risk communication tool used by the FDA to inform the public about its ongoing safety reviews of drugs. The FDA will release its findings on orlistat as soon as the review is completed.

Consumers who have used orlistat should consult a health care professional if they experience symptoms possibly associated with development of liver injury, particularly weakness or fatigue, fever, jaundice, or brown urine. Other symptoms may include abdominal pain, nausea, vomiting, light-colored stools, itching, or loss of appetite.

The FDA urges both health care professionals and consumers to report suspected side effects from the use of orlistat to FDA’s MedWatch Adverse Event Reporting program.

FDA’s Early Communication about the Ongoing Safety Review of Orlistat.

FDA is reviewing new safety information regarding reports of liver-related adverse events in patients taking orlistat. Orlistat is marketed in the United States as a prescription product, Xenical, and as an over-the-counter (OTC) product, Alli.

Xenical (orlistat 120mg) was approved as a prescription product by FDA in 1999 for obesity management in conjunction with a reduced caloric diet, and to reduce the risk of regaining weight after prior weight loss. In 2007, Alli (orlistat 60mg) was approved for OTC use for weight loss in overweight adults, 18 years and older, in conjunction with a reduced-calorie and low-fat diet. Currently, orlistat is approved for marketing in approximately 100 countries. In January 2009, a nonprescription version of orlistat was approved for sale in the European Union.

Between 1999 and October 2008, 32 reports of serious liver injury, including 6 cases of liver failure, in patients using orlistat were submitted to FDA’s Adverse Event Reporting System. Thirty of the 32 reports occurred outside the United States. The most commonly reported adverse events described in the 32 reports of serious liver injury were jaundice (yellowing of the skin or whites of the eyes), weakness, and abdominal pain. Hospitalization was reported in 27 of the 32 cases.

In addition to the 32 reported cases, this issue was discussed at the CDER Drug Safety Oversight Board in April 2009, and FDA is reviewing other data on suspected cases of liver injury submitted by the manufacturers of orlistat. FDA’s analysis of these data is ongoing and no definite association between liver injury and orlistat has been established at this time.

FDA is not advising healthcare professionals to change their prescribing practices with orlistat. Consumers currently taking Xenical should continue to take it as prescribed and those using over-the-counter Alli should continue to use the product as directed.

Consumers should consult their health care professional if they are experiencing symptoms possibly associated with the use of orlistat and development of liver injury, particularly weakness or fatigue, fever, jaundice or brown urine. Other symptoms may include abdominal pain, nausea, vomiting, light-colored stools, itching, or loss of appetite.

FDA urges both healthcare professionals and consumers to report side effects from the use of orlistat (Alli and Xenical) to FDA’s MedWatch Adverse Event Reporting program.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA will communicate its findings to the public as soon as its review of orlistat is complete.

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. The FDA will release an update when additional information or analyses become available.

Agency Investigating Dilantin Risks of SJS and TEN

FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) from phenytoin therapy in Asian patients positive for human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais. Until the FDA evaluation is completed, healthcare providers who are considering the use of phenytoin or fosphenytoin should be aware of the risks and benefits described in the current prescribing information for this drug. Healthcare providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502. A summary of the data currently being analyzed by FDA, and information for patients and healthcare professionals to consider, can be found on the FDA’s website.

SOURCE: U.S. Food and Drug Administration (FDA)

Dilantin lawsuit information: Dilantin Lawsuits

Dilantin SJS information: Dilantin Stevens Johnson Syndrome Lawsuits

Dilantin TEN information: Dilantin Toxic Epidermal Necrolysis Lawsuits

See also: Dilantin Side Effects.

Speak to a Dilantin Lawyer

If you took Dilantin and suffered Stevens Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), we encourage you to contact a Dilantin attorney at our law firm immediately. An experienced product liability attorney can assist you in a legal action against the makers of Dilantin. Contact our law firm and learn more about your legal rights and the options available to you and your family.

Biogen Idec and Elan announced on March 22, 2006, that the Food and Drug Administration (FDA) had extended the regulatory review period for the reintroduction of Tysabri (natalizumab) for multiple sclerosis (MS) by up to 90 days.

Under the Prescription Drug User Fee Act, extensions to the review period for an application can be triggered by a substantive submission from the sponsor. In this case, the information received was determined to be a major amendment to the pending application. The review period for the application was extended by up to 90 days to provide FDA time to review the new information.

This new submission is a revised Risk Management Plan (RMP), which takes into account the issues discussed, and recommendations offered, by the Peripheral and Central Nervous System Drugs Advisory Committee on March 7th and 8th of this year. Both the company and FDA believe that a RMP is important to help ensure safe use of the product.

This application continues to be a high priority. The agency is working intensively to complete review of this new information and will attempt to do so before the end of the 90 day extension period.

Tysabri PML Lawyer

If you or a family member has been diagnosed with PML, or been treated with Tysabri infusions, contact our law firm to speak to a PML lawyer about your legal options. Every attorney at our law firm is dedicated to fighting for the rights of those that have been harmed by dangerous and recalled drugs and medical devices. For over 25 years, Attorney David Willis has been a trial lawyer representing seriously injured clients in product liability and personal injury lawsuits such as defective drug litigation, class action drug lawsuits and medical device recall lawsuits. If Tysabri has harmed you, or a loved one, contact us right now to discuss your potential case in filing a Tysabri PML Lawsuit with an Attorney.

1. Why is FDA lifting the clinical hold?
   We received detailed information on the extensive re-examination that Biogen and Elan undertook on all patients who had received natalizumab in clinical studies under an IND. No additional cases of PML were identified. The better understanding of the actual occurrence of PML in these patients permitted better estimation of the potential risk of PML occurring in the future. In addition, Biogen has proposed a resumption of natalizumab administration under an IND study with very specific plans for close monitoring of patients.

 

2. Will Tysabri be available to all patients?
   Biogen has proposed to FDA only to resume administration of natalizumab to patients who had previously been receiving the drug within an IND study at the time of the suspension of use in February 2005. Those patients would need to discuss with their Study physician the potential risks and potential benefits of resuming treatment with natalizumab, and will be able to make a decision after that discussion. Biogen has not proposed to administer the drug to anyone who had not previously been receiving it under an IND study. Biogen has submitted an application to FDA to resume marketing the drug for more widespread use. That application has a due date for a decision by FDA in late March 2006.

 

3. What happens to the other holds on similar products and what is our process for lifting these holds?
   The lifting of the clinical hold on natalizumab may lead to requests from other product sponsors to begin or resume clinical studies for molecules that act in a similar manner. FDA will consider each of those proposals as they are received. An important aspect to consider is whether the potential risk of a specific product is reasonable in the setting of a specific disease, type of patient, and other currently available therapies for that type of patient.

 

4. Is there still a significant safety concern with the product, and if so, why did we lift this hold?
   FDA remains very concerned about the potential for PML associated with natalizumab use. However, the currently available information are not adequate to clearly define the level of risk or the exact circumstances when this risk occurs. Furthermore, the existing efficacy data with natalizumab indicate this is a very effective product and multiple sclerosis is a devastating neurologic disease. Therefore, if a study is done in a manner that provides as much safety monitoring as feasible, it is reasonable to resume studying this product under IND to obtain more safety-related information that may permit us to begin to better understand how large or small the true risks associated with natalizumab are.

Tysabri PML Lawyer

If you or a family member has been diagnosed with PML, or been treated with Tysabri infusions, contact our law firm to speak to a PML lawyer about your legal options. Every attorney at our law firm is dedicated to fighting for the rights of those that have been harmed by dangerous and recalled drugs and medical devices. For over 25 years, Attorney David Willis has been a trial lawyer representing seriously injured clients in product liability and personal injury lawsuits such as defective drug litigation, class action drug lawsuits and medical device recall lawsuits. If Tysabri has harmed you, or a loved one, contact us right now to discuss your potential case in filing a Tysabri PML Lawsuit with an Attorney.

1. What is Tysabri?
   Tysabri is a monoclonal antibody that binds to a protein called alpha-4-integrin. Integrins are found primarily on the surface of white blood cells, and play a role in immune system activity.

 

2. What is Tysabri used for?
   Tysabri is approved to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of exacerbations. It was approved based on results achieved after approximately one year of treatment in ongoing controlled trials.

 

3. What is Multiple Sclerosis?
   Multiple sclerosis (MS) is a serious disease in which the immune system attacks the person’s brain and spinal cord. The disease causes a wide range of symptoms including fatigue, difficulty walking, numbness, and vision problems. MS frequently progresses to severe disability and/or death. Relapsing MS is the most common form of this disease.

 

4. How is Tysabri given?
   Tysabri is given by intravenous infusion once every 4 weeks.

 

5. Why is marketing of Tysabri being suspended?
   A patient with MS in a long-term clinical trial of Tysabri recently died from progressive multifocal leukoencephalopathy (PML), a rare neurologic disease; a second patient with MS in the same trial who was receiving Tysabri has a confirmed diagnosis of PML. Because the relationship between use of Tysabri and PML is not clear, Biogen Idec, the manufacturer of Tysabri, has voluntarily suspended marketing, as well as dosing of Tysabri in clinical trials, until the relationship is better understood. The FDA concurs with this decision.

 

6. What other steps has the manufacturer taken?
   The manufacturer is notifying physicians of these cases and informing them that use of Tysabri should be discontinued until further notice. Similar notices are being sent to physicians who are studying Tysabri as part of a clinical trial. Biogen Idec is recommending that all patients who have received Tysabri and have signs and symptoms suggestive of PML be evaluated. Any potential case should be reported to Biogen Idec, or to the FDA’s MedWatch reporting system. The manufacturer is reviewing the records of all patients who have received Tysabri in a clinical trial and evaluating these patients to determine if there any other cases of PML in this population. Biogen Idec is also convening a panel of medical and scientific experts on this condition to give advice on appropriate steps, including how to assess patients who have received Tysabri and who may have developed undetected early-stage PML. The FDA will maintain close contact with the manufacturer during this process and issue further information as it becomes available.

 

7. What kinds and numbers of patients have received Tysabri?
   Patients have received Tysabri either in a clinical trial or, since its approval in November, 2004, through their personal physician. Clinical trials of Tysabri include patients with MS, Crohn’s disease, and rheumatoid arthritis. About 3000 patients have received Tysabri in clinical trials; over 1700 have received it for at least a year and approximately 1100 for over two years. Outside of a clinical trial, Tysabri is only approved for patients with MS. According to Biogen Idec, outside of clinical trials, approximately 5000 patients with MS have received Tysabri through their primary physician; however, because Tysabri was approved only recently, these patients have only received at most a few doses of Tysabri.

 

8. Have there been any cases of PML in the 5000 patients receiving Tysabri through their primary physician?
   There have been no cases of PML reported or detected in patients receiving Tysabri outside of a clinical trial and no cases outside of the trial in patients with MS.

 

9. How long will this suspension last?
   The availability of Tysabri in the future will depend on the analyses of the data being obtained by the drug’s manufacturer.

 

10. Why was marketing suspended because of just two confirmed cases of PML?
    Although these two confirmed cases of PML do not automatically mean that Tysabri causes PML, and additional information needs to be obtained to fully understand the connection, if any, between Tysabri use and PML, the FDA and Biogen Idec are concerned about the possibility that other patients who have received Tysabri may have developed undetected early-stage PML. PML is a very rare and potentially fatal condition that is not known to occur in patients with MS. Until this situation is better understood, the manufacturer has voluntarily suspended marketing of Tysabri and its use in clinical trials. The FDA concurs with this decision. The manufacturer is convening a panel of medical and scientific experts on this condition to give advice on appropriate steps, including how to assess patients who have received Tysabri and who may have developed undetected early-stage PML.

 

11. How common is PML?
    In the general population, PML is extremely rare, and virtually never occurs in individuals with normal immune systems. 1 – 5% of AIDS patients may be diagnosed during their lifetime; PML has also occurred in organ transplant recipients who have received immunosuppressive medications, as well as cancer patients.

 

12. What causes PML?
    PML is thought to be caused by a virus called JC virus (JCV). Most people are exposed to this virus in childhood and carry it in a dormant state but never develop illness. PML occurs almost exclusively in individuals with suppressed immune function who carry JCV. The immune suppression allows the virus to cause disease.

 

13. Is PML contagious?
    PML is not thought to be contagious, and isolation precautions are not needed.

 

14. Is there any treatment for PML?
    There is no known effective treatment for PML, although reversing immune system suppression may slow or arrest the progress of the disease.

 

15. Does Tysabri cause PML?
    At this point, the connection, if any, between Tysabri use and PML is not known.

 

16. Is PML more common in patients with MS?
    Although the symptoms of PML may appear similar to those of MS, there does not appear to be a direct relationship between these two diseases, and patients with MS are not thought to be at higher risk than the general population for development of PML.

 

17. Did the patients who developed PML have other possible reasons to develop this disease?
    Neither patient had typical risk factors for PML. Both patients were receiving Avonex (interferon beta-1a), another approved treatment for MS, at the same time that they were being treated with Tysabri. Prior to approval, the manufacturer of Tysabri had studied its use in combination with Avonex; no cases of PML were observed in patients receiving the combination. The use of interferons, including Avonex, has not been associated with PML. FDA has analyzed data in its post-marketing database and not found any cases of PML reported in patients receiving a beta interferon. It is not known if Tysabri in combination with a beta interferon might cause PML.

 

18. How long has the FDA known about this situation?
    FDA was first provided with preliminary information about these cases by Biogen Idec late on the afternoon of Friday, February 18, 2005. Details of the cases became available over the next week.

 

19. What is the FDA doing about this situation?
    In addition to issuing this advisory, FDA has been in close contact with the manufacturer of Tysabri, and concurs with their decision to voluntarily suspend marketing of Tysabri and dosing of Tysabri in clinical trials. FDA is also imposing a clinical hold on trials of Tysabri, legally prohibiting further investigational use of Tysabri until more information is available. Although these events occurred in clinical trials, FDA has also been analyzing data from its post-marketing database to better understand any possible connection between Tysabri, Avonex, and PML. FDA is also working with the manufacturer to determine the best methods for assessing patients who have received Tysabri in order to assure their safety and understand the connection, if any, between Tysabri and PML. FDA will issue further information as it becomes available.

 

20. When was Tysabri approved?
    Tysabri received accelerated approval in November 2004.

 

21. What does it mean that Tysabri received accelerated approval?
    Accelerated approval is a program the FDA developed to make new drug products available for serious or life threatening diseases when they appeared to provide a benefit over available therapy. Tysabri was approved on the basis of a clinical study showing that 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 in another clinical study. These results represented 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. As a condition of approval of Tysabri, the manufacturer was required to continue these clinical trials through a period of two years to show that the drug continues to provide benefit. The two cases reported here occurred in patients in the continuation phase of these trials.

 

22. Why didn’t the FDA wait longer before approving Tysabri?
    The results shown in the clinical trials of Tysabri showed an important and meaningful benefit in the treatment of MS, a serious disorder that can lead to permanent disability or death. The efficacy results, in combination with the safety profile of Tysabri observed in clinical trials, supported accelerated approval. This allowed Tysabri to be made available to patients with MS earlier than would be the case for traditional approval. No cases of PML were observed in the clinical trials supporting the approval of Tysabri.

 

23. Shouldn’t the FDA have known this might happen?
    PML is a rare condition that does not occur even in the vast majority of patients, even those with suppressed immune systems. During the review of Tysabri, the FDA conducted an intensive analysis of possible adverse events that might be connected to effects of Tysabri on the immune system. No cases of PML were seen in the clinical trials that were the basis for approval of Tysabri, nor were infections characteristic of immunosuppression observed. However, for any approved therapy, new and unexpected adverse events may occur that were not seen in clinical trials. In the case of Tysabri, required post-marketing studies were ongoing and facilitated rapid reporting of and response to these events.

 

24. Are patients with MS at more risk of developing PML if they have been treated with Tysabri for a long time?
    The relationship, if any, between length of treatment with Tysabri and development of PML is not known at this time.

 

25. What are other adverse reactions have been reported with Tysabri?
    The most frequently reported adverse events with Tysabri in clinical trials were infections, severe or life threatening allergic reactions, depression (including thoughts of suicide), and gallbladder problems. These events occurred at rates ranging from 0.8% to 2.1%. No cases of PML were observed in the clinical trials used to support approval of Tysabri.

 

26. I’ve received Tysabri for my MS. Am I going to develop PML?
    Although the risk, if any, of PML in patients receiving Tysabri is not known, it is important to recognize that only two confirmed cases of PML have been identified from among over 8000 patients who have received Tysabri. Patients should, however, discontinue use of Tysabri until further notification.

(Note: The number of confirmed PML cases has risen significantly from the time that this article was initially published)

Tysabri PML Lawyer

If you or a family member has been diagnosed with PML, or been treated with Tysabri infusions, contact our law firm to speak to a PML lawyer about your legal options. Every attorney at our law firm is dedicated to fighting for the rights of those that have been harmed by dangerous and recalled drugs and medical devices. For over 25 years, Attorney David Willis has been a trial lawyer representing seriously injured clients in product liability and personal injury lawsuits such as defective drug litigation, class action drug lawsuits and medical device recall lawsuits. If Tysabri has harmed you, or a loved one, contact us right now to discuss your potential case in filing a Tysabri PML Lawsuit with an Attorney.