Approved by the Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to hundreds of cases of suicide in the United States. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
Most recently, Roche lost several Accutane lawsuits brought by people who claimed the drug caused them to develop inflammatory bowel disease (IBD). In November 2008, a New Jersey jury ordered the company to pay $13 million to three such plaintiffs. The previous April, another New Jersey jury awarded $10.5 million to a woman who blamed the drug for her ulcerative colitis. In May 2007, another New Jersey trial resulted in an award of $2.62 million to a patient who needed to have his colon and most of his rectum removed after taking the drug. In October that same year, a Florida jury awarded $7 million in damages to another Accutane user who developed the IBD.
In announcing its decision to pull Accutane, Roche did cite the high cost of product liability suits - it currently faces 5000 such lawsuits - involving the drug. But according to Bloomberg.com, the company also said a reevaluation of its product line had shown Accutane faced serious competition from generics.
Roche said Accutane will be pulled in the U.S. and 11 other countries. The last date for distribution in the United States was June 25. According to Reuters, Accutane is now no longer available from Roche directly but patients may still be able to get it from pharmacies.
IBD refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn’s disease. These diseases cause the lining of the intestine to become inflamed and develop ulcers.
According to Bloomberg News, about 13 million people have taken Accutane since it went on the market in 1982. The medication was Roche's second-biggest selling drug before the patent expired in 2002. Accutane has been controversial, however, because of its association with various serious side effects.
It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. In addition to IBD, Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems. Because of these problems, Accutane has been named in over 500 lawsuits.
According to Bloomberg News, a jury in Atlantic City, New Jersey ruled yesterday that Roche failed to properly warn of Accutane's side effects. The jury awarded a total of $12.9 million to the three plaintiffs, all of whom were from Florida. According to Bloomberg, Jordan Speisman, 27, won compensatory damages of $8.5 million and medical expenses of $142,500; Lance Sager, 28, damages of $2.5 million and medical costs of $125,000; and Kelly Mace, 25, damages of $1.5 million and medical expenses of $128,000.
As Bloomberg reported, this is the fourth time Roche has lost an Accutane trial involving IBD. In April, we reported that another New Jersey jury awarded $10.5 million to a woman who blamed the drug for her ulcerative colitis. In May 2007, another New Jersey trial resulted in an award of $2.62 million to a patient who needed to have his colon and most of his rectum removed after taking the drug. In October that same year, a Florida jury awarded $7 million in damages to another Accutane user who developed the IBD.
Yasmin is marketed by Bayer Healthcare. Yasmin is the only birth control on the market that contains the progestin drsp, or drospirenone, which can cause increased potassium levels. Because of this, the Yasmin website says that women who have kidney, liver or adrenal disease should not use the medication because this could cause serious heart and health problems. Women considering using Yasmin are also advised to tell their doctor if they are on daily long-term treatment for a chronic condition such as cardiovascular disease or chronic inflammatory disease.
Approved by the U.S. Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. IIt first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. Accutane has also been associated with inflammatory bowel disease, problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
Women taking Accutane are advised to used birth control while on the drug because of its high risk of birth defects. Yasmin is one of the contraceptives recommended for women on Accutane. Yasmin itself is not approved to treat acne, but is often used off-label for this purpose.
The consumer advocacy group Public Citizen lists both Yasmin and Accutane on its "Worst Pills List". Yasmin garnered that distinction because it can increase blood levels of potassium, and is no more effective than other oral contraceptives in preventing pregnancy. Accutane made Public Citizen's list because of the numerous serious side effects related to its use.
According to Australian media reports, Tanya Hayes died on Monday, less than a day after collapsing. A busy student, her family has said that Hayes ignored symptoms - including "breathlessness" and "a nasty, hard cough" - of what turned out to be a pulmonary embolism for weeks.
According to the head of the emergency room that treated Hayes, her death was the result of "blood clotting caused by factors related to taking the oral contraceptive pill".
Hayes father said in an interview that if the Yasmin label had listed side effects, including warnings about "breathlessness", more prominently, his daughter might not have ignored her symptoms for so long.
Berard's team studied 30,496 people from Quebec, Canada, who received at least one Accutane or isotretinoin prescription from 1984 through 2003. During the study period, 126 of these individuals received a depression-related diagnosis, hospitalization, or treatment. Also, based on earlier research, the researchers focused on isotretinoin use in the five months prior to the depression diagnosis—the risk period—as compared with a five-month period a year before the diagnosis—the control period. After accounting for potential factors that might influence the results, isotretinoin exposure was associated with a greater than 2.6-fold relative risk of depression, the team found. "Because depression could have serious consequences, close monitoring of isotretinoin users is indicated," Berard and colleagues concluded.
Suicide is common in the US, representing the fourth leading cause of death for those aged 18 to 65 and the third leading cause for those aged 15 to 24. Add to those figures the complexity of medications. And recently, reports have been filed with drug makers and the Food and Drug Administration (FDA) on at least six drugs or drug classes that may be linked to suicide or suicidal thoughts; the acne drug, Accutane, is among these.
Recently, the Food & Drug Administration (FDA) released notices about several such medications including Singlulair; epilepsy drugs including carbamazepine, gabapentin, felbamate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, and valproate; and the smoking-cessation drug Chantix. Reports have been filed on SSRI antidepressants including Paxil and Prozac, the influenza drug Tamiflu, and the acne medicine Accutane. "The brain is a complex organ, and most of the drugs are complex as well,’’ says Dr. Thomas Laughren, head of the division of psychiatric products at the FDA. "It’s not unreasonable to think that a drug that gets into the brain may have effects other than you hope they would.’’
Kelly Posner, principal investigator at the Center for Suicide Risk Assessment at Columbia University in New York, is working with the FDA to determine suicide risks and at-risk categories; Posner’s quantitative tools and questionnaires are being applied to drugs on the market and in testing. "We know that whether or not these drugs actually cause suicidal thought or action is a question we have to answer, but up until now, none of the clinical trials for the drugs were set up to address the question,’’ says Posner.
Meanwhile, Congressman Bart Stupak (Democrat-Michigan) reported his teenage son B.J. killed himself in 1999 after several months on Accutane and said in 1998, the FDA publicly noted reports of depression, psychosis, and suicidal thoughts and actions with Accutane; in 1999 when B.J. was prescribed Accutane, their doctor did not inform them of the risk and the prescription’s patient information did not include it.
Approved by the Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. In addition to inflammatory bowel disease, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. In addition to inflammatory bowel disease, Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
Inflammatory bowel disease refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. In ulcerative colitis, the inner lining of the intestine becomes inflamed and develops ulcers. Ulcerative colitis is often the most severe in the rectal area, which can cause frequent diarrhea. Mucus and blood often appear in the stool if the lining of the colon is damaged.
According to the Wall Street Journal, Kamie Kendall, a 24-year-old Utah hairdresser, started taking Accutane at age 12. She was diagnosed with ulcerative colitis at the age of 14, and in 2006 she had her colon removed and now suffers from debilitating diarrhea. The jury awarded Kendall $10.5 million of compensatory damages plus $78,500 for medical expenses. The judge presiding over the case ruled there was insufficient evidence to allow the jury to consider punitive damages or consumer fraud.
Kendall is the third Accutane plaintiff to successfully sue Hoffman-LaRoche over inflammatory bowel disease. In May, another New Jersey jury awarded $2.62 million in damages to a patient who needed to have his colon and most of his rectum removed after taking the drug Accutane. In October, A Florida jury awarded $7 million in damages to another Accutane user who developed the disorder and said Hoffman-LaRoche failed to adequately warn of the drug's risks.
Hoffman-LaRoche has said it will appeal all of the verdicts, and insisted that the link between Accutane and inflammatory bowel disease has not yet been proven. In a statement, the company also said that "the Accutane labeling has contained a warning about IBD for more than 20 years."
But last summer, the Food and Drug Administration (FDA) heard evidence that iPledge has not ended the problem. There were 122 pregnancies in the program's first year and another 37 in the four months since. Another 19 pregnancies occurred in women who managed to get the drug despite never enrolling in iPledge. Despite this, in October, the FDA agreed to a few changes, announcing Wednesday that iPledge is now implementing these changes. Women of childbearing age who do not fill a prescription within seven days of a pregnancy test will be allowed to get another test and then fill the prescription, with the exception of the initial prescription. Until now, those who didn't act within seven days were frozen out of the program for the next 23 days. Those women will have to fill the prescription within seven days of a pregnancy test rather than within seven days of first seeing their doctor.
Accutane is considered the biggest breakthrough in acne drug therapy in the past two decades and is the only drug with the potential to clear acne permanently after once course of treatment, which is usually five months. Accutane should be reserved for cases of severe recalcitrant nodular acne, the type of acne resistant to standard acne treatment, including oral antibiotics, and is characterized by many nodules or cysts-inflammatory lesions filled with pus and lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.
Since the FDA approved Accutane in 1982, nearly 5 million people in the U.S. and 12 million worldwide have been treated with it. Half the patients taking the are females, most of childbearing age. Accutane is known to be teratogenic, or able to cause birth defects, and is designated Category X, meaning it must be avoided under all circumstances during pregnancy. Nursing mothers also should not use Accutane. Birth defect risk among pregnant women is extremely high-25 to 35 percent-and include hydrocephaly (enlargement of the brain's fluid-filled spaces) and microcephaly (small head), heart defects, facial deformities such as cleft lip and missing ears, and mental retardation. This does not account for other defects not detectable at birth, such as learning disabilities. Also, patients may develop serious problems affecting organs such as the liver, intestines, eyes, ears, and skeletal system. Some patients have developed serious psychiatric problems, including depression; some have developed suicidal behavior and others have succeeded in their suicide attempts.
Introduced in 1982, Accutane has been the subject of controversy for years. It has been associated with psychiatric problems, and has been linked to 266 cases of suicide in the United States. In addition to its connection with depression, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. Accutane has also been linked to problems of the liver, kidneys, digestive tract, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
Earlier this year, scientists from Bath University in conjunction with the University of Texas in Austin conducted experiments on mice that showed that Accutane made the mice behave in ways comparable to depression in humans. Now, in an article published in the journal Experimental Biology and Medicine, those same scientists have revealed a potential mechanism that might link Accutane to reported cases of depression in some patients taking the medication. Using cells cultured in a laboratory, the researchers monitored the effect of Accutane on the chemistry of the cells that produce serotonin. The researchers now say that Accutane could be disrupting the process by which serotonin relays signals between neurons in the brain.
Serotonin is a hormone found in the pineal gland, blood platelets, the digestive tract, and the brain. Serotonin acts both as a chemical messenger that transmits nerve signals between nerve cells and that causes blood vessels to narrow. Changes in the serotonin levels in the brain can alter the mood, and low levels of serotonin have been linked to depression, as well as bipolar disorder and anxiety disorders.
The link between low serotonin levels and Accutane use is further confirmation that this drug causes psychiatric problems – something that has been known for quite a long time. In fact, the manufacture of Accutane, Roche AG, knew about these problems long before they were made public. A 2004 USA Today article reported that, in the mid-1990s, contrary to advice from its own doctors, Roche executives chose not to issue stronger warnings about Accutane’s depression risks. According to the article, Roche decided against the warnings after its marketing department expressed concern that doing so would hurt sales. At the time, Accutane was one of Roche’s top-selling medications, bringing in more than $1.2 million every year. In 1999, in the face of mounting evidence, the Food & Drug Administration finally required Roche to include a suicide warning on the Accutane package insert.
Accutane and other forms of isotretinoin are used to treat severe acne, but they carry an extremely high risk of causing birth defects if a female patient is pregnant. For that reason, pregnant women are barred from using Accutane. The iPledge program was established in 2006 as a way to make sure that women taking Accutane were not or did not become pregnant while using it. It required, among other things, that female patients submit to regular pregnancy tests and that they sign a promise to use contraceptives while taking Accutane.
But earlier this summer, a report was released showing that the FDA’s iPledge program was not entirely successful in keeping the drug from expectant mothers. In its first year, 122 women in the iPledge program were either pregnant when they started taking Accutane, or became pregnant while doing so. In some cases, the pregnancy test the women took prior to getting their Accutane prescription had a false-negative reading. In two cases, the women actually convinced their doctor to enter fake test results into the iPledge database. But most of the pregnancies were the result of contraceptive failure.
Many dermatologists also complained that the iPledge program was too complicated and unwieldy. This summer, an FDA advisory panel agreed with this assessment and recommended several changes to the iPledge program. For example, it recommended doing away with rules that said a woman must have a pregnancy test and fill her Accutane prescription within seven days of seeing her doctor. The panel recommended changing the rule to allow such a patient to get an Accutane prescription from her doctor within seven days of the test. Another recommendation was to allow a patient to have a second pregnancy test and receive a new prescription if she misses the seven day window. The FDA has decided to follow the advisory panel’s recommendation, and the new Accutane labeling will reflect these changes to the iPledge program.
Many of the changes were originally proposed by Roche AG, the maker of Accutane, and the other isotretinoin manufacturers. They say the modifications will improve the flexibility of the iPledge program, reduce interruptions in treatment and reduce the burden on patients, doctors and pharmacies.
Approved by the Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. In addition to IBD, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
A 2004 USA Today article reported that in the mid-1990s, contrary to advice from its own doctors, Roche executives chose not to issue stronger warnings about Accutane’s depression risks. According to the article, Roche decided against the warnings after its marketing department expressed concern that doing so would hurt sales. At the time, Accutane was one of Roche’s top-selling medications, bringing in more than $1.2 million every year.
In 1997, in the face of mounting evidence, the FDA finally required Roche to include a suicide warning on the Accutane package insert. Then in 2006, the FDA began the iPledge registry program. This program requires patients to sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must sign a pledge that they would use birth control while taking Accutane. Despite these precautions, many consumer advocacy organizations have called for Accutane to be removed from the market, contending that its risks far outweigh its benefits.
In May, a New Jersey jury ordered Roche to pay another IBD victim $2.62 million for his injuries. That patient had developed IBD after having taken Accutane for 4 months in 1995. In addition to having his colon removed, that plaintiff also had most of his rectum removed and had to wear a colostomy bag for years. In addition to the $2.62 million, the jury also awarded the patient $119,000 to cover medical expenses.
Roche insists that the link between Accutane and IBD is still unproven, despite the fact that Accutane’s label includes a warning about IBD risk. Roche said it plans to appeal the New Jersey Accutane verdict, and it is expected that the company will appeal the Florida verdict as well.
Just days before the FDA advisory panel made its recommendations, a report was released showing that the FDA’s iPledge program was not entirely successful in keeping the drug from expectant mothers. The iPledge program, which became mandatory last year, requires that all patients sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must sign a pledge promising to use birth control while taking Accutane. In its first year, 122 women in the iPledge program were either pregnant when they started taking Accutane, or became pregnant while doing so. In some cases, the pregnancy test the women took prior to getting their Accutane prescription had a false-negative reading. In two cases, the women actually convinced their doctor to enter fake test results into the iPledge database. But most of the pregnancies were the result of contraceptive failure.
The FDA advisory panel wants to lift some of the restrictions of the iPledge program. For example, under current rules a woman must have a pregnancy test and fill her Accutane prescription within seven days of seeing her doctor. The panel wants to change the rule so that a patient can get an Accutane prescription within seven days of the test. Another rule change would allow a patient to have a second pregnancy test and receive a new prescription if she misses the seven day window. Currently, if a patient does miss that window, they must wait 23 days to take another test before getting Accutane.
The panel also suggested that the iPledge program should encourage Accutane users who do become pregnant to provide the FDA follow-up information on their pregnancies. Of the 122 women who became pregnant, only about a dozen supplied such information. The FDA panel criticized a questionnaire the iPledge program used for this purpose, saying that it had a “punitive” tone. For instance, the panel did not like the way questions about educational background followed those about contraceptive failure. According to an Associated Press report, one panel member said that the questions implied that a woman became pregnant because she was “stupid”.
The FDA panel said that the proposed rule changes are minor, and should not affect pregnancy rates among Accutane users. They maintained that the alterations would make compliance easier.
In addition to birth defects, Accutane has been linked to Inflammatory Bowel Disorder, as well as psychiatric problems. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems. Accutane and the other drugs in its class are only supposed to be used for the most severe types of acne. However, it has long been known that doctors prescribe these medications to patients with milder acne.
The iPledge program was initiated by the Food and Drug Administration (FDA) and became mandatory last year. All patients using isotretinoin must enroll in iPledge, as well as doctors who prescribe the drug and the pharmacies that sell it. The program requires patients to sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must sign a pledge promising to use birth control while taking Accutane.
When iPledge was first introduced, the FDA hailed the program as an effective vehicle for preventing the birth defects associated with Accutane. But a report issued by the FDA and the companies that manufacture isotretinoin-containing drugs released earlier this week says that the program is falling short. In the first year of iPledge, 122 pregnancies were reported among female participants. Of those, 78 were taking the drug when they became pregnant, and 10 were already pregnant when they were first prescribed the drug. Incredibly, two of those women are known to have had their doctors falsify their pregnancy tests. Most of the pregnancies that occurred after the woman started taking isotretinoin came about because the patients were not diligent about using contraceptives.
Accutane and other isotretinoin-containing medications are never safe during pregnancy. Even if an expectant mother takes the drug in small doses over a short period of time, her baby has a greater chance of suffering severe brain and heart defects, mental retardation and other problems. And the risk continues for about thirty days after a woman stops using Accutane. In addition to birth defects, Accutane has been associated with myriad other serious side effects. It has been linked to Inflammatory Bowel Disorder, as well as psychiatric problems. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems. Accutane and the other drugs in its class are only supposed to be used for the most severe types of acne. However, it has long been known that doctors prescribe these medications to patients with milder acne.
The March of Dimes, an organization dedicated to preventing birth defects, said on its website that it is evaluating the report and will carefully review any proposed changes to the iPledge program. The FDA has scheduled a meeting of its Dermatologic and Ophthalmic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee for later today to discuss the iPledge program’s shortcomings.
Though the Senate also passed its own bill (S 1082), the House version is seen as offering consumers the most protection against defective drugs. Both bills increase drug company user fees and grant the FDA more authority to monitor safety once a medicine is on the market. But the House version includes several provisions that should greatly improve the safety of approved drugs. For instance, the new legislation allows the FDA to conduct safety reviews of a drug seven years after it has been approved. Drug companies would also be required to submit their Direct-to-Consumer (DTC) advertisements to the FDA for approval, and would increase penalties for deceptive drug advertising. DTC ads would also be required to a carry a toll-free number and web address that consumers could access to report side effects.
The bill includes two other changes to the FDA drug approval process long sought by consumer advocates. The first limits so-called “Conflict of Interest” waivers on FDA drug advisory panels to one. Currently, these waivers are unlimited, and as a result, advisory panels are often riddled with pharmaceutical industry insiders. The House bill also makes FDA and industry negotiations more transparent by allowing consumer groups and the public to attend fee negotiations between the Agency and drug companies. The bill also requires that a transcript of such negotiations be published.
Finally, the House bill allows for better access to clinical trial results by the public than the Senate version. While both bills require that a clinical trails database be set up to keep the public informed about the effectiveness and risks of prescription drugs, the House version mandates that this be done within a year. The Senate version gives the FDA 2 ˝ years to set up the database, and is vague as to what information would be included.
A House-Senate committee now must work out the differences between the two bills before sending the legislation to President Bush. The White House has expressed more support for the Senate version, as has the pharmaceutical industry. The pharmaceutical industry is seen as one of the Bush Administration’s most important and influential constituencies.
Andrew McCarrell, the plaintiff in the case, developed Inflammatory Bowel Disease (IBD) after taking Accutane for four months in 1995. In addition to having his colon removed, McCarrel also had most of his rectum removed and had to wear a colostomy bag for years. He recently had surgery that rid him of the colostomy bag, but the 36-year-old software manager testified that he still suffers from severe, chronic diarrhea.
The jury agreed with McCarrell ˘â‚¬â„˘s lawyers that the Accutane label did not provide sufficient warning about the drug ˘â‚¬â„˘s IBD risk. In addition to the $2.62 million, the jury also awarded McCarrel $119,000 to cover medical expenses.
Introduced in 1982, Accutane has been the subject of controversy for years. In addition to IBD, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.
A 2004 USA Today article reported that, in the mid-1990s, contrary to advice from its own doctors, Roche executives chose not to issue stronger warnings about Accutane ˘â‚¬â„˘s depression risks. According to the article, Roche decided against the warnings after its marketing department expressed concern that doing so would hurt sales. At the time, Accutane was one of Roche ˘â‚¬â„˘s top-selling medications, bringing in more than $1.2 million every year.
In 1997, in the face of mounting evidence, the FDA finally required Roche to include a suicide warning on the Accutane package insert. Then in 2006, the FDA began the iPledge registry program. This program requires patients to sign a document informing them of the drug ˘â‚¬â„˘s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor ˘â‚¬â„˘s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must to sign a pledge that they would use birth control while taking Accutane. Despite these precautions, many consumer advocacy organizations have called for Accutane to be removed from the market, contending that its risks far outweigh its benefits.
The study analyzed lab tests on 13,772 patients taking the drug. While some doctors argue that further studies are needed to determine the long-term health effects of the drug, the researchers were clearly surprised by the abnormal results. The results illustrate the need to closely monitor people taking Accutane or one of the three generic versions sold as isotretinoin.
The debate about Accutane ˘â‚¬â„˘s safety is nothing new. For years the drug has been associated with serious side effects. Just this year, the FDA implemented a monitoring program for all female patients taking Accutane, because of the high rate of birth defects associated with pregnant women taking the drug. Accutane has also been associated with inflammatory bowel disease, ulcerative colitis, growth problems, bone & muscle loss and kidney failure. Patients usually take it for less than a year at a cost of $10 to $15 per daily pill.
To say that Accutane is a controversial drug would be about as much of an understatement as saying King Kong was a monkey. In fact, as the drug approaches 25 years on the market, it just may be the most controversial drug of all time in terms of how many serious medical problems it has been linked to as compared to the relatively limited purpose for which it is prescribed.
The latest probe of the drug is being launched by Health Canada as a result of an unusual number of strokes and heart attacks having been reported in people taking it. There have been 29 cases of patients between 15 and 48 who developed vascular disorders after taking the drug.
Of those, 11 involved strokes, heart attacks, and blood clots, which are not currently included in the drug ˘â‚¬â„˘s product information. Many of the people who suffered these medical complications were otherwise young and healthy.
According to a Health Canada report: ˘â‚¬Ĺ“ Health-care professionals are encouraged to report any cases of myocardial infarction, cerebrovascular and thromboembolic disorders suspected of being associated with isotretinoin."
While Health Canada points out that there is no definitive proof that Accutane causes these injuries, the number of reports and the common link to the drug have prompted the agency to take a closer look. The suspicion is there, the causation must be examined, however.
It appears that some of the patients involved had recognized risk factors like obesity and hypertension. Other underlying illnesses must also be ruled out.
In any event, the latest investigation has done nothing to improve Accutane ˘â‚¬â„˘s image .
For years, Accutane has been under siege from numerous medical experts, consumer watchdog groups, and even many officials within the FDA itself because of the many serious health risks linked to the drug.
One problem associated with the current FDA approval and review process that is quite troublesome, is the dramatic increase in the harm or risk that will be tolerated when weighing the potential benefits of a new prescription drug.
Traditionally, even drugs which promised significant benefits would be subjected to greater testing over longer periods of time when significant side-effects or adverse reactions were possible. If the drug was developed to treat a relatively minor condition, the possibility of dangerous side effects usually spelled the end of the drug in terms of FDA approval for marketing.
Today, however, drugs are routinely given FDA approval without sufficient long-term testing using large study groups and without adequate warnings despite evidence of significant side-effects and adverse reactions. Drugs are also permitted to remain on the market far longer than they should be once significant problems are suspected or even confirmed.
This has repeatedly resulted either in the need for upgraded warnings one or more times after a drug is already on the market or in dangerous drugs being pulled from the market only after causing numerous serious injuries or deaths.
Probably the most alarming situation today, however, is when a drug designed to treat a relatively minor condition is approved by the FDA and permitted to remain on the market despite clear evidence of significant side effects or adverse reactions.
In such cases, the risk versus benefit equation has all but vanished from the pharmaceutical companies ˘â‚¬â„˘ consideration and the FDA ˘â‚¬â„˘s standards. Accutane is an example of such a drug.
For all of the positive results it might have achieved, Accutane is still nothing more than an acne drug. This fact alone has caused a wide range of critics of the drug to wonder how it has been permitted to remain on the market at all.
Recent developments with respect to the drug and the manner in which Accutane is regulated and monitored requires a fresh look at the drug and its uncanny ability to survive when other drugs used to treat far more serious conditions with considerably less serious side-effects have been pulled from the market.
Accutane is manufactured by Hoffman-LaRoche Pharmaceuticals. Its active ingredient is known as isotretinoin and it is primarily used to treat nodular acne, a condition that is resistant to other treatments, including antibiotics, and is characterized by the appearance of many nodules or cysts.
These nodules are inflammatory lesions filled with pus and get lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.
Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ birth defects when taken by pregnant women
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ psychological problems including possible suicide
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ neurological problems
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ stomach, bone and muscle problems
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ hearing and vision problems
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ problems with fats and cholesterol in the blood
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ ulcerative colitis
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Crohn ˘â‚¬â„˘s disease
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ inflammatory bowel disorder
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ rectal bleeding
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ abdominal pain
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ central nervous system injuries
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ bone and muscle loss
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ cardiovascular injuries
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ liver and kidney damage
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ pancreatitis
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ immune system disorder
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ lupus
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ thyroid disorders
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ various allergic reactions
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.
In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug ˘â‚¬Ĺ“may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide. ˘â‚¬ ť
This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.
By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug ˘â‚¬â„˘s information packet had already been updated in 1986 to include information about links between Accutane and depression.
Birth defects are perhaps the most severe side effects to be linked to Accutane. ‚ The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.
The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.
As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug ˘â‚¬â„˘s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.
In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.
Since Accutane ˘â‚¬â„˘s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. ‚ The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.
It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.
Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
For some time now, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.
Both Accutane and its generic versions, which include the active ingredient known as Isotretonin, are known to cause birth defects when taken by pregnant women.
The FDA and the drug ˘â‚¬â„˘s manufacturer, Hoffman-LaRoche, now provide information about this adverse health risk in the labeling and packet information for Accutane.
New information, however, indicates, that despite all the warnings, some women continue to use Accutane while pregnant.
A 2005 report appearing online in Birth Defect Research found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn ˘â‚¬â„˘t remember hearing the guidelines relating to Accutane usage and pregnancy. (A teratogen is a substance that causes birth defects.)
Surprisingly, eight of the 34 women said that they didn ˘â‚¬â„˘t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.
In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane.
Up until recently, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.
The new program, called ˘â‚¬Ĺ“iPLEDGE, ˘â‚¬ ť requires that all women of childbearing age take the following steps:
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Sign an informed consent form in their doctor ˘â‚¬â„˘s office;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Personally register with iPLEDGE;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Take two negative pregnancy tests in a doctor ˘â‚¬â„˘s office within seven days of beginning treatment;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Agree to use two forms of birth control while taking the drug;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ And get another negative pregnancy test in a doctor ˘â‚¬â„˘s office within one week of requesting a refill.
Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.
Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. ‚ Doctors must make sure that patients are aware of the drug ˘â‚¬â„˘s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.
Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. ‚ Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.
For more information about iPLEDGE visit www.ipledgeprogram.com or call (866) 495-0654.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane ˘â‚¬â„˘s warning label.
In May of 2005, a study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. ‚ This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.
The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain ˘â‚¬â€ś an area known to mediate symptoms of depression.
The authors of the study urged the FDA and Hoffman-La Roche to conduct further research on the drug. ‚ Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak ˘â‚¬â„˘s son.
In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Feelings of sadness or crying spells
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Loss of interest in activities once enjoyed
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Sleeping too much or having trouble sleeping
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Change in appetite or body weight
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Trouble concentrating
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Withdrawal from family or friends
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Loss of energy
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Feelings of worthlessness or inappropriate guilt
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.
Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Inflammatory Bowel Disease
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Premature Closure of Growth Plates
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Birth Defects
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Ulcerative Colitis
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Crohn's Disease
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Inflammatory Bowel Syndrome
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Rectal Bleeding
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Abdominal Pain
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Central Nervous System Injuries
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Bone and Muscle Loss
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Cardiovascular Injuries
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Liver and Kidney Damage
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Pancreatitis
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Immune System Disorder
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Lupus
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Hearing and Vision Damage
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Thyroid Disorders
Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.
The basis for the strong opposition to the drug was expressed best in the Public Citizen publication Worst Pills Best Pills (April 2004 Newsletter. The more compelling sections of that article are as follow:
˘â‚¬Ĺ“Public Citizen ˘â‚¬â„˘s Health Research Group has been warning the FDA about the risks of birth defects and mental retardation for fetuses exposed to isotretinoin (Accutane) for over 20 years. In 1983 we sent a petition recommending patient package inserts and a black box warning describing the risks of birth defects and life-threatening side effects of the drug. The next year we sent a letter advocating improved pregnancy surveillance and lower dosing regimens. In 1988 we described isotretinoin as an imminent public health hazard to an FDA Advisory Committee and we urged the FDA to remove it from the market unless tight restrictions were implemented and proved effective ˘â‚¬ ¦The following year we testified and again urged the FDA to remove isotretinoin from the market unless our previously proposed restrictions were immediately adopted ˘â‚¬ ¦Then, in 2000 we testified and recommended a Patient Medication Guide and again advised removal from the market unless the restrictions were implemented and shown to be effective.
˘â‚¬Ĺ“In 1989, the CDC testified before an FDA Advisory Committee, stating that, ˘â‚¬Ëś[t]he birth of babies with defects caused by fetal exposure to Accutane is unnecessary, ˘â‚¬â„˘ and the ˘â‚¬Ëś...FDA decision to allow the marketing of Accutane [is] a failed regulatory experiment. ˘â‚¬â„˘ They also declared that a ˘â‚¬Ëś...decision to depend on better contraception alone, without active intervention to reduce the number of users, is a decision to leave the number of affected babies at an unacceptably high level. ˘â‚¬â„˘ They suggested that ˘â‚¬Ëś[p]erhaps a formal IND...would be a suitable mechanism...to reduce the frequency of Accutane embryopathy. ˘â‚¬â„˘ This echoes Public Citizen ˘â‚¬â„˘s recommendation to remove Accutane from the market and reintroduce it only under strict Investigational New Drug (IND) restrictions.
˘â‚¬Ĺ“Since there is currently no reporting requirement for pregnancies exposed to isotretinoin, the actual numbers of affected pregnancies are unknown. There is information from surveys and spontaneous reporting, however, and according to data presented at the 2000 FDA Advisory Committee meeting, there have been 1,995 pregnancies exposed to Accutane between 1982 and 2000. The known outcomes of these pregnancies included 1,214 elective abortions, 383 live births, and 162 infants with birth defects. During the first year of S.M.A.R.T., the System to Manage Accutane Related Teratogenicity, there were 156,800 ˘â‚¬Ëśunique ˘â‚¬â„˘ women who were given the drug, and the pregnancy rate was estimated at 0.35%. We can therefore calculate that there would be 548 total pregnancies, which is 4.6 times higher than the 120 pregnancies spontaneously reported. Of 61 pregnancies with known outcomes, 48/61 or 78.7% resulted in elective abortions. Applied to the 548 estimated pregnancies, there would have been 431 elective abortions in that year. Of 61 pregnancies with known outcomes, 7/61 or 11.5% resulted in deliveries. Based on the 548 estimated pregnancies, there would have been 63 deliveries. Using estimates of 25% birth defects and 50% mental retardation, this would result in 16 infants with birth defects and 31 with mental retardation.
˘â‚¬Ĺ“Proposals of S.M.A.R.T. and the new Roche, the drug ˘â‚¬â„˘s manufacturer, have failed to seriously address two major issues. The first is the need for at least a 95% reduction in prescribing. The CDC estimated in 1989 that there were no more than 4,000 women of child-bearing age with severe cystic acne. Adjusting for population growth, this number may now be 6,000. Given that there were 156,800 ˘â‚¬Ëśunique ˘â‚¬â„˘ women of child-bearing age who got the drug in 2002-2003, this represents a twenty-six fold excess in prescribing over the number of on-label prescriptions. The second problem is the need for mandatory pregnancy test results (not just assurance) before starting therapy and monthly while on therapy as a prerequisite for getting every prescription filled.
˘â‚¬Ĺ“We therefore insist on the withdrawal of isotretinoin from the market. Twenty years of failed voluntary and, more recently, mandatory restrictions have led to a total of more pregnancy exposures because the total number of prescriptions has increased. As we recommended in 1988 and the CDC suggested the next year, a ban on marketing with subsequent availability only under a tightly controlled investigational new drug application (IND) procedure is the only feasible way to significantly reduce prescriptions and pregnancy exposures ˘â‚¬ ¦The S.M.A.R.T program is clearly a failure. Without these proposed IND restrictions, this administration and this advisory committee will continue to put its imprimatur on the reckless use of a drug that each year causes the need for hundreds of abortions and many seriously deformed infants with birth defects and/or mental retardation. It is time to end the more than twenty years of voluntary restrictions that have failed to reduce its prescribing for more than ten times as many women as would be using the drug if it were limited to the approved indications. ˘â‚¬ ť
Under the circumstances, it would seem that Health Canada ˘â‚¬â„˘s latest investigation will only serve to make this drug even more controversial than it already is.
By Steven DiJoseph
Although the American Academy of Dermatology and other critics of the iPledge registry (designed to prevent pregnant women from using the acne drug Accutane) mounted a last-minute campaign to further postpone the system from going into effect, the FDA has decided to adhere to the March 1 starting date.
After only a few months of trial use of the registry system, the nation ˘â‚¬â„˘s leading dermatology association told an FDA advisory panel that the program was a ˘â‚¬Ĺ“disaster. ˘â‚¬ ť The program was originally scheduled to begin on November 1, 2005.
According to Academy member Dr. Diane M. Thiboutot: ˘â‚¬Ĺ“Pharmacies, prescribers and patients are confused and frustrated." There have been hundreds of complaints from dermatologists prompting the association to request that the FDA delay the system's mandatory starting date of March 1 by at least two months.
The agency had indicated it would rule on the postponement request within a week. Supporters of the registry system maintain that the problems being encountered are being overblown.
The iPledge system was an effort to keep Accutane from being pulled from the market. The four manufacturers of the drug fully realized that, without reducing the number of miscarriages, abortions, and birth defects, Accutane ˘â‚¬â„˘s days were numbered.
As we previously reported, the strange thing about Accutane is that it was never intended to treat the huge number of patients for whom it is being prescribed. The severe, disfiguring type of acne the drug was designed for only affects some 6,000 women of childbearing age in the U.S. Doctor ˘â‚¬â„˘s, however, may prescribe the drug as they choose. Thus, in 2002-2003, some 156,800 women of childbearing age were prescribed the drug, or 2,600% more than actually fit the profile for which the drug is intended.
As a result of what critics consider the over-prescribing of the drug, some 100,000 prescriptions each month are filled by women; many of these women become pregnant while taking the drug. The over-prescribing has also had the effect of making Accutane a big moneymaker for it s manufacturers.
The problems with the system appear to be that it is inconvenient, cumbersome, and difficult to manage, while also suffering from slow telephone support when a doctor needs assistance. As a result, doctors are becoming discouraged and may simply stop prescribing the drug.
The FDA says it is aware of the problems and Covance, the company that operates the system, claims to be fixing them as quickly as possible. The process, however, often takes weeks to complete.
The strict regulations imposed by the iPledge system are seen as absolutely necessary by those who advocate tighter control of Accutane. Although over 27,000 people have signed up so far, there is a long way to go before all those who must sign up have registered.
As reported in the New York Times, Dr. Peter A. Gross, the panel's chairman and chairman of the department of internal medicine at Hackensack University Medical Center in New Jersey, dismissed the complaints. "You get no sympathy from me. If it takes a little more time, tough."
In addition, Dr. Sidney Wolfe, director of health research at Public Citizen stated: "There is this never-ending whimpering coming from many dermatologists that someone is cramping their style and making it more difficult to prescribe something. The reason there are all these failed efforts to limit pregnancies is that dermatologists are prescribing Accutane to way too many people."
According to the New York Times article: ˘â‚¬Ĺ“Representative Bart Stupak, a Democrat from Michigan who has long advocated that Accutane be withdrawn from the market, said complaints about the new system were exaggerated. Mr. Stupak sent a letter to the committee insisting that there be no delays in putting the new control system in place. ˘â‚¬ ť
˘â‚¬Ĺ“ ˘â‚¬ËśBut I expect that the F.D.A. will once again cop out and not do the right thing ˘â‚¬â„˘ and agree to a delay, Mr. Stupak said in an interview. ˘â‚¬ ť
Apparently, however, the FDA has decided that, notwithstanding the procedural difficulties, the program should be launched. While critics of the drug are pleased by the decision, they remain adamant that Accutane (and its equivalents) should be removed from the market entirely.
For years, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.
Both Accutane and its generic versions, which include the active ingredient known as isotretodnin, are known to cause birth defects when taken by pregnant women.
The FDA and the drug ˘â‚¬â„˘s manufacturer, Hoffman-LaRoche, already provide information about this adverse health risk in the labeling and packet information for Accutane.
Unfortunately, research continues to indicate that despite all the warnings, some women continue to use Accutane while pregnant. This has been an ongoing problem for 23 years during which time the FDA has been unsuccessful in some 40 initiatives to prevent women from taking the drug while pregnant.
While most of the 2,000-plus reported pregnancies during Accutane use have resulted in abortions or miscarriages, there have been over 160 babies born with isotretodnin-related birth defects. It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies for many years.
A report appearing online in Birth Defect Research in 2005 found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn ˘â‚¬â„˘t remember hearing the guidelines relating to Accutane usage and pregnancy. (A teratogen is a substance that causes birth defects.)
Surprisingly, eight of the 34 women said that they didn ˘â‚¬â„˘t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.
In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane that will become mandatory on March 1.
Previously, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.
The new program, called ˘â‚¬Ĺ“iPLEDGE, ˘â‚¬ ť requires that all women of childbearing age take the following steps:
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Sign an informed consent form in their doctor ˘â‚¬â„˘s office;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Personally register with iPLEDGE;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Take two negative pregnancy tests in a doctor ˘â‚¬â„˘s office within seven days of beginning treatment;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ Agree to use two forms of birth control while taking the drug;
‚ · ‚ ‚ ‚ ‚ ‚ ‚ ‚ And get another negative pregnancy test in a doctor ˘â‚¬â„˘s office within one week of requesting a refill.
Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.
Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. ‚ Doctors must make sure that patients are aware of the drug ˘â‚¬â„˘s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.
Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. ‚ Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.
Information about the iPLEDGE program was also made available at (866) 495-0654, or online at www.ipledgeprogram.com.
Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
- birth defects when taken by pregnant women
- psychological problems including possible suicide
- neurological problems
- stomach, bone and muscle problems
- hearing and vision problems
- problems with fats and cholesterol in the blood
- ulcerative colitis
- Crohn ˘â‚¬â„˘s disease
- inflammatory bowel disorder
- rectal bleeding
- abdominal pain
- central nervous system injuries
- bone and muscle loss
- cardiovascular injuries
- liver and kidney damage
- pancreatitis
- immune system disorder
- lupus
- thyroid disorders
- various allergic reactions
- Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.
In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche notified doctors that the drug ˘â‚¬Ĺ“may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide. ˘â‚¬ ť
This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.
By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug ˘â‚¬â„˘s information packet had already been updated in 1986 to include information about links between Accutane and depression.
Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.
The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.
As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug ˘â‚¬â„˘s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.
In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.
Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane ˘â‚¬â„˘s warning label.
In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.
The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain ˘â‚¬â€ś an area known to mediate symptoms of depression.
The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak ˘â‚¬â„˘s son.
The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauded the recent efforts of the FDA. Still, the organization had its doubts about the new registry.
For one thing, the registry does not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.
There was also concern that people might get confused with the many generic forms of isotretodnin and may still end up taking Accutane and putting themselves at risk without even knowing it.
In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
- Feelings of sadness or crying spells
- Loss of interest in activities once enjoyed
- Sleeping too much or having trouble sleeping
- Having increased irritability, anger, or aggressively (i.e. temper outbursts, thoughts of violence)
- Change in appetite or body weight
- Trouble concentrating
- Withdrawal from family or friends
- Loss of energy
- Feelings of worthlessness or inappropriate guilt
- Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.
Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
- Inflammatory Bowel Disease
- Premature Closure of Growth Plates
- Birth Defects
- Ulcerative Colitis
- Crohn's Disease
- Inflammatory Bowel Syndrome
- Rectal Bleeding
- Abdominal Pain
- Central Nervous System Injuries
- Bone and Muscle Loss
- Cardiovascular Injuries
- Liver and Kidney Damage
- Pancreatitis
- Immune System Disorder
- Lupus
- Hearing and Vision Damage
- Thyroid Disorders
Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.
The basis for the strong opposition to the drug was expressed best in the Public Citizen publication Worst Pills Best Pills (April 2004 Newsletter. The more compelling sections of that article are as follow:
˘â‚¬Ĺ“Public Citizen ˘â‚¬â„˘s Health Research Group has been warning the FDA about the risks of birth defects and mental retardation for fetuses exposed to isotretinoin (Accutane) for over 20 years. In 1983 we sent a petition recommending patient package inserts and a black box warning describing the risks of birth defects and life-threatening side effects of the drug. The next year we sent a letter advocating improved pregnancy surveillance and lower dosing regimens. In 1988 we described isotretinoin as an imminent public health hazard to an FDA Advisory Committee and we urged the FDA to remove it from the market unless tight restrictions were implemented and proved effective ˘â‚¬ ¦The following year we testified and again urged the FDA to remove isotretinoin from the market unless our previously proposed restrictions were immediately adopted ˘â‚¬ ¦Then, in 2000 we testified and recommended a Patient Medication Guide and again advised removal from the market unless the restrictions were implemented and shown to be effective.
In 1989, the CDC testified before an FDA Advisory Committee, stating that, ˘â‚¬Ëś[t]he birth of babies with defects caused by fetal exposure to Accutane is unnecessary, ˘â‚¬â„˘ and the ˘â‚¬Ëś...FDA decision to allow the marketing of Accutane [is] a failed regulatory experiment. ˘â‚¬â„˘ They also declared that a ˘â‚¬Ëś...decision to depend on better contraception alone, without active intervention to reduce the number of users, is a decision to leave the number of affected babies at an unacceptably high level. ˘â‚¬â„˘ They suggested that ˘â‚¬Ëś[p]erhaps a formal IND...would be a suitable mechanism...to reduce the frequency of Accutane embryopathy. ˘â‚¬â„˘ This echoes Public Citizen ˘â‚¬â„˘s recommendation to remove Accutane from the market and reintroduce it only under strict Investigational New Drug (IND) restrictions.
Since there is currently no reporting requirement for pregnancies exposed to isotretinoin, the actual numbers of affected pregnancies are unknown. There is information from surveys and spontaneous reporting, however, and according to data presented at the 2000 FDA Advisory Committee meeting, there have been 1,995 pregnancies exposed to Accutane between 1982 and 2000. The known outcomes of these pregnancies included 1,214 elective abortions, 383 live births, and 162 infants with birth defects. During the first year of S.M.A.R.T., the System to Manage Accutane Related Teratogenicity, there were 156,800 ˘â‚¬Ëśunique ˘â‚¬â„˘ women who were given the drug, and the pregnancy rate was estimated at 0.35%. We can therefore calculate that there would be 548 total pregnancies, which is 4.6 times higher than the 120 pregnancies spontaneously reported. Of 61 pregnancies with known outcomes, 48/61 or 78.7% resulted in elective abortions. Applied to the 548 estimated pregnancies, there would have been 431 elective abortions in that year. Of 61 pregnancies with known outcomes, 7/61 or 11.5% resulted in deliveries. Based on the 548 estimated pregnancies, there would have been 63 deliveries. Using estimates of 25% birth defects and 50% mental retardation, this would result in 16 infants with birth defects and 31 with mental retardation.
Proposals of S.M.A.R.T. and the new Roche, the drug ˘â‚¬â„˘s manufacturer, have failed to seriously address two major issues. The first is the need for at least a 95% reduction in prescribing. The CDC estimated in 1989 that there were no more than 4,000 women of child-bearing age with severe cystic acne. Adjusting for population growth, this number may now be 6,000. Given that there were 156,800 ˘â‚¬Ëśunique ˘â‚¬â„˘ women of child-bearing age who got the drug in 2002-2003, this represents a twenty-six fold excess in prescribing over the number of on-label prescriptions. The second problem is the need for mandatory pregnancy test results (not just assurance) before starting therapy and monthly while on therapy as a prerequisite for getting every prescription filled.
We therefore insist on the withdrawal of isotretinoin from the market. Twenty years of failed voluntary and, more recently, mandatory restrictions have led to a total of more pregnancy exposures because the total number of prescriptions has increased. As we recommended in 1988 and the CDC suggested the next year, a ban on marketing with subsequent availability only under a tightly controlled investigational new drug application (IND) procedure is the only feasible way to significantly reduce prescriptions and pregnancy exposures ˘â‚¬ ¦The S.M.A.R.T program is clearly a failure. Without these proposed IND restrictions, this administration and this advisory committee will continue to put its imprimatur on the reckless use of a drug that each year causes the need for hundreds of abortions and many seriously deformed infants with birth defects and/or mental retardation. It is time to end the more than twenty years of voluntary restrictions that have failed to reduce its prescribing for more than ten times as many women as would be using the drug if it were limited to the approved indications. ˘â‚¬ ť
Clearly, the iPledge program is the last real hope of countering the devastating effects of Accutane associated with pregnant women and their unborn fetuses. Beyond that, many experts, including doctors within the FDA itself, continue to call for the complete withdrawal of the drug based upon its extremely serious side-effects and potential adverse reactions in all patients and not just pregnant women.
By Steven DiJoseph
For years, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.
Both Accutane and its generic versions, which include the active ingredient known as Isotretonin, are known to cause birth defects when taken by pregnant women.
The FDA and the drug ˘â‚¬â„˘s manufacturer, Hoffman-LaRoche, already provide information about this adverse health risk in the labeling and packet information for Accutane.
Unfortunately, research continues to indicate that despite all the warnings, some women continue to use Accutane while pregnant. This has been an ongoing problem for 23 years during which time the FDA has been unsuccessful in some 40 initiatives to prevent women from taking the drug while pregnant.
A report appearing online in Birth Defect Research in 2005 found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn ˘â‚¬â„˘t remember hearing the guidelines relating to Accutane usage and pregnancy. (A teratogen is a substance that causes birth defects.)
Surprisingly, eight of the 34 women said that they didn ˘â‚¬â„˘t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.
In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane that will become mandatory on March 1.
Previously, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.
The new program, called ˘â‚¬Ĺ“iPLEDGE, ˘â‚¬ ť requires that all women of childbearing age take the following steps:
‚ · Sign an informed consent form in their doctor ˘â‚¬â„˘s office;
‚ · Personally register with iPLEDGE;
‚ · Take two negative pregnancy tests in a doctor ˘â‚¬â„˘s office within seven days of beginning treatment;
‚ · Agree to use two forms of birth control while taking the drug;
‚ · And get another negative pregnancy test in a doctor ˘â‚¬â„˘s office within one week of requesting a refill.
Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.
Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. Doctors must make sure that patients are aware of the drug ˘â‚¬â„˘s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.
Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.
Information about the iPLEDGE program was also made available at (866) 495-0654, or online at www.ipledgeprogram.com.
Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
- birth defects when taken by pregnant women
- psychological problems including possible suicide
- neurological problems
- stomach, bone and muscle problems
- hearing and vision problems
- problems with fats and cholesterol in the blood
- ulcerative colitis
- Crohn ˘â‚¬â„˘s disease
- inflammatory bowel disorder
- rectal bleeding
- abdominal pain
- central nervous system injuries
- bone and muscle loss
- cardiovascular injuries
- liver and kidney damage
- pancreatitis
- immune system disorder
- lupus
- thyroid disorders
- various allergic reactions
- Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.
In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche notified doctors that the drug ˘â‚¬Ĺ“may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide. ˘â‚¬ ť
This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.
By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug ˘â‚¬â„˘s information packet had already been updated in 1986 to include information about links between Accutane and depression.
Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.
The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.
As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug ˘â‚¬â„˘s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.
In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.
Since Accutane ˘â‚¬â„˘s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.
It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.
Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane ˘â‚¬â„˘s warning label.
In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.
The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain ˘â‚¬â€ś an area known to mediate symptoms of depression.
The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak ˘â‚¬â„˘s son.
The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauded the recent efforts of the FDA. Still, the organization had its doubts about the new registry.
For one thing, the registry does not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.
There was also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.
In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
- Feelings of sadness or crying spells
- Loss of interest in activities once enjoyed
- Sleeping too much or having trouble sleeping
- Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
- Change in appetite or body weight
- Trouble concentrating
- Withdrawal from family or friends
- Loss of energy
- Feelings of worthlessness or inappropriate guilt
- Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.
Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
- Inflammatory Bowel Disease
- Premature Closure of Growth Plates
- Birth Defects
- Ulcerative Colitis
- Crohn's Disease
- Inflammatory Bowel Syndrome
- Rectal Bleeding
- Abdominal Pain
- Central Nervous System Injuries
- Bone and Muscle Loss
- Cardiovascular Injuries
- Liver and Kidney Damage
- Pancreatitis
- Immune System Disorder
- Lupus
- Hearing and Vision Damage
- Thyroid Disorders
Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.
Now, after only a few months of trial use of the registry system, the nation ˘â‚¬â„˘s leading dermatology association, the American Academy of Dermatology, told an FDA advisory panel that the program was a ˘â‚¬Ĺ“disaster. ˘â‚¬ ť
According to the Academy member Dr. Diane M. Thiboutot: ˘â‚¬Ĺ“Pharmacies, prescribers and patients are confused and frustrated." There have been hundreds of complaints from dermatologists prompting the association to request that the FDA delay the system's mandatory starting date of March 1 by at least two months.
The agency has indicated it will rule on the request within a week. Proponents of the registry system maintain that the problems being encountered are being overblown.
The iPledge system was an effort to keep Accutane from being pulled from the market. The four manufacturers of the drug fully realized that, without reducing the number of miscarriages, abortions, and birth defects, Accutane ˘â‚¬â„˘s days were numbered.
The strange thing about Accutane is that it was never intended to treat the huge number of patients for whom it is being prescribed. The severe, disfiguring type of acne the drug was designed for only affects some 6,000 patients in the U.S. Doctor ˘â‚¬â„˘s, however, may prescribe the drug as they choose. Thus, over 2 million prescriptions for the drug are written each year.
As a result of what critics consider the over-prescribing of the drug, some 85,000 prescriptions each month are filled by women; many of these women become pregnant while taking the drug.
The problems with the system appear to be that it is inconvenient, cumbersome, and difficult to manage, while also suffering from slow telephone support when a doctor needs assistance. As a result, doctors are becoming discouraged and may simply stop prescribing the drug.
The FDA says it is aware of the problems and Covance, the company that operates the system, claims to be fixing them as quickly as possible. The process, however, often takes weeks to complete.
The strict regulations imposed by the iPledge system are seen as absolutely necessary by those who advocate tighter control of Accutane.
As reported in the New York Times, Dr. Peter A. Gross, the panel's chairman and chairman of the department of internal medicine at Hackensack University Medical Center in New Jersey, dismissed the complaints. "You get no sympathy from me. If it takes a little more time, tough."
In addition, Dr. Sidney Wolfe, director of health research at Public Citizen stated: "There is this never-ending whimpering coming from many dermatologists that someone is cramping their style and making it more difficult to prescribe something. The reason there are all these failed efforts to limit pregnancies is that dermatologists are prescribing Accutane to way too many people."
According to the New York Times article: ˘â‚¬Ĺ“Representative Bart Stupak, a Democrat from Michigan who has long advocated that Accutane be withdrawn from the market, said complaints about the new system were exaggerated. Mr. Stupak sent a letter to the committee insisting that there be no delays in putting the new control system in place. ˘â‚¬ ť
˘â‚¬Ĺ“ ˘â‚¬ËśBut I expect that the F.D.A. will once again cop out and not do the right thing ˘â‚¬â„˘ and agree to a delay, Mr. Stupak said in an interview. ˘â‚¬ ť
For some time now, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.
Both Accutane and its generic versions, which include the active ingredient known as Isotretonin, are known to cause birth defects when taken by pregnant women.
The FDA and the drug’s manufacturer, Hoffman-LaRoche, now provide information about this adverse health risk in the labeling and packet information for Accutane.
New information, however, indicates, that despite all the warnings, some women continue to use Accutane while pregnant.
A recent report appearing online in Birth Defect Research found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn’t remember hearing the guidelines relating to Acctuane usage and pregnancy. (A teratogen is a substance that causes birth defects.)
Surprisingly, eight of the 34 women said that they didn’t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.
In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane.
Up until recently, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.
The new program, called “iPLEDGE,” requires that all women of childbearing age take the following steps:
• Sign an informed consent form in their doctor’s office;
• Personally register with iPLEDGE;
• Take two negative pregnancy tests in a doctor’s office within seven days of beginning treatment;
• Agree to use two forms of birth control while taking the drug;
• And get another negative pregnancy test in a doctor’s office within one week of requesting a refill.
Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.
Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. Doctors must make sure that patients are aware of the drug’s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.
Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.
For more information about iPLEDGE visit www.ipledgeprogram.com or call (866) 495-0654.
Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
• birth defects when taken by pregnant women
• psychological problems including possible suicide
• neurological problems
• stomach, bone and muscle problems
• hearing and vision problems
• problems with fats and cholesterol in the blood
• ulcerative colitis
• Crohn’s disease
• inflammatory bowel disorder
• rectal bleeding
• abdominal pain
• central nervous system injuries
• bone and muscle loss
• cardiovascular injuries
• liver and kidney damage
• pancreatitis
• immune system disorder
• lupus
• thyroid disorders
• various allergic reactions
• Some minor side effects include dry
skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.
In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression.
Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.” This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.
By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.
Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.
The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.
As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.
In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.
Since Accutane’s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.
It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.
Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.
In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.
The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain an area known to mediate symptoms of depression.
The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.
The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauds the recent efforts of the FDA. Still, the organization has its doubts about the new registry.
For one thing, the registry will not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.
There is also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.
In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
• Feelings of sadness or crying spells
• Loss of interest in activities once enjoyed
• Sleeping too much or having trouble sleeping
• Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
• Change in appetite or body weight
• Trouble concentrating
• Withdrawal from family or friends
• Loss of energy
• Feelings of worthlessness or inappropriate guilt
• Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.
Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
• Inflammatory Bowel Disease
• Premature Closure of Growth Plates
• Birth Defects
• Ulcerative Colitis
• Crohn's Disease
• Inflammatory Bowel Syndrome
• Rectal Bleeding
• Abdominal Pain
• Central Nervous System Injuries
• Bone and Muscle Loss
• Cardiovascular Injuries
• Liver and Kidney Damage
• Pancreatitis
• Immune System Disorder
• Lupus
• Hearing and Vision Damage
• Thyroid Disorders
Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.
One problem associated with the current FDA approval and review process that is quite troublesome, is the dramatic increase in the harm or risk that will be tolerated when weighing the potential benefits of a new prescription drug.
Traditionally, even drugs which promised significant benefits would be subjected to greater testing over longer periods of time when significant side-effects or adverse reactions were possible. If the drug was developed to treat a relatively minor condition, the possibility of dangerous side effects usually spelled the end of the drug in terms of FDA approval for marketing.
Today, however, drugs are routinely given FDA approval without sufficient long-term testing using large study groups and without adequate warnings despite evidence of significant side-effects and adverse reactions. Drugs are also permitted to remain on the market far longer than they should be once significant problems are suspected or even confirmed.
This has repeatedly resulted either in the need for upgraded warnings one or more times after a drug is already on the market or in dangerous drugs being pulled from the market only after causing numerous serious injuries or deaths.
Probably the most alarming situation today, however, is when a drug designed to treat a relatively minor condition is approved by the FDA and permitted to remain on the market despite clear evidence of significant side effects or adverse reactions.
In such cases, the risk versus benefit equation has all but vanished from the pharmaceutical companies’ consideration and the FDA’s standards. Accutane is an example of such a drug.
For all of the positive results it might have achieved, Accutane is still nothing more than an acne drug. This fact alone has caused a wide range of critics of the drug to wonder how it has been permitted to remain on the market at all.
Recent developments with respect to the drug and the manner in which Accutane is regulated and monitored requires a fresh look at the drug and its uncanny ability to survive when other drugs used to treat far more serious conditions with considerably less serious side-effects have been pulled from the market.
Accutane is manufactured by Hoffman-LaRoche Pharmaceuticals. Its active ingredient is known as isotretinoin and it is primarily used to treat nodular acne, a condition that is resistant to other treatments, including antibiotics, and is characterized by the appearance of many nodules or cysts.
These nodules are inflammatory lesions filled with pus and get lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.
Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
• birth defects when taken by pregnant women
• psychological problems including possible suicide
• neurological problems
• stomach, bone and muscle problems
• hearing and vision problems
• problems with fats and cholesterol in the blood
• ulcerative colitis
• Crohn’s disease
• inflammatory bowel disorder
• rectal bleeding
• abdominal pain
• central nervous system injuries
• bone and muscle loss
• cardiovascular injuries
• liver and kidney damage
• pancreatitis
• immune system disorder
• lupus
• thyroid disorders
• various allergic reactions
• Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.
In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.”
This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.
By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.
Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.
The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.
As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.
In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.
Since Accutane’s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.
It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.
Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.
In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.
The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain an area known to mediate symptoms of depression.
The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.
Just this past month, the FDA announced that there would be a new National Registry for all Accutane users that will take effect in December 2005. Both male and female patients will have to enroll in the registry as well as doctors and pharmacies.
The purpose of this registry, called iPLEDGE is to eliminate the risk of birth defects by strictly monitoring female patients to make sure that they are not pregnant when beginning treatment and that they do not become pregnant during treatment.
Until now, women of childbearing age have been required to use two forms of birth control, get two negative pregnancy tests before their first Accutane prescription, and show proof of another negative pregnancy test before each refill.
The computerized registry system will now make sure that these precautionary measures take place as each woman will have to enter this information into the registry either by phone or by internet.
While the registry doesn’t officially begin until December, it opened on August 22 in order to allow doctors, patients, and pharmacies time to understand how to use it before everyone signs on at the end of the year.
In addition to taking part in the registry, all patients will also have to read, review, and sign a document informing them of the risks associated with Accutane, specifically psychiatric side effects and pregnancy-related issues.
The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauds the recent efforts of the FDA. Still, the organization has its doubts about the new registry.
For one thing, the registry will not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.
There is also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.
In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
• Feelings of sadness or crying spells
• Loss of interest in activities once enjoyed
• Sleeping too much or having trouble sleeping
• Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
• Change in appetite or body weight
• Trouble concentrating
• Withdrawal from family or friends
• Loss of energy
• Feelings of worthlessness or inappropriate guilt
• Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.
Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
• Inflammatory Bowel Disease
• Premature Closure of Growth Plates
• Birth Defects
• Ulcerative Colitis
• Crohn's Disease
• Inflammatory Bowel Syndrome
• Rectal Bleeding
• Abdominal Pain
• Central Nervous System Injuries
• Bone and Muscle Loss
• Cardiovascular Injuries
• Liver and Kidney Damage
• Pancreatitis
• Immune System Disorder
• Lupus
• Hearing and Vision Damage
• Thyroid Disorders
Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.