Companies Marketing Unapproved Topical Drugs Containing Ibuprofen Receive FDA Warning
The US Food and Drug Administration has written to eight companies marketing over-the-counter (OTC) topical drugs containing the pain reliever ibuprofen and other active ingredients to warn them that they are breaking the law because their drugs are unapproved.
In a press statement released on Thursday, the federal agency said the companies should have applied for approval before marketing their drugs.
The names of the companies and their associated products are:
* Progressive Emu, Inc: Emuprofen.
* BioCentric Laboratories, Inc: BioEntopic 15% Ibuprofen Crème.
* Core Products International, Inc: Ibunex Topical Ibuprofen.
* Geromatrix Health Products: LoPain AF 15% Ibuprofen Crème.
* MEKT LLC: IB-RELIEF.
* Ridge Medical Products: Profen HP.
* Meditrend, Inc. dba Progena Professional Formulations: IbuPRO-10 Plus.
* Wonder Laboratories: IBU-RELIEF 12.
The FDA has warned them that they may not continue to market their products without agency approval and has asked them to explain in writing within 15 days how they will address these violations and stop them happening again.
While the FDA allows some OTC drugs to be marketed without first obtaining agency approval, ibuprofen is not one of them because it is not included in any OTC drug monograph, that is the regulations that set out what is required in the drug's labelling, formulations and indications.
"Companies wishing to market OTC drugs that do not meet the monograph requirements can submit and receive approval of a new drug application," said the FDA statement.
Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER) said:
"These companies have an obligation to the public to demonstrate to the FDA that their products are safe and effective, and they have failed to do so."
While orally administered ibuprofen has been approved as a safe and effective treatment for pain and inflammation, there are no approved applications for topical ibuprofen products, explained the FDA.
Also, while the agency has proposed to add orally administered ibuprofen to the applicable OTC monograph, it has never proposed adding topical ibuprofen.
Topical ibuprofen products are often promoted it as a "safer" alternative to oral ibuprofen, which is described as having long term side effects such as stomach ulcers and cardiovascular problems. However, the FDA stated that:
"These safety claims for topical ibuprofen have not been reviewed by the FDA, nor has the agency evaluated what side effects might be associated with such products."
Source: FDA.
In a press statement released on Thursday, the federal agency said the companies should have applied for approval before marketing their drugs.
The names of the companies and their associated products are:
* Progressive Emu, Inc: Emuprofen.
* BioCentric Laboratories, Inc: BioEntopic 15% Ibuprofen Crème.
* Core Products International, Inc: Ibunex Topical Ibuprofen.
* Geromatrix Health Products: LoPain AF 15% Ibuprofen Crème.
* MEKT LLC: IB-RELIEF.
* Ridge Medical Products: Profen HP.
* Meditrend, Inc. dba Progena Professional Formulations: IbuPRO-10 Plus.
* Wonder Laboratories: IBU-RELIEF 12.
The FDA has warned them that they may not continue to market their products without agency approval and has asked them to explain in writing within 15 days how they will address these violations and stop them happening again.
While the FDA allows some OTC drugs to be marketed without first obtaining agency approval, ibuprofen is not one of them because it is not included in any OTC drug monograph, that is the regulations that set out what is required in the drug's labelling, formulations and indications.
"Companies wishing to market OTC drugs that do not meet the monograph requirements can submit and receive approval of a new drug application," said the FDA statement.
Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER) said:
"These companies have an obligation to the public to demonstrate to the FDA that their products are safe and effective, and they have failed to do so."
While orally administered ibuprofen has been approved as a safe and effective treatment for pain and inflammation, there are no approved applications for topical ibuprofen products, explained the FDA.
Also, while the agency has proposed to add orally administered ibuprofen to the applicable OTC monograph, it has never proposed adding topical ibuprofen.
Topical ibuprofen products are often promoted it as a "safer" alternative to oral ibuprofen, which is described as having long term side effects such as stomach ulcers and cardiovascular problems. However, the FDA stated that:
"These safety claims for topical ibuprofen have not been reviewed by the FDA, nor has the agency evaluated what side effects might be associated with such products."
Source: FDA.
Study Links ADHD Drugs To Sudden Death In Children
A new study by researchers in the US suggests there may be a link between the use of stimulant drugs for attention-deficit hyperactivity disorder (ADHD) and sudden cardiac death in healthy children, but the US Food and Drug Administration (FDA), who funded the study with the National Institute of Mental Health, said because of its limitations, parents and carers should not stop giving children such medication on the basis of this study but should discuss any concerns with their prescribing doctor.
The study was the work of lead author Dr Madelyn S Gould of Columbia University, New York, New York, and colleagues, and is published in the 15 June issue of the American Journal of Psychiatry.
In the case-control study, using state-based mortality data from 1985 to 1996, Gould and colleagues compared the use of stimulant drugs in 564 healthy children aged 7 to 19 from across the US who died suddenly and most likely due to sudden cardiac disturbance with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents.
The primary measure of exposure was the presence of stimulant medication as noted in the medical examiner records, toxicology reports and death certificates. The stimulants involved were amphetamine, dextroamphetamine, methamphetamine, and methylphenidate.
The results showed that out of the 564 healthy children who died suddenly, 10 (1.8 per cent) were taking stimulants, specifically methylphenidate (better known in the US under its brand name of Ritalin). This compared with only 2 children (0.4 per cent) in motor vehicle accident comparison group, only one of whom was taking Ritalin (methylphenidate).
Logistical regression, a tool commonly used by epidemiologists, showed a statistically significant link between stimulant use and sudden unexplained death in a primary analysis. This result was supported qualitatively in a further "comprehensive series of sensitivity analyses", wrote the authors, who concluded that:
"This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents."
"Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment," they added.
In a Safety Communication released on 15 June, the FDA said that:
"The FDA can not conclude that the data in the study affect the overall risk-benefit profile of stimulant medications used to treat ADHD in children."
What they are saying is they are not going to change their advice about the risks versus the benefits of the medication because of the study's limitations, which they say include:
* The significant time lag between when the deaths occurred and when the data was collected.
* The different circumstances around each death that may have affected how well family members and/or carers may have remembered details of any medication the deceased child had been using.
* Sudden unexplained death in a child would be more likely to initiate a post-mortem inquiry than a death due to blunt force trauma in a motor vehicle accident.
* The low frequency of stimulant medication use by the children in both the study and the control groups.
When scientists highlight a study's limitations they are in effect saying that another study looking at the same things might reach a different result if it didn't have those limitations.
With subjects as serious as this, and with parents and carers rightly concerned about what to do about any ADHD medication their children have been prescribed, it is important that research in the service of public health produces results that are robust and reliable, so a small study like this one really needs to be confirmed by more research, preferably with a larger study, especially if there are concerns about its limitations.
In fact, the FDA is already co-sponsoring another larger study that is looking at the link between increased risk of heart attack, stroke and other cardiovascular problems and use of stimulant medication by children, the results of which are expected to come out later this year.
Dr Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research told the press:
"The FDA continues to review drug safety information for stimulant medications used to treat ADHD so that we can give health care professionals and families the most up-to-date drug safety information available."
The federal agency urged doctors to follow the current prescribing information that accompanies the product label, which recommends that young and adult patients being considered for ADHD treatment:
"Work with their health care professional to develop a treatment plan that includes a careful health history for cardiovascular disease in the child and his or her family."
Such preparation should include a physical exam that pays particular attention to the cardiovascular system, and should consider screening tests such as electrocardiogram and echocardiogram, depending on the patient's history and whether it suggests possible risk factors for heart disease.
The study was the work of lead author Dr Madelyn S Gould of Columbia University, New York, New York, and colleagues, and is published in the 15 June issue of the American Journal of Psychiatry.
In the case-control study, using state-based mortality data from 1985 to 1996, Gould and colleagues compared the use of stimulant drugs in 564 healthy children aged 7 to 19 from across the US who died suddenly and most likely due to sudden cardiac disturbance with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents.
The primary measure of exposure was the presence of stimulant medication as noted in the medical examiner records, toxicology reports and death certificates. The stimulants involved were amphetamine, dextroamphetamine, methamphetamine, and methylphenidate.
The results showed that out of the 564 healthy children who died suddenly, 10 (1.8 per cent) were taking stimulants, specifically methylphenidate (better known in the US under its brand name of Ritalin). This compared with only 2 children (0.4 per cent) in motor vehicle accident comparison group, only one of whom was taking Ritalin (methylphenidate).
Logistical regression, a tool commonly used by epidemiologists, showed a statistically significant link between stimulant use and sudden unexplained death in a primary analysis. This result was supported qualitatively in a further "comprehensive series of sensitivity analyses", wrote the authors, who concluded that:
"This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents."
"Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment," they added.
In a Safety Communication released on 15 June, the FDA said that:
"The FDA can not conclude that the data in the study affect the overall risk-benefit profile of stimulant medications used to treat ADHD in children."
What they are saying is they are not going to change their advice about the risks versus the benefits of the medication because of the study's limitations, which they say include:
* The significant time lag between when the deaths occurred and when the data was collected.
* The different circumstances around each death that may have affected how well family members and/or carers may have remembered details of any medication the deceased child had been using.
* Sudden unexplained death in a child would be more likely to initiate a post-mortem inquiry than a death due to blunt force trauma in a motor vehicle accident.
* The low frequency of stimulant medication use by the children in both the study and the control groups.
When scientists highlight a study's limitations they are in effect saying that another study looking at the same things might reach a different result if it didn't have those limitations.
With subjects as serious as this, and with parents and carers rightly concerned about what to do about any ADHD medication their children have been prescribed, it is important that research in the service of public health produces results that are robust and reliable, so a small study like this one really needs to be confirmed by more research, preferably with a larger study, especially if there are concerns about its limitations.
In fact, the FDA is already co-sponsoring another larger study that is looking at the link between increased risk of heart attack, stroke and other cardiovascular problems and use of stimulant medication by children, the results of which are expected to come out later this year.
Dr Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research told the press:
"The FDA continues to review drug safety information for stimulant medications used to treat ADHD so that we can give health care professionals and families the most up-to-date drug safety information available."
The federal agency urged doctors to follow the current prescribing information that accompanies the product label, which recommends that young and adult patients being considered for ADHD treatment:
"Work with their health care professional to develop a treatment plan that includes a careful health history for cardiovascular disease in the child and his or her family."
Such preparation should include a physical exam that pays particular attention to the cardiovascular system, and should consider screening tests such as electrocardiogram and echocardiogram, depending on the patient's history and whether it suggests possible risk factors for heart disease.
FDA Approves First Gout Drug In 40 Years
The US Food and Drug Administration has given marketing approval to a new drug that lowers levels of uric acid in the blood of patients with gout: the current treatment for the condition was developed over 40 years ago. The new drug is called ULORIC (generic name febuxostat) and Takeda Pharmaceuticals North America is the sole developer and marketer of the product in the US.
According to a statement from Takeda, febuxostat is a new highly potent non-purine selective inhibitor of xanthine oxidase, and has a completely different structure from the currently used xanthine oxidase inhibitor, which was developed over 40 years ago. Xanthine oxidase is an enzyme involved in the production of uric acid.
Febuxostat lowers the concentration of uric acid in the blood of hyperuricemic patients with gout. The drug has been proved to be safe and effective in clinical trials, and the dose does not need to be adjusted for patients with mild-to-moderate renal or hepatic impairment (kidney or liver problems).
ULORIC will be available as 40 mg or 80 mg tablets to be taken once a day. It is not recommended for asymptomatic hyperuricemia, said the company's press release.
Febuxostat was discovered by another Japanese company, Teijin Pharma. Their president Osamu Nishikawa said in a press statement released jointly with Takeda that:
"This FDA approval granted to Takeda Pharmaceuticals North America, along with the EMEA (European Medicines Agency) approval given last year to Ipsen, our licensee for febuxostat in Europe, marks a significant milestone for our global business."
He said Teijin would be developing febuxostat themselves for the Asian market, as well as collaborating with other pharma companies. The company wishes to strengthen its global operations by "expanding areas where febuxostat is available and increase the presence of the product to be widely used by patients worldwide," he added.
President of the Takeda parent company in Japan, Yasuchika Hasegawa, said:
"The approval of ULORIC offers patients and healthcare providers in the US for the first time in 40 years, a novel treatment option for patients who have hyperuricemia with gout, where there are still unmet clinical needs."
Gout is a common, painful form of arthritis that causes swollen, red, hot and stiff joints. It occurs when uric acid builds up in the blood, because the body produces too much or can't get rid of it (some medications can slow down elimination), or from eating too many foods rich in purines, such as liver and dried beans.
Pseudogout is sometimes confused with gout because the symptoms are similar; however, it is caused by calcium phosphate, not uric acid.
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), there could be as many as 6 million Americans aged 20 and older who have had gout at some time in their lives. It is more common in men aged 40 to 50, and women rarely develop it before the menopause. Also people who have had an organ transplant are more susceptible.
NIAMS suggest people may be at risk of developing hyperuricemia and gout if they are on certain medications, these include:
* Diuretics, such as furosemide (Lasix1), hydrochlorothiazide (Esidrix, Hydro-chlor), and metolazone (Diulo, Zaroxolyn).
* Drugs containing salicylate, such as aspirin.
* Niacin, a vitamin also known as nicotinic acid.
* Cyclosporine (Sandimmune, Neoral), a medication used to suppress the immune system.
* Levodopa (Larodopa), a drug used in the treatment of Parkinson's disease..
Other related articles
* What is Gout?
Takeda Pharmaceuticals North America, Inc, whose head office is in Deerfield, Illinois, is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited whose head office is in Chuo-ku, Osaka, Japan.
According to a statement from Takeda, febuxostat is a new highly potent non-purine selective inhibitor of xanthine oxidase, and has a completely different structure from the currently used xanthine oxidase inhibitor, which was developed over 40 years ago. Xanthine oxidase is an enzyme involved in the production of uric acid.
Febuxostat lowers the concentration of uric acid in the blood of hyperuricemic patients with gout. The drug has been proved to be safe and effective in clinical trials, and the dose does not need to be adjusted for patients with mild-to-moderate renal or hepatic impairment (kidney or liver problems).
ULORIC will be available as 40 mg or 80 mg tablets to be taken once a day. It is not recommended for asymptomatic hyperuricemia, said the company's press release.
Febuxostat was discovered by another Japanese company, Teijin Pharma. Their president Osamu Nishikawa said in a press statement released jointly with Takeda that:
"This FDA approval granted to Takeda Pharmaceuticals North America, along with the EMEA (European Medicines Agency) approval given last year to Ipsen, our licensee for febuxostat in Europe, marks a significant milestone for our global business."
He said Teijin would be developing febuxostat themselves for the Asian market, as well as collaborating with other pharma companies. The company wishes to strengthen its global operations by "expanding areas where febuxostat is available and increase the presence of the product to be widely used by patients worldwide," he added.
President of the Takeda parent company in Japan, Yasuchika Hasegawa, said:
"The approval of ULORIC offers patients and healthcare providers in the US for the first time in 40 years, a novel treatment option for patients who have hyperuricemia with gout, where there are still unmet clinical needs."
Gout is a common, painful form of arthritis that causes swollen, red, hot and stiff joints. It occurs when uric acid builds up in the blood, because the body produces too much or can't get rid of it (some medications can slow down elimination), or from eating too many foods rich in purines, such as liver and dried beans.
Pseudogout is sometimes confused with gout because the symptoms are similar; however, it is caused by calcium phosphate, not uric acid.
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), there could be as many as 6 million Americans aged 20 and older who have had gout at some time in their lives. It is more common in men aged 40 to 50, and women rarely develop it before the menopause. Also people who have had an organ transplant are more susceptible.
NIAMS suggest people may be at risk of developing hyperuricemia and gout if they are on certain medications, these include:
* Diuretics, such as furosemide (Lasix1), hydrochlorothiazide (Esidrix, Hydro-chlor), and metolazone (Diulo, Zaroxolyn).
* Drugs containing salicylate, such as aspirin.
* Niacin, a vitamin also known as nicotinic acid.
* Cyclosporine (Sandimmune, Neoral), a medication used to suppress the immune system.
* Levodopa (Larodopa), a drug used in the treatment of Parkinson's disease..
Other related articles
* What is Gout?
Takeda Pharmaceuticals North America, Inc, whose head office is in Deerfield, Illinois, is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited whose head office is in Chuo-ku, Osaka, Japan.