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| WASHINGTON -- The FDA has announced a formal strategy to reduce the risks of erythropoiesis-stimulating agents (ESAs) for cancer patients who take the drugs to treat anemia caused by chemotherapy. Beginning in March, the ESAs darbepoetin (Aranesp) and epoetin alfa (Epogen and Procrit) -- all made by Amgen -- will operate under a Risk Evaluation and Mitigation Strategy (REMS) that will require healthcare providers who prescribe the drugs for cancer patients to register with Amgen and enroll in a training program on use of the agents. The agency is requiring the REMS because studies have shown that ESA use can result in tumor growth and shorten survival in cancer patients who use them to combat anemia. ESAs have also been shown to increase the risk of MI, heart failure, stroke, and blood clots. Physicians who fail to enroll in Amgen's APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) program within a year will be barred from prescribing the drugs. The REMS also will require physicians to provide their cancer patients with a medication guide on how to safely use the drugs and will require doctors to discuss risks, benefits, indications, and dosing guidelines when prescribing ESAs to cancer patients. Patients will be required to sign a document indicating that they understand the risks. "We are doing this to make absolutely certain that patients are fully informed about the risks of these drugs before they begin treatment," said Richard Pazdur, the director of oncology drug products at the FDA, on a Tuesday press call. Use of the ESAs has been controversial. In 2007, CMS announced it would put limits on dose and duration of ESA therapy in reaction to an FDA decision to require a black box warning on the drugs. "We understand that the requirements of the safe use program will create new responsibilities for busy healthcare providers," Pazdur said. "It will require additional time for training, record-keeping, and other tasks related to complying with the program." "However, we are not doing this to make things more difficult for healthcare providers," he said. "We are doing this to make absolutely certain that patients are fully informed of the risks related to the use of these drugs before they begin treatment and throughout their treatment regimen." Hospitals and physicians that dispense ESAs to cancer patients can enroll in the APPRISE program by contacting Centocor Ortho Biotech Products or an Amgen field representative, according to a release from Centocor Ortho Biotech Products. ESAs, which stimulate bone marrow to make red blood cells, are often prescribed to cancer patients for chemotherapy-related anemia. The REMS does not apply to the drugs when they're used to treat kidney disease. The FDA has said it will hold an advisory panel meeting later this year to discuss using ESAs in that setting. |
Wednesday, February 17, 2010
FDA Approves REMS for Drugs That Combat Anemia
Nephro Endo Hem/Onc Rheum ID Neuro Neuro Allergy Admission Commonly used diabetes drug metformin smells bad and this may explain why many patients st
But the problem could be solved by coating the pills so they do not smell or release the odor into the stomach, where it can be burped up.
References:
http://www.reuters.com/article/idUSTRE61E54H20100215
The Misuse of Quetiapine
A lot of medication gets misused, as is the right expression, meaning not used for the intention or indication it was developed for in the first place. This reminded me of one of my first publications on the abuse of anticholinergics.
From case reports it appears that quetiapine is sought after for recreational use and inappropriate use such as intranasal and intravenous administration. Quetiapine is also for sale on the street, symptom malingering to obtain the drug and higher dosage requests. It’s always important to recognize such misuse of medication because in the case of quetiapine it can induce weight gain, glucose intolerance, in rare cases movement disorders. Moreover, these drugs are very expensive and will cost society more money when misused.
In a recent publication a case report and a review of previous case reports is discussed. The patients mostly seek the “dreamy”, calming, or soporific state with quetiapine. Most patients had a prior drug or alcohol problem and the misuse was often connected to a forensic setting.
Moreover, the authors present possible mechanism as explanation for it’s misuse. First it has an anticholinergic activity which has been described previously with other drugs as cause for misuse. Anticholinergic agents usually cause an euphoric and stimulatory state in patients which doesn’t match with the accounts of patients misusing quetiapine. The authors suggest that the antihistaminic property of questiapine is responsible for it’s misuse.
The misuse potential of quetiapine is likely related to its histaminic blockade coupled with its comparatively mild action at dopamine receptors. Accordingly, quetiapine substitutes for sedating agents and individuals with a history of alcohol, benzodiazepine, or opiate abuse are particularly at risk.
Fischer, B., & Boggs, D. (2010). The role of antihistaminic effects in the misuse of quetiapine: A case report and review of the literature Neuroscience & Biobehavioral Reviews, 34 (4), 555-558 DOI: 10.1016/j.neubiorev.2009.11.003
Tuesday, February 16, 2010
Compound Mimicking BDNF Activities Hold Potential in Developing Novel Class of Neuroprotective Drugs
February 16, 2010
MS Drug Ampyra Gets FDA Nod
From WebMD.com:
The FDA has approved Ampyra (dalfampridine), which improves walking ability in adults with multiple sclerosis (MS).
About three-fourths of MS patients have trouble walking, and 70% of those with walking problems say this is the most challenging aspect of their disease.
Ampyra is taken with other MS drugs and does not keep MS from getting worse, says Andrew D. Goodman, MD, director of the MS center at the University of Rochester, N.Y. Goodman led some of the clinical trials that led to the drug’s approval.
“A large segment of people with MS have difficulty walking, and we have found that it helps some patients — 35% in one study and 42% in another — to consistently walk faster,” Goodman tells WebMD. “Among those who do walk faster, they improve about 25% from baseline. These patients said they could walk longer distances, be on their feet longer, climb stairs better, and better perform other walking functions.”
Ampyra does not change the course of MS disease, but enhances nerve function.
“There is no indication this type of treatment slows the progressive nature of the disease process,” Goodman says. “But there is every indication that at whatever level of function an MS patient may have, there may still be room for improvement with this type of treatment.”
The drug is by no means risk-free. Ampryra is a new formulation of a drug called fampridine, which was originally used as a bird poison.
Some 20 years ago, test tube studies suggested that fampridine could improve nerve conduction. Since then, some neurologists — Goodman is not one of them — have ordered the drug from compounding pharmacies for their MS patients.
At doses higher than the approved dose — 10 milligrams twice daily — Ampyra can cause seizures. The drug cannot be used by MS patients with a history of seizure, or by those with moderate-to-severe kidney disease. The drug cannot be taken with other forms of fampridine.
Side effects seen in clinical trials include urinary tract infection, insomnia, dizziness, headache, nausea, back pain, loss of muscle strength, balance disorder, multiple sclerosis relapse, tingling or numbness in the extremities, nose or throat inflammation, constipation, upset stomach, and throat pain.
Ampyra is made by Acorda Therapeutics of Hawthorne, N.Y. Acorda says the drug should be available in the U.S. in March. It will be sold through a network of specialty pharmacies coordinated by Ampyra Support Services at 888-881-1918
Thursday, February 11, 2010
CardioFuel—another magic pill
I get a lot of email asking me about various alternative therapies and supplements. A recurring theme on this blog has been the hyperbolic claims of alternative practitioners and supplement makers, and while I can’t answer every email, I can at least address some of them in the blog. Supplements are often marketed using unsupported health claims to which is appended the Quack Miranda Warning, essentially allowing the makers to say that the pill will have such and such a benefit, while simultaneously denying any responsibility for the claim. Since the FDA isn’t examining these claims, it’s worth while to ask our own questions.
The latest email concerned a product called CardioFuel. Let’s take a closer look at this stuff.
According to the distributor:
CardioFuel is the most profound energy producing supplement on the market today! It does something like no other can: Increase energy at the most basic metabolic level, by increasing ATP (the biochemical energy unit of transfer) production. More ATP means more energy reserves to overcome chronic disease, beat the competition, and handle the everyday stressors of today’s fast paced world!
So to be taken seriously, there should be evidence that this product: 1) increases ATP, 2) increases “energy reserves”, and 3) helps overcome chronic disease and “the competition”. First, it is not possible to directly measure ATP in a human being under normal clinical conditions, so any claims about this must be an inference from markers of ATP metabolism, or a guess. We’ll see what the literature says about this below. Second, we need an operational definition of “energy reserves”. Does this mean fat stores? Glycogen stores? These things are measurable to an extent. Finally, we can do a literature search to see if CardioFuel or an acceptable analog has been tested for its effect on relevant outcomes.
First, what is ATP?
ATP is adenosine triphosphate, a biological molecule with many functions, among them the transfer of energy. ATP is produced in several ways, most famously in the Krebs cycle, a complicated biochemical process which premeds are mercilessly forced to memorize. ATP contains three phosphate bonds, and the third bond contains a great deal of energy, energy that the body uses to fuel many biochemical processes. Each molecule of ATP contains a d-ribose moiety, a simple sugar upon which the molecule is built. One of the claims being made by the CardioFuel folks is that if we ingest more d-ribose, we can make more ATP and be more “energetic”.
First, ATP synthesis, like most biochemical processes, is subject to feedback regulation; ATP production and its byproducts feed back to reduce further ATP production. Second, it is not clear to me that simply providing more of this particular substrate would significantly boost ATP production. But with my limited knowledge of biochemistry, it seems like an interesting question to investigate.
CardioFuel claims that its “ATP boosting” properties are not just from ribose, but also from other molecules such as carnitine and coenzyme Q10. There is nothing in the published literature that I can find to support these claims.
From my perspective as a physician, I want to see results. Regardless of what is posited to happen at the cellular level, I want to see outcomes studies supporting the claims that d-ribose, or preferably CardioFuel itself actually does what is claimed, which the marketer further specifies:
I created CardioFuel to help my patients who suffer serious energy-depleting chronic diseases, such as: heart disease (PVD), diabetes, neuromuscular disease, fibromyalgia, lung disease, Chronic Fatigue Syndrome, kidney disease, HIV/AIDS, etc. These diseases deplete ATP, which CardioFuel rapidly replaces, dramatically improving health, vitality, and Quality of Life (QOL).
A PubMed search for “CardioFuel” turned up nothing. Of the ingredients claimed to boost energy, d-ribose is the one with the most literature—literature which is not favorable. There are a number of pilot studies looking at d-ribose in exercise. For example, one study of twelve cyclists found that, “D-ribose supplementation has no impact on anaerobic exercise capacity and metabolic markers after high-intensity cycling exercise.” A slightly larger study of rowers compared dextrose (d-glucose) with ribose and found that, “…the dextrose group showed significantly more improvement at 8 weeks than the ribose group.” Another small study found that,” ribose had no effect on performance when taken orally, at the dose suggested by the distributor.”Since I couldn’t find literature specific to CardioFuel, and my literature search failed to find significant support for claims of the ingredients of CardioFuel, I went to the CardioFuel website for further guidance. Tellingly, there are no references to studies of CardioFuel itself but only for its purported ingredients. There are some chaotic lists of incomplete references. For example, for coenzyme Q10, some of the references are listed, some just quoted without citation, and there is little data related to the claims of CardioFuel. The section on “elite athletes” addresses ribose directly, but not with outcomes studies.
I can find no support for the claims made by the sellers of CardioFuel. But under the Dietary Supplement Health and Education Act of 1994 they are allowed to make these claims as long as they use the Quack Miranda Warning. I couldn’t find such a warning on any page of the website so I guess I must assume that all of the claims made by the company are verifiable. I can’t seem to verify them myself, but the data must be somewhere. Right?
Wednesday, February 10, 2010
New era of pain drugs advanced by Barrow researcher
Contact: Lynne Reaves
Lynne.Reaves@chw.edu
602-406-4734
St. Joseph’s Hospital and Medical Center
Research led by a scientist at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center has opened the door for the advancement of a new category of painkillers, called TRPV1 antagonists.
These drugs block the transient receptor potential vannilloid-1 (TRPV1) channel, which is the same receptor responsible for the sensation of hotness from hot peppers. However, clinical trials have revealed that TRPV1 antagonists cause hyperthermia- a dangerous, fever-like rise in body temperature.
Research has shown that TRPV1 can be activated by several stimuli, including “pepper-like” chemicals, high temperatures and protons. The same channel is responsible for pain caused by these diverse stimuli. For a number of years scientists have focused on the development of TRPV1 antagonists, but have been stymied by the dangerous hyperthermia side effect.
The groundbreaking project to eliminate the side effect was led by Andrej A. Romanovsky, MD, PhD, at Barrow and included researchers from Amgen and Arizona State University. Their findings, published last month in the in the Journal of Neuroscience, show the side effect can be avoided.
“We think we have found a recipe for making TRPV1 antagonists that do not have this fever-like side effect,” says Dr. Romanovsky. “If an antagonist does not block activation of the TRPV1channel by protons, it does not cause hyperthermia.” This research suggests that drugs that are being developed should be designed not to block the proton activation of TRPV1.
Even though pain is a major clinical problem and the search for new painkillers has been conducted by pharmaceutical companies and academic scientists for many years, the TRPV1 channel is one of the very few novel targets for pain identified so far. To continue developing TRPV1 antagonists, it was necessary to find a way to eliminate their hyperthermic side effect. “And, this is exactly what our study did,” Dr. Romanovsky said.
Scientists believe that this new generation of painkillers will be effective in treating pain related to a number of conditions including cancer, AIDS, migraines and diabetes.
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Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center in Phoenix, Arizona, is internationally recognized as a leader in neurological research and patient care. Established in 196, Barrow treats patients with a wide range of neurological conditions, including brain and spinal tumors, cerebrovascular conditions, and neuromuscular disorders. Barrow Neurological Institute is consistently rated among the top 10 best hospitals in the United States for neurology and neurosurgery by U.S. News and World Report.
Drug May Help Men With Bent Penis Disorder
This week, the U.S. Food and Drug Administration approved Xiaflex for treatment of claw hand, a condition that causes bent fingers. Research suggests the drug may also be effective in treating Peyronie's disease. Some experts believe the FDA's approval of the drug for claw hand may lead to off-label use for Peyronie's disease, ABC News reported.
Clinical trials found that injections of Xiaflex resulted in an average 29.7% improvement in curvature of the penis, compared with a placebo injection, according to Auxilium Pharmaceuticals, which is marketing the drug.
However, the company says it will discourage any off-label use of Xiaflex for treatment of Peyronie's disease, ABC News reported.
Medicines Tossed in Trash End Up in Water: Study
Unused or expired medications that are thrown in the trash can still end up in drinking water, according to a study by the Maine Department of Environmental Protection.
It found minute amounts of discarded drugs in water at three landfills in the state, the Associated Press reported. This landfill water, called leachate, eventually ends up in rivers. Many communities across the United States draw their drinking water from rivers.
Maine lawmakers are currently considering a bill that would force drug makers to create and pay for a program to collect unused prescription and over-the-counter drugs from consumers and dispose of them.
"People need a way to properly dispose of their drugs, and they're not getting it right now," Mark Hyland, director of the state Department of Environmental Quality's Bureau of Remediation and Waste Management, told the AP.
Maine is among more than a half a dozen states considering a "take-back" bill for medications. The Maine bill has won committee support and awaits further action. If enacted, it would be the first of its kind in the United States.
The bill is opposed by the drug industry lobby group, the Pharmaceutical Research and Manufacturers of America, the AP reported.
Broken Arm? Try Some Ibuprofen
Broken bones usually hurt a great deal. It’s commonly believed that the pain is always of a severity to require the administration of “strong” pain medicine, notably, something containing a narcotic compound. This may not be true. In an article (Annals of Emergency Medicine 2009;54:553-560) entitled “A Randomized Clinical Trial of Ibuprofen Versus Acetaminophen With Codeine for Acute Pediatric Arm Fracture Pain,” Amy Drendel, MD and colleagues compared the treatment of pain in children with arm fractures by using ibuprofen in a dose of 10 milligrams per kilogram (2.2 pounds) of body weight versus acetaminophen with codeine in a dose of 1 milligram per kilogram (based on the codeine component of the medication). The children were assessed for three days after discharge from an emergency department. Two hundred forty four patients were analyzed in this study.
The authors concluded that ibuprofen was at least as effective as acetaminophen with codeine for children ages 4 to 18 years with arm fractures treated as outpatients. What is also very interesting is that the children receiving ibuprofen had significantly fewer adverse effects, and both the children and their parents were more satisfied with ibuprofen. The proportion of children who had any function (play, sleep, eating, school) affected by pain was significantly lower for the ibuprofen group.
What to make of all this? The known side medication side effects measured were nausea, vomiting, drowsiness, dizziness, and constipation. Ibuprofen appears to be clearly superior in this study population. This is an eye opener for me, because I am a bit surprised (and now enlightened) by the data. I would have expected these broken bones to require more potent pain medication (e.g., a narcotic), but I see that this is not necessarily the case. In the future, I will recommend ibuprofen (if there is no contraindication) as an initial medication for many more types of pain situations, and wait to see if a more potent “rescue drug” is necessary only as needed, rather than as first choice. If remaining alert and fully functional in an outdoor setting is a priority, this makes double sense.
broken arm image courtesy of bbc.co.uk
This post, Broken Arm? Try Some Ibuprofen, was originally published on Healthine.com by Paul S Auerbach M.D., M.S..
Verdezyne Produces Adipic Acid Biologically
Verdezyne achieved proof of concept in this development program by demonstrating production and recovery of adipic acid by a yeast microorganism from an alkane feedstock. Using proprietary technologies, Verdezyne discovered and is engineering a proprietary metabolic pathway that can utilize sugar, plant-based oils or alkanes.
This is Verdezyne's first major milestone towards demonstrating an entirely feedstock flexible fermentation process for the production of bio-based adipic acid. The benefit of a feedstock flexible process is the ability to maintain a sustainable cost advantage regardless of future energy volatility. In addition to cost advantages, Verdezyne's fermentation process will reduce greenhouse gas emissions compared to the traditional petrochemical production of adipic acid.
"Our estimates indicate at least a 20% cost of manufacturing advantage for bio-based adipic acid depending on the feedstock selected," stated E. William Radany, Ph.D., President and Chief Executive Officer, Verdezyne. "Rising consumer interest in bio-based products combined with a sustainable cost advantage makes Verdezyne's adipic acid process a compelling proposition for future production."
Verdezyne is engineering the metabolic pathway to boost organism performance at lab scale and intends to partner for scale-up demonstration in the next year. In parallel, Verdezyne continues to make metabolic pathway improvements to utilize renewable feedstocks such as sugar.
"The petrochemical industry is looking for a cost-efficient alternative to produce this valuable chemical and we are thrilled that Verdezyne's platform is demonstrating considerable promise for commercialization of bio-based adipic acid," says Stephen Picataggio, Ph.D., Chief Scientific Officer, Verdezyne.
The global adipic acid market was approximately $4.9 billion in 2009 with its two major applications being polyamides and polyurethanes. Adipic acid is an important engineering resin for well-established markets like automotive, footwear, and construction and is used in everyday products such as carpets, coatings, furniture, bedding and automobile parts.
Verdezyne's Platform Technology
Verdezyne's novel combinatorial approach to pathway engineering rapidly creates and harnesses genetic diversity to optimize a metabolic pathway. The company's unique computational and synthetic biology toolbox allows effective design, synthesis and expression of synthetic genes in a heterologous recombinant microorganism. Rather than manipulating one pathway gene at a time, the company uses synthetic gene libraries to introduce diversity into each pathway gene. Combinatorial assembly of multiple pathway genes introduces enzymatic diversity into a metabolic pathway, and biological selection or high-throughput screening identifies the most productive combination of pathway genes.
Source
Verdezyne, Inc.
