The FDA warns against using quinine for leg cramps

The Food and Drug Administration on Thursday cautioned consumers against using quinine for leg cramps, warning that the drug could cause severe side effects, including death. Quinine, sold in this country under the brand name Qualaquin, is approved for treatment of uncomplicated malaria, but has a long history of use as a remedy for leg cramps, especially at night. In many countries, it is sold over the counter. Studies have shown that it can reduce the incidence of cramps by one-third to one-half but that as many as one in every 25 users can suffer serious side effects.

In a new warning to health professionals, the FDA said that between April 2005 and Oct. 1, 2008, it had received 38 reports of severe adverse events associated with the drug, including two deaths. Twenty-one patients had to be hospitalized because of severe bleeding due to a loss of blood cells called platelets -- a condition called thromobocytopenia -- and an additional 12 had bleeding in their mucosa. The agency believes many similar events went unreported.

The agency is initiating what is known as a Risk Evaluation and Mitigation Strategy that will require, among other things, that the manufacturer send a letter to healthcare professionals warning about the risks of unapproved use of quinine and that pharmacies be required to provide consumers with a medication guide illustrating what the drug is approved for and pointing out the potential side effects.

-- Thomas H. Maugh II

For more health news, follow the L.A. Times Health Facebook page.

Take care. Viagra treats erectile dysfunction, not -- repeat, not -- STDs

The benefits of erectile dysfunction drugs are well- documented. They may be double-edged as well.
 
In a study published Tuesday in Annals of Internal Medicine, researchers analyzed pharmacy data for men over 40 who had received a prescription for an erectile dysfunction drug. We'll let them sum it up:

"Men who use ED drugs have higher rates of STDs, particularly HIV infection, both in the year before and after use of these drugs."

Here's the abstract from the STD study, the journal's information for patients and the pertinent-facts WebMD story: Men on ED Drugs Get More STDs. (Reuters cast it this way: Viagra-popping seniors lead the pack for STDs. ... That's right: "Seniors.")

As for what erectile dysfunction drugs can -- and can't -- do, please refer to this Viagra (sildenafil) information from rxlist.com. It's quite blunt, stating near the top of the page:

"Use of this drug does not protect against sexually transmitted diseases (e.g., HIV, hepatitis B, gonorrhea, syphilis). Practice "safe sex" such as using latex condoms. Consult your doctor or pharmacist for more details."

The information on Levitra (vardenafil) and Cialis (tadalafil) say the same thing.

-- Tami Dennis

Photo credit: AFP/Getty Images

Testosterone gel linked to increase in heart problems in frail men, study finds

Many men use a testosterone supplement to treat symptoms linked to testosterone deficiency in older age, such as poor libido and deteriorating muscle strength. However, such treatment appears to come with additional health risks for frail, elderly men who use the gel to increase their strength and mobility.

Researchers reported Wednesday that a study designed to assess the risks and benefits of testosterone replacement therapy in men ages 65 and older who had mobility problems was stopped early -- in December 2009 -- because of a much higher rate of cardiovascular problems in the men receiving testosterone compared with those receiving a placebo gel.

The study, led by researchers at Boston University and funded by the National Institute on Aging, included 209 men, half of whom used testosterone gel daily for six months. The average age of the men in the study was 74. All of the men in the study had limited mobility and a high prevalence of chronic disease. However, among the 106 men using testosterone gel, 23 had cardiovascular-related events compared with only five men in the 103-person placebo gel group. The study is published online in the New England Journal of Medicine.

It's difficult to know just what to make of this study, the authors acknowledged. There was a broad range of cardiovascular events, including heart attack, stroke, death from suspected heart attack, exacerbation of congestive heart failure, atrial fibrillation, swelling, chest pain and other milder symptoms. With such a diversity of events, it's hard to pinpoint how testosterone replacement therapy may be responsible. The doses of testosterone used in the trial may have been higher than in previous testosterone studies that have not found cardiovascular risks. Moreover, the trial was small and was stopped early.

The elderly men using testosterone did show increased strength in leg-press and chest-press strength and in stair climbing while carrying a load.

As for younger and healthier men who use testosterone gel, it's doubtful this study can be applied to them, the authors said. Previous studies of testosterone gel in other groups of men have not shown significant increases in cardiovascular risks. "Caution is also warranted in extrapolating these findings to other doses and formulations of testosterone or to other populations, particularly young men who have hypogonadism without cardiovascular disease or limitations in mobility," they wrote.

However, long-term studies on the risks and benefits of testosterone therapy in men of all ages are lacking, according to a recent story in the Los Angeles Times. Meanwhile, the availability of testosterone in gel form has led to a huge jump in prescriptions in the U.S.; 3.3 million prescriptions were filled in 2008 compared to 64,800 in 1999, according to one pharmaceutical data company.

As for older men in poorer health: "The authors note that physicians and patients, especially older men, should consider this study's findings on adverse effects along with other information on the risks and benefits of testosterone therapy," officials from the NIA said in a statement. Further research is needed to clarify the safety issues raised by the trial, the authors note.

Additional trials on the risks and benefits of testosterone therapy in men are ongoing, the NIA statement said. Those trials will continue although investigators and participants will be advised of the findings of the Boston University study.

-- Shari Roan

Photo credit: Stephen Sedam  /  Los Angeles Times

FDA panel recommends against drug for increasing women's libido

A Food and Drug Administration advisory panel Friday recommended unanimously against the agency's approval of the drug flibanserin, which is designed to boost women's libido. The panel said the drug's efficacy is not great enough to outweigh the side effects, which include fatigue, depression and fainting spells. The FDA is not required to follow its panels' recommendations, but it generally does so.

Filbanserin is the first drug that works on a woman's brain rather than attempting to physically stimulate her body. It stimulates one serotonin receptor in the brain and blocks a second one. Experimental results from a study of 5,000 women, reported last year, indicated that the drug produced an extra 1.7 satisfying sexual events each month over a baseline of 2.7 events, compared with an average increase of 0.7 such events produced by a placebo.

But in briefing papers prepared for the advisory committee meeting, FDA staffers concluded that the results were not sufficient to overcome the side effects of the drug. Many critics have also questioned whether lack of libido is an actual medical condition or simply a diagnosis created by pharmaceutical companies to sell new drugs. Some estimates suggest a $2 billion-per-year potential market for such drugs.

-- Thomas H. Maugh II

Photo: Because the little blue pill called Viagra has been so successful, pharmaceutical companies had hoped to market a little pink pill to boost women's libido. Credit: Agence France-Presse

Become a fan: Become a fan of our Facebook page and get a steady stream of health-and medical-related news, musings and the occasional oddity.

FDA panel recommends approval of 5-day 'morning after' pill

A Food and Drug Administration advisory panel Thursday recommended that the agency approve a "morning after" pill that is effective for five days after unprotected sex, providing an alternative to existing drugs that can be used only for three days. The agency is not required to follow the advice of its advisory panels, but usually does.

The new drug, whose proposed brand name is ella, is already marketed in Europe as ellaOne. It blocks the effect of progesterone, a female hormone that spurs ovulation. There has been spirited debate about whether the drug simply blocks ovulation or, because it is related to the abortion drug RU-486, whether it actually produces an abortion. The Washington Post and the New York Times have outlined the parameters of the debate.

The agency has set no timetable for a decision. The drug will most likely be available only by prescription, at least initially.

-- Thomas H. Maugh II

Get more health information at our Facebook page.

Potential drug for female sexual dysfunction encounters skepticism

If the media attention given to today's coverage of Food and Drug Administration documents is any indication, questions about flibanserin's effectiveness in treating female sexual dysfunction are about to increase. Questions about the condition itself might increase as well.

The Food and Drug Administration will soon consider whether to approve the new medication, which many people desperately hope will become a so-called female Viagra. Some of those people will be women who want to take the drug; many others will have more prosaic (read: money-based) concerns. Amid all the hype and hope, however, are some industry watchers and female health experts who aren't convinced there's a problem that needs to be fixed.

Time neatly summarizes the issues in this recent article: Female Sexual Dysfunction: Myth or Malady?

For a more in-depth argument, read The making of a disease: female sexual dysfunction, by journalist Ray Moynihan, published in 2003 in the British Medical Journal.

And, of course, there's the new film Orgasm Inc. Here's the trailer.

The documentary's director is quoted in this earlier blog post on flibanserin research. Relationship problems, stress ... those might just play a role in libido problems, she points out.

Today's Reuters story -- on apparent skepticism from FDA drug reviewers preparing documents for the agency's advisory panel -- notes that the market for treating sexual dysfunction in women could top $2 billion a year. 

-- Tami Dennis

Photo credit: Los Angeles Times

Become a fan: Become a fan of our Facebook page and get a steady stream of health-and medical-related news, musings and the occasional oddity.

 

Unpublished FDA study says diabetes drug Avandia should be withdrawn

An unpublished study by a Food and Drug Administration researcher and colleagues at Medicare indicates that as many as 48,000 heart attacks, strokes and other cardiovascular problems in the elderly between 1999 and 2009 could have been averted if the patients had taken other medications instead of the controversial diabetes drug Avandia, the Wall Street Journal reported Friday.

The paper by Avandia critic Dr. David Graham has been submitted to the Journal of the American Medical Assn., but the journal has not acknowledged whether it is considering publication.

The Graham study, which reviewed Medicare records, was reported by the respected pharmaceutical industry blog Pharmalot, which also published an e-mail from Graham to his superiors arguing that senior FDA officials were trying to suppress the work.

The FDA is scheduled to conduct a review of Avandia's safety next month.

Previous criticisms of the drug can be found here and here. The group Public Citizen has argued that ongoing clinical trials of Avandia should be halted immediately because of the risks of the drug, as has biomedical ethicist Ruth Macklin.

Stay tuned. The argument is sure to get hotter next month.

-- Thomas H. Maugh II

FDA approves Amgen's osteoporosis drug Prolia

In a long-awaited development, the first drug in a new class of osteoporosis medications was approved Tuesday by the Food and Drug Administration. The drug is Amgen's injectable treatment, Prolia. The medication, for postmenopausal women with osteoporosis, is expected to be popular as concerns have mounted about the safety of the class of osteoporosis drugs called bisphosphonates. Bisphosphonates, including the medication Fosamax, have been linked to cases of jaw necrosis.

Prolia works differently than other medications for bone health. It blocks production of cells called osteoclasts that break down bone. Prolia will require an injection every six months. The drug was shown in clinical trials to reduce vertebral, non-vertebral and hip fractures. Side effects include back pain, musculoskeletal pain, high cholesterol levels and bladder infections as well as some skin infections and low calcium levels in the blood. Prolia too may contribute to jaw necrosis, according to the FDA. As part of the approval agreement, Amgen will continue to gather data to monitor the safety of Prolia.

The drug's wholesale cost will be $825 per injection.

-- Shari Roan

Photo: National Institute of Arthritis and Musculoskeletal and Skin Diseases

How a fat cell comes to be

Look at that fat cell! Lovely, yes? Ever wonder how one forms?

Well, it just so happens that an article in the current issue of the journal Genes and Development describes how immature fat cells pass through a fleeting, previously unappreciated "intermediate-fat-cell" stage before emerging, like a butterfly from a chrysalis, into full, fatty maturity.

Well, maybe not quite like a butterfly emerging from a chrysalis. But the finding does have implications for drug development.

Scientists at the University of Pennsylvania School of Medicine found that early stage fat cells first enter an intermediate fat-cell stage. The intermediate stage is kick-started by hormones related to cortisol, the stress hormone. All kinds of changes in gene activity happen during this intermediate stage, ones that send the fat cell inexorably down the road to maturity even after the trigger has gone away.

Study author Dr. Mitchell Lazar of Penn suggests that these gene changes may offer clues to drugs that might stop the fat cells from maturing. Leads would seem to be needed, as quite a few anti-obesity candidates have not panned out. (One current hope is Qnexa, a combination of the drugs phentermine and topiramate, currently under review by the Food and Drug Administration.)

Photo credit: Dr. Mitchell A. Lazar, PhD / University of Pennsylvania School of Medicine

Foods should be subject to the same scrutiny as drugs, experts say

They call it the Food and Drug Administration. So you might think the safety of food and drugs are tested to the same degree before they’re allowed to go on the market.

In fact, that’s not the way it works. But perhaps it should, says Dr. John Ball, executive vice president or the American Society for Clinical Pathology in Chicago.

Ball chaired a committee organized by the Institute of Medicine that was asked to come up with a way to vet some of the biomarkers that are routinely used in safety studies. (For instance, do higher levels of “bad” cholesterol really translate into an increased risk of heart disease?)

But as the committee members contemplated a box of Cheerios, they started to consider a larger question: Was it okay for the box to tell consumers “You could lower your cholesterol 4% in 6 weeks”? And that led to an even bigger question: Is there any reason to hold health claims for foods and dietary supplements to a lesser standard than health claims made for drugs?

Their answer: No way. As Ball wrote in the preface to the committee’s report, which was released Wednesday:

There is neither rationale nor scientific basis for predicating regulatory decisions on different levels of scientific evidence for different substances: “science is science.” That is, the same level of scientific evidence of benefit and risk should be required of foods as of drugs.

As for the notion that drugs should be subjected to extra scrutiny because they are inherently riskier than foods, the committee didn’t buy it:

Foods are encountered by a greater population than the target group who encounter drugs, and though drugs are subject to professional mediation (e.g., prescription and counseling), foods are not. As for risk, no one who is allergic to peanuts, eggs, or shellfish would argue that foods are less risky than drugs.

The report asks Congress to expand the FDA’s authority to police unwarranted and untested claims made by food and supplement makers. But it’s not at all clear that Congress is eager to “put the food and supplement industries on a shorter leash,” as our colleague Andrew Zajac writes on our sister blog, The Swamp:

Fresh restrictions on what food growers or producers can say about the health benefits of their tofu or Brussels sprouts likely won't go down well. Supplements manufacturers have even less incentive to welcome invitations to prove their health claims.

You can read a summary of the committee’s report on the Institute of Medicine website. If you’re interested in the full 267 pages, it’s available online as well. And here's the link to the IOM press release.

-- Karen Kaplan

Photo: The regulators in this building should test foods and drugs with equal rigor, according to an expert panel. Credit: Dennis Drenner/For the Times