Xeomin approved: but for functional uses only

Xeomin - another botulinum A toxin product - was approved earlier this month by the FDA. In an interesting twist, the FDA approved the drug for certain muscle spasm syndromes - cervical dystonia and blepharospasm - but not for cosmetic purposes yet. That all-important cosmetic approval will probably come at a later date.

Dystonias are neurological movement disorders featuring involuntary twisting and repetitive movements or abnormal postures. About 3 people per 10,000 have this problem, according to epidemiology studies.

What's interesting about Xeomin is that it doesn't have the associated complexing proteins previously needed for Botox and Dysport. The lowered protein load may theoretically reduce the incidence of allergic reactions and the potential for antibody formation.

According to Merz Pharmaceuticals, the manufacturers of Xeomin, more than 84,000 patients have been treated with Xeomin worldwide since 2005. The U.S. is the 20th country to approve the drug for the treatment of cervical dystonia and blepharospasm.

Liposonix: still waiting for FDA approval

Imagine a machine, that without anesthesia or invasive surgery, could take away fat from your abdomen, making you a dress size smaller 6-8 weeks after one treatment. Sounds pretty interesting, right? As it turns out, there are several companies that are working on machines that can safely and successfully achieve this very thing.

One of the leaders in this field, Liposonix, uses focused ultrasonic energy to coagulate a layer of fat about one-half inch beneath the skin. The body then gradually absorbs the damaged fat cells over time. Based on the presentations I've seen at recent Plastic Surgery meetings, there appears to be a real and noticeable difference in the before & after photos.

Liposonix had been pushing for FDA approval. Just last week, however, the FDA said that they wanted to see even more data....which means a delay on the release. The machine is already in clinical use in Canada and elsewhere (sound familiar?)

So far, the Liposonix machine has only been used to treat abdominal fat. The company says not to use it if you have less than a centimeter (0.5 inch) of fat, if you have surgical scars in the area, or have previously had liposuction.

It's pretty intriguing....and unlike some of the other non-invasive treatments we've discussed, (e.g. lipodissolve, zerona) this one looks as though it might actually work! Time will tell just how it fits in with the body shaping tools we have. It will be especially interesting to see how the results of Liposonix treatments compare to Zeltique, UltraShape and some of the other non-invasive body contouring contenders.

FDA issues warnings about Lipodissolve

From the FDA website...

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It's a tempting premise: Get a series of drug injections and see pockets of fat on your body go away for good. But the Food and Drug Administration (FDA) is alerting consumers about false and misleading claims being made about products used in lipodissolve, and about other misbranding of these products.

Recipients of lipodissolve get a series of drug injections intended to dissolve and permanently remove small pockets of fat from various parts of the body. The process is also known as injection lipolysis, lipozap, lipotherapy, and mesotherapy.

“We are concerned that these companies are misleading consumers,” says Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research. “It is important for anyone who is considering this voluntary procedure to understand that the products used to perform lipodissolve procedures are not approved by FDA for fat removal.”

The drugs most regularly used in the lipodissolve injection regimen are phosphatidylcholine and deoxycholate (commonly called PC and DC, respectively). Other ingredients may also be used, including drugs or components of other products such as vitamins, minerals, and herbal extracts.

What Consumers Should Know:
- FDA is alerting consumers that it has not approved products for use in lipodissolve.
- It is not aware of evidence supporting the effectiveness of the substances used in lipodissolve for fat elimination.
- The safety of these substances, when used alone or in combination, is unknown.
- It is not aware of clinical studies to support medical uses of lipodissolve.

In addition, FDA has reports of unexpected side effects in people who’ve undergone the lipodissolve procedure. These side effects include: permanent scarring, skin deformation, and deep, painful knots under the skin in areas where the lipodissolve treatments were injected.

FDA Actions:
On April 7, 2010, FDA announced it had sent warning letters to six medical spas in the United States—and a cyber letter to a company in Brazil—for making false or misleading statements on their Web sites about drugs used in the procedure, or for otherwise misbranding lipodissolve products.

The U.S. medical spas receiving warning letters make various unsupported claims about lipodissolve, such as assertions that the products used in lipodissolve:
"are safe and effective"
"have an outstanding safety record"
"are superior to other fat-loss procedures, including liposuction".

The U.S. companies receiving warning letters in regard to lipodissolve products are
Monarch Med Spa, King of Prussia, Pa.
Spa 35, Boise, Idaho
Medical Cosmetic Enhancements, Chevy Chase, Md.
Innovative Directions in Health, Edina, Minn.
PURE Med Spa, Boca Raton, Fla.
All About You Med Spa, Madison, Ind.

Experts say: Large volume buttock injections are dangerous

This press release is from our colleagues over at the PSP (Plastic Surgery Practice) website.
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The Physicians Coalition for Injectable Safety recently launched a campaign aimed at reminding consumers that no pharmaceutical filler or injected device is presently FDA-approved for large volume injection to the buttocks.

The popularity and hype surrounding buttock augmentation and other large-volume body enhancing injections on blog sites like RealSelf.com and outside U.S. borders is an alarming and potentially deadly trend, cautions the Physicians Coalition for Injectable Safety. Permanent fillers such as polymethylmethacrylate (PMMA), silicone, and polyacrylimide used in augmenting buttocks and hips can not only result in disfigurement but have resulted in death and serious injuries both in the U.S. and abroad.

The recent death of a woman in Argentina following buttock augmentation was not a result of plastic surgery," says Brazilian plastic surgeon Joao Carlos Sampaio Goes, MD, PhD, and past president of the International Society for Aesthetic Plastic Surgery. It (was) the result of a dangerous practice with fillers that are not intended to be used in this way." Buttock augmentation is a hot topic in the media and a popular procedure of surgical tourism," often performed in countries where standards are less stringent.

Recent headlines of death in the U.S. include cases in Tampa, Florida where an unlicensed, non--medical provider allegedly injected two women with a homemade combination of industrial silicone oil and saline to augment or enhance the shape of their buttocks, and a woman in the Bronx who died after illegal silicone injections resulted in the substance migrating to (traveling) her lungs, producing respiratory failure."

FDA approves Cytori's PureGraft fat grafting device

This week, the FDA approved the PureGraft device, made by Cytori Therapeutics. This device greatly simplifies the collection, processing and re-injection of fat. It could be a major "game-changer" for both cosmetic and reconstructive plastic surgery.

Until now, one of the major issues with fat grafting has been that it is a slow and tedious procedure with an unpredictable outcome: it's hard to know how much of the transferred fat will actually survive the move to the new location, even with the use of the specialized techniques developed by Dr. Sidney Coleman and others. We liposuction out the fat with specialized instruments, centrifuge it, reload the good quality fat into small syringes, then inject it slowly and carefully, just a little bit at a time, into the desired area. Then we hope and pray that the injected fat will survive in its new location. Sometimes, we watch as it melts away almost totally in several months - and that's so frustrating for both patient and surgeon!

The Cytori device should allow more predictable, less laborious fat fat grafting procedures. The PureGraft device not only purifies the fat, but increases the number of the patient's own stem cells in the material to be re-injected. This "turbo-charging" effect of the stem cells seems to lead to better outcomes, in recent research studies, with a higher rate of fat survival and less fat necrosis.

I'm very excited by this new technology. I think it's the next big thing.

Recent bulletin on Carboxytherapy and Mesotherapy

Here is a recent press release from the Physicians Coalition for Injectable Safety - a group of 7 American, Canadian and International Surgery groups, including plastic surgeons, facial plastic surgeons and ophthalmic surgeons - who review & study the latest and best methods regarding injectable cosmetic products. For the record, I agree with this bulletin, and do not currently recommend mesotherapy and carboxytherapy, based on lack of proven efficacy.

PHYSICIAN GROUP URGES CONSUMERS TO BE AWARE OF NON-APPROVED COSMETIC INJECTIONS

July 29, 2009 - The Physicians Coalition for Injectable Safety today issued a consumer warning about carboxytherapy and mesotherapy injections. These products, touting everything from cellulite treatment to weight loss are not FDA approved, and do not have clinical data that demonstrates results or safety.

Carboxytherapy uses carbon dioxide gas injected under the skin to reduce the look of cellulite, treatment of dark under-eye circles, and stretch marks and is also touted for fat sculpting on the face and the body. “Although many websites or providers claim carboxytherapy is safe and FDA approved, it has not been clinically tested or FDA approved for these purposes,” says Coalition leader Robert Weiss, MD of Baltimore, MD. “Carboxytherapy for use around the eyes is especially dangerous. It could potentially release gas bubbles into blood vessels causing blindness. In addition, the risks of putting carbon dioxide in your body are currently unknown.”

Mesotherapy, also known as injection lipolysis, is a mixture of vitamins, drugs and enzymes that are compounded (mixed together) to make the injected substance. “There is no conclusive, authoritative information that exists, such as unbiased, peer-reviewed clinical studies that meets the standards of an accepted medical journal, measuring both the efficacy and safety of mesotherapy,” says Coalition leader Mark Jewell, MD, Eugene, Oregon. “We don’t know the safety or efficacy of these compounds and, until there exists credible evidence, consumers are advised not to have these injections.”

The Coalition urges consumers to be very selective about cosmetic treatments, and the individuals who provide them. “Only accept treatment prescribed by a qualified physician and administered under that physician’s supervision. Whether an injection or treatment is to treat aging conditions, to treat cellulite or a similar body contouring condition, whether it sounds reasonable or too good to be true, you should always be aware of false claims,” says Coalition leader Jeffrey Kenkel, MD of Dallas, TX. “Verifying that the drug or device that is recommended for your injection is FDA approved is an important first step. It should be approved specifically for cosmetic use as prescribed or similarly to what is prescribed for you.”

Sculptra receives its cosmetic indication from the FDA

Sculptra, the injectible PLA filler, received official FDA approval today for cosmetic use. It had initially approved several years ago for the treatment of lipo-atrophy, (most commonly seen in HIV patients) and was used on an "off-label" basis for cosmetic purposes. It's a very useful product.

Sculptra can be very helpful to restore volume loss in the face and other body areas with a non-surgical method. Usually several treatments are required over the course of several months, but I've been very pleased with the results of these treatments. It also represents a nice alternative to fat grafting techniques, avoiding donor site issues.

One key with the use of Sculptra is to use it in a highly diluted form; this helps to avoid the formation of small lumps, known as granulomas. I also do not recommend it for use in the lips.

FDA approves "12 month" indication for Evolence

This week, the FDA approved a labelling change for the collagen-based filler Evolence, permitting what is known as a "12 month indication". In simple terms, this means the FDA was satisfied that the product has a significant effect on correcting moderate to deep facial wrinkles or nasolabial folds for 12 months. The original label indication was for six-month duration.

Evolence is the first collagen-based filler to get this "12 month indication", and you can bet that it will be featured extensively in future marketing.

What is not yet clear to me, however, is whether Evolence really performs significantly better than some of the other available filler agents (which currently have the older "6 month" label from the FDA) at 12 months after injection. There is data, for example, that Restylane also has significantly lasting effects well beyond their 6 month label.

I expect Allergan and Medicis (makers of Juvederm and Restylane respectively) will be submitting their data to the FDA, hoping for a similar 12-month approval, if only for competitive marketing purposes.

Xarelto: a new drug to reduce surgical risks

One of the most worrisome problems for surgeons is known as venous thromboembolism (VTE) - blood clots such as deep vein thrombosis and pulmonary embolism. These can occur after long operations, even in seemingly healthy people - and can be a life-threatening problem. In the past, we've used compression stockings, pneumatic sequential compression devices, or injectable blood thinners, like heparin and lovenox, to successfully reduce, but not completely eliminate, the risk of VTE's. However, these therapies have been awkward to use, especially for outpatient surgery.

Now, the FDA is looking at approving a new medication that may be very helpful with this problem. Called Xarelto, it's a once a day tablet. Technically speaking, it is classified as a direct Factor Xa inhibitor. According to the studies, it works as well or better than its injectable cousins (like lovenox) at preventing VTE. And unlike Coumadin, xarelto doesn't require frequent blood tests to get the dose right. As an oral medication, it would be easy to patients to continue on this therapy at home, while they are recovering from surgery.

Barring side effects, Xarelto could be a real breakthrough for patient safety. In the field of Plastic Surgery, the obvious application would be for abdominoplasty (tummy tucks), where the risk of VTE is significant. The optimal dosing schedule for plastic surgery patients hasn't yet been worked out.

The drug is approved in Europe. We're hoping for FDA approval soon.

Reloxin - receives FDA approval today

Botox competitor "Reloxin" (sold in Europe as "Dysport") received its FDA approval today.

The FDA decided to approve both the cosmetic indications (for wrinkles) and the functional indications (cervical dystonia) at the same time - and decided that the drug should be sold under the same name for both categories. So, it's now officially "Dysport" - just like in Europe.

We're waiting for details to be released about the pricing, marketing incentives - such as potential combinations with Medicis' line of fillers, and so forth. These details will be key to the success or failure of the product, I believe.

The next 6 months should prove to be very interesting, to see how pharma giant Allergan responds to the "new kid on the block". I'm expecting sparks to fly!!

Do the FDA recommendations for MRI's after breast augmentation make sense?

When the FDA re-approved the general use of silicone breast implants in 2006, there were some "strings" attached. One of these was the recommendation for follow-up testing of the breast, using an MRI scan, at years 3, 5, 7 (and so on) to look for clinically "silent" implant leakage.

This was a new recommendation - and a change from the earlier FDA policy of 1992, which had not recommended any screening tests at all for asymptomatic women with silicone implants.

So, does this new FDA recommendation make sense?

Well, let's look at the science, shall we? It really breaks down into two different questions:
1) Is an MRI scan a good way to look at the breast - or would a breast ultrasound be a reasonable, inexpensive first-line alternative?
2) What are the odds of having a leaking silicone implant at 3 years, or 5 years?

This is going to get a little technical, but please, bear with me.

Question one: MRI or not.

Prior to the 2006 ruling, MRI was not in routine use as a "screening" exam for women with silicone breast implants - it was used if there was a specific reason, such as a mammogram or ultrasound that was indeterminate, or a clinical situation that required investigation.

An excellent paper published in 1998 by Chung and associates, from the University of Michigan, actually developed an algorithm for decision-making for women with suspected silicone breast implant rupture, based on a statistical method called Bayes' theorem.

They found that in asymptomatic women, if they had a "normal" result on a screening ultrasound test (i.e. no rupture reported), the probability of an actual rupture was low - 2.2%. If the ultrasound reported a rupture, and this was confirmed by MRI, the likelihood of a true rupture rose to 86% - a reasonable threshold to operate.

So, Chung et al. recommended breast ultrasound as their first-line test, since ultrasound is widely available, relatively cheap, and doesn't involve radiation. They only used the expensive MRI if the ultrasound was abnormal. Makes sense to me - I like this idea because the patient saves money, and is more likely to actually get the test done, because of the lower financial barrier.

In a separate paper published in 2001, Cher and associates did a meta-analysis of MRI results in 1039 women. They found that when the MRI was used for women with specific complaints like breast hardness, shape change, etc., that it was reasonably accurate in detecting rupture - >80%. In women without these issues, the positive predictive value of an MRI was "insufficient to warrant use as a screening tool". They also recommended using the MRI to confirm the results of a screening ultrasound.

The Royal College of Radiologists (UK) echoed these views in their recently published guidelines on breast imaging. A normal ultrasound examination was highly predictive (91%) for an intact implant. Ultrasound was recommended as an initial investigation. According to the RCR, patients with an abnormal ultrasound examination should then proceed to an MRI examination, provided the more powerful 1.5 Tesla MRI machines are used with the specialized "breast coil" imaging device. Lower power MRI machines or those that don't have the breast coil are not nearly as reliable.



Question two: how often does leakage really happen?

The best way to determine whether there is implant leakage is to perform surgery, and look at the implant directly. But, as you might imagine, it's pretty darn difficult to convince a women who is feeling perfectly fine, without any symptoms at all, to undergo surgery - just so we can open her up to look and see whether her implants are OK!!

So, this data is hard to come by. Instead, we use MRI scans - to estimate the deflation rate. In Mentor's Core study, at 3 years out, just 0.5% of the 420 patients had a rupture in the primary augmentation group.

In other words, at the three year point, 199 women will have to pay to have an MRI that is completely normal, for one woman to find a rupture. That's probably not the best utilization of health-care dollars.

In the study by Sharpe and Collis (UK), no ruptures were noted until 7 years postoperatively.

Data like this really make me wonder whether it makes sense to insist on a scan at years 3 and 5, when not much is happening.

In summary: the screening recommendations of the FDA are certainly controversial. I feel that they are scientifically questionable, financially imposing, and a bit of a "CYA" move by the FDA, particularly at years 3 and 5. However, they are the "official party line", so I tell all my patients about them. The FDA rules were probably written more with political expediency in mind. I hope that, in time, they will be modified to better reflect the actual science!

Reloxin - a potential challenger to Botox Cosmetic?

"Reloxin", a form of botulinum toxin, and potential competition for Botox, could go on sale in the U.S. soon.

The FDA is currently evaluating the product, which has been sold in Europe for approximately 15 years under the name Dysport. It's a wrinkle-fighter, similar to Botox, and it also has a good track record of success and a good record of safe use.

Medicis, the U.S. distributor, said it is hoping for FDA approval of their application in early 2009.

It will be interesting to see how this situation works out. Will the newcomer try to under-cut the price of Botox? Will patients be willing to try the newcomer, or stick with the original? The dosing of Dysport and Botox is not directly comparable - so it wouldn't be a simple 1:1 substitution - but both have been shown to be effective for dynamic facial wrinkles.

Botox, made by Allergan, has been the No. 1 cosmetic medical treatment in the United States for the last few years, according to the American Society for Aesthetic Plastic Surgery (ASAPS) procedural statistics.