Botox's serious role: a life-sustaining treatment

Items on Jeff Wojciechowski's to-do list before a 2010 family vacation to Cancun included renewing his passport, shopping for beach wear, and getting a Botox injection.

The procedure wasn't to smooth out wrinkles. Instead, the injection went into his bladder muscle, to give the 63-year-old Fort Washington man a respite from incontinence that has plagued him since a 2006 construction accident left him paralyzed from mid-chest down.

Though Botox has become synonymous with the temporary elimination of wrinkles, what's less well known is its application across medicine.

In August, the U.S. Food and Drug Administration approved the use of Botox to treat loss of bladder control due to neurological conditions such as Wojciechowski's when oral medications cannot be tolerated. The approval means more patients will now likely receive the procedure because insurance will cover it.

The results typically range from slight improvements to a total elimination of incontinence episodes, said Patrick Shenot, a Thomas Jefferson University Hospital urologist leading an Allergan-sponsored clincal trial that Wojciechowski participates in.

The FDA has also approved Botox for chronic migraines, muscle stiffness in the arm, disorders of the neck and eye muscles, excessive sweating, and - its most recognized use as a cosmetic procedure - relaxing those deep vertical lines between the eyebrows.

Many people now ask for a more "natural" look from Botox, a more subtle relaxing of the muscle. They don't want to eliminate facial expressions as many did in the drug's early days.Expanded uses have translated into more sales for companies that produce botulinum toxins such as Allergan. Botox and Botox Cosmetic make up 77 percent of the market share for botulinum toxins. Global sales were $125.3 million in 1998, but they topped $1.4 billion last year, split evenly between medical and cosmetic uses.

Botulinum toxin was the top minimally invasive cosmetic procedure - averaging $375 a visit - with 5.4 million treatments in 2010, according to the American Society of Plastic Surgeons. That was a dramatic increase over the 856,000 procedures in 2001.

"We have a medication [Botox Cosmetic] that works the way that it's supposed to behave. We can use it in very specific and selective ways to relax muscles pulling on the skin that cause wrinkles," said Heidi Waldorf, a dermatologist and director of laser and cosmetic dermatology at the Mount Sinai Medical Center in New York. Waldorf has served as a consultant and is a member of the national education faculty for Botox Cosmetic.

Sales of therapeutic Botox are expected to soon overtake its cosmetic side as Allergan aggressively pursues new regulatory licenses.

Botox is a purified form of botulinum toxin, a poison produced by the bacterium that causes botulism, a serious and potentially fatal nerve disease. When Botox is injected into muscle tissue, it temporally blocks nerve signals from triggering the targeted muscle to contract.

"There are many potential areas to explore with Botox, and patient unmet medical needs are key factors important in establishing research directions," said Mitchell F. Brin, a neurologist and chief scientific officer for Botox at Allergan. "The original use was focused on exploring the therapeutic potential. The cosmetic observation was a serendipitous consequence."

In 1989, the FDA approved Botox to treat crossed eyes and twitching eyelids. Several years later, the toxin was approved cosmetically for frown lines between the eyebrows. Doctors, who are permitted with discretion to use approved drugs in unapproved ways, were already using botulinum toxins off-label. In the cosmetic setting, Botox has been used off-label for wrinkles on the forehead and around the eyes, pore shrinkage, in the chest muscles to give the breasts a lift, and for nose jobs and bigger eyes.

Allergan's promotion of off-label uses of Botox such as in children with cerebral palsy became a subject of a federal investigation.

In 2010 Allergan agreed to plead guilty and pay $600 million to resolve criminal and civil liability arising from the unlawful promotion of Botox for uses the FDA has not approved as safe and effective.

In a statement, Allergan said it agreed to plead guilty to a single misdemeanor "misbranding" charge covering 2000 through 2005. The charge is known as a strict liability offense, and does not, according to the company, involve false or deceptive conduct.

Though serious side effects after use of Botox and other botulinum toxins are rare, a few people have died after treatment. In some cases, the toxin spread from the injection site, leading to severe swallowing and breathing problems. For example, several children with cerebral palsy died after receiving large doses in their limbs. They also had underlying conditions such as previous swallowing problems or seizures, an FDA review found.

According to product-safety information, no serious case of toxin spreading from the injection site has been confirmed when Botox is used at the recommended dose and for approved therapies.

Since the 1970s, Botox has been heavily researched, including in clinical trials, and patients who have received Botox injections have been followed up on, Allergan's Brin said.

"Botox is a medical therapy. The things that patients should consider are similar to fundamental risk-benefit concerns, as would be considerations with any other medical treatment," Brin said.

In 2008, Public Citizen, a consumer advocacy nonprofit, petitioned the FDA for a stronger warning on botulinum toxins that would emphasize the risk of diffusion from the injection site and the need for patients to seek immediate medical care for swallowing or breathing difficulties.

The next year, the FDA required all four botulinum toxin drug products - Botox, Botox Cosmetic, Myobloc, and Dysport - to have boxed warnings on their labels and medication guides for patients.

"We've never asked . . . to take it off the market, but feel many weren't aware of the possibility that it could lead to death," said physician Sidney M. Wolfe, founder and director of Public Citizen's Health Research Group.

Patients should be aware of the potential for serious side effects with larger doses and if the injection area is near the esophagus, Wolfe said.

Medical treatments require much higher doses than does cosmetic therapy.

For cosmetic procedures, doctors should have an understanding of the underlying anatomy and proper training to anticipate any potential complications, said Mark Abdelmalek, chief of the division of laser and dermatologic surgery at the Drexel University College of Medicine.

A user should also know who is diluting the product coming from the manufacturer. Go to someone trained, he said.

Under proper conditions, most patients generally reap the benefits of Botox for certain medical conditions beyond the cosmetic.

With Botox, Gina Collazo, 25, of Philadelphia, finally found a way to stop excessive underarm sweating. In 2008, she mentioned to a dermatologist during an appointment that she sweated all day even under normal conditions.

The dermatologist asked whether she had tried Botox, said Collazo, a Drexel Dermatology Associates patient. Since then, she has received underarm injections every three to five months. She no longer has to wear layers of clothing or put tissues under her arms to try to hide sweat.

"I thought it was to eliminate wrinkles," Collazo said. "It's not just for that. It works wonders."

Source: Philly.com Health News , By Anna Nguyen "For The Inquirer"