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A Supplement to ® Skin Disease Skin & Allergy News Education Foundation

Roundup on Cosmetic SPRING 2006

TOPIC HIGHLIGHTS: New Options Spur Interest in Combination Treatment

Preventive Skin Care Forms Basis for Battle Against Sun and Aging

For Quick Results, Think Nonablative Resurfacing

Plasma Energy Harnessed for Damaged, Aging Skin

Horse Chestnut

New Laser System Offers Another GUEST EDITORS: Skin Tx Option David J. Goldberg, M.D., J.D. Clinical Professor of Dermatology Director, Laser Research and Mohs Surgery Maintaining Safety, Integrity of Mount Sinai School of Medicine A Adjunct Professor of Law Fordham Law School New York, N.Y. Director, Skin Laser & Surgery Specialists of New York/New Jersey New York, N.Y.

Christopher B. Zachary, F.R.C.P. Chair and Clinical Professor Department of Dermatology Co-Director, Dermatologic Surgery and Laser Center University of California at Irvine

Produced in affiliation with the 30th Hawaii Dermatology Seminar and the Cosmetic Dermatology Seminar. 2MCOSD_S.QXD 4/7/2006 8:06 PM Page 2

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Skin & Allergy News® Roundup on Cosmetic Dermatology SPRING 2006 TOPIC HIGHLIGHTS: 4 New Options Spur Interest in Combination Treatment 5 Preventive Skin Care Forms Basis for Battle Against Sun and Aging 6 For Quick Results, Think Nonablative Resurfacing 9 Plasma Energy Harnessed for Damaged, Aging Skin 10 Horse Chestnut

12 New Laser System Offers Another Skin Tx Option 15 Maintaining Safety, Integrity of Botulinum Toxin A

GUEST EDITORS:

David J. Goldberg, M.D., J.D. Christopher B. Zachary, F.R.C.P. Clinical Professor of Dermatology Chair and Clinical Professor Director, Laser Research and Mohs Surgery Department of Dermatology Mount Sinai School of Medicine Co-Director, Dermatologic Adjunct Professor of Law Surgery and Laser Center Fordham Law School University of California at Irvine New York, N.Y. Director, Skin Laser & Surgery Specialists of New York/New Jersey New York, N.Y.

President, Elsevier/IMNG Alan J. Imhoff Vice President, Medical Education & Business Development Sylvia H. Reitman, M.B.A. Contributing Writer Charles Bankhead Program Manager, Medical Education Sara M. Hagan National Account Manager Cheryl J. Gromann Art Director

Elizabeth Lobdell Director of Production and Manufacturing Yvonne Evans Roundup on Cosmetic Dermatology was produced by the medical education department of International Medical News Group. Neither the Editor of SKIN & ALLERGY NEWS, the Editorial Advisory Board, nor the reporting staff reviewed or contributed to its contents. The ideas and opinions expressed in this supplement are those of the faculty and do not

necessarily reflect the views of the supporter or the Publisher. Copyright © 2006 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form, by any means, without prior written permission of the Publisher. Elsevier Inc. will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein.

INTERNATIONAL MEDICAL NEWS GROUP 2MCosD_Spring4_13.qxd 4/17/2006 8:38 PM Page 4

New Options Spur Interest in Combination Treatment

he emergence of new options for cosmetic tually will demonstrate whether LED devices have a dermatology procedures has created a great place as sole therapy for dermatologic conditions or as potential for combining different modalities an adjunct to other technologies and treatments. T to achieve the best possible result. “In the real world of dermatology practice for , for Two of the newest technologic developments are example, we often use a laser to shrink the oil glands by light-emitting diode (LED) treatment and topical anti- heating them and combine that with red LED light, which aging agents that contain growth factors. These new decreases the bacteria involved in acne,” said Dr. Goldberg. treatment modalities can be combined with lasers, “For rosacea, we might use intense pulsed light, which pro- intense pulsed light, or other technologies to achieve cos- duces heat, and combine it with yellow LED light, which metic results that are more tailored to individual patient also is used to treat rosacea.” needs. Future experience also will define the “The general trend in cosmetic derma- role of new-generation topical agents, but tology is to have a synergistic approach in- the growth factor–containing creams have volving a variety of different agents,” said several advantages over conventional topi- David J. Goldberg, M.D., J.D., Clinical cal treatments. Conventional lotions and Professor of Dermatology and Director of creams either fail to penetrate the skin or Laser Research and Mohs Surgery at achieve concentrations that are too low to Mount Sinai School of Medicine in New produce any meaningful effects. In some York. “The synergy might come from com- cases, exposure to air and light causes a bining lasers with LED technology or, per- cream or lotion to oxidize in its container haps, with botulinum toxin, fillers, or ef- and lose whatever therapeutic potential it fective new topical creams.” might have had. The evolution of LED technology has David J. The newest additions to the topical arma- given rise to a unique new approach to skin Goldberg, M.D., J.D. mentarium contain multiple types of growth treatment. In contrast to lasers, LED devices do not heat factors developed by means of stem-cell technology. Orig- the skin and, as a result, do not cause any pain. inally developed to aid healing of burns and other wounds, Instead, the devices achieve cosmetic benefits by mod- the new agents have found a role in cosmetic dermatology ulating biologic activity inside various types of cells in because of their antiaging effects. the skin. “These new topical agents are sort of like fertilizer for Within the field of cosmetic dermatology, LED tech- the skin,” said Dr. Goldberg. “They differ from other top- nology currently comprises four wavelengths, each of ical agents in that they can actually get into the skin, they which has different effects on the skin and can be used for are packed with growth factors, and they can achieve very different cosmetic applications. Blue light and red light are nice improvement in the skin.” both used to treat acne. Red and near-infrared light are used Cosmetic dermatologists have already begun to use the to achieve antiaging effects. Yellow light has found a niche growth-factor agents in combination with other technolo- in the treatment of rosacea. gies that can achieve antiaging effects in the skin. The ex- “Each type of light has a different mechanism of ac- perience to date suggests that combination treatment offers tion, but they have in common the fact that they do not the potential to achieve better cosmetic results than does create any heat,” said Dr. Goldberg. “Generally, a treat- single-agent treatment. ■ ment can last anywhere from half a minute to 20 min- utes. The treatments do not take very long, and there is DR. GOLDBERG has received funding for clinical studies no wound.” from Photo Therapeutics, Cynosure, Inc., Neocutis Swiss The ultimate role of LED technology in cosmetic der- Technology, Inamed Corporation, Thermage, Inc., and matology remains to be determined, Dr. Goldberg added. Cutera, Inc. He is also a consultant to Bioform Medical, Continued clinical experience with the technology even- Inc., Lumenis Ltd., and Juva Medical Inc.

4 Roundup on Cosmetic Dermatology Spring 2006 2MCosD_Spring4_13.qxd 4/17/2006 8:39 PM Page 5

Preventive Skin Care Forms Basis for Battle Against Sun and Aging

dvances in skin rejuvenation techniques have matic improvement in the color, texture, and tone of the not lessened the importance of good pre- skin,” said Dr. Zachary, “although I am not so impressed ventive care to ward off the effects of sun ex- with its effects on early wrinkling.” A posure, climate, and aging. Prominent among lasers developed for skin rejuvenation “An ounce of prevention is worth a lot,” said Christo- procedures are the CoolTouch (CoolTouch, Roseville, pher B. Zachary, F.R.C.P., Chair and Clinical Professor of Calif.) and Smoothbeam (Candela Corp., Wayland, Mass.) Dermatology at the University of California, Irvine. “Good devices. Both have demonstrated the ability to improve preventive skin care can delay aging and reduce the risk wrinkling and acne scarring. of keratoses, cancer, and wrinkling. In fact, a good com- The latest addition to dermatologic laser technology is bined skin care regimen can provide as much benefit in fractional resurfacing, represented by the Fraxel, 1,550-nm terms of appearance as do many of the new laser (Reliant Technologies, Inc., Palo Alto, nonablative lasers.” Calif.). Fractional resurfacing represents a Good skin care comprises four principal new approach to laser skin treatment. Where- components: sun block, , retinoid, as traditional lasers penetrate the skin in a hor- and bleaching agent, such as hydroquinone. izontal layer, fractional resurfacing creates Among those components, a good moistur- multiple tiny cylinders of penetration that ex- izer often is overlooked, thereby depriving tend to a depth of 200 to 500 microns in an the skin of a treatment that can prevent a sig- orientation at right angles to the skin surface. nificant degree of wrinkling, according to “The key to the success of this technology Dr. Zachary. is that it treats only about 15% to 20% of the Providing a “California perspective” on skin,” said Dr. Zachary. “There is no exuda- skin aging, the Irvine cosmetic dermatology tion and very little chance of scarring. The specialist said geographically defined dif- Christopher B. treatment results in an internal structure of ferences in climate can have a profound im- Zachary, F.R.C.P. damage that heals by laying down new col- pact on the speed and extent of skin aging. As an illus- lagen and other skin components.” tration, he described hypothetical twins, one of whom Fractional resurfacing has demonstrated the ability to im- lived in Glasgow, Scotland, and the other in sunny south- prove wrinkling, acne scarring, and pigmentation defects. ern California. By 50 or 60 years of age, sun exposure will However, Dr. Zachary pointed out that chemical peels and have taken a substantial toll on the Californian’s skin. IPL also can be used to treat pigmentation problems, and “If you put the twins side by side, you wouldn’t have to either technique represents an appropriate initial choice of ask which one lived where,” said Dr. Zachary. “Genetically treatment for a patient whose sole reason for treatment is speaking, the two would be very similar. The difference a pigmentation problem. would be in exposure to light, which gives rise effectively treats acne scarring, but the to wrinkling, keratoses, lentigines, and loss of elasticity, evolution of newer, less-invasive techniques has greatly di- such that one would probably have silky smooth skin, and minished dermabrasion’s use in cosmetic dermatology. the other would be wrinkled like a California raisin.” Carbon dioxide and erbium-YAG lasers offer effective op- Good prophylactic skin care can help minimize the tions for scarring but are less frequently used now that the harmful effects of exposure to ultraviolet light. Even peo- performance of nonablative devices has improved sub- ple who have neglected preventive care can benefit from stantially. a combined skin care program, which “sometimes can be “Many patients and physicians prefer nonablative de- more effective than lasers,” said Dr. Zachary. “Before dis- vices,” said Dr. Zachary. cussing a nonablative rejuvenation procedure, a patient “They maintain that as much benefit can be obtained with should first try a good skin care regimen.” 6 to 12 treatments with the Smoothbeam, CoolTouch, or When rejuvenation is indicated, a good initial choice for Fraxel as can be achieved with the erbium-YAG or carbon many patients is intense pulsed light (IPL). Although not dioxide laser. If that is true, then I think the day of non- a laser, IPL can achieve many of the same benefits for skin ablative rejuvenation and nonablative treatment of acne that exhibits signs of premature aging, including telan- scarring has finally arrived, even for skeptics like myself.” giectasias, lentigines, and wrinkling. IPL is absorbed well Radiofrequency techniques offer additional technologic by pigment and blood vessels and improves skin tone and options for cosmetic dermatology procedures. Manufac- texture. Three or four treatment sessions can lead to “dra- Continued on page 15

Roundup on Cosmetic Dermatology Spring 2006 5 2MCosD_Spring4_13.qxd 4/17/2006 8:39 PM Page 6

For Quick Results, Think Nonablative Resurfacing

on- or minimally-ablative facial resurfacing offers The in-office erbium laser provides a one-time minimally patients the results they desire without extended ablative resurfacing with results similar to a whole course of downtime, said several presenters at the annual intense fractional resurfacing, said James Newman, M.D., a N fall meeting of the American Academy of Facial facial plastic surgeon from San Mateo, Calif. Plastic and Reconstructive Surgery. “I began using office-based laser treatments in response to “Most of my patients want nonsurgical treatments with no patients’ wanting a treatment without much downtime or pro- downtime,” said Elizabeth Rostan, M.D., a cosmetic derma- longed healing, but who also didn’t want to come into the of- tologist in Charlotte, N.C. “In my community, fice four or five times to treat a brown spot,” I can’t give away a CO2 laser resurfacing.” he said. Most of Dr. Rostan’s fractional resurfacing pa- The small erbium lasers are also relatively in- tients are women who want treatment for pho- expensive (about $30,000), which allows the toaging, acne scars, or melasma. “Many of these physician to rapidly recoup the investment and patients are the ones for whom you might con- offer patients a modestly priced treatment. sider intense pulsed light. It would burn off the “For the removal of brown spots from the face pigmentary lesions, but it would not give you the or hands, it would be about $300, and for a pe- same improvement you see in fine wrinkling.” rioral regional resurfacing, maybe $1,000 or In terms of both efficacy and recovery, frac- less,” he said. tional resurfacing falls between nonablative The small, portable lasers have lower flu- and ablative techniques. ences (about 5-7 J/cm2) and smaller spot sizes “The results we get are better than what we Elizabeth Rostan, (about 6 mm) than do their larger counterparts. would see with a nonablative technique, but not M.D. “They also have a pulse duration of about quite as good as what we would see with an ablative resur- 300 milliseconds, and because they are lower powered, they facing,” she said. “However, with the fractional resurfacing, can’t go as fast. The maximum repetition rate is about 2 Hz,” patients aren’t experiencing the 2 weeks of downtime that they Dr. Newman said. would with a CO2 laser resurfacing, either.” This makes the in-office erbium laser good for localized or The device directs its energy along the path of a comput- regional (perioral or periorbital) resurfacing, but not appro- er-generated pattern, producing about 2,000 tiny holes (mi- priate for a full-face procedure, he said. crothermal injury zones) per square centimeter. Because the The main indications for this device are solar lentigines, ear- areas of injury are so tiny, “you are treating about 20% of the ly elastosis of periorbital skin, sebaceous hyperplasia, scar skin surface, leaving 80% to renew and heal,” Dr. Rostan said. modification, and epidermal keratosis, Dr. Newman said. The laser intensity can be varied for different applications. Downtime is 4-7 days, “similar to what you would expect with The 8-J/cm2 setting penetrates about 300 micrometers, and is intense fractional resurfacing or a medium-depth chemical good for pigmentary lesions. For acne scars or rhytids, the peel.” more intense energy of the 20-J/cm2 setting is necessary; this “If they can come in and get it over with in one treatment, level penetrates about 700 micrometers. and then put up with a week at most of healing, patients will Patients require a topical anesthetic, which takes about 1 be very happy with this,” he said. hour to achieve maximum effect. The actual resurfacing pro- The plasma resurfacer gives similar results, without the epi- cedure lasts about 20 minutes, she said. However, three to five dermal sloughing that the erbium laser generates, said Edgar treatments, spaced about a week apart, are usually necessary Fincher, M.D., a dermatologic surgeon in Los Angeles. to achieve the desired result. These devices feature a nitrogen canister that pumps the gas Afterward, there is mild erythema and edema. “Patients are into a handpiece, where a radiofrequency generator heats it usually pink for 2 days, but it can sometimes last as long as and delivers it through a nozzle to the skin surface. They can 4 days,” Dr. Rostan said. “But they can easily cover it with deliver energy ranging from 1 to 4 J/cm2 and can be used in makeup and be back to work the day after the procedure.” single or multipass mode. Fractional resurfacing is also a good alternative for elder- Like a CO2 or erbium laser, the plasma resurfacer causes ly patients or for those with health issues that might compro- an immediate zone of thermal damage, with heat dissipation mise wound healing in an ablative resurfacing, she said. “I’ve into the deeper tissues, stimulating fibroblast action. done a healthy 87-year-old, as well as a transplant patient, with The difference with the plasma resurfacer, Dr. Fincher said, no adverse effects.” is that the lower fluences preserve the epidermis until reep- But she said she would carefully consider patients with scle- ithelialization is complete. “It does not vaporize the epider- roderma or rheumatoid problems. “Anyone who you’d have mis, which accelerates wound healing. About 4 days later, you concerns about for laser resurfacing, you would also have to have reepithelialization and necrotic keratinocytes moving up think about for fractional resurfacing.” Continued on page 9

6 Roundup on Cosmetic Dermatology Spring 2006 2MCOSD_S.QXD 4/11/2006 8:58 PM Page 7

For the temporary treatment of moderate to severe glabellar lines in patients 18 to 65 years of age

Trusted tool of aesthetic artistry

BOTOX® Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in patients 18 to 65 years of age.

Important Safety Information: BOTOX® Cosmetic is contraindicated in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any ingredient in the formulation. There have been rare reports of adverse events involving the cardiovascular system. Serious and/or immediate hypersensitivity reactions have been reported rarely. These reactions include anaphylaxis, urticaria, soft-tissue edema, and dyspnea. The most common adverse events following injection include blepharoptosis and nausea. Less frequently occurring (<3%) adverse reactions include facial pain, erythema at the injection site, paresthesia, and muscle weakness. Patients with neuromuscular disorders By prescription only such as ALS, myasthenia gravis, or Lambert-Eaton syndrome may be at increased risk of serious adverse events. Please see brief summary of full prescribing information on following page.

©2006 Allergan, Inc., Irvine, CA 92612 ® Marks owned by Allergan, Inc. BotoxCosmetic.com Re-order: 4960049 603280 2MCOSD_S.QXD 4/7/2006 8:26 PM Page 8

BOTOX® COSMETIC viability of the embryos. (Botulinum Toxin Type A) Nursing mothers: It is not known whether this drug is excreted in human milk. Because many Purified Neurotoxin Complex drugs are excreted in human milk, caution should be exercised when BOTOX® COSMETIC is administered to a nursing woman. INDICATIONS AND USAGE Pediatric use: Use of BOTOX® COSMETIC is not recommended in children. ® BOTOX COSMETIC is indicated for the temporary improvement in the appearance of moderate Geriatric use to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult The two clinical studies of BOTOX® COSMETIC did not include sufficient numbers of subjects patients < 65 years of age. aged 65 and over to determine whether they respond differently from younger subjects. However, CONTRAINDICATIONS the responder rates appeared to be higher for patients younger than age 65 than for patients 65 BOTOX® COSMETIC is contraindicated in the presence of infection at the proposed injection years or older. (See: CLINICAL STUDIES) site(s) and in individuals with known hypersensitivity to any ingredient in the formulation. There were too few patients (N=3) over the age of 75 to allow any meaningful comparisons. WARNINGS ADVERSE REACTIONS BOTOX® and BOTOX® COSMETIC contain the same active ingredient in the same formulation. General: Therefore, adverse events observed with the use of BOTOX® also have the potential to be BOTOX® and BOTOX® COSMETIC contain the same active ingredient in the same formulation. associated with the use of BOTOX® COSMETIC. Therefore, adverse events observed with the use of BOTOX® also have the potential to be ® Do not exceed the recommended dosage and frequency of administration of BOTOX® associated with the use of BOTOX COSMETIC. COSMETIC. Risks resulting from administration at higher dosages are not known. The most serious adverse events reported after treatment with botulinum toxin include rare Hypersensitivity Reactions spontaneous reports of death, sometimes associated with anaphylaxis, dysphagia, pneumonia, Serious and/or immediate hypersensitivity reactions have been rarely reported. These reactions and/or other significant debility. There have also been rare reports of adverse events involving the include anaphylaxis, urticaria, soft tissue edema, and dyspnea. One fatal case of anaphylaxis has cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. been reported in which lidocaine was used as the diluent, and consequently the causal agent Some of these patients had risk factors including pre-existing cardiovascular disease. (See: cannot be reliably determined. If such a reaction occurs further injection of BOTOX® COSMETIC WARNINGS). New onset or recurrent seizures have also been reported, typically in patients who are should be discontinued and appropriate medical therapy immediately instituted. predisposed to experiencing these events. The exact relationship of these events to the botulinum toxin injection has not been established. Additionally, a report of acute angle closure glaucoma one Pre-Existing Neuromuscular Disorders ® day after receiving an injection of botulinum toxin for blepharospasm was received, with recovery Caution should be exercised when administering BOTOX COSMETIC to individuals with four months later after laser iridotomy and trabeculectomy. Focal facial paralysis, syncope and peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis, or motor neuropathy) exacerbation of myasthenia gravis have also been reported after treatment of blepharospasm. or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome). ® Patients with neuromuscular disorders may be at increased risk of clinically significant systemic In general, adverse events occur within the first week following injection of BOTOX COSMETIC effects including severe dysphagia and respiratory compromise from typical doses of BOTOX® and while generally transient may have a duration of several months or longer. Localized pain, COSMETIC. Published medical literature has reported rare cases of administration of a botulinum infection, inflammation, tenderness, swelling, erythema and/or bleeding/bruising may be toxin to patients with known or unrecognized neuromuscular disorders where the patients have associated with the injection. shown extreme sensitivity to the systemic effects of typical clinical doses. In some of these cases, Glabellar Lines dysphagia has lasted several months and required placement of a gastric feeding tube. In clinical trials of BOTOX® COSMETIC the most frequently reported adverse events following Dysphagia injection of BOTOX® COSMETIC were headache*, respiratory infection*, flu syndrome*, Dysphagia is a commonly reported adverse event following treatment of cervical dystonia patients blepharoptosis and nausea. with all botulinum toxins. In these patients, there are reports of rare cases of dysphagia severe Less frequently occurring (<3%) adverse reactions included pain in the face, erythema at the enough to warrant the insertion of a gastric feeding tube. There is also a case report where a patient injection site*, paresthesia* and muscle weakness. While local weakness of the injected muscle(s) is developed aspiration pneumonia and died subsequent to the finding of dysphagia. representative of the expected pharmacological action of botulinum toxin, weakness of adjacent Cardiovascular System muscles may occur as a result of the spread of toxin. These events are thought to be associated with There have also been rare reports following administration of BOTOX® of adverse events the injection and occurred within the first week. The events were generally transient but may last involving the cardiovascular system, including arrhythmia and myocardial infarction, some with several months or longer. fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular (* incidence not different from Placebo) disease. The data described in Table 4 reflect exposure to BOTOX® COSMETIC in 405 subjects aged 18 Human Albumin to 75 who were evaluated in the randomized, placebo-controlled clinical studies to assess the This product contains albumin, a derivative of human blood. Based on effective donor screening use of BOTOX® COSMETIC in the improvement of the appearance of glabellar lines (See: and product manufacturing processes, it carries an extremely remote risk for transmission of viral CLINICAL STUDIES). Adverse events of any cause were reported for 44% of the BOTOX® diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is COSMETIC treated subjects and 42% of the placebo treated subjects. The incidence of considered extremely remote. No cases of transmission of viral diseases or CJD have ever been blepharoptosis was higher in the BOTOX® COSMETIC treated arm than in placebo (3% vs. 0). identified for albumin. In the open-label, repeat injection study, blepharoptosis was reported for 2% (8/373) of subjects PRECAUTIONS in the first treatment cycle and 1% (4/343) of subjects in the second treatment cycle. Adverse events of any type were reported for 49% (183/373) of subjects overall. The most frequently General: ® reported of these adverse events in the open-label study included respiratory infection, The safe and effective use of BOTOX COSMETIC depends upon proper storage of the product, headache, flu syndrome, blepharoptosis, pain and nausea. selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering BOTOX® COSMETIC must understand the relevant neuromuscular Because clinical trials are conducted under widely varying conditions, adverse reaction rates and/or orbital anatomy of the area involved, as well as any alterations to the anatomy due to prior observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials surgical procedures and avoid injection into vulnerable anatomic areas. Caution should be used of another drug and may not be predictive of rates observed in practice. when BOTOX® COSMETIC treatment is used in the presence of inflammation at the proposed TABLE 4. injection site(s) or when excessive weakness or atrophy is present in the target muscle(s). Reduced blinking from BOTOX® COSMETIC injection of the orbicularis muscle can lead to corneal Percent of Patients Reporting Adverse Events exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. In the use of BOTOX® for in the treatment of blepharospasm, one case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful BOTOX® Cosmetic Placebo Adverse Events by Body testing of corneal sensation in eyes previously operated upon, avoidance of injection into the (N=405) (N=130) System lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be % % employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means. Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, Overall 44 42 double vision or past pointing. Covering the affected eye may alleviate these symptoms. ® Body as a Whole Caution should be used when BOTOX COSMETIC treatment is used in patients who have an 2 1 inflammatory skin problem at the injection site, marked facial asymmetry, ptosis, excessive Pain in Face dermatochalasis, deep dermal scarring, thick sebaceous skin or the inability to substantially Skin and Appendages lessen glabellar lines by physically spreading them apart as these patients were excluded from 1 0 the Phase 3 safety and efficacy trials. Skin Tightness Needle-related pain and/or anxiety may result in vasovagal responses, (including e.g., syncope, Digestive System hypotension) which may require appropriate medical therapy. Nausea 3 2 Injection intervals of BOTOX® COSMETIC should be no more frequent than every three months Dyspepsia 1 0 and should be performed using the lowest effective dose (See Adverse Reactions, 1 0 Immunogenicity). Tooth Disorder Information for Patients Special Senses Patients or caregivers should be advised to seek immediate medical attention if swallowing, 3 0 speech or respiratory disorders arise. Blepharoptosis Drug Interactions Musculoskeletal System ® 1 2 0 Co-administration of BOTOX COSMETIC and aminoglycosides or other agents interfering with Muscle Weakness neuromuscular transmission (e.g., curare-like nondepolarizing blockers, lincosamides, polymyxins, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride ) should Cardiovascular 1 0 only be performed with caution as the effect of the toxin may be potentiated. Hypertension

The effect of administering different botulinum neurotoxin serotypes at the same time or within ® several months of each other is unknown. Excessive neuromuscular weakness may be Adverse Events Reported at Higher Frequency (>1%) in the BOTOX COSMETIC Group exacerbated by administration of another botulinum toxin prior to the resolution of the effects of Compared to the Placebo Group a previously administered botulinum toxin. Immunogenicity Pregnancy: Pregnancy Category C Treatment with BOTOX® COSMETIC may result in the formation of neutralizing antibodies that Administration of BOTOX® COSMETIC is not recommended during pregnancy. There are no may reduce the effectiveness of subsequent treatments with BOTOX® COSMETIC by adequate and well-controlled studies of BOTOX® COSMETIC in pregnant women. When inactivating the biological activity of the toxin. The rate of formation of neutralizing antibodies in pregnant mice and rats were injected intramuscularly during the period of organogenesis, the patients receiving BOTOX® COSMETIC has not been well studied. ® developmental NOEL (No Observed Effect Level) of BOTOX COSMETIC was 4 U/kg. Higher The critical factors for neutralizing antibody formation have not been well characterized. The doses (8 or 16 U/kg) were associated with reductions in fetal body weights and/or delayed results from some studies suggest that botulinum toxin injections at more frequent intervals or at ossification. higher doses may lead to greater incidence of antibody formation. The potential for antibody In a range finding study in rabbits, daily injection of 0.125 U/kg/day (days 6 to 18 of gestation) formation may be minimized by injecting the lowest effective dose given at the longest feasible and 2 U/kg (days 6 and 13 of gestation) produced severe maternal toxicity, abortions and/or fetal intervals between injections. malformations. Higher doses resulted in death of the dams. The rabbit appears to be a very sensitive species to BOTOX® COSMETIC. Rx Only If the patient becomes pregnant after the administration of this drug, the patient should be ® Marks owned by Allergan, Inc. apprised of the potential risks, including abortion or fetal malformations that have been observed in rabbits. Based on package insert 71711US13S revised January 2005 Carcinogenesis, Mutagenesis, Impairment of fertility Manufactured by: Allergan Pharmaceuticals Ireland Long term studies in animals have not been performed to evaluate carcinogenic potential of a subsidiary of: Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612 BOTOX® COSMETIC. Reference: The reproductive NOEL following intramuscular injection of 0, 4, 8, and 16 U/kg was 4 U/kg in male rats and 8 U/kg in female rats. Higher doses were associated with dose-dependent 1. Wang YC, Burr DH, Korthals GJ, Sugiyama H. Acute toxicity of aminoglycoside antibiotics Appl Environ Microbiol reductions in fertility in male rats (where limb weakness resulted in the inability to mate), and as an aid in detecting botulism. 1984; 48:951-955. testicular atrophy or an altered estrous cycle in female rats. There were no adverse effects on the 2MCosD_Spring4_13.qxd 4/17/2006 8:39 PM Page 9

Plasma Energy Harnessed for Damaged, Aging Skin

ne of the newest trends in nonablative skin reju- The device can deliver either low- or high-energy treat- venation is the use of plasma energy to rid patients ments, said Dr. Lewis, Director of Mohs Micrographic Surgery of sun damage, fine lines, and wrinkles. and Cutaneous Oncology at Tulane University Hospital and O The advantage of plasma energy technology is Clinic in New Orleans. in the conduction of uniform and efficient thermal energy to Full-face rejuvenation using low-energy typically requires the dermis without epidermal vaporization or charring, re- three 15-minute sessions spaced 21 days apart. There is no skin ported Alan T. Lewis, M.D., at the Fourth International sloughing, minimal erythema, and little downtime, he said. Pa- Academy of Cosmetic Dermatology World Congress, Paris. tients undergoing a single high-energy treatment may notice “Unlike CO2 lasers where you’re taking away the epider- tight skin after the treatment and sloughing at about 7 days. mis and the protection that it affords, the epidermis is left be- Another trend in nonablative facial rejuvenation is to hind with this device,” he said. The intact epithelium provides “stack,” or combine, different laser treatments to elicit a re- posttreatment protection and speeds healing, resulting in less sponse in different layers of the skin, he said. downtime. The approach takes a little more time but results in greater One-year clinical histology studies show continuing re- patient satisfaction. generation and improvement over time. Elastosis is reduced, Dr. Lewis cited a study in which 10 women who received five and there is a widening of the collagen band at the der- treatment sessions with a 595-nm pulsed dye laser immediate- moepidermal junction. There have been no reports of scarring ly followed by a 1450-nm diode laser had overall better and faster or hypopigmentation in clinical studies to date, according to results than did 20 women treated with either laser alone (Der- Rhytec Inc., which markets the plasma energy device, Portrait matol. Surg. 2004;30:1292-8). PSR3. The 6-month clinical outcome was best for patients re- The Portrait PSR3 system generates plasma energy by pass- ceiving the combination treatment, followed by those treated ing ultrahigh frequency energy through nitrogen gas. Plasma is with the 1450-nm diode laser and the 595-nm pulsed dye laser, formed in the device’s handpiece and delivered to the dermis in respectively. millisecond pulses without contact, about 5 mm from the skin. When stacking lasers, it’s important to use the 595-nm laser Topical anesthesia, with or without oral medication, is used. first because infrared lasers can cause a good deal of redness The Portrait PSR3 system is approved for the treatment of that can become quite problematic if followed with a vascu- facial rhytides, superficial skin lesions, and actinic keratoses. lar laser. ■ But is also helpful in improving skin tone and texture, and re- ducing laugh lines, he said. By Patrice Wendling, IMNG News Service. Reprinted from It can be used for people with darker skin tones without af- SKIN & ALLERGY NEWS, December 2005. Based on a fecting skin color because the energy absorption is not chro- presentation at the Fourth International Academy of mophore dependent. Cosmetic Dermatology World Congress, Paris.

Nonablative Resurfacing A full-face treatment can be done in about 15 minutes. Pa- Continued from page 6 tients who are being treated for dyschromia or photodam- age will probably require two or three treatments about 1 and beginning to slough.” By day 10, histology shows a ful- month apart. These low-energy treatments are usually per- ly reformed stratified epidermis and increased number of ac- formed with a topical anesthetic, although nerve blocks may tive fibroblasts generating collagen, he said. be necessary for some patients. The high-energy treatments These devices have received U.S. Food and Drug Admin- necessary for treating acne scars usually require local anes- istration approval for use in single-pass, low-energy repeat thetic or IV sedation. treatments and single-pass, high-energy treatment of facial “We still have a CO2 laser and use it occasionally, but this rhytids, and for the treatment of superficial skin lesions. has replaced it as our workhorse resurfacing device,” Dr. Dr. Fincher has used a plasma resurfacer for about 2 years, Fincher said. ■ with no incidence of scarring or hypopigmentation. He has seen some transient hyperpigmentation, however, and two pa- By Michele G. Sullivan, IMNG News Service. Reprinted tients have had prolonged (4-6 weeks) erythema. from SKIN & ALLERGY NEWS, December 2005. Based on “We tell people that, pretty reliably, they will be back to a presentation at the annual fall meeting of the American normal in 10 days,” he said. Academy of Facial Plastic and Reconstructive Surgery.

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Horse Chestnut

here are 15 known species of horse chestnut, which travascular matrix and a component of endothelium. It is spec- is found as both a tree and a shrub in the temper- ulated that aescin alters the equilibrium between proteogly- ate regions of Europe, Asia, and North America. can synthesis and degradation, resulting in the prevention of T Believed to have originated in northern Greece and vascular leakage (Arch. Dermatol. 1998;134:1356-60). the Balkan region, the European horse chestnut (Aesculus hip- Aescin is associated with the release of prostaglandin F2 pocastanum) is the species most often used in medical appli- from veins, an antagonism to histamine and 5-hydroxytrypt- cations. It is not known whether other horse amine, and a decreased catabolism of tissue mu- chestnut species have been thoroughly evaluat- copolysaccharides (Pharmacol. Res. 2001; ed for their potential medicinal value. The Eu- 44:183-93). ropean horse chestnut is not related to the more Rutin, which is believed to strengthen fragile familiar sweet chestnut (Castanea vesca). capillaries, is another active ingredient in horse Most of the aerial sections of the European chestnut seeds. Many researchers in Europe horse chestnut tree—including the seeds, leaves, claim that aescin and rutin work synergistical- and bark—have been traditionally utilized in ly with other active components to enhance cir- medical treatments. As early as the 1500s, nuts culation and ease inflammation. from the horse chestnut tree were used to treat The leaves of the horse chestnut tree purport- persistent fever; later, they were used for hem- edly have antioxidant properties that may slow orrhoids, varicose veins in the leg, and phlebitis. Leslie S. skin wrinkling; such claims, however, have not Modern horse chestnut formulations are de- Baumann, M.D. been confirmed by controlled clinical trials. rived from seed extracts, which are high in the ac- Chronic Venous Insufficiency tive component aescin (also known as escin). The seeds also con- Copious, strong evidence supports the effectiveness of oral tain hydroxycoumarins, flavonoids, tannins, sterols, saponins, HCSE for the treatment of CVI. In a thorough review of place- and glycosides. bo-controlled studies, researchers found that HCSE was su- Today, oral administration of standardized horse chestnut perior to placebo in all cases. The reviewers noted reductions seed extract (HCSE) is a well-established treatment for chron- in lower-leg volume and in leg circumference at the calf and ic venous insufficiency (CVI) and edema. CVI is character- ankle, as well as improvement in symptoms such as leg pain, ized by enlarged veins near the skin surface, edema, and leg pruritus, fatigue, and tension, with only mild adverse reactions fatigue. The extract is also effective when used in a sitz bath occurring rarely. The same study found equivalence between for the treatment of hemorrhoids. In addition, HCSE is used horse chestnut and O-(β-hydroxyethyl)rutosides against a as an astringent and an anti-inflammatory. reference medication, as well as equivalence between horse Horse chestnut is a common ingredient in lotions, creams, chestnut and compression therapy (Am. J. Clin. Dermatol. massage oils, and other skin care products, often in combi- 2002;3:341-8; Arch. Dermatol. 1998;134:1356-60). nation with other herbal ingredients. Most such topical prod- In a different literature review of six placebo-controlled tri- ucts tout the capacity of horse chestnut to combat varicose als assessing leg pain, investigators observed a significant im- veins, swelling, and water retention, but some of the newer provement in the groups treated with HCSE compared with products ascribe antioxidant potency to horse chestnut and pur- placebo. They concluded that horse chestnut is safe and ef- port to combat wrinkling. fective for short-term CVI therapy, but that more rigorous, ran- Traditional Chinese medicine uses horse chestnut (Aesculus domized, controlled trials are necessary to evaluate long-term chinensis, known as tien shi li) as an astringent, anti-inflam- efficacy (Cochrane Database Syst. Rev. 2002;1:CD003230). matory, diuretic, and expectorant, as well as for a wide range Others have noted that oral horse chestnut therapy is ade- of ailments, including circulatory problems and viral infections. quate for treating the early phases of CVI as a result of its ca- Mechanism of Action pacity to close venular endothelial gaps, but that compression HCSE may work by inhibiting leukocyte activation (Arch. Der- therapy remains indicated for later stages (BMC Cardiovasc. matol. 1998;134:1356-60). A natural bioflavonoid and saponin, Disord. 2001;1:5). Various authors note that compression ther- aescin is believed to foster normal, healthy tone in vein walls apy is associated with poor compliance because it is uncom- by inhibiting enzymes that attack vein interiors (Arzneimit- fortable and sometimes painful, rendering an oral (and perhaps telforschung. 1994;44:25-35). Aescin facilitates the contraction topical) treatment such as horse chestnut preferable. The soon- of elastic fibers in blood vessel walls, thereby elevating the flex- er such treatment is initiated, the better the chance of avoid- ibility of the vessels (Dtsch. Med. Wochenschr. 1986;111:1321- ing compression therapy. 9; Lancet. 1996;347:292-4; The Complete German Commission Another study, in which 5,000 patients with CVI were treat- E Monographs: Therapeutic Guide to Herbal Medicines. ed with standardized horse chestnut extract, showed clearing Philadelphia: Lippincott Williams & Wilkins, 1996). or improvement of all of the symptoms—discomfort, fatigue, Researchers also have shown that aescin inhibits elastase tension, edema in the leg, and pruritus—that were investigated and hyaluronidase in vitro. Both enzymes have roles in the (Fortschr. Med. 1996;114:196-200). degradation of proteoglycans, an important element in the ex- Continued on page 14

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New Laser System Offers Another Skin Tx Option

ractional photothermolysis for skin rejuvena- Patients usually require two to four treatments at 2- to tion provides results similar to those achieved 4-week intervals. Most come back monthly to complete the with ablative laser resurfacing, but without series of treatments, she said. The skin is erythematous im- F the downtime, Tina Alster, M.D. said at the mediately after each treatment and remains so for approx- joint annual meeting of the American Society for Derma- imately 2 days. On day 2 or 3, a variable amount of peel- tologic Surgery and the American College of Mohs Mi- ing occurs, resulting in rough-feeling skin. crographic Surgery and Cutaneous Oncology, Results are incremental, with additional Atlanta. improvement seen after each treatment. Most The new fiber laser technology is particu- patients will achieve 50% improvement larly good for treating dyspigmentation and when being treated for dyspigmentation rhytides, and can be used on areas other than and/or rhytides. Although the laser is not the face, such as the arms, neck, chest, and marketed as a skin tightening device, it does hands, said Dr. Alster, Director of the Wash- provide some skin tightening, Dr. Alster ington Institute of Dermatologic Laser noted. Surgery. The results are better than what she has ex- Of about 20 lasers that she uses in her prac- perienced with trichloroacetic acid peels, tice, the Fraxel laser (Reliant Technologies particularly for fine lines, she said, and the Inc., Palo Alto, Calif.) is one of those she uses Tina Alster, recovery time is much quicker than with ab- most often. M.D. lative resurfacing. According to information from Reliant, the David J. Goldberg, M.D., of Skin Laser Fraxel laser system—which is approved for the treatment & Surgery Specialists of New York/New Jersey agreed of melasma but also has been used for surgical and acne that fractional photothermolysis has several applications scars, striae, and actinic keratoses—treats the skin frac- and a relatively good safety profile, but he cautions that tionally, with patterns of microscopic laser spots that are adverse events are still possible. Scarring, for example, 70-100 µm in diameter. Each laser spot is called a mi- can occur when the device is held in one place for too crothermal zone, or MTZ, and the laser can deliver 2,000 long. MTZs per cm2 in a typical treatment session. About 200- Dr. Goldberg also noted that many of the effects of this 300 µm of untreated space is left between each MTZ. How- laser can be achieved with other modalities. “It clearly ever, the treating physician has the ability to vary spot pitch works,” he said, but it’s not the “end all and be all.” and fluence. For example, acne scarring responds well to the Fraxel The use of the MTZs with adjacent untreated tissue al- laser, but it can also be treated effectively with the lows fractional wound healing with rapid reepithelializa- CoolTouch or Smoothbeam lasers. Crow’s-feet can be tion of the epidermis and collagen remodeling to depths treated effectively with botulinum toxin, and lentigines can of 400-700 µm. This is compared with the 200-µm depth be treated effectively with the Q-switched laser and intense achieved with traditional ablative laser treatments. pulsed light, Dr. Goldberg said. Histology following treatment shows that the stratum “This is not a system that you buy simply to treat lentig- corneum remains intact and epidermal tissue is coagulat- ines; this is not a system you buy simply to treat crow’s- ed. Collagen remodeling is also demonstrated, explained feet ... but I think that you can’t argue the fact that when Dr. Alster, who reported no financial interest in the de- you put the whole picture together, it’s got tremendous di- vice. versity, and that diversity has led to its popularity,” he said. “You see reepithelialization of the whole site within 24 Dr. Goldberg has received a research grant from Reliant hours,” she said. Technologies Inc. ■ Her treatment protocol involves skin cleansing and ap- plication of a blue tint, which is required for the laser to By Sharon Worcester, IMNG News Service. Reprinted work. About 30-60 minutes prior to the procedure, she also from SKIN & ALLERGY NEWS, January 2006. Based on a applies a topical anesthetic containing 30% lidocaine. presentation at the joint annual meeting of the American Dr. Alster said she usually uses 8-10 MJ per cm2, ener- Society for Dermatologic Surgery and the American gy density of 250 MTZs per cm2, and four to eight passes. College of Mohs Micrographic Surgery and Cutaneous An air cooler is used to increase patient comfort. Oncology, Atlanta.

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Horse Chestnut Continued from page 10 such as horse chestnut, thus increasing the risk of bleeding (J. Clin. Pharm. Ther. 2002;27:391-401). In a 12-week, randomized, partially blinded, placebo-con- Topical horse chestnut has been associated, in a few in- trolled parallel study of 240 patients, significant and equivalent stances, with allergic skin reactions. reduction of edema resulted from horse chestnut and compres- At the Store sion therapy compared with placebo; both therapies were well Nature’s Life Horse Chestnut Herbal Balm ($20 for 2 ounces) tolerated with no adverse side effects (Lancet. 1996;347:292-4). is a topical formulation standardized to include 2% aescin, and Usage and Indications is intended to soothe the symptoms of varicose veins. Studies Topical and systemic HCSEs are popular in Europe for the have shown that the topical application of standardized HCSE treatment of CVI and related conditions, such as varicose veins, balm with 2% aescin supports healthy skin, blood vessels, and leg cramps, phlebitis, and hemorrhoids. Topical application of muscles, particularly in the legs and hemorrhoidal plexus gels or creams containing 2% aescin, three or four times per (Planta Med. 1993;59:394-7; Clin. Ter. 1981;98:517-24; Clin. day, is used in Europe for eliminating hemorrhoids, varicose Ter. 1986;118:339-42). A double-blind study assessing the ef- veins, and skin ulcers, as well as for healing sports injuries such fectiveness of a topical standardized HCSE balm (2% aescin) as bruises, acute sprains, and similar traumas. The aescin in for localized swelling and hematoma showed that the product HCSEs clearly possesses anti-inflammatory capacity and has significantly reduced tenderness in the affected area, compared been demonstrated to ease edema after trauma, especially fol- with placebo (Planta Med. 1993;59:394-7). lowing head and sports injury, and surgery (Arzneimit- Beauty Naturally’s Rosacea Cleansing Lotion ($18 for 4 telforschung. 1994;44:25-35; Planta Med. 1993;59:394-7). ounces) is an anti-inflammatory, antibacterial, nondetergent Standardized HCSE has been approved by Commission E cleansing lotion formulated with horse chestnut, aloe, and (a German panel of experts that is comparable to the U.S. Food chamomile. It is free of alcohol and oil, and therefore appro- and Drug Administration) for the treatment of pathologic con- priate for sensitive skin. The manufacturer claims it is effec- ditions of the leg veins, including pruritus, edema, nocturnal tive in controlling rosacea flare-ups and reducing erythema. cramping in the calves, and the sensation of heaviness, as well Beauty Naturally’s Rosacea Moisturizing Cream ($33 for as varicose and spider veins. 2 ounces) contains horse chestnut. The product is intended There are claims that horse chestnut may even be effective to arrest inflammation and reduce erythema. for treating wrinkles, hair loss, cellulite, backache, and arthri- Conclusion tis, but there is no reliable evidence in the literature to sub- The usefulness of horse chestnut for treating CVI and other stantiate these claims. As an ingredient in facial creams and venous disorders has been borne out by randomized, controlled shaving products, horse chestnut is intended for sensitive skin. clinical trials. However, much research with topical horse Contraindications chestnut is needed to support some of the more recent claims Horse chestnut is contraindicated in patients who have bleed- regarding efficacy in treating wrinkles and hair loss. ■ ing disorders or who take anticoagulant drugs, such as warfarin, because the herb reduces blood clotting. Nonsteroidal anti-in- DR. BAUMANN is Director of Cosmetic Dermatology at the flammatory drugs (NSAIDs), particularly aspirin, potentially University of Miami. Reprinted from SKIN & ALLERGY interact with herbal supplements known to contain coumarin, NEWS, January 2006. 2MCosD_Spring4_13.qxd 4/13/2006 1:55 PM Page 15

Preventive Skin Care Continued from page 5 turers of the two devices currently on the market have initi- ® ® ated a lively competition for business, which should give Brevoxyl -4 Brevoxyl -8 dermatologists and other prospective buyers reason to per- Creamy Wash Creamy Wash form a careful evaluation of the technology before making ( 4%) (benzoyl peroxide 8%) a purchasing decision. “When all is said and done, we need to look at the images ACNE WASH FOR TOPICAL USE very carefully and assess which company is putting out re- Rx only Rx only

liable and trustworthy images that you can actually believe DESCRIPTION in,” said Dr. Zachary. ■ Brevoxyl-4 Creamy Wash and Brevoxyl-8 Creamy Wash are topical preparations containing benzoyl peroxide as the active ingredient. Brevoxyl-4 Creamy Wash and Brevoxyl-8 Creamy Wash contain: 4% and 8% Benzoyl Peroxide,respectively,in a lathering cream vehicle containing Cetostearyl Alcohol, Cocamidopropyl Betaine,Corn Starch,Dimethyl Isosorbide,Glycerin,Glycolic Acid,Hydrogenated DR. ZACHARY has nothing to disclose. Castor Oil,Imidurea,Methylparaben,Mineral Oil,PEG-14M,Purified Water,Sodium Hydroxide,Sodium PCA,Sodium Potassium Lauryl Sulfate,. The structural formula of benzoyl peroxide is: o o c-o-o-c= =

Maintaining Safety, Integrity CLINICAL PHARMACOLOGY The exact method of action of benzoyl peroxide in acne vulgaris is not known. Benzoyl peroxide is an antibacterial agent with demonstrated activity against Propionibacterium acnes.This action,combined of Botulinum Toxin A with the mild keratolytic effect of benzoyl peroxide is believed to be responsible for its usefulness in acne.Benzoyl peroxide is absorbed by the skin where it is metabolized to benzoic acid and excreted as benzoate in the urine. osmetic use of botulinum toxin A has proven INDICATIONS AND USAGE Brevoxyl-4 Creamy Wash and Brevoxyl-8 Creamy Wash are indicated for use in the topical treatment of to be safe and effective and a valuable addition mild to moderate acne vulgaris. Brevoxyl-4 Creamy Wash and Brevoxyl-8 Creamy Wash may be used as an adjunct in acne treatment regimens including antibiotics,retinoic acid products,and sulfur/salicylic to cosmetic dermatology. However, a recent acid containing preparations. C scare over clinical use of unregulated botulinum CONTRAINDICATIONS Brevoxyl-4 Creamy Wash and Brevoxyl-8 Creamy Wash should not be used in patients who have toxin has reminded the dermatology community of the need shown hypersensitivity to benzoyl peroxide or to any of the other ingredients in the product.

for care in the acquisition and use of the substance. PRECAUTIONS “I think all of us who use botulinum toxin need to make sure General — For external use only. Avoid contact with eyes and mucous membranes. AVOID CONTACT WITH HAIR, FABRICS OR CARPETING AS BENZOYL PEROXIDE WILL CAUSE our suppliers are bona fide and that we are receiving the real BLEACHING. Carcinogenesis, Mutagenesis, Impairment of Fertility — Based upon all available evidence,benzoyl stuff,” said Christopher B. Zachary, F.R.C.P., Chair and Clin- peroxide is not considered to be a carcinogen. However,data from a study using mice known to be highly susceptible to cancer suggest that benzoyl peroxide acts as a tumor promoter.The clinical ical Professor of Dermatology at the University of California, significance of the findings is not known. Irvine. “Botulinum toxin type A is here to stay, and its use is Pregnancy: Category C — Animal reproduction studies have not been conducted with benzoyl peroxide. It is also not knownwhether benzoyl peroxide can cause fetal harm when administered to a well worked out. It is extremely safe and very effective when pregnant woman or can affect reproduction capacity. Benzoyl peroxide should be used by a pregnant woman only if clearly needed. used appropriately. People are becoming much more accom- Nursing Mothers — It is not known whether this drug is excreted in human milk. Because many plished in using it to reduce the effects of gravity.” drugs are excreted in human milk,caution should be exercised when benzoyl peroxide is administered to a nursing woman. Botulinum toxin type A is traditionally considered to be Pediatric Use — Safety and effectiveness in children below the age of 12 have not been established. especially useful for reducing the effects of aging on the up- ADVERSE REACTIONS Contact sensitization reactions are associated with the use of topical benzoyl peroxide products and per portion of the face. More recently, greater expertise has may be expected to occur in 10 to 25 of 1000 patients.The most frequent adverse reactions associated with benzoyl peroxide use are excessive erythema and peeling which may be expected to occur in 5 been gained in its use on the lower face, around the mouth, of 100 patients. Excessive erythema and peeling most frequently appear during the initial phase of and on the neck. The treatment has become so popular that drug use and may normally be controlled by reducing frequency of use. cosmetic application of the substance has expanded outside DOSAGE AND ADMINISTRATION Shake well before using.Wash the affected areas once a day during the first week,and twice a day the fields of dermatology and plastic, facial-plastic, and ocu- thereafter as tolerated.Wet skin areas to be treated; apply Brevoxyl-4 Creamy Wash or Brevoxyl-8 Creamy Wash,work to a full lather,rinse thoroughly and pat dry.Frequency of use should be adjusted to loplastic surgery. obtain the desired clinical response.Clinically visible improvement will normally occur by the third week of therapy.Maximum lesion reduction may be expected after approximately eight to twelve weeks of “Therein lies a problem,” said Dr. Zachary. “There is a drug use.Continuing use of the drug is normally required to maintain a satisfactory clinical response.

huge difference between an experienced physician injecting HOW SUPPLIED botulinum toxin type A and someone who is not experienced, Brevoxyl-4 Creamy Wash is supplied in 170.1 g (6.0 oz) tubes NDC 0145-2474-06. particularly when the treatment is done in an environment Brevoxyl-8 Creamy Wash is supplied in 170.1 g where there is no physician supervision. We have to be very (6.0 oz) tubes NDC 0145-2484-06. careful to protect the public.” Store at controlled room temperature,15º-30ºC (59º-86ºF). * In vitro experiment. In late 2004, the medical application of botulinum toxin Clinical significance has not been established. made headlines when several people in Florida became ill af- † US Patent No. 6,433,024. References: 1. IMS Health,September 2005. ter being injected with large doses of an unapproved bulk form 2. Data on file,Stiefel Laboratories,Inc. of botulinum toxin produced for research purposes. The case 3. Savoie PM,Whitbeck N,Fraser J. An in vitro kill rate study against P.acnes comparing four benzoyl peroxide emphasized the need to acquire botulinum toxin type A only washes. Poster presented at: 62nd Annual Meeting of the American Academy of Dermatology; from reputable distributors and to have appropriate medical February 6-11,2004; Washington,DC. Brevoxyl is a registered trademark of Stiefel Laboratories,Inc. and nursing supervision whenever the substance is used, said Research in Dermatology is a trademark of Stiefel ■ Laboratories,Inc. ©2005,Stiefel Laboratories,Inc. Stiefel Laboratories,Inc. Dr. Zachary. BVX-10-2005-USA 87384 Rev. 0904 Coral Gables,FL 33134

DR. ZACHARY has nothing to disclose. 2MCOSD_S.QXD 4/11/2006 9:06 PM Page 16