Download PDF - The Dermatologist

LETTER
DEAR DERMATOLOGIST:
Welcome to the first issue of the re-designed Derm Practice, a quarterly
newsletter for practicing dermatologists.
As a fellow dermatologist, I know how busy you are seeing patients while
managing and marketing the business end of your practice. This newsletter
is designed to include several articles on topics that are timely and relevant
to the clinical and practice management sides of your practice.
As the Medical Editor of this publication, I will do my best to ensure that
the newsletter provides you with what you need to better your practice. I
will also author the Expert Advice column in each issue.
E-mail me your questions through [email protected].
Michael H. Gold, M.D.
A LOOK AT THIS ISSUE
In this issue, I answer common questions about buying a laser and selling
skin products in the office. I then describe how the use of Levulan®
Kerastic® (aminolevulinic acid HCI) and photodynamic therapy (LevulanPDT) has steadily risen over the past several years as more dermatologists
realize the benefit of this therapy.
Contributing Editor Mike Krivda then explores the problems with compounding aminolevulinic acid (ALA). DUSA has had to bring lawsuits
against pharmacists and physicians illegally using compounded ALA in
order to protect its patents for Levulan-PDT. This was done to protect the
reputation of DUSA’s products from damage that could result from the use
of an unsafe copy of its product. This article details the current lawsuits as
well as how some leading dermatologists view the issue.
I hope you find this issue of Derm Practice valuable.
Sincerely,
Michael H. Gold, M.D.
WELCOME FROM DUSA PHARMACEUTICALS
As part of our commitment to the dermatology community, we here at
DUSA are excited to sponsor this newsletter so that it can provide you with
timely, practical advice in order to help you run the best possible practice.
We hope that you find the articles in this issue and future issues valuable
and informative.
Please e-mail [email protected] with any comments or
suggestions for the newsletter. We look forward to hearing from you.
Sincerely,
Robert F. Doman
President and Chief Operating Officer, DUSA Pharmaceuticals, Inc.
EXPERT ADVICE
THIS ESTABLISHED PRACTITIONER AND CLINICAL AND
PRACTICE MANAGEMENT EXPERT ANSWERS YOUR MOST
PRESSING QUESTIONS.
BY MICHAEL H. GOLD, M.D
If I am in the
market for a laser
or light source, which
one should I buy?
Q:
We are very fortunate to have
a great deal of lasers and light
sources at our disposal and lots of
companies manufacturing these
devices that want our business.
First, find a company and a sales
representative you are comfortable
with, and a representative who truly
knows his or her product and who
can promote it without putting down
every other device in the same product range. These devices all work
similarly, with subtle differences that
the representative should be able to
share with you without putting down
the competition. Sales representatives who like to put down their competition are not welcome in my clinic.
Also, speak with other physicians
who utilize these devices; but keep in
mind that most of us are consultants
to a variety of medical device companies and will tell you the advantages
of a specific device.
Most importantly, find out the
repair/warranty information from the
company as you cannot afford to
have these devices be “down” for a
long period. If the representative
does not take an active role in your
practice and help ensure your success, look elsewhere.
A:
VERSATILE SYSTEMS
I think every practice should own an
intense pulsed light (IPL) system,
which is one of the most versatile
devices on the market. Personally, I
like the Lumenis One, the Sciton BBL,
the Cynosure PhotoSilk and the Alma
Harmony, but there are many IPL systems available on the market. Review
them all before making a decision.
New devices are also available for
the treatment of vascular lesions,
with new combination devices
becoming available.
Furthermore, newer near-infrared
collagen remodeling devices and
radio frequency devices are adding
to the armamentarium we now have
to treat the skin non-ablatively with
minimal to no downtime. We’ll cover
these devices in a future issue.
If you advertise
in a newspaper
to showcase a
certain skincare
product, that
company can
help you with
the cost.
How do I get
skincare product
companies to help me
sell their products?
Q:
Dispensing skincare products
from our offices has become
the norm amongst many of our colleagues in dermatology. When you’re
selling products in your office, the
companies that own these products
should work with you since you’re
paying them to promote their products. They should not get your business for nothing.
A:
CO-OP DOLLARS
There are several simple initiatives
that you can use to get help from
3
these companies in promoting their
products. Most companies have coop dollars available. That is, for
every product you purchase, a certain percentage of the purchase is
put into a “pot” for you to use for
advertising or for discounts on future
purchases.
Sometimes, companies will help
you with co-op advertising. If you
advertise in a newspaper to showcase a certain product, that company
may have funds available to help you
with the cost of the advertising.
We also ask the companies to provide “gift baskets”, which we use for
in-house promotions and for charitable donations. This costs you nothing, yet gives you and the skincare
company promotional opportunities.
PROMOTIONAL OPPORTUNITIES
Skincare companies also can do
other events for your office. For
instance, one company provided the
use of an UV camera system in our
medispa so that everyone who came
to my office for a 3-day period of
time had UV pictures made of their
skin. Then, we, along with the company representative who remained
with us during the promotion, were
able to show the patients their UV
damage and make “on-the-spot” recommendations for their skin care.
Companies will work with us. It’s in
their best interests to be advocates
for our practices. But remember, if
you do not ask, you will not receive.
We will cover office dispensing in a
future issue of Derm Practice. ■
Dr. Gold is Director of the Gold Skin
Care Center and the Tennessee Clinical
Research Center in Nashville, TN. He is
also Clinical Assistant Professor in the
Department of Medicine, Division of
Dermatology at Vanderbilt University
School of Medicine and School of
Nursing in Nashville, TN.
THE GROWING ROLE OF
LEVULAN-PDT
H O W T H I S C O M B I N AT I O N I S T R E AT I N G A K S A N D M O R E .
BY MICHAEL H. GOLD, M.D.
he use of aminolevulinic acid
and photodynamic therapy
(ALA-PDT) by dermatologists
has steadily risen over the past several years as more of us realize the
benefit that this therapy brings to our
patients is outstanding.
In the United States, the first indication for ALA was for the treatment
of non-hyperkeratotic AKs of the face
and scalp with a blue light source
after a 14- to 18-hour drug incubation
for 16 minutes and 40 seconds in the
blue light.
T
PROVEN RESULTS
The ALA utilized most frequently in
the United States is a 20% 5-ALA
(Levulan® Kerastick®) and the blue
light studied is the Blu-U Illuminator,
both of which are manufactured by
DUSA Pharmaceuticals.
The pivotal Phase II clinical trial
was reported in 2001.1 In this trial, 36
individuals were evaluated after treatment of their AKs with Levulan and a
Blu-U light source with drug incuba-
tion time of 14 to 18 hours. In this
study, 66% of individual AKs
responded with one treatment; 85%
of the AKs cleared with two treatments 8 weeks apart.
The Phase III clinical trial looked at
243 individuals in a multi-center setting.2 It also utilized individualized AK
treatment and drug incubation of 14
to 18 hours and a blue light source.
The study showed >70% of the
AKs were cleared with one treatment
at 12 weeks and 88% after two treatments. This was statistically superior
to a placebo arm. As a secondary
endpoint of the clinical trial, 94% of
patients noted a cosmetic effect after
the therapy, a rejuvenation-type of
effect with improved skin texture.
Even with these results, physicians
did not “buy” into this therapy for a
variety of reasons. This included predominantly the long drug incubation
time, which required patients to have
two consecutive day visits to our clinics, something with which our
patients and the medical community
weren’t comfortable. Also, patients
complained of a great deal of pain
with the associated light therapy. The
treatments caused patients to have
“downtime” — up to a week of healing, another factor patients did not
want and that cosmetic dermatologists weren’t comfortable with either.
BETTER TREATMENT GUIDELINES
From these initial clinical trials and
in an attempt to determine an easier
and more acceptable method for all
dermatologists to adopt this therapy
into their own practices, a group of
individuals began research initiatives
exploring the idea of utilizing “shortcontact, full-face” ALA therapy with
blue light and other light sources.
These lasers and light sources
were already known to work within
the spectrum of light for protoporphyrin IX (See Figure 1), which is the
active form of Levulan once it’s
absorbed into the skin. These light
sources predominantly included the
long-pulsed pulsed dye lasers
(PDLs), KTP vascular lasers and the
intense pulsed light sources (IPLs).
ALA AND IPL
The early studies looked at the
blue light and the IPL in the treatment of AKs and photorejuvenation.
Touma and Gilchrest3 showed blue
light improved the skin’s sallowness,
fine wrinkling and mottled hyperpigmentation with similar efficacy using
1-hour drug incubation as compared
to the 14- to 18-hour drug incubation.
Their study, pivotal for the “new”
ALA-PDT treatment paradigm,
showed statistically no difference
between 1-, 2- and 3-hour drug incubation when compared to the 14- to
18-hour drug incubation time.
The first use of an IPL with ALA, as
Figure 1: A variety of other light sources have
also been used to activate ALA-induced PpIX
4
reported by Ruiz-Rodriquez, et al.4
was also shown to be useful in
reducing signs of photodamage as
well as clearing 87% of the associated AKs in one of the early ALA/IPL
clinical trials.
Subsequent researchers were able
to verify the blue light and IPL results
with ALA. This author5 used three
monthly ALA-PDT treatments to evaluate photoaging and associated AKs
in 10 individuals. Drug incubation
time was from 30 to 60 minutes. At
the conclusion of the trial (3-month
follow-up from the last ALA-IPL treatment), 83% of the AKs were found to
have cleared and all the parameters
of photorejuvenation improved:
crow’s feet 90%, tactile skin roughness 100%, mottled hyperpigmentation 90% and facial erythema 70%.
Others looked at similar types of
clinical research. Goldman, et al.6
studied 32 patients with moderate
photodamage and multiple AKs.
Using a 1-hour drug incubation and
full-face therapy, they were able to
demonstrate a 90% response rate in
AK clearance and improvement in
photorejuvenation (skin texture 72%,
pigment change 59%). More than
two-thirds of patients preferred ALAPDT over cryotherapy.
Avram et al.7 used an IPL and
short-contact drug therapy in a group
of individuals with photodamage and
AKs. Following a 1-hour drug incubation, 69% of AKs cleared with one
treatment. Also, they found photorejuvenation changes including
improvement in telangectasia (55%),
pigment changes (48%), and positive
changes in skin texture (25%).
ALA AND OTHER LASERS
Alexiades-Armenakas et al.8 evaluated 3- and 18-hour drug incubation
using PDL in treating more than
2,500 AKs on and off the face. They
found the shorter drug incubation
was as effective in AK clearance as
the long incubation; clearance rates
of 90% on the face and 74% on the
torso were reported with the shortcontact ALA.
A more recent report by the same
group9 evaluated the PDL in the
treatment of actinic chelitis with
short-contact ALA. Nineteen individuals were treated with ALA and PDL;
a 68% clearance was noted at the
12-month follow-up. The KTP laser
has also been reported to be useful
in photorejuvenation with ALA.10
SPLIT-FACE ANALYSIS
To further evaluate the treatment of
AKs/photorejuvenation with light
sources, several investigations have
been performed evaluating split-face
analyses comparing IPL or PDL on
Patient was treated with ALA-PDT for 15 to 30 minutes before IPL therapy at 550 nm to 570 nm, double pulsing,
3.5 ms pulse durations and fluences of 34 J/cm2 once a month for 3 months. Actinic keratosis improved, as well as
skin texture and sallowness.
one side of the face to the other side
treated with both ALA and an IPL or
PDL device.
Alster, et al.11 reported the first
split-face trial in 2005. Ten patients,
with mild-to-moderate photodamage
received two split-face ALA-IPL treatments on one side of the face and
IPL only on the other side. Clinical
improvement scores were consistently higher on the ALA-IPL treated side
as compared to the IPL alone side.
Key12 reported the use of the PDL
in a split-face clinical trial. The ALAPDL treated side showed more
improvement than PDL alone.
Marmur, et al.13 looked at ultrastructural changes in a group of
seven patients who received ALA-IPL
on one side of the face and IPL alone
on the other side. An increase in
Type I collagen was noted in all individuals, but was more so on the ALAIPL treated side.
Bhatia, et al.14 reported their spiltface ALA-IPL study recently. They
found the ALA-IPL treated areas had
greater global scores for photoaging,
mottled hyperpigmentation, and in
fine lines compared to IPL alone.
This group also found split-face
ALA-IPL therapy to be superior to IPL
alone in treating photoaging and
associated AKs.15 There were more
improvements noted in crow’s feet,
tactile skin roughness, mottled hyperpigmentation, facial erythema and AK
clearance in the ALA-IPL sides versus the IPL treated areas.
A FIRST-LINE THERAPY
ALA-PDT therapy is here to stay.
Phase II clinical trials for photorejuvenation are underway, and hopefully
we will see an FDA clearance for this
indication in the future. In the meantime, the use of ALA-PDT in the
treatment of AKs utilizing short-contact, full-face therapy should be considered as first line for all individuals
seeking treatment from us for these
clinical concerns. ■
5
Dr. Gold is Director of the Gold Skin
Care Center and the Tennessee Clinical
Research Center in Nashville, TN. He is
also Clinical Assistant Professor in the
Department of Medicine, Division of
Dermatology at Vanderbilt School of
Medicine and School of Nursing in
Nashville, TN.
References:
1. Jeffes EW, McCullough JL, Weinstein GD, Kaplan
R, Glazer SD, Taylor JR. Photodynamic therapy of
actinic keratoses with topical aminolevulinic acid
hydrochloride and fluorescent blue light. J Am Acad
Dermatol 2001;45:96-104.
2. Piacquadio DJ, Chen DM, Farber HF, Fowler JF
Jr, Glazer SD, Goodman JJ, Hruza LL, Jeffes EW,
Ling MR, Phillips TJ, Rallis TM, Scher RK, Taylor CR,
Weinstein GD. Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in
the treatment of multiple actinic keratoses of the face
and scalp: investigator-blinded, phase 3, multicenter
trials. Arch Dermatol 2004;140(1):41-6.
3. Touma D, Yaar M, Whitehead S et al. A trial of
short incubation, broad-area photodynamic therapy
for facial actinic keratoses and diffuse photodamage.
Arch Dermatol 2004;140:33-40.
4. Ruiz-Rodriquez R, Sanz-Sanchez T, Cordobo S.
Photodynamic photorejuvenation. Dermatol Surg
2002;28:742-744.
5. Gold MH, Goldman MP. 5-Aminolevulinic Acid
Photodynamic Therapy: Where we have been and
where we are going. Derm Surg 2004;30:1077-1084.
6. Goldman MP, Atkin D, Kincad S. PDT/ALA in the
treatment of actinic damage: real world experience. J
Lasers Surg Med 2002;14(S):24.
7. Avram DK, Goldman MP. Effectiveness and safety
of ALA-IPL in treating actinic keratoses and photodamage. J Drugs Dermatol 2004;3(1 Suppl):S36-9.
8. Alexiades-Armenakas MR, Geronemus RG. Lasermediated photodynamic therapy of actinic keratoses.
Arch Dermatol 2003;139(10):1313-20.
9. Alexiades-Armenakas MR, Geronemus RG.
Laser-mediated photodynamic therapy of actinic chelitis. J Drugs Dermatol 2004;3(5):548-551.
10. Personal communication, Kauvar 2006.
11. Alster TS, Tanzi EL, Welsh EC.
Photorejuvenation of facial skin with topical 20% 5aminolevulinic acid and intense pulsed light treatment: A split-face comparison study. J Drugs
Dermatol 2005;4:35-38.
12. Key DJ. Aminolevulinic acid-pulsed dye laser
photodynamic therapy for the treatment of
Photoaging. Cosm Derm 2005;18:31-36.
13. Marmur ES, Phelps R, Goldberg DJ.
Ultrastructural changes seen after ALA-IPL photorejuvenation: a pilot study. J Cosmet Laser Ther
2005;7(1):21-4.
14. Bhatia AC, Dover JS et al. Adjunctive use of topical aminolevulinic acid with intense pulsed light in the
treatment of photoaging. (Presentation Controversies and Conversations in Cutaneous Laser
Surgery, Mt. Tremblant, Canada, August 2004).
15. Dover JS, Bhatia AC, Stewart B, Arndt KA.
Topical 5-aminolevulinic acid combined with intense
pulsed light in the treatment of photoaging. Arch
Dermatol 2005;141(10):1247-52.
PROTECTING PATIENTS
USA Pharmaceuticals, Inc.
manufactures Levulan®
Kerastic® (aminolevulinic acid
HCl), which was FDA-approved for
the treatment of actinic keratoses in
September 2000. It is the only form
of FDA-approved ALA.
To protect the substantial investment of time and money DUSA has
made to develop and test Levulan,
DUSA has obtained patent protection for its therapies. Since its therapies are based on new uses for
ALA, an existing molecule, DUSA
has obtained what are known as
“method of use” patents. This type of
patent gives the owner or licensee
the exclusive right to perform the
“method” described in the patent. In
DUSA’s case, this is performing photodynamic therapy (PDT) with ALA
for the treatment of actinic keratosis,
acne, basal cell carcinoma and various other dermatologic conditions.
DUSA has worked diligently to
develop and obtain FDA marketing
approval for Levulan,” says D.
Geoffrey Shulman, M.D.,
F.R.C.P.C., DUSA’s Chairman and
CEO. “To obtain FDA approval, our
products have undergone years of
extensive and expensive clinical
testing and evaluation to reach the
dermatology marketplace. Our products and facilities are subject to
ongoing review and inspection by
FDA to ensure that we continue to
meet their high standards for safety,
efficacy, potency and purity.
Compounded ALA, which has not
been approved for marketing by the
FDA, does not have to meet these
high standards.”
D
BASIS FOR LAWSUITS
Most physicians purchase ALA for
PDT from DUSA, but some buy it from
compounding pharmacies. Physicians
using compounded ALA and compounding pharmacies promoting
patented uses of compounded ALA
are committing patent infringement.
Compounding pharmacies have
been selling ALA without informing
physicians about the patent infringement liability for using it for purposes covered by DUSA’s patents.
In order to protect its patent rights,
in 2004 and in early 2005, DUSA
sued the Cosmetic Pharmacy of
Tucson, AZ, and New England
Compounding Center in
Framingham, MA, alleging that
these compounding pharmacies
were promoting their compounded
ALA for use in DUSA’s patented
therapies and, therefore, inducing
physicians to infringe DUSA’s
patents. The Cosmetic Pharmacy
presented no defense resulting in a
DUSA SUES OVER COMPOUNDING OF ALA.
BY MICHAEL S. KRIVDA, CONTRIBUTING EDITOR
default judgment in DUSA’s favor
and attorney fees were also rewarded to DUSA. The second suit
against New England Compounding
Center was settled.
In November 2005, DUSA filed
patent infringement suits against
physicians in California, Florida and
Tennessee. In early 2006, DUSA
filed lawsuits against doctors in
California, Michigan and
Massachusetts. The suits allege that
ALA obtained from sources other
than DUSA is being used without
license from DUSA to perform treatments in direct infringement of
DUSA’s patent(s).
PROTECTING OUR PROPERTY
We have taken these actions to
protect our Levulan franchise from
illegal exploitation from pharmacies
and others who are promoting and
selling ALA for our patented uses
and to protect our valued customers
from unfair competition from those
who infringe our patents,” says Dr.
Shulman. “While we value the longstanding relationships we have
made with the dermatology community, we have unfortunately also had
to take action against physicians
because, by selling compounded
ALA, which can be used for DUSA’s
patented therapies, compounding
pharmacies are continuing to provide a means by which physicians
take on the risk of patent infringement.”
DUSA has obtained consent judgments in five suits with the defendants admitting to infringing DUSA’s
patents and agreeing to cease illegal conduct. In one case, the defendant also admitted to illegally using
Levulan’s trademark (a violation of
the Lanham Act) and agreed to
cease this conduct. The two remaining cases are still pending.
ASSURING QUALITY CARE
Compounding pharmacies can
provide a valuable service by delivering customized compounded medications not available through any
other source. However, there is a
distinction between formulating a
6
unique and otherwise unavailable
compound and copying an available
medication.
“As a dermatologist, I know
there’s a good use for compounding
pharmacies, but when an FDAapproved product is available, the
use of a non-FDA approved compounds presents serious potential
risks,” says Mitchel Goldman, M.D.,
Associate Clinical Professor of
Dermatology/Medicine at the
University of California, San Diego.
“If good patient care is your first
concern, then you have absolutely
no reason to obtain ALA from any
other source than the FDA-approved
manufacturer.”
Noah Scheinfeld, M.D., J.D.,
Assistant Professor of Dermatology
at Columbia University, New York,
agrees, chastising physicians who
purchase compounded ALA to save
money. “It is an unfortunate state of
affairs when a licensed physician
buys a compounded medication
merely to save money,” he says. “It
is unethical when that physician
isn’t making his patients aware that
he or she is charging patients for
the name-brand product and pocketing the difference.”
TOO MANY RISKS
Dr. Goldman notes that many of
these purchases are being made by
medical spas whose staffs may not
understand the risks they’re taking.
“Compounding pharmacies are not
as experienced as they used to be
as the need for compounding is not
nearly as great as it was in the
past,” he explains. “Should you
really be relying on what may be an
inexperienced pharmacist to accurately compound a medication that
you can simply buy off the shelf?
What risks are you exposing your
patients to and what risk are you
putting yourself in? It just doesn’t
seem worth it to me, just to save a
few dollars.”
“It’s not really a question of legality
to me, that’s for the lawyers to settle;
it’s about proper care and knowing
that you are doing the best thing for
your patients,” says Dr. Scheinfeld. ■
Project2
2/1/06
3:00 PM
Page 1
Levulan® Kerastick®
(aminolevulinic acid HCI) for
Topical Solution, 20%
Nursing Mothers: The levels of ALA or its metabolites in the milk of subjects treated with LEVULAN
KERASTICK Topical Solution have not been measured. Because many drugs are excreted in human
milk, caution should be exercised when LEVULAN KERASTICK Topical Solution is administered to a
nursing woman.
ADVERSE REACTIONS
In Phase 3 studies, no non-cutaneous adverse events were found to be consistently associated
with LEVULAN KERASTICK Topical Solution application followed by blue light exposure.
INDICATIONS AND USAGE
The LEVULAN KERASTICK for Topical Solution plus blue light illumination using the BLU-U® Blue Light
Photodynamic Therapy Illuminator is indicated for the treatment of minimally to moderately thick actinic
keratoses (Grade 1: slightly palpable, better felt than seen or Grade 2: moderately thick, easily seen and
felt) of the face or scalp.
Photodynamic Therapy Response: The constellation of transient local symptoms of stinging and/or
burning, itching, erythema and edema as a result of LEVULAN KERASTICK Topical Solution plus BLU-U
treatment was observed in all clinical studies of LEVULAN KERASTICK for Topical Solution Photodynamic
Therapy for actinic keratoses treatment. Stinging and/or burning subsided between 1 minute and 24
hours after the BLU-U Blue Light Photodynamic Therapy Illuminator was turned off, and appeared qualitatively similar to that perceived by patients with erythropoietic protoporphyria upon exposure to sunlight. There was no clear drug dose or light dose dependent change in the incidence or severity of stinging and/or burning.
CONTRAINDICATIONS
The LEVULAN KERASTICK for Topical Solution plus blue light illumination using the BLU-U Blue Light
Photodynamic Therapy Illuminator is contraindicated in patients with cutaneous photosensitivity at
wavelengths of 400-450 nm, porphyria or known allergies to porphyrins, and in patients with known
sensitivity to any of the components of the LEVULAN KERASTICK for Topical Solution.
In two Phase 3 trials, the sensation of stinging and/or burning appeared to reach a plateau at 6 minutes
into the treatment. Severe stinging and/or burning at one or more lesions being treated was reported by
at least 50% of the patients at some time during treatment. The majority of patients reported that all
lesions treated exhibited at least slight stinging and/or burning. Less than 3% of patients discontinued
light treatment due to stinging and/or burning.
WARNINGS
The LEVULAN KERASTICK for Topical Solution contains alcohol and is intended for topical use only. Do
not apply to the eyes or to mucous membranes. Excessive irritation may be experienced if this product
is applied under occlusion.
The most common changes in lesion appearance after LEVULAN KERASTICK for Topical Solution
Photodynamic Therapy were erythema and edema. In 99% of active treatment patients, some or all
lesions were erythematous shortly after treatment, while in 79% of vehicle treatment patients, some or
all lesions were erythematous. In 35% of active treatment patients, some or all lesions were edematous,
while no vehicle-treated patients had edematous lesions. Both erythema and edema resolved to baseline
or improved by 4 weeks after therapy. LEVULAN KERASTICK Topical Solution application to photodamaged perilesional skin resulted in photosensitization of photodamaged skin and in a photodynamic
response. (see Precautions).
For Topical Use Only • Not for Ophthalmic Use
Brief Summary (For full prescribing information, see physician’s insert)
PRECAUTIONS
General: During the time period between the application of LEVULAN KERASTICK Topical Solution and
exposure to activating light from the BLU-U Blue Light Photodynamic Therapy Illuminator, the treatment
site will become photosensitive. After LEVULAN KERASTICK Topical Solution application, patients should
Other Localized Cutaneous Adverse Experiences: Table 1 depicts the incidence
avoid exposure of the photosensitive treatment sites to sunlight or bright indoor light (e.g., examination
and severity of cutaneous adverse events, stratified by anatomic site treated.
lamps, operating room lamps, tanning beds, or lights at close proximity) during the period prior to blue
light treatment. Exposure may result in a stinging and/or burning sensation and may cause erythema
and/or edema of the lesions. Before exposure to sunlight, patients should, therefore, protect treated
TABLE 1 Post-PDT Cutaneous Adverse Events - ALA-018/ALA-019
lesions from the sun by wearing a widebrimmed hat or similar head covering of light-opaque material.
SCALP
FACE
Sunscreens will not protect against photosensitivity reactions caused by visible light. It has not been
LEVULAN (n=42)
LEVULAN (n=139) Vehicle (n=41)
determined if perspiration can spread the LEVULAN KERASTICK Topical Solution outside the treatment
site to eye or surrounding skin.
Application of LEVULAN KERASTICK Topical Solution to perilesional areas of photodamaged skin of the
face or scalp may result in photosensitization. Upon exposure to activating light from the BLU-U Blue
Light Photodynamic Therapy Illuminator, such photosensitized skin may produce a stinging and/or
burning sensation and may become erythematous and/or edematous in a manner similar to that of
actinic keratoses treated with LEVULAN PDT. Because of the potential for skin to become photosensitized, the LEVULAN KERASTICK for Topical Solution should be used by a qualified health professional to
apply drug only to actinic keratoses and not perilesional skin.
Degree of
Severity
Scaling/
Crusting
Pain
The LEVULAN KERASTICK for Topical Solution has not been tested on patients with inherited or
Tenderness
acquired coagulation defects.
Itching
Information for Patients:
Edema
LEVULAN Photodynamic Therapy for Actinic Keratoses. The first step in LEVULAN KERASTICK photodyUlceration
namic therapy (PDT) for actinic keratoses is application of the LEVULAN KERASTICK for Topical Solution
Bleeding/
to actinic keratoses located on the patient’s face or scalp. After LEVULAN KERASTICK for Topical
Solution is applied to the actinic keratoses in the doctor’s office, the patient will be told to return the
Hemorrhage
next day. During this time the actinic keratoses will become sensitive to light (photosensitive). Care
Hypo/hypershould be taken to keep the treated actinic keratoses dry and out of bright light. After LEVULAN KERApigmentation
STICK Topical Solution is applied, it is important for the patient to wear light-protective clothing, such
as a wide-brimmed hat, when exposed to sunlight or sources of light. Fourteen to eighteen hours after Vesiculation
application of LEVULAN KERASTICK Topical Solution the patient will return to the doctor’s office to
Pustules
receive blue light treatment, which is the second and final step in the treatment. Prior to blue light
Oozing
treatment, the actinic keratoses will be rinsed with tap water. The patient will be given goggles to
Dysesthesia
wear as eye protection during the blue light treatment. The blue light is of low intensity and will not
heat the skin. However, during the light treatment, which lasts for approximately 17 minutes, the
Scabbing
patient will experience sensations of tingling, stinging, prickling or burning of the treated lesions.
These feelings of discomfort should improve at the end of the light treatment. Following treatment, the Erosion
Excoriation
actinic keratoses and, to some degree, the surrounding skin, will redden, and swelling and scaling
may also occur. However, these lesion changes are temporary and should completely resolve by 4
Wheal/Flare
weeks after treatment.
Skin disorder
Photosensitivity
NOS
After LEVULAN KERASTICK Topical Solution is applied to the actinic keratoses in the doctor’s office, the
patient should avoid exposure of the photosensitive actinic keratoses to sunlight or bright indoor light
(e.g., from examination lamps, operating room lamps, tanning beds, or lights at close proximity) during
the period prior to blue light treatment. If the patient feels stinging and/or burning on the actinic keratoses, exposure to light should be reduced. Before going into sunlight, the patient should protect treated lesions from the sun by wearing a wide-brimmed hat or similar head covering of light-opaque material. Sunscreens will not protect the patient against photosensitivity reactions.
If for any reason the patient cannot return for blue light treatment during the prescribed period after application of LEVULAN KERASTICK Topical Solution (14 to 18 hours), the patient should call the doctor. The
patient should also continue to avoid exposure of the photosensitized lesions to sunlight or prolonged or
intense light for at least 40 hours. If stinging and/or burning is noted, exposure to light should be reduced.
Drug Interactions: There have been no formal studies of the interaction of LEVULAN KERASTICK for
Topical Solution with any other drugs, and no drug-specific interactions were noted during any of the
controlled clinical trials. It is, however, possible that concomitant use of other known photosensitizing
agents such as griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides and tetracyclines might increase the photosensitivity reaction of actinic keratoses treated with the LEVULAN KERASTICK for Topical Solution.
Carcinogenesis, Mutagenesis, Impairment to Fertility: No carcinogenicity testing has been carried out
using ALA. No evidence of mutagenic effects was seen in four studies conducted with ALA to evaluate
this potential. In the Salmonella-Escherichia coli/mammalian microsome reverse mutation assay (Ames
mutagenicity assay), no increases in the number of revertants were observed with any of the tester
strains. In the Salmonella-Escherichia coli/mammalian microsome reverse mutation assay in the presence of solar light radiation (Ames mutagenicity assay with light), ALA did not cause an increase in the
number of revertants per plate of any of the tester strains in the presence or absence of simulated solar
light. In the L5178Y TK± mouse lymphoma forward mutation assay, ALA was evaluated as negative with
and without metabolic activation under the study conditions. PpIX formation was not demonstrated in
any of these in vitro studies. In the in vivo mouse micronucleus assay, ALA was considered negative
under the study exposure conditions. In contrast, at least one report in the literature has noted genotoxic
effects in cultured rat hepatocytes after ALA exposure with PpIX formation. Other studies have documented oxidative DNA damage in vivo and in vitro as a result of ALA exposure.
No assessment of effects of ALA HCl on fertility has been performed in laboratory animals. It is unknown
what effects systemic exposure to ALA HCl might have on fertility or reproductive function.
Pregnancy Category C: Animal reproduction studies have not been conducted with ALA HCl. It is also
not known whether LEVULAN KERASTICK Topical Solution can cause fetal harm when administered to a
pregnant woman or can affect reproductive capacity. LEVULAN KERASTICK Topical Solution should be
given to a pregnant woman only if clearly needed.
Vehicle (n=21)
Mild/
Mild/
Mild/
Mild/
Moderate Severe Moderate Severe Moderate Severe Moderate Severe
71%
1%
12%
0%
64%
2%
19%
0%
1%
1%
25%
1%
4%
4%
0%
0%
1%
0%
0%
0%
0%
0%
7%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
2%
14%
0%
2%
2%
0%
0%
7%
0%
0%
0%
0%
0%
19%
0%
0%
0%
0%
0%
0%
0%
0%
0%
22%
4%
4%
1%
2%
2%
14%
1%
7%
5%
20%
0%
0%
0%
0%
1%
1%
0%
1%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
36%
0%
0%
0%
0%
0%
0%
0%
0%
0%
5%
0%
0%
0%
0%
2%
0%
2%
12%
33%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
5%
0%
0%
0%
0%
0%
0%
0%
0%
0
Adverse Experiences Reported by Body System: In the Phase 3 studies, 7patients experienced a serious adverse event. All were deemed remotely or not related to treatment. No clinically significant patterns of clinical laboratory changes were observed for standard serum chemical or hematologic parameters in any of the controlled clinical trials.
OVERDOSAGE
LEVULAN KERASTICK Topical Solution Overdose: LEVULAN KERASTICK Topical Solution overdose have
not been reported. In the unlikely event that the drug is ingested, monitoring and supportive care are
recommended. The patient should be advised to avoid incidental exposure to intense light sources for at
least 40 hours. The consequences of exceeding the recommended topical dosage are unknown.
BLU-U® Light Overdose: There is no information on overdose of blue light from the BLU-U Blue Light
Photodynamic Therapy Illuminator following LEVULAN KERASTICK Topical Solution application.
HOW SUPPLIED
The LEVULAN KERASTICK for Topical Solution, 20%, is a single-unit dosage form, supplied in packs of 6.
Each LEVULAN KERASTICK for Topical Solution applicator consists of a plastic tube containing two sealed
glass ampules and an applicator tip. One ampule contains 1.5 mL of solution vehicle. The other ampule contains 354 mg of aminolevulinic acid HCl. The applicator is covered with a protective cardboard sleeve and cap.
Product Package
Individual LEVULAN KERASTICK for Topical Solution, 20%
Carton of 6 LEVULAN KERASTICKS for Topical Solution, 20%
NDC number
67308-101-01
67308-101-06
Storage Conditions: Store between 20º– 25ºC (68º– 77ºF); excursions permitted to 15º– 30ºC (59º–
86ºF) [See USP Controlled Room Temperature]. The LEVULAN KERASTICK for Topical Solution should be
used immediately following preparation (dissolution). Solution application must be completed within 2
hours of preparation. An applicator that has been prepared must be discarded 2 hours after mixing (dissolving) and a new LEVULAN KERASTICK for Topical Solution used, if needed.
LEVULAN®, KERASTICK®, BLU-U®, DUSA Pharmaceuticals, Inc.® and DUSA® are registered
trademarks of DUSA Pharmaceuticals, Inc.®
US Patents: 5,079,262, 5,211,938, 5,422,093, 5,954,703, 6,710,066
Manufactured for: DUSA Pharmaceuticals, Inc.® 25 Upton Drive, Wilmington, MA 01887
For more information please contact:
1-877-533-3872 or 1-978-657-7500
www.dusapharma.com
7
MKT-1330 Rev B
Levulan
®
Photodynamic Therapy
Treats AKs without weeks
of red, raw skin.
Instead, skin response usually subsides within a week after
treatment, which is why 4 out of 5 patients prefer Levulan
to previous 5-FU treatments.3
The BLU-U® Blue Light Photodynamic Therapy Illuminator
is also FDA cleared for light alone treatment of moderate
inflammatory acne.
Levulan® Kerastick®
(aminolevulinic acid HCI) for Topical Solution, 20%
Levulan® is the only FDA approved ALA
Call DUSA at 877-533-3872 or www.dusapharma.com
Reference: 1. Data from Phase III Clinical Trials. Data on file, DUSA Pharmaceuticals Inc®. 2.Data based on 173 patients treated and assessed for cosmetic results and
physician evaluation of 1340 lesions. 3.Data based on 27 patients who had previous 5-fluorouracil treatment
83 General Warren Blvd., Suite 100
Malvern, PA 19355
94%
of patients rated cosmetic
response as good
to excellent1, 2