Joel Schlessinger MD discusses skin bleaching compound hydroquinone. Topics include FDA, customer satisfaction and customer reported side effects.

1. Hydroquinone Update/Strategies
Joel Schlessinger MD
Course Director, Cosmetic Surgery Forum

2. Disclosure of Relevant Relationships with Industry
Joel Schlessinger, MD
Advisory Board / Consultant Researcher
Abbott 3M Pharma., Abbot
Pharma., Allergan, Amgen, Artes, Derm Pharma., Allergan, Amgen, Astellas,
ik, Galderma, Genentech, Glaxo, Health Barrier
and Wellness Council of Therapeutics, Biogen, Centocor, Clay-
America, Kythera, MEDICIS, Mentor, M Park
erz, MJD Labs, Collagenix, Connetics, Dermik,
Communications, Novartis, Obagi, Orth
Dow, ESC
Medical, Fujisawa, Galderma, Genent
o Pharma. (Johnson &
ech, Glaxo Pharma., Glenmark
Johnson), Stiefel, TheDerm.org
Stockholder Pharma., HealthPoint, Immunex, Ipse
n/
Allergan, Excel
Inamed, Kythera, MEDICIS, Mentor,
Cosmeceuticals, MEDICIS, J and Merz, Novartis, Novum, NUCRYST, Or
J, Obagi tho Pharma. (Johnson &
Johnson), Penederm
Pharma., Perrigo, Pfizer, QLT
USA, Regeneratio Pharma
AG, Sandoz, Schering Plough, Stiefel

3. Proposed Rule
• Skin Bleaching Drug Products for OTC Use
• August 29, 2006
• No decision yet
• Could affect over 200 products in use

4. Current
• OTC 1.5% to 2% have GRASE (generally recognized as
safe and effective)
• Majority of OTC and Rx HQs have 2% to 4%
• New rule would extend DESI, a 1962 rule, (Drug
Efficacy Study Implementation) to those currently
exempted from an NDA

5. Quote from Dr. Kligman
“If we give up on
hydroquinone, we’re
damn fools!”

6. New Rule
• FDA intends to consider all HQs, whether Rx or
OTC, as new drugs!
• Could it extend even to TriLuma?

7. Evidence
• Some evidence of carcinogenicity in rats and mice in
1989 and 1992 following gavage (not dermal)
administration
• HQ is highly absorbed (57%) in humans
• ? Ochronosis reports

8. Do the studies add up?
• 100 mg/kg/day HQ to mice via oral gavage
• 50 mg/kg/day HQ to rats via oral gavage
• No toxicity when administered via dermal route in
animals
• 5% HQ for 13 weeks in rats only showed irritation

9. Absorption
• Absorption is highly species characteristic
• Metabolism is hepatic in humans and results in
deactivation and detoxification in humans vs rats
• Rats tend to activate HQ
• Exposure route matters (oral vs dermal)

10. Ochronosis
• Unclear why it is so high in reports, but not
evidenced in US
• Dermchat experience (no reports of ochronosis over
1400 members
• No reports of ochronosis in chemical factory workers
or other issues
• Kligman: Concerns of ochronosis and cancer come
from “bureaucrats who have no background.”

11. What else is there?
• Lumixyl: Oligopeptide that inhibits mushroom
tyrosinase and human tyrosinase
• 43% reduction in melanin activity
• Non-toxic to melanocytes
• Can be used as an alternative to HQ

12. Obagi system and other HQ compounds
• Obagi with Botox study
• Obagi along with Botox had significant improvement
in results than Botox with Cetaphil
• 100% of patients wished to continue on Obagi vs
20% in the Cetaphil group

13. Figure 1. Hyperpigmentation.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
Mean 3 Moderate
hyperpigmentation
score
2 Mild
1 ** * *** *** Trace
0 None
0 30 60 90 120
Day
* P≤.05, ** P≤.01, *** P≤.001 compared with standard skin care

14. Figure 2. Fine lines and wrinkles.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
3 Moderate
Mean
fine lines/ 2 Mild
wrinkles
score ** * *
1 Trace
0 None
0 30 60 90 120
Day
* P≤.05, ** P≤.01 compared with standard skin care

15. Figure 3. Patient satisfaction with overall improvement in facial appearance.
Hydroquinone system Standard skin care
+ tretinoin
100 89% 88% 89%
82%
80 Satisfied
Patients Extremely satisfied
(%)
60 55%
40
22%
20 20%
11% 12% 12%
0
0 30 60 90 120 0 30 60 90 120
Day
[Significant between-group difference in overall ratings at days 30, 60, 90, and 120, P≤.001]

16. Figure 4. Effect of study treatment in further enhancing facial appearance
after botulinum toxin type A treatment (a comparison with the effect of past
treatment using botulinum toxin type A alone).
Hydroquinone system Standard skin care
+ tretinoin Somewhat improved
Improved
Greatly improved
100 92%
86%
79%
80 71%
Patients 60
(%)
40
20 11% 12% 7% 8%
0
30 60 90 120 30 60 90 120
Day
[Significant between-group difference in overall ratings at all timepoints, P≤.001]

17. Figure 5. Patient evaluation of facial appearance compared to age.
Hydroquinone system Standard skin care
+ tretinoin
10% 7% Look younger/much younger
Baseline 30% 29% Look current age
Look older/much older
60% 65%
8%
23%
36%
Day 120
64%
69%
[Significant between-group difference in overall ratings at days 60, 90, and 120, P≤.05]

18. Figure 6. Burning.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
3 Moderate
Mean
burning 2 Mild
score
1 *** Trace
*
*
0 None
0 30 60 90 120
Day
* P≤.05, *** P≤.001 compared with standard skin care

19. Figure 7. Dryness.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
3 Moderate
Mean
dryness 2 Mild
score ***
1 ** ** Trace
**
0 None
0 30 60 90 120
Day
** P≤.01, *** P≤.001 compared with standard skin care

20. Figure 8. Peeling.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
3 Moderate
Mean
peeling 2 Mild
score
*** *** *** ***
1 Trace
0 None
0 30 60 90 120
Day
*** P≤.001 compared with standard skin care

21. Figure 9. Erythema.
Hydroquinone system + tretinoin
Standard skin care
4 Severe
3 Moderate
Mean ***
erythema 2 * ***
Mild
score
1 Trace
0 None
0 30 60 90 120
Day
* P≤.05, *** P≤.001 compared with standard skin care

22. Before and After

23. Before and After

24. Before and After

25. Before and After