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1
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Optimizing Oral Antibiotic Treatment for Acne Vulgaris
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.DORYX® is a registered trademark of Warner Chilcott Company, LLC.
1
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
2PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Presenter
James Q. Del Rosso, DODermatology Residency Program Director
Valley Hospital Medical CenterLas Vegas, Nevada
Dermatology & Cutaneous SurgeryLas Vegas Skin & Cancer Clinics
Las Vegas and Henderson, Nevada
3PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Table of Contents
Presentation Highlights • Acne Vulgaris: Epidemiology and Classification
• Acne Vulgaris: Impact on Quality of Life (QOL)
• Acne Vulgaris: Treatment Options
• DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP)
• Efficacy of Doxycycline
• Safety and Tolerability of Doxycycline
• Dermatologists’ Prescribing Trends
• Treatment Challenges for Acne Patients
• Summary of Key Points and Data
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
4
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Vulgaris:Epidemiology and
Classification
4
5PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Vulgaris Is a Common Dermatologic Condition
• Accounts for 14 million office visits per year1
• Most patients are teenagers2
– 85% of teenagers between the ages of 15 and 17 years have some degree of acne1
• 10% of visits are reported to be for patients 35 to 44 years of age2,3
1. Mancini JA. Johns Hopkins Adv Stud Med. 2008;8:100-105. 2. Del Rosso JQ, Kim G. Dermatol Clin. 2009;27:33-42.3. Weinstock MA, Boyle MM. In: Del Rosso JQ, ed. Year Book of Dermatol and Dermatol Surg 2010. Philadelphia, PA:
Elsevier; 2010:35-50.
6PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Lesion
Healthy Skin
Sebaceous Gland
Hair Follicle
Oily Secretion
s From Sebaceous Gland
Keratinocytes
Inflammation
Anatomy of the Pilosebaceous Follicle1,2
1. Adapted from Management of acne vulgaris. http://healthproductsreviewed.org/management-of-acne-vulgaris.html#more-105. Accessed April 13, 2011.
2. Gollnick H. Drugs. 2003;63:1579-1596.
7PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Types of Acne Lesions
Comedonal Acne Inflammatory Acne
Cysts2,3 Pustule2,4 Papule2,5
Scarring6,7 Hyperpigmentation7,8
Open Comedones1,2
Closed Comedones1,2
1. Acne types. http://www.acne101.org/types.html. Accessed April 13, 2011. 2. Gollnick H, et al. Drugs. 2003;63:1579-1596. 3. Cystic acne treatment. http://www.hbbase.com. Accessed April 13,2011. 4. Teens about acne. http://www.clearupskincare.org/aboutacnea.html. Accessed April 13, 2011. 5. Acne papules treatment - there is a cure. http://www.getacnehomeremedies.info/search/acne-papules-treatment-there-is-a-cure. Accessed April 13, 2011. 6. Facial acne scars. http://www.bioskincream.com. Accessed April 13,2011. 7. Gollnick H, et al. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37. 8. Skin site. http://www.skinsight.com/info/blog/2009/03/12/qa-acne-scars. Accessed April 13, 2011.
8PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
MILD2 MODERATE3 SEVERE4
Comedones <20 20-100 >100
Papules/Pustules
<15 15-50
>50
Nodules/Cysts >5
Total <30 30-125 >125
Classification of Acne Vulgaris1
1. Lehmann HP, et al. J Am Acad Dermatol. 2002;47:231-240. 2. How to treat acne marks. http://hubpages.com/hub/How-To-Treat-Acne-Discolorations. Accessed April13, 2011. 3. The skin center. http://lagunaskincare.com. Accessed April 13, 2011. 4. Preventing scars. http://cure-your-acne.com. Accessed April 13, 2011.
9PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Progression of an Acne Lesion
Hair
Skin Surface
Sebum
Hair Follicle
Sebaceous Gland
Dead Skin Cells
Blackhead
Trapped Sebum
Rupture
Inflamed Tissue
Pus
Epidermis
Normal Pilosebaceous UnitFormation of Comedones
(Blackheads and Whiteheads)
Formation of Papules, Pustules, Nodules,
or Cysts; Inflammation; Rupture
Adapted from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 5th ed. New York: McGraw-Hill; 2005.
Pugliese S. Acne: Fact vs Fiction. http://dermhub.com/2009/08/the-411-on-acne. Accessed April 13, 2011.
10PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Lesions and Pathophysiology1
Papule
Pustule
Nodule
Cyst
ACNE2
P. acnesInflammatio
n
Keratinization
Sebum Production
1. Monk E, et al. Pharmacol Res. 2011;63:130-145.2. What is acne? http://www.acne.org. Accessed April 13, 2011.
11PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
P. acnes Induces Inflammation1,2
Disruption of Follicular
Epithelium
Neutrophil and Lymphocyte Infiltration
Lipases, Proteases, Other
Enzymes
P. acnes
Chemotactic Factors
Proinflammatory
Mediators
Proinflammatory Mediators
1. Webster GF. J Am Acad Dermatol. 1995;33:247-253.2. Holland DB, Jeremy AHT. Semin Cutan Med Surg. 2005;24:79-83.
SCARRING
INFLAMMATION
12PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Current Consensus: Acne Is an Inflammatory Condition1
1. Kircik L. Pract Dermatol. 2011;3:35-39.2. Jeremy AH, et al. J Invest Dermatol. 2003;121:20-27.
Increase in CD4+ T cells observed near uninvolved follicles from acne patients2
IL-1 and IL-1 receptor expression increased2
• The cause of the increase in IL-1 activity is unknown
• Could be due to low linoleic acid levels
• In the absence of evidence of hyperkeratinization
• T cells were not activated
• Possibly a response to cytokine stimulation of endothelium
IL=interleukin.
13
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Vulgaris:Impact on Quality of Life
(QOL)
13
14PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Presents Significant Challenges
Physical1
• Scarring • Hyperpigmentation
Emotional1
• Anxiety• Depression• Suicidal thoughts• Frustration• Anger
• Scarring develops in approximately 95% of patients with clinical acne2
• Emotional impact of acne is particularly difficult during the period of adolescence, when there is pronounced vulnerability1
1. Gollnick H, et al. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37. 2. Layton AM, et al. Clin Exp Dermatol. 1994;19:303-308.
15PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Severely Affects QOL
Klassen AF, et al. J Am Acad Dermatol. 2000;43:229-233.
Anxiety and Depression Are the Biggest Challenges
That Adversely Affect QOL
QOL Areas of Measure
16PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
•Acne should be approached as a chronic disease•Acne can be a psychologically damaging
condition that lasts for many years
•Limit the duration of active acne by effective treatment
•Reduce the likelihood of physical and emotional scarring
Consensus of the Global Alliance to Improve Outcomes in Acne Group
Acne should not be dismissed as a natural part of growing up
Early and aggressive treatment of acne is recommended by the Global Alliance to Improve Outcomes in Acne Group
Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50.
17
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Acne Vulgaris:Treatment Options
17
18PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Considerations for Acne Treatment1
Severity of Acne
Presence ofAcne
Scarring
Type of Acne Lesions
Psychologicaland
Social Impact
1. Goulden V. Pediatr Drugs. 2003;5:301-313.2. Kircik L. Pract Dermatol. 2011;3:35-39.
Choice of Therapy
Depends on
A Goal of Acne Therapy Is to Prevent Scarring2
19PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Global Alliance: Acne Treatment Algorithm1,2
Mild Moderate Severe
Comedonal Mixed and
Papular/Pustular
Mixed and Papular/Pustula
r Nodular* Nodular/
Conglobate
Topical retinoid
Topical retinoid + topical antibiotic
Oral antibiotic+ topical retinoid
± BPO
Oral antibiotic + topical retinoid
+ BPO
Oral isotretinoin†
Alt. topical retinoid or azelaic
acid§ or salicylic
acid
Alt. topical antibiotic + alt. topical retinoid or
azelaic acid§
Alt. oral antibiotic
+ alt. topical retinoid ± BPO
Oral isotretinoin or alt.
oral antibiotic + alt. topical
retinoid ± BPO/azelaic
acid§
High-dose oral antibiotic
+ topical retinoid + BPO
See 1st choice See 1st choice
Hormonal therapy,
oral antiandrogen
+ topical retinoid/
azelaic acid§ ± topical antibiotic
Hormonal therapy,
oral antiandrogen+ topical retinoid
± oral antibiotic
± alt. antibiotic
High-dose oral antiandrogen
+ topical retinoid
± alt. topical antibiotic
Topical retinoid Topical retinoid ± BPO
1st Choice
Alternatives‡
Alternatives for
Female Patients‡§
Maintenance Therapy
BPO=benzoyl peroxide. *With small nodules (<0.5-1 cm); †Second course in case of relapse; ‡Consider physical removal of comedones; §There was no consensus on this alternative recommendation; however, in some countries, azelaic acid prescribing is considered appropriate practice.
1. Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50.2. Gollnick H, et al. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37.
20PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Use of Antibiotics in Dermatology
• Annual number of antibiotic prescriptions written by dermatology practices
• Based on US usage data, 2001 to 2006
8-9 million oral antibiotic prescriptions
• Majority of prescriptions are written for tetracycline derivatives
• Primarily doxycycline and minocycline
Two-thirds of prescriptions
• Most oral antibiotics are prescribed for treating acne vulgaris and rosacea
Acne vulgaris and rosacea
• Annual number of topical antibiotic prescriptions written by dermatology practices
• Based on US usage data, 2001 to 2006
3-4 million topical antibiotic
prescriptions
Del Rosso JQ, Kim G. Dermatol Clin. 2009;27:33-42.
21PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Actions of Acne Therapies1-3
Anti-comedonal
Effect Anti-P. acnesAnti-
inflammatory
Oral antibiotics + +++ +++
Topical antibiotics + benzoyl peroxide
+ +++ +
Topical retinoids +++ – ++
1. Bikowski J. Pract Dermatol Ped. 2011;1:23-26.2. Kircik L. Pract Dermatol. 2011;3:35-39.3. Sapadin AN, Fleischmajer R. J Am Acad Dermatol. 2006;54:258-265.
22PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Oral Antibiotics for Treatment of Acne
1. IMS Health, Inc. National Prescription Data: July 2004–July 2009 (estimate derived from the use of information under license from IMS Health, Inc., which expressly reserves all rights, including rights of copying). 2. Del Rosso JQ, Kim G. Dermatol Clin. 2009;27:33-42. 3. Strauss JS, et al. J Am Acad Dermatol. 2007;56:651-663. 4. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 5. Tetracycline hydrochloride [package insert]. Corona, CA: Watson Pharma, Inc.; 2010. 6. Minocycline hydrochloride [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2010.
•More effective than first-generation tetracyclines3
•Less bacterial resistance than first- generation tetracyclines or erythromycin2
•More convenient dosing4-6
Minocycline and doxycycline are the most frequently prescribed antibiotics for acne in the United States1,2
23PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Effects of Tetracycline
1. Ochsendorf F. Am J Clin Dermatol. 2010;11:327-341.2. Sapadin AN, Fleischmajer R. J Am Acad Dermatol. 2006;54:258-265.
24PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Doxycycline
• Highly lipophilic drug with excellent tissue penetration1,2
– More lipophilic than first-generation tetracyclines3
• Almost completely absorbed after oral administration1,2
– Absorption is largely unaffected by foods4
• Several different formulations3,5
– Doxycycline monohydrate
– Doxycycline hyclate
1. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.2. Saivin S, Houin G. Clin Pharmacokinet. 1988;15:355-366. 3. Cunha BA, et al. Ther Drug Monit. 1982;4:115-135. 4. Welling PG, et al. Antimicrob Agents Chemother. 1977;11:462-469.5. Kitzes-Cohen R, et al. Curr Ther Res. 1998;59:315-323.
25
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
26PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
• Enteric-coated: contains specially coated pellets of doxycycline hyclate
• Indicated as adjunctive therapy for severe acne
• Primarily bacteriostatic and exerts its antimicrobial effect by the inhibition of protein synthesis
• Effective against a wide range of gram-positive and gram-negative bacteria and other pathogens
• Effective against P. acnes
DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
27PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
• Tablets contain an enteric-coated delivery system of delayed-release, specially coated pellets of doxycycline hyclate
– The enteric coating is pH sensitive; it does not dissolve in acidic pH environments such as the stomach
– When the pellets are exposed to a more alkaline pH such as found in the small intestine, the enteric coating dissolves and the active drug is released and absorbed
• Designed to minimize the exposure of the upper gastrointestinal tract to doxycycline
– Tablets dissolve in the stomach, and the enteric-coated pellets are dispersed
– Enteric-coated pellets dissolve in the small intestine, where the doxycycline is absorbed
27
DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
28PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Dosing flexibility• Scored tablets facilitate dose titration
• Tablets may be taken at any time during the day, and do not need to be taken with milk or food
• Tablets can be taken more easily by patients who have difficulty swallowing
– DORYX® tablets may also be administered by carefully breaking up the tablet and sprinkling the tablet contents (delayed-release pellets) on a spoonful of applesauce
DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by yoursales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
29
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Efficacy of Doxycycline
29
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by yoursales representative and at www.doryx.com.
30PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Doxycycline and Minocycline Have Comparable Efficacy in Acne
• Randomized, double-blind study†
• 3 months of treatment
• Comparable efficacy
P>0.75
*Score included grading for extension of symptoms; seborrhea; comedones and whiteheads; papules and pustules; infiltration; and abscesses, before treatment and after 3 months.
†n=18.
Smit F. Dermatologica. 1978;157:186-190.
Mean
Diff
ere
nce i
n E
fficacy S
core
*
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by yoursales representative and at www.doryx.com.
31PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Consistent Results: Comparable Efficacy
• 12-week, randomized, double-blind study*
• Doxycycline 50 mg BID (4 weeks), 50 mg QD (8 weeks) was as effective as minocycline 50 mg BID (4 weeks), 50 mg QD (8 weeks)
Ólafsson JH, et al. J Dermatolog Treat. 1989;1:15-17.
Figure 1. The number of all lesions (with SEM) in all three areas (All) as well as the sum of all lesions on the face, back, and chest during treatment with doxycycline and minocycline.*n=79
Doxycycline
Minocycline
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
32
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Safety and Tolerability of Doxycycline
32
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
33PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Tetracycline-class AEs: Class Effects*
*All tetracyclines carry common labeling with regard to adverse reactions.
AE=adverse event, GI=gastrointestinal.
Tetracycline Minocycline Doxycycline
Class Effects
GI upset Yes1-3 Yes1,2,4-6 Yes1,2,5,7
Photosensitivity Yes1-3 Yes4,5 Yes1,2,5,7
Known or possible P. acnes resistance
Yes1,2 Yes1,2 Yes1,2,7
Tooth discoloration in children ≤8 years or in developing fetuses
Yes1-3,8 Yes1,2,4,5,8 Yes1,2,5,7
Pseudotumor cerebri Yes2,9 Yes1,2,4,9 Yes2,7,9
Clostridium difficile– associated diarrhea (CDAD)
Yes10,11 Yes4,10,11 Yes7,10,11
1. Ochsendorf F. Am J Clin Dermatol. 2010;11:327-341. 2. Zouboulis CC, Piquero-Martin J. Dermatology. 2003;206:37-53. 3. Tetracycline hydrochloride [package insert]. Corona, CA:Watson Pharma., Inc.;2010. 4. Minocycline hydrochloride [package insert]. Morgantown, WV; Mylan Pharmaceuticals Inc.;2010. 5. Kircik LH. J Drugs Dermatol. 2010;9:1407-1411. 6. Schlienger RG, et al. Dermatology. 2000;200:223-231. 7. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 8. Sánchez AR, et al. Int Soc Dermatol. 2004;43:709-715. 9. Friedman DI. Am J Clin Dermatol. 2005;6:29-37. 10. Delaney JAC, et al. Emerg Inf Dis. 2007;13:761-763. 11. Bartlett JG. Clin Infect Dis. 2008;46(Suppl1):S4-S11.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
34PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Tetracycline-class AEs: Drug-specific Effects*
*There are some important differences in drug-specific AEs between doxycycline and minocycline.
Tetracycline Minocycline Doxycycline
Drug-specific Effects
Vertigo No Yes1-4 No
Skin hyperpigmentation No Yes1-5 No
Autoimmune hepatitis No Yes1-3,5 No
Hypersensitivity reactions Rare3 Yes1-5 Rare3,6
Drug-induced lupus-like syndrome No Yes1-5,7 No
1. Smith K, Leyden JJ. Clin Ther. 2005;27:1329-1342. 2. Ochsendorf F. Am J Clin Dermatol. 2010;11:327-341. 3. Zouboulis CC, Piquero-Martin J. Dermatology. 2003;206:37-53. 4. Kircik LH. J Drugs Dermatol. 2010;9:1407-1411 5. Schlienger RG, et al. Dermatology. 2000;200:223-231. 6. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 7. Margolis DJ, et al. Br J Dermatol. 2007:157:540-546.
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
35PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Doxycycline Safety/Tolerability Compared With That of Minocycline
• Doxycycline was written 3 times more often than minocycline
• Over 5 times as many AEs were reported with minocycline
• Minocycline-specific AEs and warnings– Skin hyperpigmentation– CNS side effects (vertigo,
dizziness)– Lupus-like syndrome– Hepatitis
• Doxycycline-specific AEs and warnings– Esophageal erosion– Skin side effects (photosensitivity
and photo-onycholysis)– CNS side effects (intracranial
hypertension)– Hypoglycemia
Rep
ort
ed
AEs/M
illion
New
Pre
scri
pti
on
s D
isp
en
sed
US AE Rates, FDA Reports (1998-2003)*
n=628 AEs Reported
n=1099 AEs Reported
†
†
Smith K, Leyden JJ. Clin Ther. 2005;27:1329-1342.
*Based on spontaneous reporting.†Calculated AEs.‡Central Nervous System
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
36
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
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Dermatologists’Prescribing Trends
36
37PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Dermatologists Prefer Doxycycline
IMS Health, Inc. National Prescription Data: April 2005–April 2010 (estimate derived from the use of information under license from IMS Health, Inc., which expressly reserves all rights, including rights of copying).
Doxycycline: Prescribed by Dermatologists More Often Than Minocycline*
New
Pre
scri
pti
on
s,
million
s
*Includes brand and generic.
Years(April 2005 – April 2010)
38
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
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Treatment Challengesfor Acne Patients
38
39PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Issues With Compliance to Acne Therapy
Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50.
•48% compliance was reported in a study of college-aged patients using BPO (over the counter)
•44% of patients (with dermatologic conditions) reported that they did not follow their prescription regimen exactly
Poor compliance may be a major contributor to
treatment failure
• In a study, 87% of patients took a QD dose on schedule, whereas only 39% were able to take a QID dose on schedule
Frequency of administration is
negatively correlated with
compliance
40PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
For the Adolescent, Acne Therapy Is Only as Good as Compliance
• Acne is most common in adolescence
– 58% of patients are aged 10 to 19 years2
• Adolescents are a high-risk group for noncompliance3
– Dosing – BID dosing and administration restrictions discourage compliance3,4
– AEs – lead to missed doses3
– Delayed onset of action – leads to frustration and noncompliance3
• Female patients are more adherent than male patients5
– 71% vs 60%, P<0.00011. Zaghloul SS, et al. Br J Dermatol. 2005;152:1015-1021. 2. IMS Health, Inc. NDTI Audit: July 2006–June 2007 (estimate derived from the use of information under license from IMS Health, Inc., which expressly reserves all rights, including rights of copying). 3. Baldwin HE. Dermatol Therapy. 2006;19:224-236. 4. McNabb JJ, et al. AIDS. 2003;17:1763-1767. 5. Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50.
Mean
Med
icati
on
Ad
here
nce,
%
Compliance Among Acne Patients Who Reported These Reasons for Missing
Treatment (n=403)1
Treatment Success = Efficacy + Tolerability + Compliance
Rationale for Noncompliance
41PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
GI Side Effects: #1 Reason for Noncompliance in Teenagers
Physicians’ Opinions, AAD 2008: Ranking of Causes of Teenaged Acne Patients’
Noncompliance With Oral Antibiotics
Acne survey conducted at the 66th Annual Meeting of the American Academy of Dermatology (n=100); February 1-5, 2008; San Antonio, TX. Report # RD07-M028. Rockaway, NJ: Warner Chilcott (US), LLC.
CNS=central nervous system; GI=gastrointestinal.
*eg, take with food.
42
Please see Selected Safety Information for DORYX® on slide 43, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILINGPROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
DORYX®: Summary of Key Points and Data
42
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
43PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
• DORYX® is indicated as adjunctive therapy for severe acne1
Indication
• Comparable efficacy to minocycline2-5
• Effective against a wide range of gram-positive and gram-negative bacteria and other pathogens1
Doxycycline Efficacy
• Well tolerated2
• No CNS (vestibular) warnings (dizziness, lightheadedness, vertigo, problems driving or operating machinery)1
• No drug-induced lupus-like syndrome1
• No reported skin hyperpigmentation1
Doxycycline Safety
1. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 2. Kircik LH. J Drugs Dermatol. 2010;9:1407-1411. 3. Harrison PV. Clin Exp Dermatol. 1988;13:242-244. 4. Smit F. Dermatologica. 1978;157:186-190. 5. Ólafsson JH, et al. J Dermatol Treat. 1989;1:15-17.
PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 43
Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
44PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
• Delivery system of pH-sensitive enteric-coated pellets of doxycycline hyclate
• Designed to minimize the exposure of the upper gastrointestinal tract to doxycycline
Delayed-release enteric-coated pellets
• Can be taken once daily, at any time of the day, whenever it is most convenient
• Can be administered without regard to food or milk• Scored tablets can be broken/cut to allow for easier
administration or dose titration• For patients who have difficulty swallowing tablets,
the tablet can be broken apart and sprinkled over applesauce
Dosing flexibility
DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
45PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Selected Safety Information:
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne
Selected Safety Information about DORYX®
Doxycycline is contraindicated in patients who have shown hypersensitivity to any of the tetracyclines and, like other tetracycline-class antibiotics, can cause fetal harm when administered to a pregnant woman. Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years), may cause permanent discoloration of teeth and should not be used unless other drugs are not likely to be effective or are contraindicated. Oral antibiotics may lessen the effectiveness of oral contraceptives.
Patients should be advised that photosensitivity can occur with tetracycline-class drugs. Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents including doxycycline, and may range from mild diarrhea to fatal colitis. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of DORYX® and other antibacterial drugs, DORYX® should be used only as indicated.
Please see Full Prescribing Information from your sales representative and at www.doryx.com.
DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.Please see Selected Safety Information for DORYX® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
DORYX® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne.
46PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
SPEAKER TRAINING CERTIFICATIONDoryx® (doxycycline hyclate delayed-release tablets, USP)
1. I have completed the Warner Chilcott Product training on Doryx® and I reviewed the Regulatory Compliance Training slides on the rules and regulations governing speaking on behalf of Warner Chilcott.
2. I have read and understand the prescribing information for Doryx® (doxycycline hyclate delayed-release tablets, USP).
3. I understand Doryx® is a tetracycline-class antimicrobial indicated for adjunctive therapy for severe acne.
Next
47PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
SPEAKER TRAINING CERTIFICATIONDoryx® (doxycycline hyclate delayed-release tablets, USP)
4. I understand the following safety information about Doryx®:– Doxycycline is contraindicated in patients who have shown
hypersensitivity to any of the tetracyclines and, like other tetracycline-class antibiotics, can cause fetal harm when administered to a pregnant woman. Tetracycline-class antibiotics used during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years), may cause permanent discoloration of teeth and should not be used unless other drugs are not likely to be effective or are contraindicated.
– Patients should be advised that photosensitivity can occur with tetracycline-class drugs.
– Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents including doxycycline, and may range from mild diarrhea to fatal colitis.
– To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of Doryx® and other antibacterial drugs, Doryx® should be used only as indicated.
– Oral antibiotics may lessen the effectiveness of birth control pills.
Next
48PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
SubmitI Agree I Disagree
SPEAKER TRAINING CERTIFICATIONDoryx® (doxycycline hyclate delayed-release tablets, USP)
5. I understand that when presenting information about Doryx® as a speaker for Warner Chilcott, I must only use Warner Chilcott-approved slides and must follow all applicable rules and regulations for speakers.
6. I understand that when presenting information about Doryx® as a speaker for Warner Chilcott, I must present only information contained in the product label or new drug application. If an unsolicited question requires an answer that is off-label, I will briefly answer the question, state that the answer is off-label and derived from my professional experience, and return to the Warner Chilcott-approved presentation and messaging.
49PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
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