Doryx

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  • Key Points Acne vulgaris is the most common dermatologic condition encountered by ambulatory dermatologists 1,2 Each year, physicians conduct at least 14 million office visits for the management of this condition 1 The onset of acne typically occurs for the first time during adolescence, with roughly 85% of teenagers between the ages of 15 and 17 years affected to some degree 1 Acne can extend beyond the teenage years. In fact, 10% of office visits are reported in individuals between the ages of 35 and 44 years 2,3 References Mancini JA. Incidence, prevalence, and pathophysiology of acne. Johns Hopkins Adv Stud Med. 2008;8:100-105. Weinstock MA, Boyle MM. Statistics of interest to the dermatologist. In: Del Rosso JQ, ed. Year Book of Dermatology and Dermatalogic Surgery 2010 . Philadelphia, PA: Elsevier; 2010:35-50. Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27:33-42.
  • Key Points Shown here are cross-sections of the skin, one under normal, healthy conditions and the other, affected by acne 1 In healthy skin, the formation/desquamation of corneocytes and the production and excretion of sebum are well regulated. When acne is present, these processes are disregulated, and an increase in sebum production and excretion occurs 2 Inflammation also occurs, as a result of bacterial colonization of the follicle 1 References Management of acne vulgaris. http://healthproductsreviewed.org/ management-of-acne-vulgaris.html#more-105. Accessed April 13, 2011. Gollnick H. Current concepts of the pathogenesis of acne: Implications for drug treatment. Drugs . 2003;63:1579-1596.
  • Key Points Shown here are 2 different types of comedonal acne lesions 1,2 Open comedones (blackheads) and closed comedones (whiteheads) are considered non-inflammatory lesions There are also various types of inflammatory acne lesions 2-5 Cysts are deep lesions that are severely inflamed and can be extremely painful. These lesions contain substantial amounts of fluid Pustules are round, pus-filled lesions that are typically red and very painful. These lesions result from rupture of the follicular sac Papules are smaller, slightly raised lesions approximately 5 mm or smaller in diameter As a result of inflammatory acne, hyperpigmentation (discoloration of the skin) and scarring can result 6-8 References Acne types. http://www.acne101.org/types.html. Accessed April 13, 2011. Gollnick H. Current concepts of the pathogenesis of acne: implications for drug treatment. Drugs. 2003;63:1579-1596. Cystic acne treatment. http://www.hbbase.com. Accessed April 13, 2011. Teens about acne. http://www.clearupskincare.org/aboutacnea.html. Accessed April 13, 2011. Acne papules treatment - there is a cure. http://www.getacnehomeremedies.info/search/acne-papules-treatment-there-is-a-cure. Accessed April 13, 2011. Facial acne scars. http://www.bioskincream.com. Accessed April 13, 2011. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37. Skin site. http://www.skinsight.com/info/blog/2009/03/12/qa-acne-scars. Accessed April 13, 2011.
  • Key Points Acne is classified as mild, moderate, or severe based on the number of comedones, papules/pustules, and nodules/cysts 1-4 Physicians typically do not count the number of lesions present, but they make qualitative judgments 1-4 References Lehmann HP, Robinson KA, Andrews JS, et al. Acne therapy: a methodologic review. J Am Acad Dermatol . 2002;47:231-240. How to treat acne marks. http://hubpages.com/hub/How-To-Treat-Acne-Discolorations. Accessed April 13, 2011. The skin center. http://lagunaskincare.com. Accessed April 13, 2011. Preventing scars. http://cure-your-acne.com. Accessed April 13, 2011.
  • Key Points The figure on the left shows a normal pilosebaceous unit, consisting of a hair follicle and sebaceous gland The middle figure shows the formation of a comedone, in which there is an accumulation of shed corneocytes and sebum. The follicular ostium also becomes dilated On the right, the figure shows the formation of an inflammatory lesion. There is expansion of the follicle unit, proliferation of bacteria ( Propionibacterium acnes [P. acnes] ), and marked inflammation, followed by rupture of the follicular wall Reference Pugliese S. Acne: Fact vs Fiction. http://dermhub.com/2009/08/the-411-on-acne. Accessed April 13, 2011.
  • Key Points Four main factors in the pathophysiology of acne and acne lesions are shown here 1,2 Increased follicular colonization by P. acnes Increased sebum production by sebaceous glands Altered keratinization Release of inflammatory mediators into the skin These factors are interdependent and are known to influence one another References Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res. 2011;63:130-145. What is acne? http://www.acne.org. Accessed April 13, 2011.
  • Key Points P. acnes proliferation in follicles leads to inflammation through a number of mechanisms 1 First, the bacteria themselves appear to release proinflammatory mediators 2 In addition, P. acnes releases lipases, proteases, and other enzymes that break down the follicular epithelium, leading to infiltration by immune cells 1 Adding to the immune response, P. acnes releases chemotactic factors that attract neutrophils and lymphocytes, which in turn release proinflammatory mediators 1 Treatment with tetracyclines can reduce acne inflammation, suggesting a prominant role for bacteria in acne inflammation 1 References Webster GF. Infl ammation in acne vulgaris. J Am Acad Dermatol. 1995;33:247-253. Holland DB, Jeremy AHT. The role of inflammation in the pathogenesis of acne and acne scarring. Semin Cutan Med Surg . 2005;24:79-83.
  • Key Point In addition to the inflammation that is secondary to P. acnes colonization of the comedone, inflammatory events have also been found to precede hyperkeratinization, meaning that acne may be a primary inflammatory condition 1,2 References Kircik L. Early anti-inflammatory topical acne therapy may improve outcomes and reduce bacterial resistance. Pract Dermatol . 2011;3:35-39. Jeremy AH, Holland DB, Roberts SG, et al. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121:20-27.
  • Key Points Individuals with acne encounter significant challenges, both physically and emotionally 1 Scarring develops in approximately 95% of patients who are diagnosed with acne. Hyperpigmentation can also occur 2 The emotional impact of acne is particularly difficult for adolescents when there is pronounced vulnerability. Emotional concerns include anxiety, depression, suicidal thoughts, frustration, and anger 1 References Gollnick H, Cunliffe W. Management of acne. A report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37. 2. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol. 1994;19:303-308.
  • Key Points Shown here are results from a questionnaire sent to patients who were referred for managment of acne These results indicate that anxiety and depression are the biggest challenges that adversely affect QOL of these patients Upwards of 50% of patients with acne reported anxiety or depression, compared with roughly 15% of the general population Pain and discomfort are also significant concerns for individuals who have acne Reference Klassen AF, Newton JN, Mallon E. Measuring QOL in people referred for specialist care of acne: comparing generic and disease-specific measures. J Am Acad Dermatol. 2000;43:229-233.
  • Key Points In 2003, the Global Alliance to Improve Outcomes in Acne Group published recommendations for the management of acne Many physicians and also the lay public often dismiss acne as a natural part of growing up However, growing evidence shows that acne can leave lasting emotional and physical scars Therefore, acne should be approached as a chronic disease Early and aggressive treatment is recommended to limit the duration of active acne and decrease the likelihood of physical and emotional scarring Reference Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol . 2009;60(suppl 5):S1-S50.
  • Key Points There are a number of different considerations that need to be taken into account when choosing the most effective acne treatment 1 The choice of therapy will depend on the severity of acne, the type of lesions present, the degree of psychological and social impact that may result, and the possiblity of acne scarring 1 A main goal of treatment is to prevent scarring, as scarring can have long-lasting consequences and is considered the most devasting sequelum of inflammatory acne 2 References Goulden V. Guidelines for the management of acne vulgaris in adolescents. Pediatr Drugs. 2003;5:301-313. Kircik L. Early anti-inflammatory topical acne therapy may improve outcomes and reduce bacterial resistance. Pract Dermatol. 2011;3:35-39.
  • Key Points This slide shows the 2009 Global Alliance Acne Treatment Algorithm 1,2 Oral antibiotic use is a mainstay of treatment for many acne patients For moderate acne, first-line recommended therapy is an oral antibiotic in combination with a topical retinoid Additional use of the nonantibiotic bactericidal agent benzoyl peroxide (BPO) is recommended for patients with nodular acne For individuals with moderate, mixed, or papular/pustular acne, BPO is considered a useful addition This is particularly true for individuals who require long-term antibiotic therapy BPO can help to limit the development of bacterial resistance at its application sites References Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol . 2009;60(suppl 5):S1-S50. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol . 2003;49(suppl 1):S1-S37.
  • Key Points Each year in the United States, 8-9 million oral antibiotic prescriptions are written by dermatology practices Two-thirds of these prescriptions are written for tetracycline derivatives, mainly doxycycline and minocycline, and most are prescribed for treating acne vulgaris and rosacea In comparison, approximately 3-4 million prescriptions for topical antibiotics are written each year Reference Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27:33-42.
  • Key Points There are various treatment options for acne, which target the various factors associated with it 1-3 Shown here are factors targetted by oral tetracycline antibiotics of the tetracycline class, topical antibiotics and BPO, and retinoids 1 Oral antibiotics of the tetracycline class are effective in reducing the P. acnes population and thereby helping control inflammation 3 References Bikowski J. P rinciples of oral acne therapy. Pract Dermatol Ped. 2011;1:23-263. Kircik L. Early Anti-inflammatory topical acne therapy may improve outcomes and reduce bacterial resistance. Pract Dermatol . 2011;3:35-39 Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties in their clinical implications. J Am Acad Dermatol. 2006;54:258-265.
  • Key Points In the United States, the second-generation tetracycline agents minocycline and doxycycline are used more frequently than first-generation tetracyclines or erythromycin 1 ,2 This is mainly because of relatively lower levels of resistance of P. acnes than with the older agents and, thus, greater levels of efficacy 2,3 Doxycycline and minocycline are also favored over these earlier drugs because of more convenient once-daily dosing options 4-6 Both doxycycline and minocycline are indicated for the treatment of numerous bacterial infections; among these approved indications is adjunctive therapy for the treatment of severe acne 4,6 References 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). Del Rosso JQ, Kim G. Optimizing use of oral antibiotics in acne vulgaris. Dermatol Clin. 2009;27:33-42. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol . 2007;56:651-663 . DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Tetracycline hydrochloride [package insert]. Corona, CA: Watson Pharma, Inc.; 2010. Minocycline hydrochloride [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2010.
  • Key Points Tetracyclines treat acne through a variety of mechanisms, both antimicrobial and anti-inflammatory 1,2 Antimicrobial mechanisms of action include the down-regulation of P. acnes lipase and inhibition of bacterial reproduction, in addition to other actions 1 Anti-inflammatory mechanisms of action include the inhibition of neutrophil chemotaxis and inflammatory cytokines 2 Reference Ochsendorf F. Minocycline in acne vulgaris. Am J Clin Dermatol. 2010;11:327-341. 2. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol . 2006;54:258-265.
  • Key Points As summarized on this slide, doxycycline is available in several formulations, each with different solubility characteristics 1,2 Doxycycline is well absorbed following oral administration, and gastrointestinal side effects, such as diarrhea, tend to be infrequent 1-4 Because doxycycline is highly lipophilic, it exhibits excellent tissue distribution 2,3,5 Doxycycline concentrations measured in various tissues are generally higher than those measured in serum 5 References Kitzes-Cohen R, Farin D, Laor A, et al. Bioequivalence study of two formulations of doxycycline. Curr Ther Res. 1998;59:315-323. DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Cunha BA, Sibley CM, Ristuccia AM. Doxycycline. Ther Drug Monit. 1982;4:115-135. Welling PG, Koch PA, Lau CC, et al . Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects. Antimicrob Agents Chemother . 1977;11:462-469 Saivin S, Houin G. Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet. 1988;15:355-366.
  • Key Points DORYX ® is a delayed-release formulation that contains specially coated pellets of doxycycline hyclate DORYX ® is indicated as an adjunctive therapy for severe acne The therapeutic effect of DORYX ® is bacteriostatic; its antimicrobial effects are thought to occur through inhibition of protein synthesis DORYX ® is effective against a wide range of gram-positive and gram-negative bacteria, as well as other pathogens, including P. acnes Reference DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
  • Key Points DORYX ® tablets contain an enteric-coated delivery system of delayed-release, specially coated pellets of doxycycline hyclate This special, coated-pellet delivery system allows for the tablets to be broken up for patients who have difficulty taking pills, without losing the delayed-release properties The pH sensitivity of the enteric coating prevents DORYX ® from dissolving in the acidic environment of the stomach As the pellets enter the alkaline environment of the small intestine, the coating dissolves, releasing active drug for absorption Reference DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
  • Key Points The flexibility of the DORYX ® dosing schedule has many advantages Dose titration is facilitated by the scored tablets DORYX ® tablets can be taken at any time throughout the day, and do not need to be taken with milk or food DORYX ® tablets can be broken up, making it easier for patients to take who have difficulty swallowing pills DORYX ® can also be administered by carefully breaking up the tablet and sprinkling the contents on a spoonful of applesauce The delayed-release pellets must not be crushed or damaged when breaking up the tablet. Reference DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
  • Key Points Smit conducted a 12-week, double-blind, randomized, parallel-group clinical trial of doxycycline (100 mg, QD) and minocycline (100 mg, QD) in 18 patients with severe acne vulgaris; 16 patients completed the study The primary outcome measure was the overall acne score based on assessments of global symptom severity, seborrhea, comedones and whiteheads, papules and pustules, infiltration, and abscesses At the end of 12 weeks, acne scores were similar between the 2 treatment groups, indicating comparable effectiveness of minocycline and doxycycline in acne vulgaris after 3 months of treatment No serious side effects were noted with either treatment Reference Smit F. Minocycline versus doxycycline in the treatment of acne vulgaris. A double-blind study. Dermatologica . 1978;157:186-190.
  • Key Points Ólafsson et al conducted a 12-week double-blind trial comparing doxycycline and minocycline This figure illustrates lesion counts at baseline and throughout the 12-week treatment period In both groups, there was a statistically significant reduction in the average lesion count between the first and the fourth visit (12 weeks of treatment); no difference was seen between the 2 drugs at any time point examined In 85% of cases, both physicians and patients rated doxycycline therapy effective or very effective 90% of patients and 87% of investigators rated minocycline treatment effective or very effective The results were not statistically significant and the investigators concluded that doxycycline and minocycline were similarly effective for treating acne Reference Ólafsson JH, Gudgeirsson J, Eggertsdóttir GE, et al. Doxycycline versus minocycline in the treatment of acne vulgaris: a double-blind study. J Dermatol Treat. 1989;1:15-17.
  • Key Points The table shows types of AEs common to all drugs in the tetracycline group 1-11 GI upset may include, but is not limited to, anorexia, nausea, and vomiting; more serious GI AEs with tetracyclines include rare instances of esophagitis and esophageal erosion 3,4,7 Photosensitivity, marked by an exaggerated sunburn reaction with exposure to sunlight or ultraviolet light, is also seen with these agents 3,4,7 Use of agents in the tetracycline class may also be associated with development of bacterial antibiotic resistance, including that of P. acnes 3,4,7 Other AEs seen among the tetracycline class include the potential for permanent tooth discoloration in infants or children exposed to tetracyclines during tooth development and, rarely, pseudotumor cerebri (benign intracranial hypertension in adults; bulging fontanels in infants) 2-4,7 As with all antibiotic agents, the tetracyclines alter the normal flora found in the colon and may allow an overgrowth of Clostridium difficile. This may result in CDAD, which may range from mild to fatal colitis 3,4,7 References Ochsendorf F. Minocycline in acne vulgaris: benefits and risks. Am J Clin Dermatol. 2010;11:327-341. Zouboulis CC, Piquero-Martin J. Update and future of systemic acne treatment. Dermatology. 2003;206:37-53. Tetracycline hydrochloride [package insert]. Corona, CA:Watson Pharma., Inc.; 2010. Minocycline hydrochloride [package insert]. Morgantown, WV; Mylan Pharmaceuticals Inc.; 2010. Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. J Drugs Dermatol. 2010;9:1407-1411. Schlienger RG, Bircher AJ, Meier CR. Minocycline-induced lupus. A systematic review. Dermatology. 2000;200:223-231. DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Sánchez AR, Togers RS 3rd, Sheridan PJ. Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity. Int Soc Dermatol . 2004;43:709-715. Friedman DI. Medication-induced intracranial hypertension in dermatology. Am J Clin Dermatol . 2005;6:29-37. Delaney JA , Dial S, Barkun A, et al. Antimicrobial drugs and community-acquired Clostridium difficile-associated disease, UK. Emerg Inf Dis . 2007;13:761-763. Bartlett JG. Historical perspectives on studies of Clostridium difficile and C. difficile infection. Clin Infect Dis . 2008;46(Suppl 1):S4-S11.
  • Key Points This slide summarizes several AEs that are specific to members of the tetracycline antibiotic class 1-7 Systematic reviews of safety information (from case reports and clinical trials) indicate that AEs such as vertigo, skin hyperpigmentation, autoimmune hepatitis, and drug-induced lupus-like syndrome have been reported with minocycline but not with doxycycline or tetracycline 1-5,7 Hypersensitivity reactions are rarely seen with tetracycline and doxycycline treatment; they are seen more frequently with minocycline treatment 1-6 References Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther . 2005;27:1329-1342. Ochsendorf F. Minocycline in acne vulgaris: benefits and risks. Am J Clin Dermatol . 2010;11:327-341. Zouboulis CC, Piquero-Martin J. Update and future of systemic acne treatment. Dermatology . 2003;206:37-53. Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. J Drugs Dermatol . 2010;9:1407-1411. Schlienger RG, Bircher AJ, Meier CR. Minocycline-induced lupus. A systematic review. Dermatology . 2000;200:223-231. DORYX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Margolis DJ, Hoffstad O, Bilker W. Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus. Br J Dermatol . 2007:157:540-546.
  • Key Points In 2005, Smith and Leyden published a systematic analysis of safety and AEs comparing doxycycline and minocycline As part of this analysis, the FDA’s MedWatch database was searched for reports of AEs associated with these drugs between the years 1998 and 2003 According to a prescription database (IMS Health), between 1998 and 2003, approximately 47.63 million prescriptions for doxycycline and approximately 15.23 million prescriptions for minocycline were dispensed Doxycycline was written 3 times more often than minocycline Based on estimated numbers of prescriptions dispensed and MedWatch reports, there were fewer reported AEs with doxycycline (13 per million) than with minocycline (72 per million) between 1998 and 2003 About 5 times as many AEs were reported with minocycline AEs specifically associated with minocycline were skin hyperpigmentation, CNS/vestibular disturbance, and lupus-like syndrome Reference Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther . 2005;27:1329-1342.
  • Key Points Data shown here demonstrates the trend in doxycycline and minocycline prescribing habits by dermatologists from April 2005 to April 2010 Since mid-2007, the use of doxycycline increased from approximately 1.25 million new prescriptions to 1.5 million, while the number of minocycline prescriptions remained fairly stable at roughly 1.2 million Reference 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).
  • Key Points A number of factors contribute to noncompliance to acne therapy Poor compliance can be attributed to treatment failure 48% compliance rate was reported in a study of college-aged patients using BPO 44% of patients (with dermatologic conditions) reported that they did not precisely follow the prescribed regimen The frequency of administration has been negatively correlated with compliance In one study, 87% of patients on a QD dosing schedule adhered to treatment, whereas only 39% were able to comply with a QID dosing schedule Reference Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol . 2009;60(suppl 5):S1-S50.
  • Key Points Occurrence of acne is most common in adolescents; 58% of patients who seek treatment for acne are between the ages of 10 and 19 years 1 Adolescents are a high-risk group for noncompliance with treatment for many reasons Dosing – BID dosing and other administration restrictions can be discouraging 2,3 AEs often lead to missed doses 2 Delayed onset of action leads to frustration and noncompliance 2 Other studies show additional reasons as to why adolescents are noncompliant In one questionnaire, adolescents reported that the #1 reason they did not adhere to their acne treatment was because they were “too busy” and were “forgetful” 4 Interestingly, study results have indicated that females are more adherent than male patients 5 These studies, however, did not speculate as to why this may be References IMS Health, Inc. National Prescription Data: 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). Baldwin HE. Tricks for improving compliance with acne therapy. Dermatol Therapy . 2006;19:224-236. McNabb JJ, Nicolau DP, Stoner JA, et al. Patterns of adherence to antiretroviral medications: the value of electronic monitoring. AIDS. 2003;17:1763-1767. Zaghloul SS, Cunliffe WJ, Goodfield MJD. Objective assessment of compliance with treatments in acne. Br J Dermatol. 2005;152:1015-1021. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol . 2009;60(suppl 5):S1-S50.
  • Key Points This figure shows the results from a survey in which physicians were asked to rank the top causes of teenaged acne patients’ noncompliance with oral antibiotics The most commonly reported reason for noncompliance was GI side effects (49%), followed by BID dosing (26%), dosing restrictions (19%), and CNS side effects (6%) Reference 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.
  • Key Points DORYX ® is indicated as adjunctive therapy for severe acne 1 Three direct, head-to-head, comparative clinical trials demonstrate that doxycycline is comparable to minocycline in terms of efficacy 2-5 DORYX ® is not associated with CNS disturbances such as vertigo, light-headedness, or dizziness, and there are no warnings about driving/operating machinery when taking DORYX ®1 References DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. J Drugs Dermatol. 2010;9:1407-1411. Harrison PV. A comparison of doxycycline and minocycline in the treatment of acne vulgaris. Clin Exp Dermatol . 1988;13:242-244. Smit F. Minocycline versus doxycycline in the treatment of acne vulgaris. A double-blind study. Dermatologica . 1978;157:186-190. Ólafsson JH, Gudgeirsson J, Eggertsdóttir GE, et al. Doxycycline versus minocycline in the treatment of acne vulgaris: a double-blind study. J Dermatol Treat. 1989;1:15-17.
  • Key Points DORYX ® tablets contain a unique delivery system of delayed-release enteric-coated pellets of doxycycline designed to minimize exposure of the upper GI tract to doxycycline DORYX ® is a once-a-day formulation, which can be more convenient for patients than twice-daily dosing DORYX ® can be taken with food or dairy products; this may help to decrease gastric irritation The scored tablets allow for easier administration of the dose and for dose titration Reference DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
  • Doryx

    1. 1. 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.   Please see Selected Safety Information for DORYX ® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
    2. 2. Presenter <ul><li>James Q. Del Rosso, DO Dermatology Residency Program Director Valley Hospital Medical Center Las Vegas, Nevada Dermatology & Cutaneous Surgery Las Vegas Skin & Cancer Clinics Las Vegas and Henderson, Nevada </li></ul>
    3. 3. Table of Contents <ul><li>Presentation Highlights </li></ul><ul><li>Acne Vulgaris: Epidemiology and Classification </li></ul><ul><li>Acne Vulgaris: Impact on Quality of Life (QOL) </li></ul><ul><li>Acne Vulgaris: Treatment Options </li></ul><ul><li>DORYX ® (Doxycycline Hyclate Delayed-Release Tablets, USP) </li></ul><ul><li>Efficacy of Doxycycline </li></ul><ul><li>Safety and Tolerability of Doxycycline </li></ul><ul><li>Dermatologists’ Prescribing Trends </li></ul><ul><li>Treatment Challenges for Acne Patients </li></ul><ul><li>Summary of Key Points and Data </li></ul>DORYX ® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne. 
    4. 4. Acne Vulgaris: Epidemiology and Classification
    5. 5. Acne Vulgaris Is a Common Dermatologic Condition <ul><li>Accounts for 14 million office visits per year 1 </li></ul><ul><li>Most patients are teenagers 2 </li></ul><ul><ul><li>85% of teenagers between the ages of 15 and 17 years have some degree of acne 1 </li></ul></ul><ul><li>10% of visits are reported to be for patients 35 to 44 years of age 2,3 </li></ul><ul><li>Mancini JA. Johns Hopkins Adv Stud Med . 2008;8:100-105. </li></ul><ul><li>Del Rosso JQ, Kim G. Dermatol Clin. 2009;27:33-42. </li></ul><ul><li>Weinstock MA, Boyle MM. In: Del Rosso JQ, ed. Year Book of Dermatol and Dermatol Surg 2010 . Philadelphia, PA: Elsevier; 2010:35-50. </li></ul>
    6. 6. Anatomy of the Pilosebaceous Follicle 1,2 Acne Lesion Healthy Skin Sebaceous Gland Hair Follicle Oily Secretions From Sebaceous Gland Keratinocytes Inflammation <ul><li>Adapted from Management of acne vulgaris. http://healthproductsreviewed.org/management-of-acne-vulgaris.html#more-105. Accessed April 13, 2011. </li></ul><ul><li>Gollnick H. Drugs . 2003;63:1579-1596. </li></ul>
    7. 7. Types of Acne Lesions Comedonal Acne Inflammatory Acne Scarring 6,7 Hyperpigmentation 7,8 1. Acne types. http://www.acne101.org/types.html. A ccessed 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. Cysts 2,3 Pustule 2,4 Papule 2,5 Open Comedones 1,2 Closed Comedones 1,2
    8. 8. Classification of Acne Vulgaris 1 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. MILD 2 MODERATE 3 SEVERE 4 Comedones <20 20-100 >100 Papules/ Pustules <15 15-50 >50 Nodules/ Cysts >5 Total <30 30-125 >125
    9. 9. 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 Unit Formation 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.
    10. 10. Acne Lesions and Pathophysiology 1 Papule Pustule Nodule Cyst ACNE 2 <ul><li>Monk E, et al. Pharmacol Res. 2011;63:130-145. </li></ul><ul><li>What is acne? http://www.acne.org. Accessed April 13, 2011. </li></ul>P. acnes Inflammation Keratinization Sebum Production
    11. 11. P. acnes Induces Inflammation 1,2 Lipases, Proteases, Other Enzymes P. acnes Chemotactic Factors Proinflammatory Mediators Proinflammatory Mediators <ul><li>Webster GF. J Am Acad Dermatol. 1995;33:247-253. </li></ul><ul><li>Holland DB, Jeremy AHT. Semin Cutan Med Surg . 2005;24:79-83. </li></ul>INFLAMMATION Disruption of Follicular Epithelium Neutrophil and Lymphocyte Infiltration SCARRING
    12. 12. Current Consensus: Acne Is an Inflammatory Condition 1 <ul><li>Kircik L. Pract Dermatol. 2011;3:35-39. </li></ul><ul><li>Jeremy AH, et al. J Invest Dermatol. 2003;121:20-27. </li></ul><ul><ul><li>The cause of the increase in IL-1 activity is unknown </li></ul></ul><ul><ul><li>Could be due to low linoleic acid levels </li></ul></ul><ul><ul><li>In the absence of evidence of hyperkeratinization </li></ul></ul><ul><ul><li>T cells were not activated </li></ul></ul><ul><ul><li>Possibly a response to cytokine stimulation of endothelium </li></ul></ul>IL=interleukin. Increase in CD4+ T cells observed near uninvolved follicles from acne patients 2 IL-1 and IL-1 receptor expression increased 2
    13. 13. Acne Vulgaris: Impact on Quality of Life (QOL)
    14. 14. Acne Presents Significant Challenges <ul><ul><li>Scarring </li></ul></ul><ul><ul><li>Hyperpigmentation </li></ul></ul><ul><ul><li>Anxiety </li></ul></ul><ul><ul><li>Depression </li></ul></ul><ul><ul><li>Suicidal thoughts </li></ul></ul><ul><ul><li>Frustration </li></ul></ul><ul><ul><li>Anger </li></ul></ul><ul><li>Scarring develops in approximately 95% of patients with clinical acne 2 </li></ul><ul><li>Emotional impact of acne is particularly difficult during the period of adolescence, when there is pronounced vulnerability 1 </li></ul>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. Physical 1 Emotional 1
    15. 15. Acne Severely Affects QOL Klassen AF, et al. J Am Acad Dermatol. 2000;43:229-233. QOL Areas of Measure Anxiety and Depression Are the Biggest Challenges That Adversely Affect QOL
    16. 16. Consensus of the Global Alliance to Improve Outcomes in Acne Group Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50. <ul><ul><li>Acne should be approached as a chronic disease </li></ul></ul><ul><ul><li>Acne can be a psychologically damaging condition that lasts for many years </li></ul></ul><ul><ul><li>Limit the duration of active acne by effective treatment </li></ul></ul><ul><ul><li>Reduce the likelihood of physical and emotional scarring </li></ul></ul>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
    17. 17. Acne Vulgaris: Treatment Options
    18. 18. Considerations for Acne Treatment 1 <ul><li>Goulden V. Pediatr Drugs. 2003;5:301-313. </li></ul><ul><li>Kircik L. Pract Dermatol. 2011;3:35-39. </li></ul>Severity of Acne Presence of Acne Scarring Type of Acne Lesions Psychological and Social Impact Choice of Therapy Depends on A Goal of Acne Therapy Is to Prevent Scarring 2
    19. 19. Global Alliance: Acne Treatment Algorithm 1,2 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. <ul><li>Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50. </li></ul><ul><li>Gollnick H, et al. J Am Acad Dermatol. 2003;49(suppl 1):S1-S37. </li></ul>Mild Moderate Severe Comedonal Mixed and Papular/Pustular Mixed and Papular/Pustular 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
    20. 20. Use of Antibiotics in Dermatology Del Rosso JQ, Kim G. Dermatol Clin. 2009;27:33-42. <ul><ul><li>Annual number of antibiotic prescriptions written by dermatology practices </li></ul></ul><ul><ul><li>Based on US usage data, 2001 to 2006 </li></ul></ul>8-9 million oral antibiotic prescriptions <ul><ul><li>Majority of prescriptions are written for tetracycline derivatives </li></ul></ul><ul><ul><li>Primarily doxycycline and minocycline </li></ul></ul>Two-thirds of prescriptions <ul><ul><li>Most oral antibiotics are prescribed for treating acne vulgaris and rosacea </li></ul></ul>Acne vulgaris and rosacea <ul><ul><li>Annual number of topical antibiotic prescriptions written by dermatology practices </li></ul></ul><ul><ul><li>Based on US usage data, 2001 to 2006 </li></ul></ul>3-4 million topical antibiotic prescriptions
    21. 21. Actions of Acne Therapies 1-3 <ul><li>Bikowski J. Pract Dermatol Ped. 2011;1:23-26. </li></ul><ul><li>Kircik L. Pract Dermatol. 2011;3:35-39. </li></ul><ul><li>Sapadin AN, Fleischmajer R. J Am Acad Dermatol. 2006;54:258-265. </li></ul>Anti-comedonal Effect Anti- P. acnes Anti-inflammatory Oral antibiotics + +++ +++ Topical antibiotics + benzoyl peroxide + +++ + Topical retinoids +++ – ++
    22. 22. Oral Antibiotics for Treatment of Acne <ul><li>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. </li></ul><ul><ul><li>More effective than first-generation tetracyclines 3 </li></ul></ul><ul><ul><li>Less bacterial resistance than first- </li></ul></ul><ul><ul><li>generation tetracyclines or erythromycin 2 </li></ul></ul><ul><ul><li>More convenient dosing 4-6 </li></ul></ul>Minocycline and doxycycline are the most frequently prescribed antibiotics for acne in the United States 1,2
    23. 23. Effects of Tetracycline <ul><li>Ochsendorf F. Am J Clin Dermatol. 2010;11:327-341. </li></ul><ul><li>Sapadin AN, Fleischmajer R. J Am Acad Dermatol . 2006;54:258-265. </li></ul>
    24. 24. Doxycycline <ul><li>Highly lipophilic drug with excellent </li></ul><ul><li>tissue penetration 1,2 </li></ul><ul><ul><li>More lipophilic than first-generation tetracyclines 3 </li></ul></ul><ul><li>Almost completely absorbed after oral administration 1,2 </li></ul><ul><ul><li>Absorption is largely unaffected by foods 4 </li></ul></ul><ul><li>Several different formulations 3,5 </li></ul><ul><ul><li>Doxycycline monohydrate </li></ul></ul><ul><ul><li>Doxycycline hyclate </li></ul></ul><ul><ul><li>DORYX ® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. </li></ul></ul><ul><ul><li>Saivin S, Houin G. Clin Pharmacokinet. 1988;15:355-366. </li></ul></ul><ul><ul><li>Cunha BA, et al. Ther Drug Monit. 1982;4:115-135. </li></ul></ul><ul><ul><li>Welling PG, et al. Antimicrob Agents Chemother. 1977;11:462-469. </li></ul></ul><ul><ul><li>Kitzes-Cohen R, et al. Curr Ther Res . 1998;59:315-323. </li></ul></ul>
    25. 25. 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.  
    26. 26. <ul><li>Enteric-coated: contains specially coated pellets of doxycycline hyclate </li></ul><ul><li>Indicated as adjunctive therapy for severe acne </li></ul><ul><li>Primarily bacteriostatic and exerts its antimicrobial effect by the inhibition of protein synthesis </li></ul><ul><li>Effective against a wide range of gram-positive and gram-negative bacteria and other pathogens </li></ul><ul><li>Effective against P. acnes </li></ul>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.  
    27. 27. <ul><li>Tablets contain an enteric-coated delivery system of delayed-release, specially coated pellets of doxycycline hyclate </li></ul><ul><ul><li>The enteric coating is pH sensitive; it does not dissolve in acidic pH environments such as the stomach </li></ul></ul><ul><ul><li>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 </li></ul></ul><ul><li>Designed to minimize the exposure of the upper gastrointestinal tract to doxycycline </li></ul><ul><ul><li>Tablets dissolve in the stomach, and the enteric-coated pellets are dispersed </li></ul></ul><ul><ul><li>Enteric-coated pellets dissolve in the small intestine, where the doxycycline is absorbed </li></ul></ul>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.  
    28. 28. <ul><li>Dosing flexibility </li></ul><ul><li>Scored tablets facilitate dose titration </li></ul><ul><li>Tablets may be taken at any time during the day, and do not need to be taken with milk or food </li></ul><ul><li>Tablets can be taken more easily by patients who have difficulty swallowing </li></ul><ul><ul><li>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 </li></ul></ul>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.  
    29. 29. Efficacy of Doxycycline Please see Selected Safety Information for DORYX ® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
    30. 30. Doxycycline and Minocycline Have Comparable Efficacy in Acne <ul><li>Randomized, </li></ul><ul><li>double-blind study † </li></ul><ul><li>3 months of treatment </li></ul><ul><li>Comparable efficacy </li></ul>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 Difference in Efficacy Score* Please see Selected Safety Information for DORYX ® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
    31. 31. Consistent Results: Comparable Efficacy <ul><li>12-week, randomized, double-blind study* </li></ul><ul><li>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) </li></ul>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. 32. Safety and Tolerability of Doxycycline Please see Selected Safety Information for DORYX ® on slide 45, and Full Prescribing Information provided by your sales representative and at www.doryx.com.
    33. 33. Tetracycline-class AEs: Class Effects * <ul><li>*All tetracyclines carry common labeling with regard to adverse reactions. </li></ul><ul><li>AE=adverse event, GI=gastrointestinal. </li></ul>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. Tetracycline Minocycline Doxycycline Class Effects GI upset Yes 1-3 Yes 1,2,4-6 Yes 1,2,5,7 Photosensitivity Yes 1-3 Yes 4,5 Yes 1,2,5,7 Known or possible P. acnes resistance Yes 1,2 Yes 1,2 Yes 1,2,7 Tooth discoloration in children ≤8 years or in developing fetuses Yes 1-3,8 Yes 1,2,4,5,8 Yes 1,2,5,7 Pseudotumor cerebri Yes 2,9 Yes 1,2,4,9 Yes 2,7,9 Clostridium difficile – associated diarrhea (CDAD) Yes 10,11 Yes 4,10,11 Yes 7,10,11
    34. 34. Tetracycline-class AEs: Drug-specific Effects * *There are some important differences in drug-specific AEs between doxycycline and minocycline. 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. Tetracycline Minocycline Doxycycline Drug-specific Effects Vertigo No Yes 1-4 No Skin hyperpigmentation No Yes 1-5 No Autoimmune hepatitis No Yes 1-3,5 No Hypersensitivity reactions Rare 3 Yes 1-5 Rare 3,6 Drug-induced lupus-like syndrome No Yes 1-5,7 No
    35. 35. Doxycycline Safety/Tolerability Compared With That of Minocycline <ul><li>Doxycycline was written 3 times more often than minocycline </li></ul><ul><li>Over 5 times as many AEs were reported with minocycline </li></ul><ul><li>Minocycline-specific AEs and warnings </li></ul><ul><ul><li>Skin hyperpigmentation </li></ul></ul><ul><ul><li>CNS side effects (vertigo, dizziness) </li></ul></ul><ul><ul><li>Lupus-like syndrome </li></ul></ul><ul><ul><li>Hepatitis </li></ul></ul><ul><li>Doxycycline-specific AEs and warnings </li></ul><ul><ul><li>Esophageal erosion </li></ul></ul><ul><ul><li>Skin side effects (photosensitivity </li></ul></ul><ul><ul><li>and photo-onycholysis) </li></ul></ul><ul><ul><li>CNS side effects (intracranial hypertension) </li></ul></ul><ul><ul><li>Hypoglycemia </li></ul></ul>Reported AEs/Million New Prescriptions Dispensed 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. 36. Dermatologists’ Prescribing Trends
    37. 37. 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). New Prescriptions, millions *Includes brand and generic. Years (April 2005 – April 2010) Doxycycline: Prescribed by Dermatologists More Often Than Minocycline*
    38. 38. Treatment Challenges for Acne Patients
    39. 39. Issues With Compliance to Acne Therapy Thiboutot D, et al. J Am Acad Dermatol. 2009;60(suppl 5):S1-S50. <ul><ul><li>48% compliance was reported in a study of college-aged patients using BPO (over the counter) </li></ul></ul><ul><ul><li>44% of patients (with dermatologic conditions) reported that they did not follow their prescription regimen exactly </li></ul></ul>Poor compliance may be a major contributor to treatment failure <ul><ul><li>In a study, 87% of patients took a QD dose on schedule, whereas only 39% were able to take a QID dose on schedule </li></ul></ul>Frequency of administration is negatively correlated with compliance
    40. 40. For the Adolescent, Acne Therapy Is Only as Good as Compliance <ul><li>Acne is most common in adolescence </li></ul><ul><ul><li>58% of patients are aged 10 to 19 years 2 </li></ul></ul><ul><li>Adolescents are a high-risk group for noncompliance 3 </li></ul><ul><ul><li>Dosing – BID dosing and administration restrictions discourage compliance 3,4 </li></ul></ul><ul><ul><li>AEs – lead to missed doses 3 </li></ul></ul><ul><ul><li>Delayed onset of action – leads to frustration and noncompliance 3 </li></ul></ul><ul><li>Female patients are more adherent than male patients 5 </li></ul><ul><ul><li>71% vs 60%, P <0.0001 </li></ul></ul>1. 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 Medication Adherence, % Rationale for Noncompliance Compliance Among Acne Patients Who Reported These Reasons for Missing Treatment (n=403) 1 Treatment Success = Efficacy + Tolerability + Compliance
    41. 41. GI Side Effects: #1 Reason for Noncompliance in Teenagers 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. Physicians’ Opinions, AAD 2008: Ranking of Causes of Teenaged Acne Patients’ Noncompliance With Oral Antibiotics
    42. 42. DORYX ® : Summary of Key Points and Data 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.  
    43. 43. 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 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.   <ul><ul><li>DORYX ® is indicated as adjunctive therapy for severe acne 1 </li></ul></ul>Indication <ul><ul><li>Comparable efficacy to minocycline 2-5 </li></ul></ul><ul><ul><li>Effective against a wide range of gram-positive and gram-negative bacteria and other pathogens 1 </li></ul></ul>Doxycycline Efficacy <ul><ul><li>Well tolerated 2 </li></ul></ul><ul><ul><li>No CNS (vestibular) warnings (dizziness, lightheadedness, vertigo, problems driving or operating machinery) 1 </li></ul></ul><ul><ul><li>No drug-induced lupus-like syndrome 1 </li></ul></ul><ul><ul><li>No reported skin hyperpigmentation 1 </li></ul></ul>Doxycycline Safety
    44. 44. 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.   <ul><ul><li>Delivery system of pH-sensitive enteric-coated pellets of doxycycline hyclate </li></ul></ul><ul><ul><li>Designed to minimize the exposure of the upper gastrointestinal tract to doxycycline </li></ul></ul>Delayed-release enteric-coated pellets <ul><ul><li>Can be taken once daily, at any time of the day, whenever it is most convenient </li></ul></ul><ul><ul><li>Can be administered without regard to food or milk </li></ul></ul><ul><ul><li>Scored tablets can be broken/cut to allow for easier administration or dose titration </li></ul></ul><ul><ul><li>For patients who have difficulty swallowing tablets, the tablet can be broken apart and sprinkled over applesauce </li></ul></ul>Dosing flexibility
    45. 45. Selected Safety Information: <ul><li>DORYX ® (Doxycycline Hyclate Delayed-Release Tablets, USP) is indicated as adjunctive therapy for severe acne </li></ul><ul><li>Selected Safety Information about DORYX ® </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul><ul><li>Please see Full Prescribing Information from your sales representative and at www.doryx.com . </li></ul><ul><li>  </li></ul>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.  
    46. 46. SPEAKER TRAINING CERTIFICATION Doryx ® (doxycycline hyclate delayed-release tablets, USP) <ul><li>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. </li></ul><ul><li>I have read and understand the prescribing information for Doryx ® (doxycycline hyclate delayed-release tablets, USP). </li></ul><ul><li>I understand Doryx ® is a tetracycline-class antimicrobial indicated for adjunctive therapy for severe acne. </li></ul>Next
    47. 47. SPEAKER TRAINING CERTIFICATION Doryx ® (doxycycline hyclate delayed-release tablets, USP) <ul><li>I understand the following safety information about Doryx ® : </li></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>Patients should be advised that photosensitivity can occur with tetracycline-class drugs. </li></ul></ul><ul><ul><li>Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents including doxycycline, and may range from mild diarrhea to fatal colitis. </li></ul></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>Oral antibiotics may lessen the effectiveness of birth control pills. </li></ul></ul>Next
    48. 48. SPEAKER TRAINING CERTIFICATION Doryx ® (doxycycline hyclate delayed-release tablets, USP) <ul><li>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. </li></ul><ul><li>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. </li></ul>Submit I Agree I Disagree

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