Acne vulgaris

what is Acne vulgaris? How to classify your acne? How to chose the best therapeutic agent to treat your acne?
All these questions can be answered with this presentation.

1. Acne Vulgaris Asmaa Y. Al-Mubarak Hospital Pharmacy Course

2. Introduction Acne vulgaris is an inflammatory skin disorder of the pilosebaceous units of the skin . Although most commonly seen on the face, acne can also be present on the chest, back, neck, and shoulders The pilosebaceous unit of the skin consists of a hair follicle and the surrounding sebaceous glands. Sebum is released by the sebaceous glands and naturally maintains hair and skin hydration. Acne can cause psychological symptoms of stress, anxiety, frustration, embarrassment, and even depression. Evaluating both physical and psychological aspects of acne is imperative.

3. Etiology Acne is a multifactorial disease. Genetic, racial, hormonal, dietary, and environmental factors have been implicated in its development Four major etiologic factors involved in the development of acne: increased sebum production, due to hormonal influences; alteration in the keratinization process and hyperproliferation of ductal epidermis; bacterial colonization of the duct with Propionibacterium acnes (P. acnes); and production of inflammation with release of inflammatory mediators in acne sites.

4. Risk factors Nonmodifiable factors : 1-Gender: males during adolescence and females during adulthood/ female>male. 2-Age : adult between age 12 to 25 years. 3-Genetic factors. Modifiable Factors : Environmental factors : Heat and humidity may induce comedones (initial acne lesion) pressure or friction caused by protective devices such as helmets, shoulder pads, or pillows, and excessive scrubbing or washing can exacerbate existing acne by causing comedones to rupture. emotional factores such as stress and anger. Diet : While the link between diet and acne has continued to be controversial, there is evidence to suggest that high glycemic load diets may exacerbate acne ( chocholate ,cola drinks,milk and milk products.) some types of cosmetics : Espeically which contain Isopropyl myristate, cocoa butter, and fatty acids. Drugs: Systemic Corticosteroids, Topical(But not with Hydrocortisone), B12 injection , Antiepileptics and tuberculostatics ,Lithium.

5. Lesion Type: Acne Vulgaris Can be Noninflammatory or Inflammatory Mild Acne: either open (Black Comedon ) or closed (White Comedon ) , there is no inflammation , treated by Topical Agents Moderate Acne : Red color comedon with inflammation , treated by Topical antibiotics + Topical Retinoids + Systemic Antibiotics . Severe Acne : Presence of nodules / cyst / scar with inflammation , treated with Oral Isotretinoin.

6. Diagnosis The diagnosis of acne vulgaris is clinical observation . Lesion cultures may be warranted when treatment regimens fail to rule out other skin infections. Most clinicians describe acne as mild (few noninflammatory lesions), moderate (many inflammatory lesions) or severe (numerous severe inflammatory lesions and evidence of scarring).

7. MANAGEMENT: Acne treatment regimens should be based on acne severity and type of acne lesion. Other factors such as response to previous treatment, patient preference, cost and adherence should also be considered. Mild Acne: treated by Topical Agents . Moderate Acne : treated by Topical Agents + Systemic Antibiotics . Severe Acne : treated with Oral Isotretinoin . Improvement of symptoms following induction therapy occurs gradually, sometimes taking 6 to 8 weeks for results to be physically apparent. Patients need to be educated on continual treatment compliance during this time and should not get discouraged if acne lesions appear to worsen before getting better.

8. Nonpharmacological: Patients should be counseled to avoid aggressive skin washing and to use a non-fragranced opaque or glycerin soap or soapless wash twice daily. Scrubbing should be minimized to prevent follicular rupture. Cationic-bond strips that become activated by water are available. The dirt and oil in the pores are anionic. As the strip dries, the cationic-bond binds the anionic dirt and removes it when the strip is peeled off. Furthermore, discourage the use of abrasive cleansers and manipulating or squeezing lesions to minimize scarring. Use of an oil-free, noncomedogenic moisturizer may improve the tolerability of topical drug therapy. low-glycemic-load diet. control stress. Prevention of cosmetic acne: The patient should restrict cosmetic use to products labeled oil-free rather than water-based, Including makeup, moisturizers or sunscreens Shaving using a safety razor, the beard should be softened with soap and warm water or shaving gel, Strokes should be in the direction of hair growth, shaving each area only once. Before exposure to sunlight, patients with acne should apply sunscreens (sun protection factor [SPF] 15). Sunscreen should be applied as the first product. Because the action of most therapeutic acne agents is to dry the skin, the use of moisturizers is counterproductive

9. Pharmacological therapy

10. Topical Agents Benzoyl peroxide Retinoids Antibacterial Azelaic Acid Dapsone Keratolytic

11. Benzoyl peroxide MOA : increases the rate of epithelial cell turnover and helps to unclog blocked pores. It also has antibacterial activity against P. acnes . Dosage Forms :1% – 10%, Various Lotion, gel, foam, pads over the counter and prescription products. Side Effects : Excessive drying, peeling, erythema, allergic contact sensitization /dermatitis ,Bleaching of hair ,Photosensitivity If severe irritation or an allergic reaction develops, benzoyl peroxide should be discontinued

12. Counseling : - غسل المنطقة المصابة بالماء الدافئ والقليل من الصابون وشطفها بالماء ثم تجفيفها بلطف والانتظار حتى تجف تماما ثم يتم وضع كمية كافية ودهن المنطقة والابتعاد عن المناطق الحساسة . - الاستجابة الموضعية تعتمد على الجرعة ، وزيادة الجرعة تدريجيا حتى الوصول الى اعلى جرعة يتحملها المري ض . - تجنب التعرض لضوء الشمس بشكل مباشر. - استخدام واق ي الشمس والملابس الواقية الموصى بها . - في حالة حدوث تهيج حاد أو تفاعل تحسسي ، يجب إيقاف استخدام البنزويل بيروكسايد باستشارة الطبيب . - تجنب ملامسته للعينين والفم والانسجة المخاطية الأخرى وتجنب ملامسته للشعر. - الترطيب المستمر . Pregnancy Category C (آمن في الحمل والرضاعة ) Brands : Benoxyphil 5% - 10% , Panoxyl 5% , benzac 5% Administration : A typical regimen for benzoyl peroxide is to apply the product to clean, dry skin no more than two times a day. The strength and dosage form selected may vary from patient to patient depending on acne severity and the sensitivity of the patient ’ s skin.

13. MOA : stimulate epithelial cell turnover and aid in unclogging blocked pores. also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis. using topical retinoids in combination with benzoyl peroxide or topical antibacterial agents is preferred for inflammatory acne lesions. Side Effect : peeling, redness, or unusual dryness of the skin - T opical retinoids include: A. Tretinoin : Brands: Acnelin 0.5 mg/1g Cream , Acretin 0.025% / 0.05% Cream , Optimal 0.025% Gel and 0.05% Cream , Acticare 1.2% , 0.025% (clindamycin , tretinoin) Gel. Pregnancy Category : C ( Possibly teratogenic , Use cautiously in pregnancy ) B. Tazarotene ( Tazo rac ) - NOT Available in Jordan. Pregnancy Category: X , Teratogenic Use in pregnancy is contraindicated . Retinoids:

14. C. Adapalene:   (First choice of topical retinoid) Brands: Differin 0.1% cream 0.1% gel SureCure 0.1% gel SE: Photosensitivity. Counseling for Retinoids: - غسل المنطقة المصابة بالماء الدافئ والقليل من الصابون وشطفها بالماء ثم تجفيفها بلطف والانتظار حتى تجف تماما ثم يتم وضع كمية كافية ودهن المنطقة والابتعاد عن المناطق الحساسة . - وضع الكريم/المرهم مرة واحدة يوميًا قبل النوم ، بدءًا من جرعة منخفضة الفعالية , ثم تبدأ زيادة القوة وفقا لنتائج العلاج . -من الممكن ان تحدث ردود فعل سلبية موضعية على الأرجح في أول أسبوعين إلى أربعة أسابيع من الاستخدام ، وعادة تتناقص مع الاستخدام المستمر - تقليل التعرض لضوء الشمس بشكل مباشر - استخدام واقي الشمس مع التجديد كل 4 ساعات والملابس الواقية الموصى به ا مع الترطيب المستمر - يجب أن نخبر المرضى انه من الممكن تدهور أعراض حب الشباب عادة في الأسابيع القليلة الأولى من العلاج ، مع تحسن يحدث في 3 إلى 4 أشهر . - ت جنب استخدام هذه الادوية في الأطفال الأصغر من 12 عامًا والنساء الحوامل . - التأكد من عدم وجود حمل باجراء اختبار قبل باسبوعين من البدء بالعلاج ويتم البدء به في اليوم الثاني او الثالث من الدورة الشهرية القادمة

15. Antibacterials : MOA : Topical antibacterials directly suppress P. acnes and are first-line agents used in combination with benzoyl peroxide, topical retinoids or azelaic acid for the treatment of mild to moderate inflammatory acne. To reduce the likelihood of bacterial resistance, topical antibiotics should never be used as monotherapy or as long-term maintenance therapy . 1. Clindamycin: Brands : Clindaderm 1% solution , clindacin gel , A c ticare ) 1.2% clindamycin phosphate ,0.025% tretinoin) Gel . Administration : applied once or twice daily for 3 months SE : burning sensation of skin, exfoliation of skin, oily skin, dryness, itching C ounseling : - قبل وضع المرهم يجب غسل المنطقة جيداً بماء دافئ و صابون و تنشيف المنطقة. - يتم ملاحظة التحسن بعد 6 اسابيع من العلاج تقريبا - يجب وقف استخدامه على الفور وطلب العناية الطبية إذا حدث الإسهال. - يجب أن يتم دمجه مع البنزويل بيروكسيد الموضعي - عدم استخدامه بالقرب من مصدر حراري لاحتواءه على الكحول وتجنب ملامسة للعين .

16. 2.Erythromycin: Brands : Akne-Mycin 2% s olution ,1% emulsion,2% ointment , Zineryt 40mg/ml Lotion, Spotex 4% gel Administration :applied once or twice daily for 3 months SE : Burning, peeling, dryness, pruritus, erythema ,desquamation. Safe in pregnancy : B C ounseling : - يتم ملاحظة التحسن بعد 6 اسابيع من العلاج تقريبا. - يجب التوقف عن على الفور وطلب العناية الطبية إذا حدث الاسهال - قبل وضع المرهم يجب غسل المنطقة جيداً بماء دافئ و صابون و تنشيف المنطقة. - يجب أن يتم دمجه مع البنزويل بيروكسيد الموضعي - عدم استخدامه بالقرب من مصدر حراري لاحتواءه على الكحول وتجنب ملامسة للعين.

17. Zineryt contains 40mg/ml Erythromycin and Zinc acetate 12mg/ml : zinc acetate increases efficacy of erythromycin and provide moisturizing effect. Reconstitution : mix solution on Powder. CI : Hypersensitivity to erythromycin, other macrolide antibiotics, zinc acetate Storage: after reconstitution 8 weeks in fridge. Can we use Clindamycin with Erythromycin??? No, there’s DDI Erythromycin m ay diminish the therapeutic effect of Clindamycin (Topical).  Risk X: Avoid combination

18. Azelaic Acid : MOA : A ntibacterial and anti-inflammatory properties, and ability to stabilize keratinization . an effective alternative in the treatment of mild to moderate acne in patients who cannot tolerate benzoyl peroxide or topical retinoids. Least effective (weak) Brands : Azeclear 20% cream , Azelderm 20% cream , Skinoren 20% S.E : Erythema, skin irritation ,tingling. Pregnancy Category : B. Administration : apply twice daily, with improvement of symptoms seen in 4weeks.

19. Dapsone (NOT available in Jordan): MOA : a sulfone drug, has antimicrobial and anti-inflammatory properties Aczone 5% gel SE : Dryness, erythema, oiliness, and peeling . Does not have a risk of phototoxicity. Administration : applied in a thin layer to the affected areas twice daily. Pregnancy : not recommended.

20. Keratolytics: (peeling, Exfoliating agents) Sulfur, R esorcinol , and salicylic acid are not as effective as other topical agents, but can be used as second-line therapies in the treatment of mild to moderate acne. less skin irritation than benzoyl peroxide or the topical retinoids, but several disadvantages exist, Sulfur preparations produce an unpleasant odor when applied to the skin whereas R esorcinol may cause reversible brown scaling. SE : Severe dryness - Salicylic acid : Its keratolytic effect may enhance the absorption of other agents. Available As gel , lotion , cleanser, pads, masks Administration : Apply thin layer to affected area 1 to 3 times daily , Reduce to once daily or every other day if dryness or peeling occur. Contraindication : in children <2yrs,Hypersensitivity to the product. Pregnancy Category : C , Can be used in pregnancy. SE : Itching ,Burning, photosensitivity. Brands : Salidex , Salibet , Diprosalic , Algesal Baume . -Sulfur : often combined with salicylic acid or Resorcinol. Pregnancy Category : C SE : unpleasant odor , satin clothes.

21. Oral Agents Antibacterial Isotretinoin Hormonal agents

22. That use in moderate to severe acne can be effectively treated with oral antibiotics, especially when treatment with topical therapy has failed. Use of oral antibiotics should be limited to short periods of time, ideally 3 months or less . the use of topical antibiotics in combination with oral antibiotics is should be avoided. Assessment of response to oral antibiotics after (6 to 8)weeks of therapy is recommended. Tetracycline, doxycycline, and minocycline are the most commonly prescribed oral antibiotics for acne. Erythromycin, azithromycin, and trimethoprim (± sulfamethoxazole) are appropriate second-line agents for use when patients cannot tolerate or have developed resistance to tetracycline or its derivatives. Antibacterial

23. Doxycycline MOA: Inhibits bacterial protein synthesis by binding with the 30S ribosomal subunit. Trade name: Doxydar , Vibramycin , doxymid,Dumoxins,medomycin Unidox , Dosage form: 50,75,100 tab and cap ,200 delayed release tablet Dose: 100mg twice or 200 mg once per day S.E: diarrhea, photosensitivity, hives, discoloring of teeth . DDI : Isotretinoin (increase ICP ) X Food-Interaction : Doxycycline serum levels may be slightly decreased if taken with high-fat meal or milk . Pregnancy Category : D (Cross the placenta) CI : Children <8 yrs , allery to tetracycline, pregnancy 2 nd ,3 rd trimester. Monitor : CBC , KFT, LFT. Renal/Hepatic Impairment : There are no dosage adjustments provided in the manufacturer's labeling. ROA : IV , PO Tetracycline :

24. Counseling: يجب ان يؤخذ على معدة فارغة بمعنى ان يؤخذ قبل الاكل بساعة او بعده بساعتين. لابد من تناول الدواء مع كمية كبيرة من الماء او السوائل لانه قد يسبب تهيج في المرئ. لا يجب الاستلقاء او النوم بعد تناوله ابقى في وضع قائم لمدة نصف ساعة. يجب الفصل بينه وبين أدوية الحموضة او الفيتامينات وخاصة الكالسيوم والحديد والمغنسيوم. لا يمكن استخدامه من قبل الاطفال الذي يقل عمرهم عن 8 سنوات لأنه يسبب اصفرار الاسنان الدواء يسبب حروق الشمس والتهابات البشرة ، لذلك يجب تناول الدواء بعد التأكد من عدم التعرض للشمس لمدة ساعتين على الاقل واستخدام واقي ضد الشمس . يمنع تناوله تماماً اثناء الحمل او الرضاعة.

25. Erythromycin : MOA : It inhibits bacterial protein synthesis ,may be bacteriostatic or bactericidal depending on the organism and drug concentration. Brands : Erythrodar , Erythrocin , Rythromac Dosage form : 250,500 tablets Dose : 250-500 mg twice daily then once daily. S.E : GI upset ,QT-prolong , torsade de pointes , rash, hypersenstivity reaction, N/V , Diarrhea. ROA : IV, PO CI : concomitant use with lovastatin, or simvastatin Limited to patient can’t use tetracycline : pregnant , child<8yrs. Counseling : Macrolides يؤخذ على معدة فارغة او بعد الاكل.

26. Drug Brand Dose Dosage Form ROA SE CI Monitoring parameters Counseling Tetracyclin Tetradar 250-500mg twice daily. 250,500 capsule PO Hepatotoxicity, pericarditits , exacerbate SLE, Anorexia Severe Renal,liver disease ,Children <12 , pregnancy ,Breastfeed. KFT,LFT, temperature , WBC,CBC,mental status, appetite -اخذ الدواء على معدة فارغة قبل الاكل بساعة او بعد بساعتين و المباعدة بينه و بين ادوية الحموضة بساعتين ل اربع ساعات. Minocycline Vulga 50-100 mg twice 50,75,100 IR tablets/ capsule IV,PO Dizziness, fatigue, tooth discolor Pregnancy , Breastfeed, children <13, liver,renal disease LFT,BUN,serum Mg in pts with renal impair - مع او بدون الاكل, مع كمية كبيرة من الماء. Azithromycin Zomax Zocin Azomycin Azox Azimax 500 mg once daily for 4 consecutive days per month for 3 consecutive months 500 tablet IV , PO Diarrhea, headache, cough, Increase LDH History of chol.Jaundice , hepatic dysfunction with azithro . LFT, CBC with differential. - اخذ الدواء بعد الاكل بنصف ساعة - اذا اخذه على معدة فاضية يجب ان يأكل مباشرة. و المباعدة بينه و بين ادوية الحموضة TMP-SMX Bactrim 400,80 -800,160 mg one – two times daily 400/80,800/160 tablet IV , PO GI upset, rash, possible teratogenicity Photosensitivity Pregnancy, breastfeed, sulfa allergy, CBC, serum potassium, creatinine, BUN Minimize exposure to sun light and sun lamps. Sunscreen use and protective clothing recommended

27. Retinoic Acid Derivative Isotretinoin Used as first-line therapy in patients with severe nodular acne due to clinical effectiveness. MOA : works on the four pathogenic factors that contribute to acne development ; decrease sebum production , inhibit P.acne growth,reduce inflammation. should be continued for 6 months , but may be extended for patients with an insufficient response. Dosage form :10, 20, 30, 40 mg tablets. Dose : Initial dose 0.5 to 1 mg/kg/day in two divided doses, Continue until a total  cumulative  dose of 120 to 150 mg/kg is reached(monthly dose) Max: 2mg/kg/day. Brands : Roaccutane 10mg , 20mg capsule Ruatine , isusopra , xeractan , curacne ) Isotrex gel 0.05%,Isotrexin( Iso+erythromycin ) *topical agents used at night*

28. S.E :.dryness of mucus membrane, peeling ,IBD, loss BMD , Depression, Tachycardia , acne flare up at start of therapy, Teratogenicity and Photosensitivity Nasal sprays, lip moisturizers, may help to reduce drying of mucous membrane Apply oil-free moisturizers to face to relieve drying of skin. Renal Impairment : No dose Adjustment. Hepatic Impairment : May reduce the dose. CI : in pregnancy (Category X ),Breastfeeding ,Hepatic Impairment, concurrent tetracycline therapy , hypersensitivity , excessive hyperlipidemia. Laboratory monitoring : pretreatment >CBC/ LFT /KFT / two pregnancy test should be negative /glucose / fasting lipid profile during treatment : LFT and lipid (TG) monthly or Biweekly until response is established , pregnancy.

29. DDI ISOTRETINOIN ↓ effect of : Estrogen derivative , Progestin contraceptives. ↑ effect of : Aminolevulinic acid Drugs ↑ its Concentration : -Alcohol , Folate , Iron , tetracycline , Vit A .

30. Counseling: 1. يؤخذ مع الأكل أو بعد الأكل مباشرة يفضل أن تكون الوجبة دسمه لزيادة امتصاص الدواء ولتقليل من اثارة الجانبية على المعدة . 2. اذا كانت الجرعة المتناولة اقل من 80 مغ يأخذها مرة واحده أكثر من ذلك تأخذ على فترتين . 3. اخبار المريض ان من الممكن ان يسبب الدواء سوء في الحالة في بداية العلاج وتكون بفترة 6-8 اسابيع 4. نؤكد على المريض الالتزام بالدواء وعدم تركه , وفي حال توقف عن تناوله اكثر من اسبوعين يجب بدء كورس جديد من العلاج. 5. يمنع قطعيا تناول هذا الدواء اثناء الحمل حيث يسبب في حدوث اجهاض وتشوهات لدى الجنين , لذلك قبل تناوله يلزم اجراء فحصين للحمل باليوم 19 واليوم الخامس من الدورة الشهرية على ان يكون الفحصين سالب. و الفحص اثناء العلاج شهرياً 6. لتجنب حدوث حمل اثناء تناوله يأخذ نوعين من موانع الحمل قبل استعماله بشهر physical + pill وتستمر بأخذها لمده 3-6 اشهر من بعد ايقاف الدواء. 7.ان لا يتبرع بالدم أثناء وبعد ايقافه بشهر .

31. 8. يمنع القيام بعمليات للعيون أثناء استخدامه و لحد 6 اسابيع من ايقافه . 9.يمنع استخدام العدسات الا للضرورة وفي حال استخدامها يجب استخدام قطرة للعين كل نصف ساعة , حيث ان من الاعراض الجانبية للدواء جفاف العين . 10. كما انه يسبب جفاف في الجسم كاملا , لذا يجب القيام بالترطيب الدائم للوجه والجسم والشفتين , واستخدام قطرة للعين iso-tears وأن يزيد من كمية شرب السوائل . 11. يسبب الدواء زيادة الحساسية لدى الشمس ,لذا يجب تجنب اشعة الشمس قدر الامكان وان يضع واقي شمس ويقوم بتجديده كل ساعتين . 12. التقليل من الأطعمة المحتوية على فيتامين A مثل الكبدة والجزر . 13. يتداخل هذا الدواء مع بعض الأدوية مثل ال doxycycline حيث يزيد من intracranial pressure . 14. يؤثر على السمع , الرؤية ليلا ويسبب اكتئاب .

32. Oral contraceptives and Antiandrogens (spironolactone and cyproterone acetate) are valuable second-line treatment options for moderate to severe acne in female patients. MOA : primarily work by decreasing androgen production resulting in reduced sebum formation Because sebum production occurs early in the pathogenesis of acne, it may take up to 3 to 6 months to see the full effect of hormonal agents. Many contraceptives are effective, agents containing norgestimate with ethinyl estradiol , norethindrone acetate with ethinyl estradiol , and drospirenone with ethinyl estradiol , have been FDA approved for the treatment of acne. Hormonal Agents :

33. Norgestimate/ ethinylestradiol Norethindrone acetate/ ethinyl estradiol Dose : One tablet daily S.E : Nausea, headache, weight gain, breast tenderness, break through bleeding, venous thromboembolism Not for treatment of acne in men. Use only in females ≥ 15 years of age. Increased risk of venous thromboembolism in women who use tobacco products.

34. Spironolactone Dosage form: 25, 50, 100 tablet Dose : 50 – 200 mg daily S.E : Menstrual irregularities, breast tenderness,nausea , dizziness, headache, transient diuretic effect, hyperkalemia Not recommended for treatment of acne in men. Brand : Aldactone

35. Other Agents Although use is infrequent, several other agents are available as second- or third-line treatment options for acne when first-line therapies fail • Corticosteroids • Chemical peels • Surgical extraction • Phototherapy/photodynamic therapy • Laser treatments

36. REF: Pharmacotherapy principle& practice 4 th edition. lexi.comp Jodrug