Acne Medications - Fall 2024 - Student Version.pptx

Acne Bau P Tran, PhD, PharmD, MMS, PA-C, FCCP Assistant Professor | UTSW Dept of PA Studies Clinical Assistant Professor | TX Tech Dept of Pharmacy Practice Physician Assistant | UTSW Dept of Internal Medicine  WHAT IS ACNE? Pores...

Acne Bau P Tran, PhD, PharmD, MMS, PA-C, FCCP Assistant Professor | UTSW Dept of PA Studies Clinical Assistant Professor | TX Tech Dept of Pharmacy Practice Physician Assistant | UTSW Dept of Internal Medicine  WHAT IS ACNE? Pores of the skin become clogged, inflamed, and sometimes infected Pathogenesis is multifactorial Follicular hyperkeratinization Bacteria (Cutibacterium acnes)* Sebum production Androgens Inflammation Published by the American Academy of Dermatology (2016)  ACNE MEDICATIONS ~ TOPICAL & ORAL  TOPICAL AGENTS Two groups Topical retinoids Adapalene (Differin) Tazarotene (Tazorac) Tretinoin (Retin-A), Tretinoin microspheres (Retin-A Micro) Trifarotene (Aklief) Topical antimicrobials Benzoyl peroxide Clindamycin Erythromycin Dapsone  TOPICAL RETINOIDS - Retinoids – bind to retinoic acid receptors RAR-alpha, RAR- beta, RAR-gamma – resulting in reduced follicular occlusion Retinoids also down-regulate the expression of toll-like receptor (TLR)-2 Enhance the penetration of other topical acne meds Examples: Adapalene (Differin), tazarotene (Tazorac), tretinoin (Retin-A, Retin-A Micro), and trifarotene (Aklief)  Tretinoin is the single most effective comedolytic agent Is usually first-line agent for both inflammatory and non-inflammatory acne Retinoid delivery vehicle can have a TOPICAL substantial effect on drug tolerability RETINOIDS Most common adverse effects Photosensitivity, dry skin, scaling, erythema, burning, and pruritus Vary with the formulation, concentration, and frequency of application Pregnancy Category: X  Tretinoin (Retin-A, Retin-A micro) A metabolite of Vitamin A Adapalene 0.3% gel (Differin) A retinoid-like napthoic acid compound Tazarotene 0.5/0.1% cream and gel (Tazorac) TOPICAL For Acne and Psoriasis RETINOIDS ages 12 and older Selective targets RAR-beta and RAR-gamma Trifarotene 0.005% cream (Aklief) For Acne ages 9 and older Selective targets RAR- gamma  Increase collagen production TOPICAL Induce epidermal RETINOIDS – hyperplasia PHOTOAGING Decrease keratinocyte and melanocyte atypia  Benzoyl peroxide - MOA – Unknown – exerts keratolytic effects and antibacterial activity Considered by many to be the mainstay therapy for inflammatory acne (papules/pustules) Rapidly kills and inhibits growth of C. acnes Has not been shown to induce the development of bacterial resistance. TOPICAL SE: skin irritation, bleaching of skin and fabrics, and contact dermatitis ANTIMICROBIAL Clindamycin and Erythromycin MOA: Clindamycin – binds to 50s ribosomal subunit; inhibiting protein synthesis; Erythromycin – binds to P site of 50s ribosomal subunit, interfering with protein synthesis Often used for treatment of mild to moderate inflammatory acne Generally safe and well-tolerated Monotherapy not recommended SE: skin irritation  TOPICAL ANTIMICROBIAL Dapsone (Aczone) MOA: Competes with PABA, inhibiting folic acid synthesis Effective for treatment of both inflammatory and noninflammatory acne Concurrent application of dapsone and benzoyl peroxide can cause temporary yellow or orange discoloration of the skin and facial hair. Azelaic acid (Azelex) MOA: Inhibits protein synthesis, exerting antibacterial effects; normalizes the keratin process, decreasing microcomedo formation Effective for treatment of both inflammatory and noninflammatory acne Causes less irritation than benzoyl peroxide. Hypopigmentation can occur, particularly in darker-skinned patients  Salicylic acid MOA: Unknown – keratolytic agent Well-tolerated comedolytic agent Available in many different forms TOPICAL ACNE SE: skin irritation AGENTS - Clascoterone (Winlevi) Androgen receptor inhibitor – OTHERS similar in structure to dihydroxytestosterone (DHT) SE: erythema, pruritus, dry skin, scaling, edema, stinging, and burning HPA axis suppression  SUMMARY – ACNE MEDICATIONS – TOPICAL Topical Agent Class Therapy/Notes Adapalene (Differin) Retinoid (with anti-inflammatory mild to severe Tretinoin (Retin-A) property) Tazarotene (Tazorac) Retinoid (with anti-inflammatory mod to severe Trifarotene (Aklief) property) Benzoyl peroxide Antibacterial/Keratolytic mild to moderate Clindamycin/Erythromycin Antibacterial mild to moderate Dapsone (Aczone) Antibacterial/Anti-inflammatory mild to moderate Antibacterial/Keratolytic/ Anti- Azelaic acid inflammatory mild to moderate Salicylic acid Keratolytic mild 12 years of age and older Clascoterone (Winlevi) Anti-androgen Male and female; place in therapy to be determined SYSTEMIC THERAPY  S Y S TE MI C T HE RAPY – ORAL AB X Tetracycline (drug class) – doxycycline (Doryx) and minocycline (Solodyn) MOA: Binds to 30S and possibly 50S ribosomal subunit(s), inhibiting protein synthesis Anti-inflammatory – inhibits neutrophil chemotaxis and proinflammatory cytokines Generally used for those who are unresponsive to topical agents SE: Both agents: GI adverse effects (C. diff associated diarrhea), vaginal candidiasis, photosensitivity, intracranial hypertension, hyperpigmentation, inhibits tooth and bone development in children < 8 years, avoid in pregnancy. Minocycline: dizziness and vertigo; impaired spermatogenesis Prolonged use can lead to bacterial resistance Newer agent – Sarecycline – modestly effective in reducing inflammatory lesions in patients with non-nodular moderate to severe acne For ages 9 and older Narrow spectrum tetracycline SYSTEMIC THERAPY – ORAL ABX Trimethoprim/sulfamethoxazole MOA: sulfamethoxazole competes with PABA, inhibiting folic acid synthesis; trimethoprim selectively inhibits dihydrofolate reductase Generally used when other oral antibiotics are ineffective or not tolerated  SYSTEMIC THERAPY – HORMONAL AGENTS Treated with combination oral contraceptives (estrogen and progestin) Estrogen decreases the formation of ovarian and adrenal androgens and suppresses sebum secretion. The newer progestins desogestrel, norgestimate, and drospirenone are less androgenic and are claimed to improve acne more than older progestins (norethindrone and ethynodiol diacetate – moderate androgenic effect; levonorgestrel and norgestrel – strong androgenic effect) Progestin-only oral contraceptives containing norethindrone can exacerbate acne  ORAL CONTRACEPTIVE CHOICES Less Androgenic More Androgenic Ortho-Tri-Cyclen* Levlen Estinyl Levora Ovcon 50 Lo/Ovral Demulen 1/50 Nordette Enovid 5mg Ovral Ortho-Cyclen Ovrette Ovcon 35 Tri-Levlen Brevicon, Modicon Tri-Phasil * = FDA approved  SYSTEMIC THERAPY – HORMONAL AGENTS Spironolactone Not FDA Approved MOA: Antagonized aldosterone-specific mineralocorticoid receptors primarily in the distal convoluted tubule (classified as an anti-androgen) Blocks androgen receptors in the body (sebaceous glands) This prevents signaling, leading to inhibited sebum production and reduced secretion of inflammatory cytokines Common dosage – 50mg QAM but can be increased to 100mg QAM Common side effects are breast tenderness, irregular menstrual cycle Watch for low blood pressure  SYSTEMIC THERAPY – ORAL RETINOID Isotretinoin (Accutane) Most effective drug available for treatment of severe nodulocystic acne Inhibits C. acnes colonization by reducing sebum production and has keratolytic and anti-inflammatory effects 0.5-1.0mg/kg/day in 2 doses with food At 0.5mg/kg/day 20% require retreatment At 1.0mg/kg/day 10% require retreatment Treat for 20 to 24 weeks 95% of patients that complete therapy are still under control 2 to 5 yrs later  CONTRAINDICATED IN PREGNANCY Need two forms of contraception one month before, during, and two months after treatment unless abstinence is assured ISOTRETINOI Need negative HCG one month prior to commencing and monthly N negative HCG prior to refill PRESCRIBING Fasting triglycerides/LFTs Discontinue other acne drugs and Vit. A Must be a certified Accutane prescriber  ISOTRETINOIN – SIDE EFFECTS Dry Angular skin/mucous Conjunctivitis Hyperlipidemi cheilitis membranes (40%) a (25%) (90%) (80%) Headaches, Arthralgias Hepatotoxicit diminished Rash (10%) (16%) y (15%) night vision - rare  Summary – Acne Medications – Systemic Systemic agent Class Therapy/Notes Doxycycline Antibacterial/ First-line; mod to severe (Doryx) (Targadox) Anti-inflammatory Minocycline Antibacterial/ First-line; mod to severe (Ximino) (Minolira) Anti-inflammatory Sarecycline Antibacterial/ (Seysara) Anti-inflammatory First-line; mod to severe Trimethoprim/Sulfameth Antibacterial Second-line; mild to severe Second-line; mild to mod Oral contraceptives Antiandrogen (female patients) Spironolactone Antiandrogen Second-line; mild to mod (female patients) First-line: severe treatment- Isotretinoin Retinoid resistant  KEY POINTS Topical salicylic acid and benzoyl peroxide, both available OTC, are often used for initial treatment of acne. A topical antibiotic such as clindamycin or erythromycin, preferably in combination with benzoyl peroxide, is commonly used to treat mild to moderate inflammatory acne. A topical retinoid, alone or in combination with benzoyl peroxide and/or a topical antibiotic, is often used for first-line treatment of inflammatory and noninflammatory acne. Retinoid/antimicrobial combinations are more effective than either component alone, especially in patients with inflammatory acne. For moderate to severe inflammatory acne that does not respond to topical combination therapy, addition of an oral tetracycline is recommended. Oral contraceptives and spironolactone are effective options for post-pubertal females. The most effective drug available for treatment of inflammatory acne is isotretinoin; it can clear severe recalcitrant nodular acne, but it is teratogenic and has many adverse effects. QUESTIONS