Dermatologic Therapeutics Teresa OSullivan Pharm D BCPS University

Dermatologic Therapeutics Teresa O’Sullivan, Pharm. D, BCPS University of Washington School of Pharmacy

Learning goal: a basic comfort level with choice of agent, vehicle/route, directions, and duration of therapy when prescribing medications for common skin and eye conditions, plus what to consider when someone presents with or is labeled as having a drug allergy 2

Online Videos • Before presentation, you had an opportunity to view videos on choosing products and multiple use agents. • Please provide this feedback to your coursemaster, after this presentation: – Did you view videos and were they helpful? If you didn’t have time to view the videos, that is useful information. – Should more background information be provided online prior to lecture with classroom time spent in problemsolving? If you do or don’t prefer to view online information prior to classroom time, that is useful information. 3

What are the characteristics of these lesions? 4

Treating atopic dermatitis • • Avoid triggers Soap substitutes? Emollients after bath and prn (why? ) Mild exacerbation HC 1% BID until lesion gone • Infants: topical tacrolimus 0. 03% BID if HC needed regularly or not controlling adequately 5

Treating atopic dermatitis • Moderate exacerbation: med potency ‘roid until lesions discrete or 2 -3 weeks; tacro/pimecrolimus when at chronic stage • Severe exacerbation: high potency x 2 weeks; to medium potency if response; inadequate response? consider Staph, add phototherapy, or use immunomodulator 6

What kind of lesion is this? 7

Antipsoriatics Used for: post-acute psoriatic lesion (to induce/maintain remission) Mechanism: inhibition of DNA synthesis (slow down that cell division!) Effect: onset 1 -2 days; peak 3 -5 days Side effects: individualized per agent; see handout 8

Antipsoriatics: agents • Calcipotriene (vitamin D analog; well-tolerated) • Methotrexate (good for psoriatic arthritis) • Apremilast (Otezla®) titrate up to 30 mg po BID; dbl response rate vs ADRs, DIs, $23 K/yr • For severe pustular/refractory psoriasis dermatologist may use PUVA; etretinate, acitretin; cyclosporine; alefacept, infliximab, etanercept • Most patients with psoriasis will have other systemic problems that you will need to treat 9

Psoriasis: treatment plan • Emollients for all • Topical steroid for flare – med potency for extensor; high potency (or occlusion) if plaques thick, fluocinolone sol on scalp, HC 1% intertrigenous areas • Calcipotriene for maintenance (and flare) • Methotrexate oral if joint involvement • Refer to dermatologist if severe pustular/refractory psoriasis 10

What is this problem? 11

What is this problem? What does it have in common with the previous slide? 12

Antibacterials Used for: acne, rosacea, small areas of superficial cellulitis, conjunctivitis, BV Mechanism: inhibition of bacterial protein synthesis Effect: onset 24 -48 hours; peak 3 -5 days Side effects: minimal; see individual agents 13

Antibacterial agents Skin infections • Spectrum: bacitracin vs. triple antibiotic vs. mupirocin • Minor wounds: ointment application promotes healing with less scarring than no ointment • Oral cephalexin if area larger than a fingerprint; TMP/SMX if abcess • Mupirocin for catheter-related infections without pus; chlorhexidene for prophylaxis 14

Antibacterial agents Burns • Cool water • Silver sulfadiazine protects and acts as antibiotic • Apply 1/16 inch until eschar formation • 20 g small burns, 50 g if area < 2" x 2", 400 g for larger areas 15

Acne: the treatment plan • Step 1: benzoyl peroxide (2. 5% or 5% q. Od initially) ; tea tree oil if patient prefers “natural” product • Step 2: topical erythromycin or clindamycin • Step 3: oral antibiotic or oral contraceptive – Doxycycline, erythromycin, SMX/TMP – Tri-Levlen vs. other OCs vs. spironolactone • Step 4: topical tretinoin – Isotretinoin or etretinate should only be used for severe cystic acne; i. Pledge program 16

Antibacterial agents Rosacea 1. 2. 3. 4. Avoid triggers (vascular dilation), use mild cleansers, sunscreen Brimonodine 0. 33% gel daily can erythema Topical antibiotics for papules: metronidazole 0. 75% cream or gel BID good initial therapy; backup azelaic acid 20% cream, 15% gel BID Oral antibiotics if unsatisfactory response to topical therapy (tetra, erythro, doxy, metro) 17

Antibacterial agents Bacterial conjunctivitis • Sodium sulfacetamide 10% • Gentamicin, tobramycin • Azithromycin, erythromycin • Floxacins: cipro, levo, moxi, o, gati, besi • Sig: 1 drop OU QID x 5 days BV • Oral metronidazole; can do vag gel but more expensive; clindamycin vag gel if woman in 1 st trimester 18

Identify these lesions 19

Antifungals Used for: athlete’s foot, ringworm, jock itch, onychomycosis, thrush, vaginal yeast infection, tinea versicolor Mechanism: alteration of fungal cell membrane or mitochondrial activity Effect: onset 2 -3 days; resolution 2 -6 weeks Side effects: rare with topical agents; oral azole drug interactions 20

Antifungal agents • Dermal infections: OTC creams or powders; fluconazole orally if treatment failure; selenium sulfide topically for tinea versicolor • Vaginal: clotrimazole or miconazole cream OTC; butaconazole or terconazole (Rx); fluconazole single dose • Thrush: nystatin S&S; clotrimazole troches; fluconazole oral; oral nystatin for baby and topical for mom if breastfeeding infant thrush • Nail: terbinafine AOC; itraconazole; griseofulvin if drug interactions or cheap agent needed – 12+ weeks 21

Identify these lesions What do they have in common? 22

Antivirals Used for: warts, cold sores, shingles, chicken pox, ocular viral infections Mechanism: inhibits viral DNA replication Effects: onset 2 -3 days; 1 -2 weeks for eradication (longer for some infections) Side effects: skin irritation with topical wart products, otherwise rare 23

Antiviral agents • Warts: cryotherapy first line for plantar warts; salicyclic acid (OTC) plasters or lotion; duct tape; podophyllum or cantharidin applied in prescriber office for genital warts • Chicken pox/shingles: oral acyclovir x 5 -10 days; vaccine for chicken pox, shingles prevention • Ocular viral infection: education/hygeine if URI; trifluridine ophth soln for ocular herpes infection • Cold sores: acyclovir or pencyclovir ointment 24

What’s happening here? 25

Head Lice Facts • Infestations usually occur in autumn after start of school and peak in Nov/Dec/Jan. • Eggs hatch in 7 -10 days; lice mature to adults in 1012 days; mature adults live as long as 40 days. Females lay 6 -7 eggs/day. • Look for eggs near ears and in back of head. • Eggs/nits > 1/4 inch from hairline will not be viable 26

Head Lice Facts • Mature lice easiest to locate in wet hair. • Mechanical removal with comb is effective and should accompany use of pediculocide; adult lice white, brown, or dark gray: usually have enough colour to be seen on white tissue. • Soak combs in isopropyl alcohol after combing session. 27

Treating Head Lice • Products don’t penetrate nit shell well, + nits have no nervous system x first 4 days, so pediculocide needs residual activity or > 1 application • Apply pediculocide to dry hair • Avoid standard conditioners 2° impaired pediculocide penetration in nymphs and adults • No mayonnaise or petroleum jelly (messy, no evidence of effectiveness) • Mechanical removal crucial to eradication of infestation; need fine-toothed nit or flea comb 28

Antipediculocides • Head lice: – Permethrin (residual activity up to 10 days); check for chrysanthemum or ragweed allergy – 10 -12 minute dwell time, rinse, then mechanical removal with comb; may need 2 nd application – Rx: spinosad 0. 9% suspension – same directions • Scabies: permethrin (Elimite - Rx) • Pinworms: pyrantel 5 mg/lb single dose; OTC: several brands (Antiminth, Pin-Rid, Pin-X) 29

Topical chemotherapy Used for: actinic keratosis (AK) and superficial skin cancers Mechanism: inhibits DNA synthesis (5 -FU); IL production (masoprocol); immunomodulation (imiquimod) Effect: days to erythema; weeks to DC and resolution Side effects: mild/moderate - severe skin irritation; need sunscreen during treatment 30

Actinic Keratosis (AK) • Sun-induced; develops only on sun-exposed skin • Grayish-brown, discrete, raised scaly lesions • Cosmetically bothersome; few convert to SCC, but patient should watch and report any in lesion height, size, or thickness 31

Squamous Cell Carcinoma (SCC) • Sun-induced; often develop from AK • Small oval nodule with erythematous border; sometimes with scab; may appear in lip as fissure • On backs of hands, face, lower lip, ear, scalp • Slow-growing; rarely metastasize 32

Basal Cell Carcinoma (BCC) • Sun-induced; arsenic and radiation also cause • Small papule spreads outwards, leaving central ulcer; edges raised and pearl covered; persistent scab, bleeding • On face, particularly nose and below eyes • Slow-growing; rarely metastasize 33

Topical chemotherapy agents 5 -FU: AK, superficial basal cell carcinoma (BCC); notable skin irritation during application Masoprocol: BID x 2 -4 weeks for AK; may stain clothes Imiquimod: BID for AK, superficial BCC Diclofenac: BID x 2 -3 months for AK; less effective 34

Malignant Melanoma • Sun-influenced, not induced; genetic component • Solitary pigmented lesions that initially look like mole, then spread; can ulcerate and bleed • Can occur anywhere on skin; generally legs on females, back on males • Can metastasize; deeper lesions carry poor prognosis • Requires surgical excision; chemotherapy if metastatic Remembering Stacey… 35

Malignant Melanoma Remember the dysplastic nevi / nodular melanoma alphabet Asymmetry Border irregularity Color variation Diameter (> pencil eraser) Evolving Elevated Firm to the touch Growing 36

Skin Cancer Treatment • Topical therapy for AK; may be used also for superficial SCC, BCC • Surgical excision important for SCC, BCC, early malignant melanoma • Metastatic disease – Platin tx for SCC, BCC – Melanoma: goal is extra months of life – Immunomodulators widely used: high-dose IFN, IL-2; vemurafenib, ipilimumab therapy – Dacarbazine monotherapy if patient can’t tolerate immunomodulators 37

Drug Allergy • Pertinent to dermatology: the most common allergic reactions involve the skin • Common drug rashes: hives, maculopapular rash • Some skin lesions that appear allergic may be nonallergic – viral rashes – non-allergic amoxicillin rashes • One scary drug rash: Stevens-Johnson Syndrome/ TEN – Allergic? Non-allergic? Does it matter? 38

Drug Rashes: Hives Urticaria • Distribution: anywhere; usually appears first on upper chest • Appearance: pink and raised; larger lesions have red border with paler interior • Onset: minutes to hours; rarely > 12 hours • Treatment: antihistamine 39

Drug Rashes: Hives 40

Drug Rashes: Maculopapular Other descriptors: exanthematous, morbilliform • Distribution: usually trunk first, often spares head • Appearance: dusky to bright red, amorphous, raised, itchy • Onset: 12 - 48 hours • Treatment: antihistamine, steroid if patient frantically itchy 41

Maculopapular drug rash Note confluency of many lesions, toxic appearance 42

Maculopapular Rash vs. Hives Appearance is a little different 43

Maculopapular Rash vs. Hives Distribution is a little different 44

Viral Rash • Lesions discrete • preceding URI highly likely OR 20. 5 (95%CI 5. 2 -94. 5) • rash very common with penicillin + EBV 45

Viral Rash versus Drug Rash 46

Non-allergic Amoxicillin Rash • • Occurs > day 3 of therapy Lesions macular (more common) or maculopapular Pruritis mild or absent Rash duration ~ 3 days whether or not therapy discontinued • Not an allergy; rash won’t reappear with readministration 47

Stevens-Johnson Syndrome 48

Stevens-Johnson Syndrome 49

Stevens-Johnson Syndrome 50

Cross-sensitivity • Penicillins-cephalosporins: – Traditional #s of 7 -10% based on poor science – Most common in drugs with similar side chains – Can skin test (expired Pen G) OK sens, good spec if recent anaphylaxis; follow neg results w/2 small oral doses • Sulfonamide antibiotics and other sulfonamides: no evidence of cross-sensitivity in most people 51

The Allergy Interview • DISCERN (distribution, itchiness, shape, confluency, elevation, redness (colour), number) • Timing of reaction with regard to drug administration – How soon after therapy initiation? – How long since most previous dose? – How many times has drug been taken previously? 52

Words to live by… “all patients, regardless of drug allergy status, should be supervised when they take their first dose of any medication, particularly an antibiotic” 53

What Should Be Done? 54

What Should Be Done? 55

What Should Be Done? 56

What Should Be Done? 57

What Should Be Done? 58

Thank you!! 59