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Acne Therapy
Supplement to the Acne Drug Comparison Chart March 2007
The RxFiles Academic Detailing Program
www.RxFiles.ca
Key Messages, Tips and Pearls
ACNE Therapy: Pharmacological Overview
• Benzoyl Peroxide (BP) is used as 1st line monotherapy for mild-
1) Acne drug therapies require consistent use for
several weeks before optimal results are seen.
o BP produces powerful anaerobic antibacterial activity due to slow 2) Topical therapies need to be applied to the entire
affected area, not just specific lesions.
o BP is also a useful adjunct to topical retinoids, antibiotics (ABX) topical/oral, combination oral contraceptives (COCs) & spironolactone. 3) Benzoyl Peroxide (BP) is a very effective and
• Topical retinoids (e.g. tretinoin, adapalene) are important in acne relatively inexpensive acne therapy. Strengths
treatment.1 They affect the desquamation process, reducing the greater than 5% are no more effective but more
number of microcomedones & comedones. irritating than strengths ≤ 5%.
o Used for mild-moderate comedonal acne (inflammatory or non- 4) Topical retinoids are an effective first line option
inflammatory) or as adjunct with BP, ABX, COCs & for comedonal acne.
• Topical ABX are best used in combination with topical retinoids a. Tretinoin
(e.g. Retin-A, Stieva-A, Vitamin A Acid):
or BP (↓ potential for antimicrobial resistance).1 i. 0.025-0.05% products are most useful; lower
• Systemic ABX (tetracyclines, erythromycin, & trimethoprim) are concentrations do not work; higher
concentrations are seldom tolerated
indicated for moderate-severe acne. Due to resistance concerns monotherapy should be avoided and therapy courses limited where b. Adapalene
(Differin) may be preferred if:
possible to short durations or “pulses” of 8-12 weeks.2 i. less skin irritation is important
• COCs may be considered over antibiotics for females with ii. part of a combination regimen where morning
moderate-severe acne. Spironolactone has been used for adult application of agent causing minimal sun
women with moderate-severe acne when COCs are sensitivity is important (e.g. BP+ABX at night,
contraindicated or other treatments fail. retinoid in am)
• Isotretinoin monotherapy is the most effective therapy for 5) Topical antibiotic monotherapy should be avoided.
moderate-severe inflammatory acne; care must be taken to ensure Addition of BP to antibiotic regimens is strongly
potential serious adverse events are avoided/recognized. recommended to reduce bacterial resistance.
Isotretinoin causes a high rate of birth defects in the (Combo products useful: Benzamycin, BenzaClin / Clindoxyl) Depression & suicide have been reported in people taking 6) Oral antibiotics should be used for shorter
isotretinoin; direct correlation not established. “pulses” of therapy (e.g. 8-16 weeks) to reduce the
development of bacterial resistance.
Other OTC agents: salicylic acid, sulphur, resorcinol, glycolic acid & tea tree oil (limited data; all less efficacious than BP).1 7) Any combination oral contraceptive (COC) may
{Tea tree oil 5%: 1 trial showed effectiveness but slow onset.3} result in improvement in acne.

General Considerations for Topical Therapies
isotretinoin
(Accutane, Clarus) is the most
• If two topicals are being used, apply one qam & the other qhs effective therapeutic option for severe acne.
Physicians should be familiar with cost effective
Multiple agents are useful if from different therapeutic classes dosing strategies,
Potency: Solution > Gel > Cream / Lotion pregnancy precautions, required
monitoring and side effect management.
For very oily skin consider a solution or gel 9) Acne can cause significant stress, psychosocial
For very dry skin choose a cream or a lotion (or add a moisturizer) concerns to the patient. Early intervention is
recommended when presentation or family history
Topical Retinoids: Initiation Considerations
suggests a severe course is likely.
• Apply a thin layer to dry skin 30 minutes after gently cleansing. 10) Identification of sensitive skin issues is important
Rub in gently. {For creams and gels, medication should become so that steps can be taken to reduce drug related
invisible within a minute; if not, patient may be using too much.} irritation {e.g. patients with non-oily skin, previous
• Begin by applying only on every 3rd night, moving up to every 2nd eczema or a history of sensitivity}.
night and eventually every night if tolerated. • In some cases, a shorter application time may be useful. Acknowledgements: Contributors & Reviewers: Dr. D. Lichtenwald (Saskatoon-Derm), Dr. J. Taylor (C. of
Pharmacy, U. of S.), Dr. R. McKay (Regina-Derm), Dr. T. Laubscher (SHR-FM),Dr. M. Evans (CCFP, U. of T., A non-comedogenic skin moisturizer (various e.g. Complex-15, Toronto) & RxFiles Advisory Committee. Prepared by: M. Jin PharmDc Candidate; L. Regier BSP, BA, B. Jensen BSP Moisturel) may be applied in the morning to manage skin dryness. DISCLAIMER: The content of this newslet er represents the research, experience and opinions of the authors and not those of the Board or Administration of Saskatoon
Health Region (SHR). Neither the authors nor Saskatoon Health Region nor any other party who has been involved in the preparation or publication of this work warrants or
represents that the information contained herein is accurate or complete, and they are not responsible for any errors or omissions or for the result obtained from the use of such Sunscreen with SPF-15 or greater protection (e.g. Ombrelle) is information. Any use of the newsletter will imply acknowledgment of this disclaimer and release any responsibility of SHR, its employees, servants or agents. Readers are encouraged to confirm the information contained herein with other sources. Additional information and references online at www.RxFiles.ca. important especially with tretinoin and tazarotene. Copyright 2007 – RxFiles, Saskatoon Health Region (SHR) www.RxFiles.ca
BP: Initiation Routines to Minimize Irritation
Antibiotics (ABX): Considerations
• Less frequent (every 2-3 night) application may be useful • Using BP with topical ABX is strongly recommended to reduce early in therapy; begin with low concentration [2.5%]; avoid more irritating formulations (e.g. acetone- & alcohol- based • Oral ABX are useful for more extensive/severe inflammatory acne; however, due to bacterial resistance concerns, shorter • Alternatively, apply for 15 minutes the 1st evening. Each “pulse” courses may be preferred over longer-term maintenance evening the time should be doubled until left on for 4 hours & subsequently all night. Once tolerance is achieved, the • Topical antibiotics are useful as follow-up to an oral ABX course. • Alternatively, BP can be applied for 2 hours for 4 nights, 4 COCs: Role in women with acne 6
hours for 4 nights, and then left on all night. • Acne accompanied by mild or moderate hirsutism • Inadequate response to other acne treatments Managing Adverse Effects (Skin)
• Acne that began or worsened in adulthood • Dryness can be managed with non-comedogenic moisturizers; avoid use of scrubs and astringents. • If irritation occurs with tretinoin, switch to adapalene. • Inflammatory acne limited to the “beard area” • If possible, ↓ the strength or contact time (topicals) initially to prevent further irritation, and gradually ↑ as tolerated. What COCs have the official indication for acne tx?
• For sensitive skin: 2% clindamycin in Complex 15 Lotion or • In Canada, Alesse, Tri-cyclen & Diane 35 have official indications Cetaphil Cleanser qHS + 2.5% H2O-based BP qAM.4 Yasmin is as efficacious as Tri-cyclen7 & Diane 358 for mild- Facts for the Patient
moderate acne, but not officially indicated. {Yaz in the USA recently got acne FDA indication} • Stress may exacerbate psychological reaction to acne. • All COCs are generally beneficial, likely due to estrogens effect • It can take at least 8 weeks of a prescribed treatment before on sex hormone binding globulin (SHBG) resulting in an the patient sees any improvement. Acne may even get antiandrogenic effect.9,10 Limited and conflicting evidence does worse before it gets better. Focus on less new lesions. not support the superiority of one progestin over another. • Wash the face no more than twice per day with a mild non- alkaline soap / soap-free cleanser & lukewarm water. Can Diane 35 be used as contraceptive?
Cleaning the skin too often may aggravate acne & cause • Berlex Canada does not recommend that Diane 35 be prescribed flare ups. Acne is not caused by dirt or surface oil. as contraception alone. They recommend the use of alternative • Use the fingertips or a soft wash cloth to wash the face. contraception while on Diane 35. However, Diane 35 is indicated • Picking at acne lesions may cause scarring – NO PICKING. for contraceptive monotherapy in other countries (e.g. Australia). • There is no evidence to support that chocolate or sugar will Isotretinoin (Accutane, Clarus) Highlights11
cause acne. Certain foods may make some patients’ acne • Official indications: severe nodular and/or inflammatory acne, worse and should be avoided. No specific food/diet has acne conglobata & recalcitrant acne. • Acne affects adults as well as children. ♦ extensive acne involving face and trunk, associated with scarring; failure to respond to or inability to tolerate systemic antibiotics Acne Vulgaris Versus Acne Rosacea
Significant psychological distress because of acne Acne rosacea is a chronic skin eruption with flushing and • Due to common side effects, avoid concurrent acne topicals, vitamin dilation of small blood vessels in the face, especially nose A supplements, and follow-up topical retinoids for about 4 months and cheeks. Its etiology differs significantly from acne vulgaris and should not be confused given the different • There is anecdotal evidence that certain foods exacerbate acne12 Effective treatments include topical metronidazole, benzoyl • Chocolate – the evidence that chocolate is acnegeic had several peroxide 5%/erythromycin 3% gel, benzoyl peroxide methodological flaws12: small sample size13; treatment duration 5%/clindamycin 1% gel, benzoyl peroxide (BP) alone, and follow-up not long enough to detect changes14,15; and high fat azelaic acid, and sodium sulfacetamide10%/sulfur 5%. Oral content of control bar may have been acnegenic16 tetracycline was effective by physician assessment, but not Advice regarding diet should be individualized. Table 2: Acne Vulgaris vs Acne Rosacea
Acne variant
Most: ages 12-24; may improve in sunshine; Vulgaris
Ages 30-70; erythema, edema, telangiectasia, metronidazole topical, BP+/- Clinda gel, sulphur flushing, rhinophyma, ocular rosacea; head area topical, isotretinoin if severe; other azelaic acid; tetracycline? Closed comedone (whitehead): non-inflamed (non-red) follicular opening containing a keratotic plug with a thin overlying epidermal membrane; Open comedone (blackhead):
non-inflamed (non-red) follicular opening containing a keratotic plug that appears black; Papule: small round to oval red elevation of the skin (1-4 mm); Pustules: resembles a papule
with a central pocket of pus; Nodule/Cyst: poorly marginated, red tender, sometimes draining, 0.2-3.0cm, indurated mass in the skin
RxFiles - Acne - Online Extras
Possible Contributing Factors for Acne:
Table 3: Adverse drug reactions of topical agents in acne therapy 18
{Removed from main text due to conflicting literature!}
Signs of androgen excess would include precocious puberty Possible causes of androgen excess would include polycystic ovary disease, adrenal tumor, ovarian tumor and pituitary Physical pressure from headbands, violins, chin straps, sports - = none; + = weak; ++ = moderate; +++ = strong; ++++ = very strong helmets, guitar straps and orthopedic braces have induced localized acne; wool and other rough textured fabrics and References – RxFiles Acne Newsletter
occlusive clothing may also be irritants {for additional references – see those specific to RxFiles Acne Drug Comparison Chart} Oil-based cosmetics, oil-based scalp lubricants, topical tar Work Group:; Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007 Feb 2; [Epub ahead of print] Occupational materials such as coal tar, pitch, mineral oil and Zaenglein AL, Thiboutot DM. Expert committee recommendations for acne management. Ingestion, inhalation or transcutaneous penetration of halogenated aromatic hydrocarbons, including components in Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus paint, varnishes, lacquers, fungicides, insecticides, herbicides, benzoylperoxide in the treatment of acne. Med J Aust. 1990 Oct 15;153(8):455-8. 4 Dr. Lichtenwald, dermatologist; discussion, September 21, 2006. van Zuuren EJ, Gupta AK, Gover MD, Graber M, Hollis S. Systematic review of rosacea treatments. J Am Acad Dermatol 2006;online:Nov 3. 6 Zouboulis CC and Piqero-Martin J. Update and Future of Systemic Acne Treatment. Pressure, friction, and excessive scrubbing or washing can exacerbate existing acne by causing microcomedones to 7 Thorneycroft H. Gollnick H. Schellschmidt I. Superiority of a combined contraceptive containing drospirenone to a triphasic preparation containing norgestimate in acne Hair styles low on the forehead/neck may cause excess treatment. [Clinical Trial. Journal Article. Multicenter Study. Randomized Controlled van Vloten WA. van Haselen CW. van Zuuren EJ. Gerlinger C. Heithecker R. The effect of 2 combined oral Contraceptives containing either drospirenone or cyproterone Intense anger or stress can exacerbate acne, causing flares or acetate on acne and seborrhea. [Clinical Trial. Journal Article. Multicenter Study. Randomized Controlled Trial] Cutis. 69(4 Suppl):2-15, 2002 Apr. 9 van Vloten WA, Sigurdsson V. Selecting an oral contraceptive agent for the treatment of Hormones: androgenic hormones in women, corticosteroids, acne in women. Am J Clin Dermatol. 2004;5(6):435-41. corticotrophin (ACTH), oral contraceptives high in progestin 10 Arowojolu AO, Gallo MF, Grimes DA, Garner SE. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2004;(3):CD004425. Bromides, chlorides, halothane, iodides (e.g., Kelp) 11 Katsambas A & Papakonstantinou A. Acne: Systemic Treatment. Clin Derm. Antiepileptic drugs: gabapentin, phenytoin, phenobarbital & 12 Magin P, Pnd D, Smith W, et al. A systematic review of the evidence for “myths and Tuberculostatic drugs: ethambutol, isoniazid & thionamide misconceptions” in acne management: diet, face-washing and sunlight. Family Practice – an international journal;2005(Jan 11):62-70 Miscellaneous: cyclosporine, cyanocobalamin, dantrolene, gold 13 Grant JD and Anderson PC. Chocolate and acne: a dissenting view. Missouri Medicine salts, lithium salts, maprotiline, psoralens, quinidine, quinine & 14 Anderson PC. Foods as the cause of acne. Am Fam Phys 1971;3:102-3 Select cancer drugs: cetuximab, erlotinib & gefitinib 15 Fulton JE Jr, Plewig G, Kligman AM. Effect of chocolate on acne vulgaris. J Am Med Family history (genetics) often provides prognostic clues 16 Zouboulis CC. Bohm M. Neuroendocrine regulation of sebocytes -- a pathogenetic link between stress and acne. Experimental Dermatology. 13 Suppl 4:31-5, 2004. Table 1: Topical acne therapies and their associated
17 Dreno B. Topical Antibacterial Therapy for Acne Vulgaris. Drugs 2004;64(21):2389-2397 activities17,18,6
18 Krautheim A and Gollnick HPM. Acne: Topical Treatment. Clin Derm 2004;22:398-407 Cli) + Ada
- = none; + = weak; ++ = moderate; +++ = strong ADA adapalene BP benzoyl peroxide
CLIN clindamycin ERY erythromycin TAZ tazarotene TET tetracycline TRE tretinoin

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