Evidence-based answers from the Family Physicians Inquiries Network
Meghan Gannon, MD Spring Hill Family Health Group, Spring Hill, Tenn Which oral antibiotics
Michael Underhill, DO Paseo Family Physicians, are best for acne? Glendale, Ariz
Kay E. Wellik, MLS, AHIP Mayo Clinic Arizona, EVIDENCE-BASED ANSWER Scottsdale doxycycline is effective ion). For these patients, erythromy- ASSISTANT EDITOR Carmen G. Strickland, A (strength of recommendation cin is eff ective and better studied than MD, MPH [SOR]: B, randomized controlled trial) and azithromycin (SOR: C, expert opinion). Wake Forest School the antibiotic of choice (SOR: C, expert Otherwise, emerging resistance and GI dis- of Medicine, Family opinion) for moderate to severe infl amma- turbances make erythromycin a third-line Medicine Residency Program, tory acne requiring oral treatment. Limit- treatment. Winston-Salem, NC ing side eff ects include photosensitivity Th e use of oral antibiotics should be and gastrointestinal (GI) disturbance. limited to moderate to severe infl ammato- Other members of the tetracycline ry acne unresponsive to topical therapies, family are considered second-line agents including retinoids and antibiotics (SOR: because of their side-eff ect profi le and C, expert opinion). Oral antibiotics should are contraindicated in pregnancy and for be used for at least 6 to 8 weeks and dis- children younger than 12 years (SOR: A, continued after 12 to 18 weeks of therapy meta-analysis, and C, expert opin- (SOR: C, expert opinion).
Evidence summary Minocycline: Probably effective, Acne vulgaris is an extremely common disor- but not the fi rst choice der aff ecting up to 95% of adolescents.1 Doxy- A 2003 Cochrane review examined 27 ran- cycline improves infl ammatory lesions and domized trials that compared oral minocy- has a tolerable side-eff ect profi le. cline with placebo or other active treatments, including topical and systemic antibiotics, Doxycycline: in a total of 3031 patients with acne vulgaris Fewer lesions, few side effects on the face or upper trunk.4 Th e review de- A 2003 randomized, double-blind, controlled termined that minocycline is probably an ef- trial of 51 patients demonstrated that a sub- fective treatment for moderate acne vulgaris. antimicrobial dose of doxycycline (20 mg oral- However, no reliable evidence from random- ly twice a day) reduced comedonal lesions by ized controlled trials (RCTs) justifi es its use as 53.2% (from 31 to 16; P=.04) and infl ammatory a fi rst-line agent, especially given its higher lesions by 50.1% (from 55 to 25; P<.01), where- cost relative to other treatments. as placebo decreased comedonal lesions by 10.6% (from 51 to 46; P=.4) and infl ammatory Drug resistance weakens lesions by 30.2% (from 27 to 19; P<.01).2 macrolides’ “punch” Th e most commonly reported adverse Macrolide antibiotics, primarily erythromy- eff ects of doxycycline are GI disturbance and cin, were at one time considered fi rst-line sensitivity to ultraviolet radiation (sunlight). treatment for acne, but have fallen out of A recent systematic review found an adverse favor because of emerging drug resistance. event rate of 13 per 1 million prescriptions Nevertheless, erythromycin’s price and safety written.3 in pregnant women and young children has
290 THE JOURNAL OF FAMILY PRACTICE | MAY 2011 | VOL 60, NO 5 TABLE 1 Estimated cost of oral acne medications
Dose, formulation, Medication and frequency Cost of 30-day supply*
Doxycycline hyclate 100 mg capsule daily $12.99
Doxycycline hyclate 100 mg tablet daily $20.99
Extended-release minocycline 45 mg tablet daily $450.97
Minocycline 100 mg capsule twice a day $45.98
Minocycline 100 mg tablet twice a day $227.98
Erythromycin base 250 mg enteric-coated capsule $154.62 4 times a day
Erythromycin base 250 mg tablet 4 times a day $114.62
Azithromycin 500 mg tablet daily, $175.20 3 days/wk *http://www.drugstore.com. Accessed April 10, 2011. Doxycycline is the antibiotic TABLE 2 of choice for Safety and adverse-eff ect profi les of acne medications8 moderate to severe Medication Adverse effects Pregnancy Lactation Appropriate age infl ammatory category safety range acne requiring oral treatment. Doxycycline Photosensitivity, GI D Avoid >12 y hyclate disturbance, elevated BUN
Minocycline Tooth discoloration, D Avoid; >12 y dizziness, hypersensitivity milk effects syndrome possible
Erythromycin GI disturbance, nausea B Safe FDA-approved base for children
Azithromycin Abdominal pain, B Minimal risk Extended-release GI disturbance formula not FDA-approved for children
BUN, blood urea nitrogen; GI, gastrointestinal. maintained its standing in acne therapy. A then 250 mg every other day for 2 months) 1986 RCT that compared erythromycin with or tetracycline (1 g daily for 1 month, then tetracycline found comparable effi cacy: a 500 mg daily for 2 months). Th e drugs pro- 65% reduction in papules, from 21 to 12 le- duced comparable results: an 84.7% im- sions, for erythromycin and a 62% reduc- provement with azithromycin and a 79.7% tion, from 17 to 10 lesions, for tetracycline improvement with tetracycline (P<.05).6 (P<.0001).5 Th e main side eff ect of macrolide Compared with other macrolides and tetra- antibiotics is GI disturbance. cycline , azithromycin has a more tolerable A 2006 RCT randomized 290 patients to side- eff ect profi le with fewer GI disturbances. the macrolide azithromycin (500 mg daily for Lack of suffi cient data on trimethoprim 3 consecutive days a week in the fi rst month, ± sulfamethoxazole, fl uoroquinolones, and
JFPONLINE.COM VOL 60, NO 5 | MAY 2011 | THE JOURNAL OF FAMILY PRACTICE 291 cephalosporins precludes their inclusion in to children younger than 10 years because of routine acne treatment. the risk of permanent discoloration of teeth and abnormal skeletal development.7,8 Th e American Academy of Dermatology Recommendations also recommends topical retinoids as fi rst- Th e American Academy of Pediatrics (AAP) line therapy for acne followed by oral doxycy- recommends topical retinoids as the founda- cline or minocycline if needed. Erythromycin tion of treatment for most acne patients, and a is recommended for patients who can’t use topical microbial agent for additional therapy. tetracyclines, but with a warning about pos- Oral antibiotics should be reserved for moder- sible bacterial resistance.9 ate to severe infl ammatory acne; tetracyclines TABLE 1 shows the cost of various acne are the standard fi rst-line choice in most cas- medications. TABLE 2 outlines their safety and es. Th e AAP warns against giving tetracyclines risk profi les. JFP
References 1. Amin K, Riddle CC, Aires DJ, et al. Common and alternate of oral erythromycin versus oral tetracycline in the treatment oral antibiotic therapies for acne vulgaris: a review. J Drugs of acne vulgaris. A double-blind study. J Am Acad Dermatol. Dermatol. 2007;6:873-880. 1986;14:183-186. 2. Skidmore R, Kovach R, Walker C, et al. Eff ects of subantimicro- 6. Rafi ei R, Yaghoobi R. Azithromycin versus tetracycline in the bial-dose doxycycline in the treatment of moderate acne. Arch treatment of acne vulgaris. J Dermatol Treat. 2006;17:217-221. Dermatol. 2003;139:459-464. 7. Hurwitz S. Acne vulgaris: pathogenesis and management. 3. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a Pediatr Rev. 1994;15:47-52. systematic review. Clin Th er. 2005;27:1329-1342. 8. Zaenglein AL, Th iboutot DM. Expert committee recommen- 4. Garner SE, Eady EA, Popescu C, et al. Minocycline for acne dations for acne management. Pediatrics. 2006;118:1188-1199. vulgaris: effi cacy and safety.Cochrane Database Syst Rev. 9. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care 2003;(1):CD002086. for acne vulgaris management. J Am Acad Dermatol. 2007; 5. Gammon WR, Meyer C, Lantis S, et al. Comparative effi cacy 56:651-663.
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