Often primary care clinicians use only benzoyl peroxide, topical antibiotics, topical retinoids, and oral doxycycline. While effective, newer therapies add useful mechanisms and may be a better fit for many patients with treatment resistant acne. We select treatment according to acne type, severity, location, scarring risk, previous response, pregnancy potential, medical history, medication interactions, cost, and patient preference.¹

Established Acne Therapies

We use the full range of established treatments when they are appropriate:

• Topical clindamycin is an antibiotic used primarily for inflammatory acne. To reduce the development of antibiotic-resistant Cutibacterium acnes, topical clindamycin should not be used as long-term monotherapy. It is generally paired with benzoyl peroxide and may also be combined with a topical retinoid.^1,2
• Tretinoin (Retin-A) is a topical retinoid that helps prevent microcomedone formation and treats both comedonal and inflammatory acne. Redness, dryness, peeling, burning, and stinging are common during the first several weeks. Starting with less frequent application, using a moisturizer, and gradually increasing use can improve tolerability.^1,3
• Adapalene is another topical retinoid used for comedonal and inflammatory acne. Comparative studies involving specific formulations have found efficacy similar to tretinoin with generally better local tolerability. The choice between adapalene and tretinoin depends on the concentration, formulation, sensitivity of the skin, previous response, and treatment goals.^1,4
• Doxycycline is an oral tetracycline antibiotic strongly recommended in current acne guidelines for moderate-to-severe inflammatory acne. It should ordinarily be used for a limited period and combined with benzoyl peroxide and other topical maintenance therapy rather than prescribed as antibiotic monotherapy. Potential adverse effects include gastrointestinal irritation and photosensitivity.¹

Newer and More Targeted Therapies

We also offer newer treatment options when their mechanism, dosing, or evidence makes them appropriate for an individual patient:

• Sarecycline (Seysara) is a tetracycline-class antibiotic approved by the FDA in 2018 for inflammatory lesions of nonnodular moderate-to-severe acne in patients 9 years and older. It is taken once daily using weight-based dosing and may be taken with or without food. Sarecycline has less in vitro activity than doxycycline or minocycline against many gram-negative and anaerobic organisms associated with the intestinal microbiome.^5,6,7 This narrower laboratory activity suggests that sarecycline may exert less pressure on some intestinal bacteria.^1,5,6,7
• Trifarotene (Aklief) is a topical retinoid with selectivity for retinoic acid receptor gamma, or RAR-γ. It is FDA-approved for acne in patients 9 years and older and is applied once daily to affected areas of the face and/or trunk. Two large phase 3 trials demonstrated efficacy for both facial and truncal acne, making trifarotene a particularly relevant option when the chest, shoulders, or back require treatment.^8,9 Trifarotene can still cause dryness, scaling, redness, stinging, and burning.
• Spironolactone is an oral antiandrogen used off-label for persistent acne in adult women. It reduces androgen signaling that can contribute to sebum production and acne. In the randomized SAFA trial, participants received 50 mg daily followed by 100 mg daily when tolerated; spironolactone improved outcomes compared with placebo, with a larger treatment difference at 24 weeks than at 12 weeks.^1,10 Dosing is individualized. Before prescribing spironolactone, clinicians review pregnancy potential, blood pressure, kidney disease, and medications or medical conditions that may increase potassium. Laboratory monitoring is based on age and individual risk factors rather than applied identically to every patient.^1,10
• Clascoterone (Winlevi) is the first FDA-approved topical androgen-receptor inhibitor for acne. It is approved for patients 12 years and older and may be used in both male and female patients. Two phase 3 trials demonstrated greater reductions in inflammatory and noninflammatory facial lesions with clascoterone than with vehicle cream.^11,12 Clascoterone provides a topical way to target androgen signaling without using a systemic oral antiandrogen. However systemic absorption is still possible to a degree can occur with warnings regarding possible hypothalamic-pituitary-adrenal axis suppression. Local redness, dryness, scaling, itching, burning, and stinging may also occur.^11,12

Combination Strategies

Acne usually responds best when treatment targets more than one part of the disease process. A regimen may include the following:

• Predominantly comedonal acne: A topical retinoid such as adapalene, tretinoin, or trifarotene, with benzoyl peroxide or azelaic acid added when appropriate.¹
• Inflammatory facial acne: Benzoyl peroxide plus a topical retinoid. Topical clindamycin may be added, but it should be paired with benzoyl peroxide. Moderate-to-severe disease may also warrant a limited course of doxycycline or sarecycline while topical treatment is continued.^1,2,5
• Truncal or back acne: Benzoyl peroxide washes and topical retinoids are common options. Trifarotene has direct phase 3 evidence for treatment of both facial and truncal acne. Extensive inflammatory truncal acne may require systemic treatment.^1,8,9
• Persistent acne in adult women: Spironolactone may be combined with a topical retinoid and benzoyl peroxide. Clascoterone offers an additional topical androgen-receptor treatment when clinically appropriate.^1,10,11
• Persistent or treatment-resistant acne: We reassess the diagnosis, medication adherence, treatment duration, acne distribution, possible medication triggers, scarring risk, and tolerability before escalating therapy. Multiple complementary mechanisms are often more useful than prolonged antibiotic monotherapy.¹
• Severe nodular or cystic acne: Oral isotretinoin may be appropriate when acne is severe, causes scarring or substantial psychosocial burden, or has not responded to standard topical or oral therapy. Referral to Dermatology or iPLEDGE registered clinician may be recommended in this case.^1,13

Our approach utilizes some of the most advanced, targeted therapies available rather than limiting ourselves to common over the counter skin creams.

Important safety information: Acne medications have different restrictions during pregnancy, pregnancy planning, and breastfeeding. Age, kidney function, medication interactions, and other medical conditions may also affect treatment selection. Isotretinoin is contraindicated during pregnancy and is available only through the iPLEDGE risk-management program. Treatment should be selected and monitored by a qualified healthcare professional.

References

1. Reynolds RVS, Yeung H, Cheng CE, Cook-Bolden F, Desai SR, Druby KM, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30. doi:10.1016/j.jaad.2023.12.017. Article. 2026 correction.
2. Jackson JM, Fu JJ, Almekinder JL. A randomized, investigator-blinded trial to assess the antimicrobial efficacy of a benzoyl peroxide 5%/clindamycin phosphate 1% gel compared with a clindamycin phosphate 1.2%/tretinoin 0.025% gel in the topical treatment of acne vulgaris. J Drugs Dermatol. 2010;9(2):131-136. PubMed.
3. US Food and Drug Administration. Retin-A Micro (tretinoin) gel microsphere prescribing information. Revised 2025. Prescribing information.
4. Cunliffe WJ, Danby FW, Dunlap F, Gold MH, Gratton D, Greenspan A. Randomised, controlled trial of the efficacy and safety of adapalene gel 0.1% and tretinoin cream 0.05% in patients with acne vulgaris. Eur J Dermatol. 2002;12(4):350-354. PubMed.
5. Moore A, Green LJ, Bruce S, Sadick N, Tschen E, Werschler P, et al. Once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate-to-severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. J Drugs Dermatol. 2018;17(9):987-996. PubMed.
6. Zhanel G, Critchley I, Lin LY, Alvandi N. Microbiological profile of sarecycline, a novel targeted-spectrum tetracycline for the treatment of acne vulgaris. Antimicrob Agents Chemother. 2019;63(1):e01297-18. doi:10.1128/AAC.01297-18. Article.
7. US Food and Drug Administration. Seysara (sarecycline) tablets prescribing information. Revised March 2023. Prescribing information.
8. Tan J, Thiboutot D, Popp G, Gooderham M, Lynde C, Del Rosso J, et al. Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol. 2019;80(6):1691-1699. doi:10.1016/j.jaad.2019.02.044. Article.
9. US Food and Drug Administration. Aklief (trifarotene) cream prescribing information. Revised October 2019. Prescribing information.
10. Santer M, Lawrence M, Renz S, Eminton Z, Stuart B, Sach TH, et al. Effectiveness of spironolactone for women with acne vulgaris in England and Wales: pragmatic, multicentre, phase 3, double-blind, randomised controlled trial. BMJ. 2023;381:e074349. doi:10.1136/bmj-2022-074349. Article.
11. Hebert A, Thiboutot D, Stein Gold L, Cartwright M, Gerloni M, Fragasso E, et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(6):621-630. doi:10.1001/jamadermatol.2020.0465. Article.
12. Sun Pharmaceutical Industries, Inc. Winlevi (clascoterone) cream 1% prescribing information. Revised July 2022. Prescribing information.
13. US Food and Drug Administration. Absorica and Absorica LD (isotretinoin) capsules prescribing information. Revised July 2023. Prescribing information.