The FDA has approved Cabtreo (Bausch Health), a gel containing the retinoid adapalene, the oxidizing agent benzoyl peroxide, and the antibiotic clindamycin, for treatment of acne vulgaris in patients ≥12 years old. Cabtreo is the first three-drug topical formulation to become available in the US for treatment of acne.

Acne is common among adolescents and adults. Guidelines for treatment of acne were last published by the American Academy of Dermatology in 2016.

The FDA has approved Twyneo (Galderma), a cream containing the retinoid tretinoin and the oxidizing agent benzoyl peroxide, for once-daily topical treatment of acne in patients ≥9 years old.

The FDA has approved Winlevi (Sun), a 1% cream formulation of the androgen receptor inhibitor clascoterone, for treatment of acne vulgaris in patients ≥12 years old. It is the first topical androgen receptor inhibitor to be approved by the FDA.

Acne is common among adolescents and young adults, but its prevalence appears to have increased in people of all ages due to prolonged wearing of masks during the COVID-19 pandemic. Guidelines for treatment of acne were last published in 2016.

The FDA has approved a 4% aerosol foam formulation of minocycline (Amzeeq – Foamix) for topical treatment of inflammatory lesions of non-nodular moderate to severe acne in patients ≥9 years old. It is the first topical tetracycline formulation to be approved for use in patients with acne. Oral minocycline (Minocin, Solodyn, and generics) is

In our article on Slynd (Med Lett Drugs Ther 2020; 62:18), the drospirenone-only oral contraceptive, we mentioned that drospirenone has antiandrogenic activity that could improve acne and antimineralocorticoid activity that could cause hyperkalemia. We should have added that concurrent use of drospirenone with other drugs that increase potassium levels, such as the anti-androgen aldosterone receptor antagonist spironolactone (Aldactone, and generics), which is often used off-label for treatment of acne, can increase the risk of hyperkalemia.

The FDA has approved trifarotene 0.005% cream (Aklief – Galderma) for topical treatment of acne vulgaris in patients ≥9 years old. Trifarotene is the fourth topical retinoid to be approved in the US for treatment of acne; tretinoin (Retin-A, and others), adapalene (Differin, and generics), and tazarotene (Tazorac, and others) have been available by prescription for decades. Adapalene 0.1% gel has been available over the counter since 2016 for treatment of acne in patients ≥12 years old.

The FDA has approved a 1% cream formulation of ozenoxacin (Xepi – Cutanea), a nonfluorinated quinolone antibiotic, for treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes in patients ≥2 months old.

Sarecycline (Seysara — Allergan), a new oral tetracycline antibiotic, has been approved by the FDA for once-daily treatment of inflammatory lesions of non-nodular moderate to severe acne in patients ≥9 years old.

Intrauterine devices (IUDs) and the etonogestrel implant are the most effective reversible contraceptive methods available. Hormonal oral contraceptives, patches, rings, and injectables are also highly effective in preventing pregnancy. When used alone, barrier and fertility-based methods generally have higher failure rates than other methods.

Differin Gel 0.1% (Galderma), a topical formulation of the retinoid adapalene, will soon be available over the counter (OTC) for once-daily treatment of acne in patients ≥12 years old. It is the first topical retinoid to be approved for sale over the counter.

All topical retinoids normalize keratinization and appear to have anti-inflammatory effects; whether any one topical retinoid is more effective than any other is not clear. Many dermatologists now recommend topical retinoids for first-line treatment of acne; they can be used alone or in combination with antibiotics to treat both inflamed and noninflamed acne lesions, or for maintenance treatment. Retinoid/antimicrobial combinations are more effective than either component alone, particularly for patients with inflammatory lesions.1

Adverse effects of topical retinoids include dry skin, scaling, photosensitivity, erythema, burning, and pruritus. Although only small amounts of the drug are absorbed systemically following topical application, adapalene is classified as category C (teratogenic in rats; no adequate studies in pregnant women) for use during pregnancy.

Adapalene (Differin, and generics) is available by prescription in 0.1% gel, cream, and lotion formulations and in a 0.3% gel formulation. It is also available by prescription in combination with the oxidizing agent benzoyl peroxide (Epiduo; Epiduo Forte).

The cost of one 45-gram tube ranges from about $157 for generic adapalene to $580 for Differin.2 The cost of OTC Differin Gel 0.1% was not available at the time of publication.

1. Drugs for acne. Med Lett Drugs Ther 2016; 58:13.
2. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. September 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

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Our article earlier this year on Drugs for Acne1 stated that the oral retinoid isotretinoin (Accutane, and others) is the most effective drug available for patients with severe nodulocystic acne, but warned that depression, suicidality, myalgia, hypertriglyceridemia, and other adverse effects can occur. One of our readers objected to our listing depression and suicidality, which are the subject of a prominent warning in the package insert, in the same sentence as indisputable side effects such as hyperlipidemia and myalgia.

Depression and suicidal ideation have been reported in patients with severe acne after starting treatment with isotretinoin, including some cases in which symptoms resolved after discontinuation of the drug and reappeared after rechallenge.2 A cause-and-effect relationship has not been established, however, and acne itself is associated with symptoms of anxiety and depression.

Two large population-based cohort studies conducted in Canada and the UK found no evidence that treatment of acne with isotretinoin was associated with an increased risk of depression, suicide, or other psychiatric adverse effects.3 In a small US cohort study in 132 patients 12-19 years old with moderate to severe acne, use of isotretinoin did not increase depressive symptoms compared to use of topical drugs and oral antibiotics, and treatment of acne appeared to decrease symptoms of depression.4 A prospective, observational study in 346 patients ≥16 years old with moderate acne found that treatment with isotretinoin for 30 weeks reduced symptoms of anxiety and depression.5 Other studies have reached similar conclusions.

1. Drugs for acne. Med Lett Drugs Ther 2016; 58:13.
2. JD Bremner et al. Retinoic acid and affective disorders: the evidence for an association. J Clin Psychiatry 2012; 73:37.
3. SS Jick et al. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 2000; 136:1231.
4. CY Chia et al. Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study. Arch Dermatol 2005; 141:557.
5. SE Marron et al. Anxiety, depression, quality of life and patient satisfaction in acne patients treated with oral isotretinoin. Acta Derm Venereol 2013; 93:701.

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The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens, and inflammation all play a role. The gram-positive microaerophilic bacteria Propionibacterium acnes promotes development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

The FDA has approved another fixed combination of the antibiotic clindamycin phosphate and the oxidizing agent benzoyl peroxide (Onexton Gel 1.2%/3.75% – Valeant) for topical treatment of acne in patients ≥12 years old. Topical products containing the same drugs have been available for many years. Onexton Gel contains a new strength of benzoyl peroxide.

Bellafill (Suneva), a dermal filler approved earlier for correction of nasolabial folds, has now also been approved by the FDA for correction of moderate to severe, atrophic, distensible facial acne scars on the cheek in adults ≥21 years old. It is the only dermal filler approved in the US for correction of facial acne scars.

The oral retinoid isotretinoin (Accutane, and others) is the most effective drug available for treatment of acne.1 The FDA has recently approved a new oral isotretinoin product (Absorica – Cipher/Ranbaxy) for treatment of severe, recalcitrant nodular acne.

Isotretinoin can completely clear severe nodulocystic lesions, in some cases leading to remission that can persist for years after treatment is stopped. Mucocutaneous adverse effects include dry skin, dry eye, epistaxis, nasopharyngitis, cheilitis, alopecia, eczema, skin fragility and photosensitivity. Musculoskeletal symptoms, hypertriglyceridemia, hepatitis, pancreatitis, pseudotumor cerebri, depression and psychosis can occur.

The manufacturer’s package insert states that isotretinoin has been associated with inflammatory bowel disease, but a recent population-based cohort study found no significant association.2 The drug is a potent human teratogen (pregnancy category X); the prescriber, the pharmacist, the distributors, and the patient must register with iPLEDGE, a computer-based risk management program (www.ipledgeprogram.com).

The recommended dosage is 0.5 to 1 mg/kg/day given in 2 divided doses for 15-20 weeks. Unlike other formulations of isotretinoin, which are highly lipophilic and must be taken with a high-fat meal to achieve therapeutic plasma levels, Absorica can be taken with or without food, but serum concentrations are higher when it is taken with food. It should be taken with a full glass of water to reduce the risk of esophageal irritation. Absorica has not been shown to be more effective or better tolerated than generic formulations of isotretinoin.

1. Drugs for acne, rosacea and psoriasis. Treat Guidel Med Lett 2013; 11:1.

2. RO Alhusayen et al. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol 2012 Oct 25 (epub).

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Veltin Gel (Stiefel), a fixed-dose combination of the antibiotic clindamycin phosphate 1.2% and the retinoid tretinoin 0.025%, has been approved by the FDA for topical treatment of acne vulgaris in patients ≥12 years old. Another product containing the same active ingredients (Ziana) has been on the market since 2006.

Epiduo gel (Galderma), a fixed-dose combination of adapalene 0.1% (Differin), a synthetic retinoid analog, and benzoyl peroxide (BPO) 2.5%, an oxidizing agent, has been approved by the FDA for topical treatment of acne vulgaris in patients ≥12 years old.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens and inflammation all play a role. The gram-positive microaerophilic bacteria Propionibacterium acnes promote development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

The FDA has approved ThermaClear (Therative), a battery-powered, handheld device, to treat individual acne lesions with heat. ThermaClear is indicated only for use on mild to moderate inflammatory acne, not severe nodular or severe cystic acne, and it is not meant to be used on blackheads and whiteheads. Two similar devices are already on the market: Zeno, another handheld device that delivers heat to acne lesions, and the Radiancy Clear Touch Lite Acne Clearance System, a larger heat-delivery device.

The FDA has approved an extended-release formulation of minocycline (Solodyn - Medicis) for once-daily treatment of non-nodular moderate to severe acne.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, Propionibacterium acnes bacteria, sebum production, androgens and inflammation have all been implicated. P. acnes, a gram-positive microaerophilic bacterium, plays an important role in the development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

A high-intensity, narrow-band blue light (ClearLight -Lumenis) approved by the FDA for treatment of moderate inflammatory acne vulgaris has been featured in some stories in fashion magazines. This review describes the etiology and treatment of acne, as well as the mechanism of action, clinical studies, adverse effects, dosage and cost of the drug.

Isotretinoin (Accutane - Roche), an effective oral drug for treatment of acne, will soon be available generically. Concerns about its adverse effects, particularly psychiatric symptoms in adolescents, have been widely reported in the media.

Tazarotene (taz ar' oh teen, Tazorac - Allergan), an acetylinic retinoid marketed for treatment of psoriasis (Medical Letter 1997; 39:105), is also available as a 0.1% gel and cream for treatment of acne.

Azelaic acid, a naturally occurring heptanedicarboxylic acid, has been marketed in the USA as a 20% cream (Azelex - Allergan) for treatment of acne. The drug has been available in Europe for several years.

Tretinoin (all-trans-retinoic acid; Retin-A), a vitamin A metabolite used for years for topical treatment of acne, is now being used (without the approval of the US Food and Drug Administration) to improve the appearance of aging skin. Available by prescription in various concentrations in cream, gel and liquid formulations, tretinoin is chemically similar to isotretinoin (13-cis-retinoic acid; Accutane), an oral drug used for treatment of severe acne which has recently caused concern because of its teratogenicity (Morbid Mortal Weekly Rep, 37:171, March 25, 1988).