Pharmacologic Therapy for Acne: A Primer for Primary Care

Topical antibiotic and anti-inflammatory agents

Topical agents used to treat inflammatory lesions include benzoyl peroxide, erythromycin, clindamycin, dapsone, azelaic acid, and sulfacetamide (Table 1).^1,6,9-16 These topical agents are generally well tolerated, with most adverse reactions limited to facial irritation and erythema. They come in an array of vehicle formulations, including washes, creams, gels, solutions, foams, and lotions. Vehicle selection should be based upon patient preference and skin type. Gels and solutions have a drying effect, making them more appropriate for individuals with oily skin, whereas creams are moisturizing and appropriate for individuals with dry skin. Lotions are appropriate for all skin types.¹¹

Benzoyl peroxide (BPO) has both keratolytic and comedolytic activity and is available in concentrations ranging from 2.5% to 10%. It is available OTC, as well as by prescription, and is thus readily accessed by the patient. Because BPO is bactericidal for P acnes, resistance to BPO among P acnes has not occurred.¹ All concentrations are equally effective, but the higher concentrations are more likely to cause skin dryness and other adverse effects.¹² Combination therapy with topical antibiotics, tretinoin, and BPO is more clinically effective than monotherapy.¹⁷ Combination products reduce the complexity of acne treatment and likely increase therapy adherence.¹¹ Currently available combination products in various percentages are erythromycin with BPO, clindamycin with BPO, adapalene with BPO, and clindamycin with tretinoin.¹

Oral antibiotics

Oral antibiotics should be reserved for use in situations where topical therapy is ineffective. All antibiotics are effective in treating acne due to their antimicrobial activity against P acnes.¹ These agents play a key role in managing moderate to severe acne that is likely to scar, as well as in cases of widespread acne involving the face, arms, and trunk. Note that the use of oral antibiotics in acne treatment is controversial, as chronic use contributes to rising rates of bacterial resistance.¹⁸ For this reason, antibiotic therapy for acne should be limited to a duration of three months or less, and these agents should not be used as monotherapy.⁶ In particular, recent recommendations restrict the use of erythromycin for acne treatment due to an increase of P acnes resistance.¹ Cephalosporins, macrolides, and penicillin class antibiotics are not routinely recommended due to lack of data regarding their clinical effectiveness in treating acne.¹

Tetracycline class antibiotics are the most commonly used oral antibiotics for acne therapy, particularly doxycycline and minocycline.⁵ Common adverse effects include gastrointestinal upset, photosensitivity, and some pigmentation issues.¹⁹ Trimethoprim-sulfamethoxazole (TMP-SMX) is a folate synthesis inhibitor class antibiotic also used to treat acne. Its use should be reserved for individuals who are allergic to tetracyclines or in cases of acne resistant to other antimicrobials.¹ Potential adverse reactions include photosensitivity and severe hypersensitivity conditions ranging from a mild rash to toxic epidermal necrolysis.¹⁹ Table 2 summarizes the dosage ranges, pregnancy category risk, and potential adverse effects of oral antibiotics used to treat acne.^1,19,20

The firstline choice for treating moderate acne with papules and pustules is oral antibiotics with topical retinoids and BPO.⁵ Patients should be educated about potential adverse effects of these agents, including the development of antibiotic resistance.

Hormonal agents

Hormonal therapies should be reserved for females with acne lesions influenced by fluctuations in hormone levels.²¹ Pubertal changes initiate the production of adrenal dehydroepiandrosterone, which leads to increased testosterone production. Testosterone is converted to dihydrotestosterone (DHT), which binds to androgen receptors in the sebaceous glands, stimulating the glands and potentially increasing production of sebum. Hormonal agents act by reducing androgen activity in the sebaceous gland. Combined oral hormones, those containing both estrogen and progesterone, reduce the amount of free testosterone and ovarian androgens by suppressing ovulation.¹ Hormonal therapy can be quite effective for females of childbearing age. Females who report acne flares with their menstrual cycles may be good candidates for hormonal therapy.¹

The estrogen agent most frequently used in oral contraceptives is ethinyl estradiol. Numerous progesterone agents can also be used, but those with low androgenicity or antiandrogenic properties are more effective for acne therapy.²¹ It is prudent to screen patients for thromboembolic risks, as this is a major adverse effect of combined hormonal agents. Risks of thromboembolic episodes are increased in obese persons, those who smoke, and those older than age 35.¹⁵ Other contraindications for combined hormonal therapy are pregnancy, liver disease, current breast cancer, heart disease, hypertension, and migraines with neurologic symptoms. Minor adverse effects include nausea, breast tenderness, cyclic weight gain, and headaches.¹⁵ Although many combined oral contraceptives improve acne, only four have FDA indications for the treatment of acne: ethinyl estradiol/norgestimate, norethindrone acetate/ethinyl estradiol, drospirenone/ethinyl estradiol, and drospirenone/ethinyl estradiol/folate.⁵

Spironolactone, a potassium-sparing diur­etic, may also be appropriate for treating acne in women due to its antiandrogenic properties. The drug binds androgen receptors in the skin, which then blocks testosterone and DHT. Spironolactone can be an effective firstline agent in treating hormonal-pattern acne, which presents as inflammatory lesions located on the lower face and neck. In particular, it can be an appropriate choice for women with adult-onset acne.¹⁵ Spironolactone is not approved by the FDA for acne treatment, but it has been used successfully for many years.⁵ Spironolactone was found in rodent studies to cause feminization of the male rat fetus, so patients taking this drug should use reliable birth control methods. It can be used concomitantly with oral contraceptives.⁵ Common side effects include breast tenderness, diuretic effects, headaches, and menstrual irregularities. Although the risk for hypokalemia is low in healthy young women, it may be prudent to periodically assess potassium, sodium, and renal function in patients.¹ Spironolactone should be avoided in patients with renal disease and those on other diuretics.¹⁵