Erythromycin. In a randomized study of 200 patients with moderate-to-severe acne, erythromycin, 1 g in 2 divided doses daily, significantly reduced the comedone, papule, and pustule count after 8 weeks (SOR: B).28 The side-effect rate was 8%, usually associated with gastrointestinal irritation. Studies have shown that P acnes exhibits greater resistance to erythromycin than to tetracycline.29
Tetracycline/doxycycline/minocycline.Tetracycline and its lipophilic derivatives, doxycycline and minocycline, are the most commonly prescribed oral agents for acne vulgaris. As a class, tetracyclines should not be prescribed for pregnant women or for those younger than 9 years of age, to avoid the risks of tooth discoloration and bone growth retardation in the fetus or child.30 Various double-blinded, randomized controlled trials involving patients with mild-to-moderate acne have shown that tetracycline confers a statistically significant improvement over placebo as early as 6 weeks (SOR: A).31-33 Adverse effects include gastrointestinal upset, vaginal yeast infection, and a theoretical decrease in the efficacy of oral contraceptives.
Doxycycline, 100mg/d, has been shown to significantly reduce inflammatory lesions in a crossover trial of 62 patients (SOR: B).34 Its adverse effect profile is similar to that of tetracycline, though it tends to cause more photosensitivity (4% vs 1%).35
In a recent Cochrane review of 27 studies, minocycline was shown to be an effective treatment for acne, but no randomized controlled trial evidence was found to support the benefits of minocycline in acne resistant to other therapies (SOR: A).36 A recent study demonstrated that minocycline has a greater tendency than tetracycline or doxycycline to cause rare adverse side effects, including serumsickness-like reactions, drug-induced lupus, and hypersensitivity reactions.35 These factors, in addition to the higher cost, suggest that minocycline should not be a first line antibiotic choice for treating acne.
Oral contraceptives
Oral contraceptives (OCs) reduce the severity of acne vulgaris by decreasing the amount of circulating androgens.37 In 1997, a triphasic combination OC containing ethinyl estradiol 0.035 mg and increasing doses of norgestimate (0.180 mg, 0.215 mg, and 0.250 mg) was approved by the FDA for the treatment of acne in women. This decision was based on the results of a randomized, double-blind trial involving 257 patients in which the triphasic contraceptive was compared with placebo over 6 months (SOR: A).38 The OC group showed statistically significant improvement greater than that of the placebo group in all types of acne lesions. It also reduced total lesion counts by more than 53% in female subjects at 26 weeks, compared with lesion reductions of about 27% in controls. The principal adverse effect noted in this study was nausea.
Isotretinoin
Isotretinoin (Accutane) is an oral retinoid labeled for use in patients with severe, refractory, nodulocystic acne. In a randomized, crossover trial that included 33 patients, isotretinoin significantly decreased the number of nodulocystic lesions by 95% when compared with placebo, with only rare side effects of cheilitis and dermatitis (SOR: B).39 However, other studies suggest that cheilitis is fairly common and its absence may imply noncompliance or malabsorption of the drug.40 In addition, the FDA issued a warning in 1998 regarding possible increased risks in depression, psychosis, suicidal thoughts, and suicide attempts, though no conclusive evidence has been found.40 The typical dosage of isotretinoin is 0.5 to 1 mg/kg daily in two divided doses, with a standard cumulative maximum dose of 120 to 150 mg/kg per treatment course.41
In April 2002, Roche Laboratories released the System to Manage Accutane Related Teratogenicity (S.M.A.R.T) program, aimed at preventing pregnant women from receiving isotretinoin.42 Major malformations may occur in 25% to 30% of fetuses exposed to isotretinoin.43 Under this program, female patients must have both a screening and confirmation pregnancy test (urine or serum) prior to receiving a prescription for isotretinoin. In addition, patients must commit to using 2 forms of birth control for at least 1 month prior to initiation of therapy, during therapy, and 1 month after discontinuing isotretinoin. During monthly visits, a pregnancy test must be obtained and no more than a 30-day supply of isotretinoin may be prescribed. Finally, pharmacists will fill prescriptions only if an isotretinoin qualification sticker is affixed, obtained after signing and returning the S.M.A.R.T Letter of Understanding.
In addition to procedural safeguards, it is necessary to monitor lipid levels (hypertriglyceridemia and hypercholesterolemia) and liver enzymes at the start of therapy and at each monthly visit. If elevations occur in these measurements, dosage reduction or drug discontinuation should be considered. Given the intensity of monitoring that is required, some family physicians may wish to refer patients who require Accutane to a dermatologist.