Managing rosacea: a review of the use of metronidazole alone and in combination with oral antibiotics

Journal of Drugs in Dermatology, May, 2007 by Jennifer F. Conde, Christopher B. Yelverton, Rajesh Balkrishnan, Alan B. Fleischer, Jr., Steven R. Feldman

A 16-week, placebo-controlled, randomized, double-blind study compared twice-daily metronidazole 0.75% lotion plus placebo to twice-daily metronidazole plus 20 mg of doxycycline hyclate. (18) The total number of inflammatory lesions was significantly decreased in the combination treatment group at 12 and 16 weeks with the severity of the lesions being decreased as early as 4 weeks of treatment. (19) The dual therapy group also had significant improvement in erythema as well as overall global severity. (20)

Maintenance Therapy

Rosacea is a chronic skin condition with a relapsing and remitting course. Approximately 25% of patients will relapse in one month, 66% will relapse within 6 months, and 70% will relapse within 4 years of discontinuation of treatment. (20) Maintenance treatment is recommended to reduce the rate of relapse of rosacea, for which topical metronidazole is often successful. (2)

In a multicenter study, 113 subjects received treatment with metronidazole 0.75% gel and tetracycline (initially 250 mg 4 times a day for 12 weeks, then twice daily for 2 weeks, and then once daily for 2 weeks). (2) After 16 weeks, 92% of participants had fewer papules and/or pustules and 73% had less erythema; 39% of participants experienced elimination of all inflammatory lesions. (2)

The next 6 months of the study were the double-blind portion, which assessed metronidazole's ability to maintain remission. Eighty-eight out of the original 113 participants were included in this portion of the study. They were divided equally into 2 groups: one receiving metronidazole 0.75% gel and the other receiving its vehicle. (2)

At the end of 6 months, more metronidazole-treated subjects (53%) were free of lesions than vehicle-treated subjects (32%). (13) The number of inflammatory lesions was also significantly decreased in the metronidazole treatment arm with the average count being 3.3 compared to 5.8 in the vehicle arm. (2) Erythema was also reduced, but not to a significant value with 74% of the metronidazole-treated subjects having absent to mild erythema compared to 55% in the vehicle group (P=.14). (2)

Of the subjects that experienced relapse in the metronidazole-treated group, all did so within the first 3 months after discontinuation of the tetracycline as opposed to the vehicle-treated group that experienced relapse throughout the 6 months. (2) Relapse occurred more often in younger subjects with no or minimal skin dryness. (2)

Discussion

Topical therapy is still the mainstay of treatment for rosacea, and metronidazole is widely used due to its proven effectiveness with minimal side effects. Other topical therapies offer benefit to rosacea patients as long as side effects can be tolerated. Some evidence supports combining 2 topical treatments for improved outcomes.

Oral therapy with a tetracycline family antibiotic has recently gained favor both alone and in combination with metronidazole in subantimicrobial dosing. These low-dose treatment regimens are as effective as traditional antimicrobial dosing without the side effect profile. There is also evidence suggesting that maintenance therapy with topical metronidazole should be continued after treatment. This 2-step approach consisting of both topical and oral therapy initially followed by topical therapy for maintenance is becoming a mainstay in the treatment of rosacea.