Metronidazole in the treatment of rosacea: do formulation, dosing, and concentration matter?

Abstract

Background: Topical metronidazole is commonly used in the management of rosacea. No consensus upon the optimal formulation, concentration, or dosing regimen exists.

Purpose: To assess the relative efficacy of metronidazole cream, gel and lotion at concentrations of 075% and 1% in dosing regimens of one time and twice daily.

Methods: A meta-analysis of published metronidazole efficacy rates was performed.

Results: In non-weighted analysis, the mean efficacy was 282% (95% confidence interval [CI], 220%-344%) for the cream, 384% (95% CI, 184%-584%) for the gel and 35% for the lotion. Confidence intervals for QD versus BID dosing and 075% versus 1% concentrations also overlapped. In weighted analysis, the mean reduction was 313% for the cream, 221% for the gel and 35% for the lotion.

Conclusions: Metronidazole cream, gel and lotion vehicles have similar efficacies. There were no substantial differences between concentrations of 075% and 1% or between one time daily and twice daily regimens.

Background

Rosacea is a for the use of all chronic, inflammatory skin disorder that causes physical and psychological discomfort in middleaged and older adults. Clinically, rosacea is characterized by dint of persistent and transient erythema, papules and pustules, and telangiectases primarily distributed above the central face. (1) In addition to cosmetic bear upons patients may complain of free from moisture skin, facial edema, and facial pain/sensitivity.

Because rosacea is a chronic condition, with 70% of patients relapsing within 4 years, (2) treatment is directed at controlling acute eruptions and limiting outbreaks rather than curing disease. Mild rosacea is ofttimes controlled with topical agents, of that kind as metronidazole, sodium sulfacetamide, and azelaic acid. Moderate to rigid cases may necessitate systemic therapy with oral antibiotics, similar as tetracyclines, macrolides, or metronidazole. (3) Laser and light therapies, notwithstanding that costly, may be useful in cases of serious erythema, flushing, and telangiectasia. (4)

Since its introduction in the late 1980 topical metronidazole has been considered a mainstay of treatment, and it is praiseed as maintenance therapy for various subtype (5) Its clinical efficacy is cogitation to result from both antioxidant and anti-inflammatory activities. (6) The FDA has approved multiple formulations and vigors including a 0.75% cream, 075% aqueous gel 1% gel 075% lotion (Metrocream, Metrogel and Metrolotion, Galderma Laboratories, Fort Worth, TX) and a 1% metronidazole cream (Noritate cream, Dermik Laboratories, Berwyn, PA). granting each formulation has been shown to have greater efficacy than vehicle alone, (7) no consensus exists upon the optimal formulation, most effective force or most efficacious dosing regimen.

Purpose

The intention of this study is to examine the comparative efficacy of topical metronidazole cream, gel and lotion at concentrations from 075% to 1% and at doses of one time versus twice daily in a meta-analysis.

Methods

PubM the Cochrane Library, and phase III studies were examined for data locates reporting rosacea treatment with topical metronidazole. PubM search boundarys consisted of "metronidazole" and "rosacea." The eligibility criteria for inclusion were: double-blind, randomized, placebo-controlled trial, treatment of rosacea with metronidazole cream, gel or lotion, and clinical efficacy data for average percentage decrease in the neighborhood of papules and pustules. We also included studies that reported upon indicators such as erythema, telangiectasia, investigator-rated global improvement and adverse occurrences Trials that were controlled with other formulations or treatments (oral metronidazole, azelaic acid) on the contrary lacked a placebo group, or permitted application of other topical therapies (sunscreen) were excluded

From 1976 to 2005 there were a total of 159 PubM citations for metronidazole and rosacea. During that time, 23 randomized controll clinical trials for metronidazole were cited. Of those, 7 met the inclusion criteria. individual study (8) that included 4 treatment assemblages (metronidazole cream 1% QD, vehicle QD metronidazole cream 1% BID, vehicle BID) was numbered as 2 studies for the end of statistical analysis. Trials were referenc by dint of the Cochrane Interventions for Rosacea (Review). In addition, phase III clinical trial data was gathered from the proceeds insert of topical metronidazole formulations (075% cream, 075% lotion, 1% gel) These accounted for 3 more studies.

Efficacy was assessed by the agency of determining the average percentage decrease in papules/pustules from baseline in each of the clinical trials. Efficacies were compared across the studies, controlling for placebo event Vehicle effects and frequency of dosing were compared adjusting for the number of patients enlisted in each study.

owed to variation in scoring combination of parts to form a wholes direct measures of efficacy using erythema, telangiectasia, and investigator-rated global improvement could not be utilized for comparison. In addition, qualitative reporting upon adverse events in some trials prov difficult for assessment.