Department of Medicine, University of Calgary, Calgary, Alberta, Canada


Topical metronidazole (Noritate® 1% Cream, Dermik; MetroCream™ 0.75% Cream, MetroLotion® 0.75% Lotion, Metrogel® 0.75% and 1% Topical Gel, Galderma) has been used for the treatment of rosacea for over 30 years. Several placebo-controlled trials have demonstrated its effectiveness in the treatment of moderate-to-severe rosacea. It is also effective in preventing relapses of disease and is well tolerated by most patients. A growing number of formulations are available.

Key Words:
rosacea, metronidazole, antibiotic, anti-inflammatory

Rosacea is one of the most common conditions seen by dermatologists. Its etiology and pathogenesis are unknown despite its high prevalence. Topical metronidazole, which was first reported to be effective in the treatment of rosacea in 1983,1 remains a cornerstone of therapy. Although the use of metronidazole in the treatment of rosacea has been reviewed previously,2,3 continued research has prompted this updated review.

Mechanism of Action

The mechanism of action of metronidazole in the treatment of rosacea is unclear. The efficacy of this broad spectrum antibiotic has been attributed to its antimicrobial and anti-inflammatory effects. In vitro studies have shown that metronidazole interferes with neutrophil release of reactive oxygen species that cause tissue injury at sites of inflammation.4 This antioxidant activity may be the basis of its anti-inflammatory effect in rosacea.


Metronidazole is poorly absorbed after topical application, with either undetectable or trace serum concentrations reported after topical use.1,5 Based on pharmacokinetic data on the original 0.75% gel formulation, it was originally thought that the optimal application frequency should be twice daily. More recent research has shown that metronidazole is degraded into active metabolites that may prolong the clinical efficacy of the parent drug.6

Placebo-Controlled Trials

Metronidazole has been shown to be effective for the treatment of moderate-to-severe rosacea in a number of placebo-controlled trials (Table 1).5,7-13 In a recent trial comparing metronidazole 1% gel, 1% cream, and gel vehicle applied once daily for 10 weeks, the efficacy of the 1% gel was at least that of the 1% cream and superior to the gel vehicle.8

Comparative Trials With Other Rosacea Treatments

A number of studies have compared topical metronidazole with other treatment options for rosacea. These are summarized in Table 2. Regardless of the formulation, studies have shown a significant reduction of papulopustular lesions and erythema scores compared with placebo. Although most studies have not shown improvement of telangiectasias, Tan, et al. reported a significant reduction in the telangiectasia score in patients with moderate-to-severe rosacea using metronidazole 1% cream with sunscreen SPF 15 (Rosasol®, Steifel Canada) for 12 weeks.12 In their review of randomized controlled trials of patients with moderate-to-severe rosacea in the Cochrane Database of Systemic Reviews, van Zuuren, et al. concluded that topical metronidazole is more effective than placebo, but that the quality of studies evaluating rosacea treatments was generally poor, and that good randomized controlled trials that include quality of life assessments are needed.14

Comparative Trials Between Different Formulations of Metronidazole

Metronidazole is currently available in a variety of formulations, and comparative studies have shown equal efficacy. In a study comparing commercially available formulations of both metronidazole 0.75% and 1% cream, applied once daily for 12 weeks for the treatment of moderate-to-severe rosacea, both were equally effective.15




Number of

in Lesion
Count vs.

in Erythema


Onset of
0.75% gel
Aronson, et al.5
R, SF, DBb.i.d.
9 wks
4751 vs. 4YesNone3
0.75% gel
Bleicher, et al.7
R, SF, DBb.i.d.
9 wks
4065 vs. 15YesNone3
1% gel
Beutner, et al.8
R, PG, SB,
1% gel vs.
1% cream
vs. gel
10 wks
>1200 total67 (1%
gel) vs. 58
(1% cream)
vs. 46 (gel
3% (1% gel),
4% (1%
cream and
gel vehicle)
0.75% cream
Drake, et al.9
R, PG, DBb.i.d.
12 wks
143 total62.5 vs. 43
1% cream
Breneman, et
R, PG, DBq.d.
10 wks
8953 vs. 17Yes2% had
adverse skin
1% cream
Jorizzo, et al.11
R, PG, DBb.i.d.
12 wks
6165 vs. 25YesMild
site reactions
1% cream with
Tan, et al.12
R, PG, DBb.i.d.
12 wks
6165 vs. 25YesMild
site reactions
0.75% lotion
Breneman, et al.13
R, PG, DBb.i.d.
12 wks
6557 vs. 27
Table 1:
Placebo-controlled trials of metronidazole for rosacea*
R=randomized, SF=split-face, PG=parallel group, DB=double-blind, SB=single-blind, P=Placebo
* table includes studies using commercially available products
**all changes in lesion count were significant compared with placebo



Azelaic acid 15% gel vs. metronidazole 0.75% gel16,17Azelaic acid superior in improving
lesion counts and erythema
Study design has been criticized
Azelaic acid 20% cream vs. metronidazole
0.75% cream18
Similar reductions in lesions but
better global improvement with
azelaic acid
Split-face design
Sodium sulfacetamide 10% and
sulfur 5% lotion or cream vs. metronidazole
0.75% gel or cream19,20
Greater reduction in lesions
and erythema with sodium
More treatment related adverse
effects with sodium sulfacetamide/
Metronidazole 1% cream or 0.75%
gel vs. tetracycline 250 mg b.i.d.-
No significant difference in
Tetracycline may have a more rapid
onset of action
Table 2: Comparative trials with other rosacea treatments.

Remission and Relapse

In a study of patients who achieved remission of rosacea with the use of systemic tetracycline, two thirds relapsed within 6 months of treatment cessation.23 Nielsen reported that metronidazole 1% cream applied daily or every other day is at least as effective in preventing relapses as tetracycline 250mg taken twice daily.24 In a more recent study, metronidazole 0.75% gel applied twice daily maintained remission compared with vehicle after successful treatment with a combination of metronidazole gel and oral tetracycline.25

Adverse Effects

Metronidazole is generally well tolerated, with adverse events reported in less than 5% of patients. Local reactions include dryness, redness, pruritus, aggravation of acne or rosacea, burning, and stinging. True allergic contact dermatitis is rare.26


Topical metronidazole remains a cornerstone in the treatment of rosacea. Several placebo-controlled trials have confirmed its ability to reduce both inflammatory lesions and erythema. Daily dosing has been shown to be effective in numerous clinical trials. As well, metronidazole is effective is preventing relapses of rosacea.


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  3. Gupta AK, Chaudhry M. Topical metronidazole for rosacea. Skin Therapy Lett 7(1):1-3,6 (2002 Jan).
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  10. Breneman DL, Stewart D, Hevia O, Hino PD, Drake LA. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. Cutis 61(1):44-7 (1998 Jan).
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  18. Maddin S. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. J Am Acad Dermatol 40(6 Pt 1):961-5 (1999 Jun).
  19. Lebwohl MG, Medansky RS, Russo CL, Plott RT. The comparative efficacy of sodium sulfacetamide 10%/sulfur 5% lotion and metronidazole 0.75% in the treatment of rosacea. J Geriatr Dermatol 3(5):183-5 (1995).
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  21. Schachter D, Schachter RK, Long B, et al. Comparison of metronidazole 1% cream versus oral tetracycline in patient with rosacea. Drug Invest 3(4):220-4 (1991).
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