Metronidazole for Rosacea

Based on "Papulopustular rosacea Alfredo"
written by Francesco Drago, MD; Alfredo Rebora, MD

Topical Metronidazole formulations:

• Metronidazole Cream 0.75% (MetroCream®)
• Metronidazole Cream 1% (Noritate®)
• Metronidazole Gel 0.75% (MetroGel ®, Rozex®)
• Metronidazole Gel 1% (MetroGel ®)
• Metronidazole Lotion 0.75% (MetroLotion®)

Rosacea (also known as acne rosacea or adult acne) is a chronic relapsing skin disorder characterized by facial flushing, persistent erythema, telangiectasia (dilated superficial blood vessels), and inflammatory papules and pustules affecting the central face (cheeks, nose, or forehead).

Topical Metronidazole

Topical metronidazole was first reported to be effective for rosacea in 1983 and it was the first topical therapy approved for rosacea. Topical metronidazole is still considered the most appropriate rosacea treatment by many dermatologists. It remains the most commonly prescribed topical medication for rosacea in the United States.

Important benefit of topical formulations is the lack of systemic toxicity that can occur with oral medications.

Oral Metronidazole

Oral metronidazole (Flagyl ®) is effective in reducing papules and pustules of rosacea6. However, oral formulation is not suitable for long-term use.

Recent research5 has shown that oral metronidazole is an effective treatment for ocular and cutaneous rosacea in children.

How effective is Metronidazole for rosacea?

Topical metronidazole is very safe and effective in treating rosacea. It reduces the redness, erythema, and the number of inflammatory papules and pustules. It is also effective in maintaining achieved improvements of rosacea symptoms10. However, metronidazole does not affect telangiectasia.

Metronidazole 1% gel applied once daily is as effective as azelaic acid 15% gel applied twice-daily 1. It provides up to 77% reduction in the number of inflammatory lesions.

Metronidazole is helpful in maintenance therapy for rosacea. Continuous application allows for longer intervals between flare-ups2.

The efficacy of topical metronidazole is constant regardless of the formulation, strength, and frequency of application 3.

How long does it take for Metronidazole to work?

The improvement should be noted within the first 3 weeks of therapy, and the condition usually continues to improve through 9 weeks of treatment. As soon as an acceptable level of response is obtained, the frequency and duration of therapy should be adjusted.

Topical metronidazole has shown to reach significant reduction of erythema as early as week 2 and as late as week 10 depending on the formulation.

How does Metronidazole work?

Metronidazole appears to work through antimicrobial, anti-inflammatory, and antioxidant7 mechanism. The studies have shown that metronidazole interferes with neutrophil release of reactive oxygen species that cause tissue injury at sites of inflammation. This antioxidant activity may be the basis of its anti-inflammatory effect in rosacea.

The best treatment for rosacea

Topical metronidazole and azelaic acid are equally effective for acne rosacea. However, metronidazole is better tolerated.

The sodium sulfacetamide with sulfur cream reduces the number of inflammatory lesions and erythema better than topical metronidazole4.

Ivermectin cream vs Metronidazole cream

In December 2014 FDA approved a novel treatment for rosacea -- Soolantra® Cream (ivermectin). Ivermectin 1% cream is considerably more effective than metronidazole 0,75% cream in the treatment of inflammatory lesions of rosacea8. Successful treatment with ivermectin cream ensures significantly longer remission of rosacea compared with metronidazole cream following treatment discontinuance9.

Further reading

• Metronidazole facts - uses, mode of action

References

• 1. Wolf JE Jr, Kerrouche N, Arsonnaud S. Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. Cutis. 2006 Apr;77(4 Suppl):3-11.
• 2. Dahl MV, Katz HI, Krueger GG, Millikan LE, et al. Topical metronidazole maintains remissions of rosacea. Arch Dermatol. 1998 Jun;134(6):679-83. PubMed
• 3. Yoo J, Reid DC, Kimball AB. Metronidazole in the treatment of rosacea: do formulation, dosing, and concentration matter? J Drugs Dermatol. 2006 Apr;5(4):317-9.
• 4. Torok HM, Webster G, Dunlap FE, Egan N, Jarratt M, Stewart D. Combination sodium sulfacetamide/sulfur cream with sunscreens versus metronidazole 0.75% cream for rosacea. Cutis. 2005 Jun;75(6):357-63.
• 5. Léoni S, Mesplié N, Aitali F, Chamaillard M, Boralevi F, Marques da Costa C, Taïeb A, Léauté-Labrèze C, Colin J, Mortemousque B. Metronidazole: alternative treatment for ocular and cutaneous rosacea in the pediatric population. J Fr Ophtalmol. 2011 Dec;34(10):703-10
• 6. van Zuuren EJ, Graber MA, Hollis S, Chaudhry M, Gupta AK, Gover M. Interventions for rosacea. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003262.
• 7. Narayanan S, Hünerbein A, Getie M, Jäckel A, Neubert RH. Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system. J Pharm Pharmacol. 2007 Aug;59(8):1125-30.
• 8. Taieb A, Ortonne JP, Ruzicka T, Roszkiewicz J, Berth-Jones J, Peirone MH, Jacovella J; Ivermectin Phase III study group. Superiority of ivermectin 1% cream over metronidazole 0·75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol. 2015 Apr;172(4):1103-10. PubMed
• 9. Taieb A, Khemis A, Ruzicka T, et al. Maintenance of remission following successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of the ATTRACT randomized study. J Eur Acad Dermatol Venereol. 2016 May;30(5):829-36. PubMed
• 10. McClellan KJ, Noble S. Topical metronidazole. A review of its use in rosacea. Am J Clin Dermatol. 2000 May-Jun;1(3):191-9. PubMed

Published: September 01, 2012
Last updated: January 28, 2017