BMJ  2007;334:154 (20 January), doi:10.1136/bmj.39048.540394.BE

Practice

Change page

Don't use minocycline as first line oral antibiotic in acne

¹ Drug and Therapeutics Bulletin, BMA House, London WC1H 9JR

Introduction

Key points Introduction Key points The clinical problem The evidence for change Barriers to change How should we change... References Oral minocycline is no more effective than other oral tetracyclines in treating acne The risk of rare but serious unwanted effects with minocycline makes it less suitable for use than other drugs in its class Oral minocycline is more expensive than most other oral tetracyclines Patients who need treatment with an oral tetracycline should be prescribed doxycycline, lymecycline, or oxytetracycline

The clinical problem

Most people develop acne vulgaris at some point in life. Typified by inflammation of hair follicles and accompanying sebaceous glands, acne may require oral antibacterial treatment, particularly in those with moderate to severe disease (an estimated 11% of adolescents¹). Minocycline is a common choice of drug and is often wrongly assumed to be more effective, easier to take, and less likely to cause bacterial resistance than other tetracyclines.

Search methods We searched Medline and the Cochrane Library to identify published randomised controlled trials and systematic reviews that assessed the safety and efficacy of oral minocycline in the treatment of acne vulgaris. We also consulted widely among specialists and generalists, as well as drug companies, to identify relevant published evidence.

The evidence for change

Efficacy
A Cochrane review assessed 27 randomised trials, involving a total of 3031 patients with acne vulgaris affecting the face or upper trunk, which compared oral minocycline with placebo or other active treatment.² Although minocycline seemed to be an effective treatment for acne, there was no convincing evidence from good-quality studies that it was superior to other oral antibacterials. These findings were echoed in a pivotal study involving 649 patients with mild to moderate acne randomised to one of the following regimens: oral minocycline, modified release, 100 mg daily; oral oxytetracycline 500mg twice daily; topical benzoyl peroxide 5% twice daily; topical benzoyl peroxide 5% plus topical erythromycin 3% twice daily; and topical erythromycin 2% each morning and topical benzoyl peroxide 5% each evening.³

At 18 weeks, significantly more participants rated themselves at least moderately improved (the primary outcome measure) with benzoyl peroxide plus erythromycin (the regimen with the highest response rate) than with minocycline (which had the lowest response rate) (66% v 54% of patients, odds ratio 1.74 (95% confidence interval 1.04 to 2.90)). Otherwise, there was no significant difference between treatments. The presence of skin colonisation by erythromycin resistant propionibacteria did not affect reported response to erythromycin based treatments, but, crucially, colonisation with tetracycline resistant propionibacteria reduced the effectiveness of both minocycline and oxytetracycline. We can find no published evidence to support claims that minocycline is less likely than other tetracyclines to cause propionibacterial resistance or that switching to minocycline from another tetracycline will improve response.

Further evidence comes from a randomised trial involving 134 patients with moderate to moderately severe acne, which reported mean reductions in the number of inflammatory lesions of around 60% at 12 weeks with either modified release minocycline 100 mg daily or lymecycline 300 mg daily, with no significant difference between the drugs.⁴

Evidence that oral minocycline might be more effective than other tetracyclines is, at best, weak, being limited to a few, poor quality trials with highly questionable results.^{2 5} Fundamental flaws in these studies include a lack of blinding, failure to specify the power of the study, reporting of data for only a proportion of participants, only graphical presentation of data, and failure to cite confidence intervals for key results.

Unwanted effects
Like other tetracyclines, minocycline can cause unwanted effects such as gastrointestinal upset, candidiasis, photosensitivity, hypersensitivity reactions, and benign intracranial hypertension.⁶ However, minocycline seems to be unique within the group in causing potentially irreversible slate-grey hyperpigmentation of the skin. The drug also seems much more likely than other tetracyclines to lead to lupus-like syndrome.

Convenience
The once daily administration of minocycline is a theoretical advantage over oxytetracycline and tetracycline, which need to be taken at least twice daily.⁷ In addition, minocycline need not be taken on an empty stomach, unlike these other two tetracyclines. However, lymecycline and doxycycline are also taken once daily, and their absorption is not affected by food.⁷

Cost
The cost to the NHS of six months' treatment with minocycline 100 mg daily (the licensed dose) as either tablets or modified release capsules is around £69. By comparison, six months' treatment with doxycycline 50 mg once daily costs £27, lymecycline 408 mg once daily costs £46, oxytetracycline 500 mg twice daily costs £40, and tetracycline 500 mg twice daily costs £114.

Barriers to change

Years of effective marketing and preferential use in secondary care have helped to establish minocycline as the oral antibacterial of choice for acne. Despite the emergence of data on serious unwanted effects, the drug remains widely prescribed. Of note, the British National Formulary singles out minocycline as offering "less likelihood of bacterial resistance," without discussing its unfavourable risk to benefit profile in acne.⁸ Unawareness of, or failure to appreciate, the lack of an evidential basis for preferring minocycline, coupled with practitioners' and patients' individual experience of the drug's undoubted efficacy in acne, therefore represent the greatest barriers to change.

How should we change our practice?

Minocycline should no longer be prescribed as the first line oral tetracycline for patients with acne. There is no compelling evidence that it is more effective or less likely to produce antibacterial resistance than safer, less expensive tetracyclines that are just as easy for patients to take.⁷ Where such treatment is indicated, doxycycline, lymecycline, or oxytetracycline is a much better option.

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Change page aims to alert clinicians to the immediate need for a change in practice to make it consistent with current evidence. The change must be implementable and must offer therapeutic or diagnostic advantage for a reasonably common clinical problem. Compelling and robust evidence must underpin the proposal for change

Guarantor: Ike Iheanacho

Competing interests: None declared.

Series editor: Joe Collier (jcollier@sgul.ac.uk), professor of medicines policy, St George's Hospital and Medical School, London. Anyone wishing to propose a change in clinical practice should discuss the proposal with Joe Collier at an early stage.

References

1. Smithard A, Glazebrook C, Williams HC. Acne prevalence, knowledge about acne and psychological morbidity in mid-adolescence: a community-based study. Br J Dermatol 2001;145:274-9.[CrossRef][ISI][Medline]
2. Garner SE, Eady EA, Popescu C, Newton J, Li WA. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2003;(1):CD002086.
3. Ozolins M, Eady EA, Avery AJ, Cunliffe WJ, Po AL, O'Neill C, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial. Lancet 2004;364:2188-95.[CrossRef][ISI][Medline]
4. Bossuyt L, Bosschaert J, Richert B, Cromphaut P, Mitchell T, Al Abadie M, et al. Lymecycline in the treatment of acne: an efficacious, safe, and cost-effective alternative to minocycline. Eur J Dermatol 2003;13:130-5.[ISI][Medline]
5. Pierard-Franchimont C, Goffin V, Arrese JE, Martalo O, Braham C, Slachmuylders P, et al. Lymecycline and minocycline in inflammatory acne: a randomized, double-blind intent-to-treat study on clinical and in vivo antibacterial efficacy. Skin Pharmacol Appl Skin Physiol 2002;15:112-9.[CrossRef][ISI][Medline]
6. Minocin MR Summary of product characteristics.
7. Is minocycline overused in acne? Drug Ther Bull 2006;44:60-2.[Abstract/Free Full Text]
8. British Medical Association, Royal Pharmaceutical Society of Great Britain. British national formulary. 52nd ed. London: BMA, RPS, 2006.

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