Update on Topical Acne Treatments

J. Tan, MD, FRCP


Windsor, Ontario, Canada

ABSTRACT

Topical acne treatment can positively benefit patients with acne. This review summarizes clinical and prescribing information on currently available topical agents. The efficacy of the medications included in this report is supported by properly designed randomized clinical trials^2-8,14.

Key Words:
acne, tretinoin, adapalene, isotretinoin, tazarotene, clindamycin, erythromycin, azelaic acid, benzoyl peroxide

Topical acne medications are indicated for treatment of comedonal and mild inflammatory acne, or as adjuncts to systemic therapy in moderate acne¹. The newer, more frequently prescribed drugs are summarized herein.

Table 1: Mechanism of action for topical acne medications⁹
Any mechanism that is enclosed in parentheses denotes a minimal effect.

Pathogenesis

Some of the factors responsible for acne include heredity and the role of hormones. Exposure to ultraviolet light and the use of certain drugs can also affect acne¹³. Acne is multifactorial, involving (1) sebaceous hypersecretion due to increased levels of circulating androgens and/or sebaceous gland hypersensitivity, and (2) follicular hyperkeratinization leading to pore occlusion. Inflammatory acne includes (3) the proliferation of Propionibacterium acnes (P. acnes) within the comedone and (4) the generation of chemotactic and proinflammatory factors¹.

Treatment Options

The presence of multiple comedones suggests the use of agents directed at follicular hyperkeratinization. Inflammatory lesions may warrant the use of agents with antimicrobial and/or antiinflammatory effects. Other factors that should be considered in therapeutic selection are side effect profile, cost, and individual patient preference.

In a recent survey, acne patients who were referred to a dermatologist’s office were asked, “Which form of treatment would you prefer: topical or systemic?” Female patients were five times more likely than males to prefer topical treatments, as were those with lesser grades of acne severity (see Table 2).

Generally, topical acne agents require a trial period of at least 8– 12 weeks to determine therapeutic benefit. During this time, the patient should be given appropriate advice to minimize the potential for adverse effects. Maintenance of improvement thereafter requires ongoing treatment with periodic tapering to establish ongoing need.

When prescribing for female patients the clinician should be aware of possible teratogenicity. For example, the potential link between topical tretinoin and the fetal malformation is not clear. The USP Drug Information for the Health Care Professional (1999) carries the Pregnancy category C for tretinoin. To be safe, topical tretinoin should not be used during pregnancy.

A multicenter, single-blind, randomized 12 week study in Europe compared clindamycin with a clindamycin phosphate/tretinoin gel formulation (Velac) which is approved for use in France. Velac was found to reduce overall acne scores and was faster acting¹⁴. A new drug application for this drug for acne treatment is currently awaiting approval by the US FDA.

Table 2: Acne survey results (in percent of responses) when patients were asked, “Which form of treatment would you prefer: topical or systemic?”¹⁵

Table 3: Topical acne preparations.
*FDA Pregnancy categories are A: Controlled studies show no risk, B: No evidence of risk in humans, C: Risk cannot be ruled out, D: Positive evidence of risk, X: Contraindicated in pregnancy^11,12.

Adverse Effects

The most common adverse effect of topical acne therapy is mild irritation. Aqueous-based gels may be less irritating than their alcohol-based counterparts, and creams tend to be less irritating and drying than gels. Irritation can be minimized by advising shorter initial application times. These can then be progressively titrated upwards, with less frequent application, and the use of appropriate nonacneigenic moisturizers.

Table 4: Adverse effects of topical acne medications⁹.
Legend: 3+ very strong, 2+ strong, 1+ moderate

Summary

Mild acne can be effectively managed by topical medications based on lesional morphology. Appropriate counselling on the use of these medications can minimize adverse effects and enhance compliance.

References

1. Leyden JJ. Therapy for Acne Vulgaris. N Engl J Med 336(16):1156-62 (1997 Apr).
2. Lucky AW, Cullen SI, Jarratt MT, Quigley JW. Comparative efficacy and safety of two 0.025% tretinoin gels: Results from a multicenter, double-blind, parallel study. J Am Acad Dermatol 38(4):S17-23 (1998 Apr).
3. Cunlif fe WJ, Caputo R, Dreno B, et al. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and US multicenter trials. J Am Acad Dermatol 36:S126-34 (1997 Jun).
4. Cunlif fe WJ, Caputo R, Dreno B, et al. Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and US multicenter trials. J Am Acad Dermatol 36:S126-34 (1997 Jun).
5. Eady EA, Cove JH, Joanes DN, Cunliffe, WJ. Topical antibiotics for the treatment of acne vulgaris: a critical evaluation of the literature on their clinical benefit and comparative efficacy. J Dermatol Treat 1:215-226 (1990).
6. Cunlif fe WJ. The Clinical Efficacy of Azelaic Acid in the Treatment of Acne. Rev Contemp Pharmacother 4: 433-39 (1993).
7. Lookingbill DP, Chalker DK, Lindholm JS, et al. Treatment of acne with a combination clindamycin/benzoyl peroxide gel compared with clindamycin gel, benzoyl peroxide gel and vehicle gel: Combined results of two double-blind investigations. J Am Acad Dermatol 37(4):590-5 (1997 Oct).
8. Shalita AR, Chalker DK, Ellis CN, Parish LC, Smith JG. A multicenter, doubleblind, controlled study of the combination of erythromycin/benzoyl peroxide, erythromycin alone, and benzoyl peroxide alone in the treatment of acne vulgaris. Cutis 49(6A):1-4 (1992).
9. modified from Gollnick H, Schramm M. Topical Drug Treatment in Acne. Dermatology 196(1):119-25 (1998).
10. Leyden JJ: Topical treatment of acne vulgaris: Retinoids and cutaneous irritation. J Am Acad Dermatol 38(4):S1-4 (1998 Apr).
11. Stockton D, Paller A. Drug administration to the pregnant or lactating woman: A reference guide for dermatologists. J Am Acad Dermatol 23(1):87-103 (1990 Jul).
12. Reed BR. Dermatologic drugs, pregnancy and lactation. Arch Dermatol 133(7):894-898 (1997 Jul).
13. Zouboulis C, Orfanos CE. Retinoids. In Millikan L (ed) Drug Therapy in Dermatology. Marcel Dekker, New York, in press.
14. Zouboulis C, Derumeaux L, Decroix L, Maciejewska-Udziela B, Cambazard F, Stuhlert A. A multicentre, single-blind, randomised comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac) applied once daily and a clinidamycin lotion formuation (Dalacin T) applied twice daily in the topical treatment of acne vulgaris. Br J Dermatol, in press.
15. Tan J, Vasey K. Perceptions and Attitudes of Acne Patients. Manuscript in preparation for publication (1999).

News about Photodynamic Therapy

On November 5 1999, the US FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee
considered certain issues related to Dusa Pharmaceuticals’ New Drug Application (NDA) for
Levulan Photodynamic Therapy (5-aminolevulinic acid). Following presentations by Dusa and the
FDA, the agency asked the panel for feedback with respect to proposed product labelling and
postmarketing studies.

Earlier this year the US FDA issued an approvable letter for this device for the treatment of
actinic keratoses of the face and scalp. The letter said that certain items had to be completed
before final FDA marketing approval would be granted. These included:

• Compliance with the FDA’s Good Manufacturing Practices (GMPs) by all Dusa’s manufacturers
• Agreement on revised labelling for the product.

Dusa recently submitted revised labelling to the FDA, and reported that re-inspection of its drug
manufacturer had taken place.

Because the FDA had already designated Dusa’s NDA as approvable, the agency did not ask
for a panel vote on approvability. The FDA is now expected to take these suggestions into
consideration when developing final labelling and postmarketing study recommendations.
Though nothing is cast in stone, it is possible that this device and associated technologies might
be given approval sometime during December 1999.