What's old is new: Topical formulation brings dapsone into safer territory

May 1, 2009

With oral dapsone plagued by concerns of hematological side effects, a topical formulation has given dapsone a safer, new role in treating some dermatologic conditions.

Key Points

Omaha, Neb. - Though long used for the treatment of dermatitis herpetiformis, as well as severe acne, leprosy and other conditions, oral dapsone therapy has been associated with dose-dependent adverse hematological reactions.

The new formulation is gaining a place in the armamentarium as an effective acne treatment that avoids the problematic side effects seen with the oral form.

Clinical trials

Extensive clinical trials on a gel formulation included a prominent study in which the gel formulation was used in various settings from two to 12 weeks.

The results showed systemic exposures to dapsone and its metabolites at levels that were 100-fold less than those seen following oral dapsone at a therapeutic dose level (Clinical Pharmacokinetics. 2007;46(8):697-712).

Nevertheless, due to the concern about side effects of dapsone in patients who are G6PD-deficient, there was much debate over whether blood tests should be required with the topical formulation, Dr. Schlessinger tells Dermatology Times.

"This drug languished in development for at least two years while awaiting FDA (Food and Drug Administration) word on whether it would be able to be prescribed without a blood test," Dr. Schlessinger says.

"Nearly all of the dermatologists who were researching this drug agreed that a blood test prior to prescription of a topical acne drug would be a 'death sentence' for the drug," he says.

The FDA still had concerns, however, after blood tests for one patient in a pivotal study showed a slight decrease in hemoglobin after multiple blood draws.

"For this reason, the company ended up doing much more testing to prove that this drug was safe without an initial blood test," Dr. Schlessinger says.

In August 2005, 5 percent dapsone gel, marketed by QLT as Aczone, won FDA approval for the topical treatment of acne vulgaris in patients 12 years and older, and the product was sold to Allergan in 2008. And while the topical dapsone gel may not be as effective as oral dapsone, the pay-off is a safer modality.

Efficacy

Aside from its comparison to oral dapsone, Aczone's efficacy in the treatment of acne has been shown to, nevertheless, be significant in studies including two recent randomized, double-blinded studies and a third long-term open-label trial of 3,516 participants, ages 12 to 15 years.

The studies found significantly greater results on a Global Acne Assessment Score for dapsone gel-treated patients, compared with those treated with a vehicle gel, after 12 weeks. Clinically meaningful improvements in acne lesion counts were also seen for up to 12 months in a long-term safety study. (Cutis. February 2008;81(2):171-178).

"As a topical medication, (Aczone) has limited activity and won't ever approach the effectiveness of an oral antibiotic, let alone something like isotretinoin," Dr. Schlessinger says.

"It won't even compete with some of the stronger topicals, such as benzoyl peroxide or some of the new combination topicals. But I place it in my practice as an excellent alternative for sensitive-skinned individuals with acne and/or rosacea, and for those patients, the vehicle is particularly pleasant," he says.

Dr. Schlessinger was on the original investigative team for Aczone, and says that the drug was shown to be very well tolerated. "Nearly all the patients in our clinical trials for this drug finished the trial without any significant irritation or complications."

Caveats

Some caveats include that Aczone can't be used in conjunction with benzoyl peroxide, because an orange color develops on the skin and lasts for several days. In addition, there is a relative contraindication with sulfa drugs, Dr. Schlessinger says.

In addition to acne, other potential uses include inflammatory diseases and rosacea, a well as the prime oral dapsone target - dermatitis herpetiformis, Dr. Schlessinger says.

"The prototypical condition that we use oral dapsone for is dermatitis herpetiformis, and I feel this is a great off-label use for Aczone," he says.

And without the unwanted risks of oral dapsone, Aczone, and any other topical formulations, could give dapsone an important new role in dermatology.

"The development of a topical form was a great idea, and one that may change the dermatology community's approach to many medical conditions and their view towards this drug," Dr. Schlessinger says.

Disclosure: Dr. Schlessinger reports no relevant financial disclosures.

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