Overview of Topical Tazarotene
Topical tazarotene is a synthetic topical retinoid that has been available in the United States since 1997. It is formulated in 2 vehicles, a gel and a cream, and in 2 concentrations, 0.1% and 0.05%.1-4 The US Food and Drug Administration (FDA) approved tazarotene 0.1% gel applied once daily for moderate to severe facial acne vulgaris (AV) in 1997 and tazarotene 0.1% cream applied once daily for AV in 2000. The latter application does not mandate anatomic location or severity in the approved package insert under “Indications and Usage”.2,3 Both concentrations and vehicles of tazarotene are FDA approved for once-daily topical treatment of plaque psoriasis, and the 0.1% cream applied once daily is approved for adjunctive treatment of facial fine wrinkling, mottled facial hypopigmentation and hyperpigmentation, and benign facial lentigines, along with comprehensive skin care and photoprotection from sunlight.2-4 This article discusses the use of topical tazarotene in the management of AV.
Pharmacologic Properties of Topical Tazarotene
After topical application, tazarotene undergoes rapid deesterification with conversion to the active metabolite, tazarotenic acid.1-3,5 Due to rapid conversion and a very short half-life (<20 minutes), systemic absorption of tazarotene is negligible.2,3,5 The early pharmacokinetic data on topical tazarotene were completed using the gel formulation, with data on the cream formulation completed later. Tazarotenic acid is metabolized to inactive metabolites that are excreted in the urine and exhibit an elimination half-life of 1 to 2 hours and a terminal half-life of 18 hours; maximum concentrations in systemic circulation are achieved at 9 hours after application, with less than 5% of systemic absorption after topical application to normal skin, less than 1% absorption within 10 hours of application to unoccluded psoriatic skin, and less than 6% absorption within 10 hours of application to occluded normal skin.6-11 In females with AV treated over 28 days with tazarotene 0.1% cream to the face, or to 15% of their body surface area (BSA), the mean maximum serum concentration (Cmax) and area-under-the-curve (AUC) levels of tarazotenic acid were achieved by day 15 in both groups, with 10-fold higher mean Cmax and AUC levels noted in the group treating 15% of their BSA.3 In a study comparing Cmax and AUC values in healthy subjects, these values were 40% in those treated with tazarotene 0.1% gel compared with 0.05% gel.2
Importantly, the repeated application of tazarotene 0.1% cream to female patients with facial AV over 28 days demonstrated that continued systemic accumulation of either tazarotenic acid or tazarotene did not occur after peak bloods levels were reached at day 15, with very low blood levels of tazarotenic acid (~0.1 ng/mL) noted in the group applying it only to facial skin.3,11 Although the overall systemic absorption of both tazarotene and tazarotenic acid appear to be low in both healthy and diseased skin, the use of a higher drug concentration and application to a greater BSA than only the face have been shown to correlate with an increase in systemic absorption, especially of tazarotenic acid, albeit still to levels that are believed to be low and apparently
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