Advertisement

American Journal of Clinical Dermatology

, Volume 6, Issue 4, pp 255–272 | Cite as

Topical Tazarotene

A Review of its Use in the Treatment of Plaque Psoriasis
Adis Drug Evaluation

Summary

Abstract

Tazarotene (Tazorac®) is a topical retinoid indicated for the treatment of plaque psoriasis. When used as monotherapy, topical tazarotene was effective at controlling signs and symptoms of plaque psoriasis, and had significantly lower post-treatment relapse rates than fluocinonide cream. The most common adverse events associated with tazarotene therapy are skin-associated events, such as pruritus, burning, and erythema. Combination therapy with tazarotene and mid-to-high potency topical corticosteroids generally resulted in a greater therapeutic effect than that with tazarotene alone, reduced the irritancy of tazarotene, and decreased the risk of post-treatment disease flare seen with corticosteroids; it also has the potential to reduce the degree of skin atrophy associated with topical corticosteroids. The combination of tazarotene and phototherapy also appears promising. Thus, tazarotene, as monotherapy or in combination with topical corticosteroids or UV light therapy, represents a useful treatment option in patients with plaque psoriasis

Pharmacological Profile

The active form of tazarotene, tazarotenic acid, has selective affinity for the retinoic acid receptors -γ and -β. The exact molecular mechanism of action of topical tazarotene in the treatment of psoriasis has not been elucidated. However, the drug appears to modulate abnormal differentiation of keratinocytes, increased keratinocyte proliferation, and inflammation.

Topical tazarotene is metabolized, in part, to tazarotenic acid by esterases in the skin. In animal studies, oral tazarotene was teratogenic. However, the penetration across the skin and systemic absorption of topical tazarotene are limited. In patients with psoriasis, the bioavailability (relative to an intravenous dose) of tazarotene from topical tazarotene 0.05% or 0.1% gel varied over 12 weeks but ranged from <1% to 5.3%. In 12-week clinical trials of topical tazarotene, 1–3% of patients with plaque psoriasis had detectable plasma levels of tazarotene and 47–69% of patients had low but detectable levels of tazarotenic acid.

Both tazarotene and tazarotenic acid are metabolized to sulfoxides, sulfones, and other polar metabolites. In healthy volunteers and patients with psoriasis who applied topical tazarotene, the half-life of tazarotenic acid was ≈18 hours. Tazarotene and its metabolites are eliminated by urinary and fecal routes.

Therapeutic Efficacy

Monotherapy

Once-daily topical tazarotene 0.05% or 0.1% cream or gel effectively controlled signs and symptoms of plaque psoriasis in adult patients in randomized, single- or double-blind studies of 12 weeks duration. Clinical success (mild, minimal, or no psoriasis) rates were significantly higher for patients with plaque psoriasis receiving tazarotene 0.05% or 0.1% cream than for those receiving vehicle cream in two trials. In these trials, and two trials of tazarotene 0.05% or 0.1% gel, topical tazarotene was significantly more effective than vehicle in terms of global treatment success (≥50% improvement in overall psoriasis from baseline) rates, reduction in plaque elevation and, generally, reduction in scaling scores. Using the same endpoints, tazarotene gel had similar efficacy to twice-daily fluocinonide 0.05% cream in one trial. In two unpublished trials, once-daily tazarotene gel 0.05% or 0.1% was generally significantly less effective than twice-daily fluocinonide 0.05% cream or calcipotriol 0.005% ointment. Erythema was generally not as responsive to tazarotene treatment, and fluocinonide cream reduced erythema scores from baseline significantly more than tazarotene gel. For many patients, the efficacy of tazarotene cream or gel was maintained over a 12-week post-treatment period. Moreover, significantly more fluocinonide than tazarotene 0.1% gel recipients experienced relapse of psoriasis by the end of the 12-week, post-treatment phase of one trial.

Combination Therapy

The addition of some, but not all, mid-to-high-potency topical corticosteroids to tazarotene 0.1% gel monotherapy significantly improved global success rates, and afforded greater reductions in plaque elevation, scaling, and erythema scores in several 12-week trials in patients with stable plaque psoriasis. Treatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment (applied on alternate days, with a total of five treatments per week) was significantly more effective than that with vehicle gel (at all timepoints) or tazarotene plus vehicle gel (at some timepoints) in the 20-week, double-blind, maintenance phase of a trial in patients with plaque psoriasis.

At the end of 12 weeks, treatment with once-daily tazarotene 0.1% gel plus once-daily mometasone furoate 0.1% cream was significantly more effective than twice-daily mometasone furoate cream in terms of reduction in scaling scores, but similar in terms of reduction in plaque elevation, erythema, and pruritus scores. However, at the end of the 4-week, post-treatment phase, patients who had received tazarotene plus mometasone furoate had significantly better results for global treatment success rates, plaque elevation, and scaling than those who had received mometasone furoate monotherapy. Additionally, in this phase significantly more mometasone furoate monotherapy recipients discontinued the trial because of disease flare.

After treatment for 8 weeks, there were no significant differences between tazarotene 0.1% gel plus mometasone furoate 0.1% cream (both once-daily) and twice-daily calcipotriol 0.005% ointment in the proportion of patients achieving a ≥75% global improvement in psoriasis, or in the mean reductions from baseline in plaque elevation, scaling, or erythema scores, or the percentage of body surface area affected by psoriasis.

Tolerability

The most common adverse events associated with tazarotene gel or cream monotherapy in patients with plaque psoriasis were mild-to-moderate, skin-associated events, such as pruritus, burning, and erythema. In trials of tazarotene gel monotherapy, 9–20% of patients discontinued treatment because of adverse events

When tazarotene gel was applied in combination with a topical corticosteroid or phototherapy, the most common adverse events were generally mild-to-moderate local irritation, pruritus, erythema, and burning sensation. Although statistical analyses were generally not reported, it was noted that the addition of a corticosteroid to tazarotene therapy generally reduced the incidence of adverse events, compared with tazarotene monotherapy.

Keywords

Psoriasis Plaque Psoriasis Calcipotriol Mometasone Furoate Tazarotene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Lebwohl M. Psoriasis. Lancet. 2003; 361 (9364): 1197–204PubMedCrossRefGoogle Scholar
  2. 2.
    Gudjonsson JE, Johnston A, Sigmundsdottir H, et al. Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol. 2004; 135: 1–8PubMedCrossRefGoogle Scholar
  3. 3.
    Travis L, Weinberg JM. Medical backgrounder: psoriasis. Drugs Today. 2002; 38 (12): 847–65PubMedCrossRefGoogle Scholar
  4. 4.
    Peters BP, Weissman FG, Gill MA. Pathophysiology and treatment of psoriasis. Am J Health Syst Pharm. 2000; 57 (7): 645–62PubMedGoogle Scholar
  5. 5.
    Prussick R, Ebaugh BK. Psoriasis: an overview. Trauma. 2003; 45 (4): 73–84Google Scholar
  6. 6.
    Kuenzli S, Saurat JH. Retinoids for the treatment of psoriasis: outlook for the future. Curr Opin Investig Drugs. 2001 May; 2 (5): 625–30PubMedGoogle Scholar
  7. 7.
    Endzweig-Gribetz CH, Brady C, Lynde C, et al. Drug interactions in psoriasis: the pros and cons of combining topical psoriasis therapies. J Cutan Med Surg. 2002; 6 (3 Suppl.): 12–6PubMedCrossRefGoogle Scholar
  8. 8.
    Allergan (US). Tazorac© (tazarotene topical cream): prescribing information. Irvine (CA). 2001Google Scholar
  9. 9.
    Chandraratna RAS. Rational design of receptor-selective retinoids. J Am Acad Dermatol. 1998 Oct; 39 Suppl. Pt 2: S124–8CrossRefGoogle Scholar
  10. 10.
    Foster RH, Brogden RN, Benfield P. Tazarotene. Drugs. 1998 May; 55: 705–11PubMedCrossRefGoogle Scholar
  11. 11.
    Nagpal S, Patel S, Asano AT, et al. Tazarotene-induced gene 1 (TIGI), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol. 1996; 106 (2): 269–74PubMedCrossRefGoogle Scholar
  12. 12.
    Nagpal S, Patel S, Jacobe H, et al. Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol 1997; 109 (1): 91–5PubMedCrossRefGoogle Scholar
  13. 13.
    Esgleyes-Ribot T, Chandraratna RA, Lew-Kaya DA, et al. Response of psoriasis to a new topical retinoid, AGN 190168. J Am Acad Dermatol. 1994; 30 (4): 581–90PubMedCrossRefGoogle Scholar
  14. 14.
    Nagpal S, Thacher SM, Patel S, et al. Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ. 1996; 7: 1783–91PubMedGoogle Scholar
  15. 15.
    Duvic M, Nagpal S, Asano AT, et al. Molecular mechanisms of tazarotene action in psoriasis. J Am Acad Dermatol. 1997; 37: S18–24PubMedCrossRefGoogle Scholar
  16. 16.
    Nagpal S, Athanikar J, Chandraratna AS. Separation of transactiviation and API antagonism functions of retinoic acid receptor alpha. J Biol Chem. 1995; 270 (2): 923–7PubMedCrossRefGoogle Scholar
  17. 17.
    Sebok B, Bonnekoh B, Kerenyi M, et al. Tazarotene induces epidermal cell differentiation in the mouse tail test used as an animal model for psoriasis. Skin Pharmacol Appl Skin Physiol. 2000; 13 (5): 285–91PubMedGoogle Scholar
  18. 18.
    Kaidbey K, Kopper S, Sefton J. A pilot study to determine the effect of tazarotene 0.1% gel on steroid-induced epidermal atrophy. Int J Dermatol. 2001; 40: 468–71PubMedCrossRefGoogle Scholar
  19. 19.
    Hecker D, Worsley J, Yueh G, et al. Interactions between tazarotene and ultraviolet light. J Am Acad Dermatol. 1999 Dec; 41 (6): 927–30PubMedCrossRefGoogle Scholar
  20. 20.
    Menter A. Pharmacokinetics and safety of tazarotene. J Am Acad Dermatol. 2000 Aug; 43 (2 Pt 3): S31–5PubMedCrossRefGoogle Scholar
  21. 21.
    Tang-Liu DD-S, Matsumoto RM, Usansky JI. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet. 1999 Oct; 37: 273–87PubMedCrossRefGoogle Scholar
  22. 22.
    Marks R. Pharmacokinetics and safety review of tazarotene. J Am Acad Dermatol. 1998 Oct; 39 Suppl. Pt 2: 134–8CrossRefGoogle Scholar
  23. 23.
    Lebwohl M, Ast E, Callen JP, et al. Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis. J Am Acad Dermatol. 1998 May; 38 (Pt 1): 705–11PubMedCrossRefGoogle Scholar
  24. 24.
    Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol. 1997; 37 (1): 85–92PubMedCrossRefGoogle Scholar
  25. 25.
    Weinstein GD, Koo JY, Krueger GG, et al. Tazarotene cream in the treatment of psoriasis: two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks. J Am Acad Dermatol. 2003 May; 48 (5): 760–7PubMedCrossRefGoogle Scholar
  26. 26.
    Allergan (US). Tazorac© (tazarotene topical gel): prescribing information. Irvine (CA). 2003Google Scholar
  27. 27.
    FDA. Medical review. Study #R168-121-8606: safety and efficacy of once-daily tazarotene (AGN 190168) 0.1% gel or 0.05% gel versus vehicle gel in stable plaque psoriasis [online]. Available from URL: http://www.fda.gov/cder/ [Accessed 2005 Mar 21]
  28. 28.
    FDA. Medical review. Study #R168-126-8606: safety, efficacy and duration of therapeutic effect of tazarotene (AGN 190168) 0.1% or 0.05% gel applied once daily versus lidex© 0.05% cream applied twice daily in stable plaque psoriasis [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 21]
  29. 29.
    FDA. Medical review. Study #R168-145-8606: safety, efficacy and duration of therapeutic effect of once-daily tazarotene (AGN 190168) 0.1 % gel or once-daily 0.05% gel versus twice-daily calcipotriol 0.005% ointment in plaque psoriasis: an investigator-masked study [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 21]
  30. 30.
    FDA. Medical review. Study #R168-120-8606: safety, efficacy and duration of therapeutic effect of once-daily tazarotene (AGN 190168) 0.1% gel or 0.05% gel versus vehicle gel in stable plaque psoriasis [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 21]
  31. 31.
    FDA. Medical review. Study #R168-125-8606: safety, efficacy and duration of therapeutic effect of tazarotene (AGN 190168) 0.1% or 0.05% gel applied once daily versus lidex© 0.05% cream applied twice daily in stable plaque psoriasis [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 21]
  32. 32.
    FDA. Medical review. Multicenter, double-blind, randomized, vehicle-controled study of the safety and efficacy of 0.05% and 0.1% tazarotene creams applied once daily for 12 weeks, with a 12-week follow-up, in the treatment of plaque psoriasis (Study #190168-016C) [initiated 12/29/97, completed 1/22/99] [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 10]
  33. 33.
    FDA. Medical review. Multicenter, double-blind, randomized, vehicle-controled study of the safety and efficacy of 0.05% and 0.1% tazarotene creams applied once daily for 12 weeks, with a 12-week follow-up, in the treatment of plaque psoriasis (Study #190168-017C) [initiated 12/30/97, completed 10/16/98] [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 10]Google Scholar
  34. 34.
    Feldman SR. A quantitative definition of severe psoriasis for use in clinical trials. J Dermatol Treat. 2004; 15: 27–9CrossRefGoogle Scholar
  35. 35.
    FDA. Medical review: tazarotene gel [online]. Available from URL: http://www.fda.gov/cder [Accessed 2005 Mar 10]
  36. 36.
    Green L, Sadoff W. A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid-high-potency corticosteroid, in patients with stable plaque psoriasis. J Cutan Med Surg. 2002; 6 (2): 95–102PubMedCrossRefGoogle Scholar
  37. 37.
    Lebwohl MG, Breneman DL, Goffe BS, et al. Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis. J Am Acad Dermatol. 1998 Oct; 39 (Pt 1): 590–6PubMedCrossRefGoogle Scholar
  38. 38.
    Gollnick H, Menter A. Combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis. Br J Dermatol. 1999 Apr; 140 Suppl. 54: 18–23PubMedCrossRefGoogle Scholar
  39. 39.
    Koo JY, Martin D. Investigator-masked comparison of tazarotene gel q.d. plus mometasone furoate cream q.d. vs. mometasone furoate cream b.i.d. in the treatment of plaque psoriasis. Int J Dermatol. 2001 Mar; 40 (3): 210–2PubMedCrossRefGoogle Scholar
  40. 40.
    Guenther LC, Poulin YP, Pariser DM. A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. Clin Ther. 2000 Oct; 22: 1225–38PubMedCrossRefGoogle Scholar
  41. 41.
    Lebwohl M, Lombardi K, Tan MH. Duration of improvement in psoriasis after treatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment: comparison of maintenance treatments. Int J Dermatol; 2001 Jan; 40 (1): 64–6PubMedCrossRefGoogle Scholar
  42. 42.
    Koo JY, Lowe NJ, Lew-Kaya DA, et al. Tazarotene plus UVB phototherapy in the treatment of psoriasis. J Am Acad Dermatol. 2000 Nov; 43 (5 Pt 1): 821–8PubMedCrossRefGoogle Scholar
  43. 43.
    Tzaneva S, Honigsmann H, Tanew A, et al. A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis. Br J Dermatol. 2002 Oct; 147 (4): 748–53PubMedCrossRefGoogle Scholar
  44. 44.
    Behrens S, Grundmann-Kollmann M, Schiener R, et al. Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel. J Am Acad Dermatol. 2000 Mar; 42 (3): 493–5PubMedCrossRefGoogle Scholar
  45. 45.
    Allergan Ltd (UK). Zorac 0.05% gel: summary of product characteristics [online]. Available from URL: http://eme.medicines.org.uk [Accessed 2004 Oct 17]
  46. 46.
    Allergan Ltd (UK). Zorac 0.1% gel: summary of product characteristics [online]. Available from URL: http://eme.medicines.org.uk [Accessed 2004 Oct 21]
  47. 47.
    Khachemoune A, Phillips TJ. Current treatment options in psoriasis. Hosp Pract (Off Ed). 2000; 35 (7): 93–107Google Scholar
  48. 48.
    van de Kerkhof PC. Textbook of psoriasis. Oxford: Blackwell Science Ltd, 1999Google Scholar
  49. 49.
    van de Kerkhof PC, Vissers WH. The topical treatment of psoriasis. Skin Pharmacol Appl Skin Physiol. 2003; 16 (2): 69–83PubMedGoogle Scholar
  50. 50.
    Feldman S. Advances in psoriasis treatment. Dermatol Online J. 2000 Sep; 6 (1): 4PubMedGoogle Scholar
  51. 51.
    Berson DS. Topical retinoids in primary care practice: CME [online]. Available from URL: http://www.medscape.com [Accessed 2005 May 20]
  52. 52.
    Lebwohl M, Ting PT, Koo JYM. Psoriasis treatment: traditional therapy. Ann Rheum Dis. 2005; 64 Suppl. II: ii83–6PubMedCrossRefGoogle Scholar
  53. 53.
    Connetics Corporation US. Soriatane© (acitretin) capsule: prescribing information [online]. Available from URL: http://www.soriatane.com/include/pi.pdf [Accessed 2004 May 20]
  54. 54.
    Minor SN, Monk BE. Zorac. Business Briefing: European Pharmacotherapy [online]. Available from URL: http://www.bbriefings.com/pdf/26/eptO32tallergan.pdf [Accessed 2005 Jul 20]
  55. 55.
    Hecker D, Worsley J, Yueh G, et al. In vitro compatibility of tazarotene with other topical treatments of psoriasis. J Am Acad Dermatol. 2000 Jun; 42 (6): 1008–11PubMedCrossRefGoogle Scholar
  56. 56.
    Lebwohl M, Ali S. Treatment of psoriasis: part 1. Topical therapy and phototherapy. J Am Acad Dermatol. 2001 Oct; 45 (4): 487–98; quiz 499–502PubMedCrossRefGoogle Scholar
  57. 57.
    Guenther LC. Optimizing treatment with topical tazarotene. Am J Clin Dermatol 2003; 4 (3): 197–202PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Adis International Inc.YardleyUSA

Personalised recommendations