Psoriasis (Oral & Topical agents)

Intro	acitretin - Soriatane ®
alefacept - Amevive ®	Anthralin - Drithocreme ®
Calcipotriene - Dovonex ®	efalizumab - Raptiva ®
Tazarotene - Tazorac ®

Intro

Approximately one percent of the population is affected by psoriasis. The typical clinical findings of erythema and scaling are the result of hyperproliferation and abnormal differentiation of the epidermis, plus inflammatory cell infiltrates and vascular changes.

acitretin - Soriatane ®

Drug Category: Retinoid-Like Compound. Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects.
Dosing (Adults) : ( treatment of severe psoriasis) Therapy should be initiated at 25 or 50 mg per day, given as a single dose with the main meal. Maintenance doses of 25 to 50 mg per day may be given after initial response to treatment. In general, therapy should be terminated when lesions have resolved sufficiently. Relapses may be treated as outlined for initial therapy.

[Supplied: 10, 25mg capsule]

alefacept - Amevive ®

CLINICAL PHARMACOLOGY
AMEVIVE® interferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. The majority of T lymphocytes in psoriatic lesions are of the memory effector phenotype characterized by the presence of the CD45RO marker1, express activation markers (e.g., CD25, CD69) and release inflammatory cytokines, such as interferon

.

AMEVIVE® also causes a reduction in subsets of CD2+ T lymphocytes (primarily CD45RO+), presumably by bridging between CD2 on target lymphocytes and immunoglobulin Fc receptors on cytotoxic cells, such as natural killer cells. Treatment with AMEVIVE® results in a reduction in circulating total CD4+ and CD8+ T lymphocyte counts. CD2 is also expressed at low levels on the surface of natural killer cells and certain bone marrow B lymphocytes. Therefore, the potential exists for AMEVIVE® to affect the activation and numbers of cells other than T lymphocytes. In clinical studies of AMEVIVE®, minor changes in the numbers of circulating cells other than T lymphocytes have been observed.

Dosing (adults): 7.5 mg IV weekly or 15 mg IM have been effective in plaque psoriasis. Optimal doses/schedules remain to be established. Usual duration of treatment is 12 weeks. Second course: A second course of treatment may be initiated at least 12 weeks after completion of the initial course of treatment, provided CD4+ T-lymphocyte counts are within the normal range.

Monitoring: CD4+ T-lymphocyte counts should be monitored before initiation of treatment and weekly during therapy. Dosing should be withheld if CD4+ counts are <250 cells/µL, and dosing should be permanently discontinued if CD4+ lymphocyte counts remain at <250 cell/µL for longer than 1 month.

[Supplied: Injection (powder for reconstitution): 7.5mg, 15 mg. ]

Anthralin - Drithocreme ®

Synthetic tar derivative.
Dosing: Apply once daily at bedtime, covered with dressing, and removed after 8 to 24 hours. Therapy is usually initiated with 0.1% topical cream, ointment, or paste, gradually increasing concentrations to an optimal response level within acceptable patient skin irritation limits. Alternatively, a short-contact regimen that uses higher initial concentrations of anthralin (1% to 3%) may be applied for 5 to 60 minutes. Anthralin concentrations are increased every 3 to 4 days until patient intolerance occurs. Therapy continues until psoriatic plaques clear. Maintenance therapy is infrequently used.

Supplied: [ointment, cream: 0.1, 0.25, 0.5, 1%].

Calcipotriene - Dovonex ®

Synthetic vitamin D3 derivative.
Indicated for the treatment of plaque psoriasis.
Dosing: Apply twice daily.

Supplied: 0.005% ointment /cream/ solution.

efalizumab - Raptiva ®

Mechanism of Action
RAPTIVA binds to CD11a, the

subunit of leukocyte function antigen-1 (LFA-1), which is expressed on all leukocytes, and decreases cell surface expression of CD11a. RAPTIVA inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1), thereby inhibiting the adhesion of leukocytes to other cell types. Interaction between LFA-1 and ICAM-1 contributes to the initiation and maintenance of multiple processes, including activation of T lymphocytes, adhesion of T lymphocytes to endothelial cells, and migration of T lymphocytes to sites of inflammation including psoriatic skin. Lymphocyte activation and trafficking to skin play a role in the pathophysiology of chronic plaque psoriasis. In psoriatic skin, ICAM-1 cell surface expression is upregulated on endothelium and keratinocytes. CD11a is also expressed on the surface of B lymphocytes, monocytes, neutrophils, natural killer cells, and other leukocytes. Therefore, the potential exists for RAPTIVA to affect the activation, adhesion, migration, and numbers of cells other than T lymphocytes.

Dosing (adults): Tx of psoriasis: 0.7 mg/kg SQ initially, followed by weekly dose of 1 mg/kg (maximum: 200 mg/dose).

Supplied: Injection (powder for reconstitution): provides 125 mg/1.25 ml after dilution.

Tazarotene - Tazorac ®

Retinoid.
Psoriasis: The mechanism of tazarotene action in psoriasis is not defined. Topical tazarotene blocks induction of mouse epidermal ornithine decarboxylase (ODC) activity, which is associated with cell proliferation and hyperplasia. In cell culture and in vitro models of skin, tazarotene suppresses expression of MRP8, a marker of inflammation present in the epidermis of psoriasis patients at high levels. In human keratinocyte cultures, it inhibits cornified envelope formation, whose build-up is an element of the psoriatic scale. Tazarotene also induces the expression of a gene which may be a growth suppressor in human keratinocytes and which may inhibit epidermal hyperproliferation in treated plaques. However, the clinical significance of these findings is unknown.

Acne: The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and cross-linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown.

Psoriasis: Apply a thin film to lesions at bedtime (no more than 20% of body surface area). Avoid application to unaffected skin. ACNE: apply a thin film to dry skin once a day in the evening.

Supplied: gel: 0.05, 0.1%

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.