Psoriasis tacrolimus

Tacrolimus is a macrohde immunosuppressive agent indicated for the prevention of organ transplant rejection and useful as an alternative treatment in severe recalcitrant psoriasis. Tacrolimus, like cyclosporine, inhibits T-ceU activation. ... 

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Hydroxyurea is an older agent still used occasionally today for patients with psoriasis however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.29 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.29 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis prolonged oral steroid use should be avoided.10... 

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. 

Lipid-based carrier systems have been investigated to improve treatment of inflammatory skin diseases such as atopic eczema and psoriasis by glucocorticoids and T-cell inhibitors such as ciclosporin and tacrolimus. 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

Scheinfeld NS. (2004) Use of topical tacrolimus and pimecrolimus to treat psoriasis. Dermatol Online 710 3. 

It is a newer agent derived from Streptomyces hygroscopicus that binds immunophylin (same as in tacrolimus and cyclosporine). It is indicated in the management of psoriasis and uveoretinitis. 

Because of the effectiveness of systemic tacrolimus in some dermatologic diseases, a topical preparation is now available. Tacrolimus ointment is currently used in the therapy of atopic dermatitis and psoriasis. 

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can he administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral fohc acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

Pimecrolimus and tacrolimus are calcineurin inhibitors capable of exerting a local immunomodulating effect that may serve to normalize hyperproliferation of epidermis. As topical agents, tacrolimus and pimecrolimus are approved for the treatment of atopic dermatitis however, regulatory approval regarding the efficacy of these agents in psoriasis is yet to be completed. 

In recalcitrant plaque-type psoriasis, patients receive tacrolimus at oral doses of 0.05 mg/kg per day (increased up to 0.15 mg/kg per day as needed). ... 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

The effectiveness of systemic tacrolimus on psoriasis has been demonstrated in a double-blind, placebo-controlled study [83]. 

Because rapamycin exerts its immunosuppressive effects by inhibiting T- and B-cell functions that are, however, different from those of tacrolimus or cyclosporin, it might also have a therapeutic potential in rheumatoid arthritis and the other autoimmune diseases. Unfortunately, few reports exist on the clinical benefit of this agent in such diseases, with the exception of psoriasis [133, 134], where its efficacy was clearly shown, when used systemically. 

IL-8/IL-8 receptor expression in psoriasis and the response to systemic tacrolimus (FK506) therapy. Clin. Exp. Immunol. 99, 148-154. 

European FK506 Multicentre Psoriasis Study Group (1996). Systemic tacrolimus (FK506) is effective for the treatment of psoriasis in a double-blind placebo controlled study. Arch. Dermatol. 132, 419- 23. 

Tacrolimus is available in oral and topical forms for the treatment of skin disease. Systemic tacrolimus has shown some efficacy in the treatment of inflammatory skin diseases such as psoriasis, pyoderma gangrenosum, and Beh9et s disease. When administered systemicaUy, the most common side effects are hypertension, nephrotoxicity, neurotoxicity, GI symptoms, hyperglycemia, and hyperhpidemia. Topical formulations of tacrolimus penetrate into the epidermis. 

In commercially available topical formulations (0.03% and 0.1%), tacrolimus ointment (PROTOFnc) is effective in and approved for the treatment of atopic dermatitis in adults (0.03% and 0.1%) and children (0.03%). Other uses in dermatology include intertriginous psoriasis, vitiligo, mucosal lichen planus, graft-versus-host disease, allergic contact dermatitis, and rosacea. It is applied to the affected area twice a day and generally is well tolerated. 

Clinical uses and pharmacokinetics Use of these immunosuppressants is a major factor in the success of solid organ transplantation. Cyclosporine is used in solid organ transplantation and in graft-versus-host syndrome in bone marrow transplants. Tacrolimus is used in liver and kidney transplant recipients and may be effective as rescue therapy in patients who fail standard therapy. Sirolimus is used alone or in combination with cyclosporine in kidney and heart transplantation. The agents, particularly cyclosporine, may also be effective in immune diseases, including rheumatoid arthritis, uveitis, psoriasis, asthma, and type 1 diabetes. 

C44H69NO12, Mr 804.04, prisms, mp. 127-129°C, [ajj, -84.4° (CHCI3), a macrolactam lactone produced by Streptomyces tsukubaensis, in which a long-chain hy-droxycarboxylic acid is cyclized with L- pipecoUc acid as bridging unit. FK-506 is structurally related to rapamycin and has been prepared synthetically. It exhibits immunosuppressive activity by suppression of cell-mediated and humoral immune responses. It has been available in Japan since 1993, in Europe and USA since 1996 under the name Prograf tacrolimus) for use in transplantation medicine to suppress rejection reactions. FK-506 is also effective in the treatment of autoimmune diseases, e. g., multiple sclerosis, psoriasis, or rheumatoid arthritis. 

Thapa, R. K. Yoo, B. K. (2014). Evaluation of the effect of tacrolimus-loaded liquid crystalline nanoparticles on psoriasis-like skin inflammation. Journal of Dermatology Treatment, 25(1), 22-5. 

De Simone C, Maiorino A, Tassone F, D Agostino M, Caldarola G. Tacrolimus 0.1% ointment in nail psoriasis a randomized controlled open-label study. J Eur Acad Dermatol Venereol August 2013 27(8) 1003-6. PubMed PMID 22788697. Epub 2012/07/14. eng. 

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