Tacrolimus: profile and news

Possible New Treatment For Stroke Victims 16 May 2006
The findings say the immunosuppressive drug FK506 (also known as Tacrolimus or Prograf) that is often given to patients receiving transplants to prevent organ ... - All Headline News

Eczema on Infants' Arms and Joints Linked to Future Atopic ... May 15, 2006
Dermatology by Harvard's Abrar Qureshi, MD, and Michael Fischer, MD, warned about the use of topical calcineurin inhibitors, Protopic (tacrolimus) and Elidel ... - MedPage Today,

International Approvals: Omnitrope, Prograf, Cetrotide May 1, 2006
...approved a generic formulation of somatropin for use as long-term replacement therapy in children and adults, and a new indication for tacrolimus that allows ... - Medscape (subscription)

Chronic Hepatitis Common in Kids After Liver Transplant May 4, 2006
..."Since 2000, we have routinely used tacrolimus as the primary immunosuppressive agent. We do not yet know the incidence of chronic ... - MedPage Today,

Prograf Now Approved for Prophylaxis Use in Heart Transplantation ... Apr 21, 2006
...and CEO: Toichi Takenaka) today announced that the European Commission has approved the immunosuppressant Prograf(R) (generic name: tacrolimus) for the ... - PR Newswire UK (press release),

NICE Issues Guidance On Immunosuppressive Therapy For Young Kidney ... Apr 27, 2006
...adolescents receiving a kidney transplant, but most children in the UK received triple therapy with a calcineurin inhibitor (ciclosporin or tacrolimus), a DNA ... - Medical News Today (press release),

Astellas Pharma's Immunosuppressant Prograf Now Available in ... Apr 24, 2006
2006 (JCN) - Astellas Pharma recently announced the European Commission's approval of the Company's proprietary immunosuppressant Prograf (tacrolimus) for the ... - Japan Corporate News (press release),

Other information

Indication
Tacrolimus is indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. Used in a topical preparation in the treatment of severe atopic dermatitis, also used after bone marrow transplants and for severe refractory uveitis.

Pharmacology
Tacrolimus, a macrolide immunosuppressant produced by Streptomyces tsukubaensis, is an immunosuppressive agent indicated for the treatment of patients receiving kidney and/or liver transplants. Tacrolimus has been demonstrated to suppress humoral immunity and, to a greater extent, cell-mediated reactions such as allograft rejection, delayed type hypersensitivity, collagen- induced arthritis, experimental allergic encephalomyelitis, and graft versus host disease. It has similar immunosuppressive properties to cyclosporine, but is much more potent in equal volumes.

Mechanism Of Action
Tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of Tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines. Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-, all of which are involved in the early stages of T-cell activation. Additionally, Tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to downregulate the expression of FceRI on Langerhans cells.

Drug Category
Immunosuppressive Agents; ATC:D11AX14; ATC:L04AA05

Brand Names/Synonyms
FK 506; FK-506; FK5; K506; Prograf; Protopic; Tacarolimus; Tacrolimus

Dosage Forms
CAPSULE; OINTMENT; SOLUTION

Absorption
Generally incomplete with absolute bioavailability of 17-22%

Interactions
-->Interactions for Tacrolimus:

Formal topical drug interaction studies with PROTOPIC Ointment have not been conducted. Based on its minimal extent of absorption, interactions of PROTOPIC Ointment with systemically administered drugs are unlikely to occur but cannot be ruled out. The concomitant administration of known CYP3A4 inhibitors in patients with widespread and/or erythrodermic disease should be done with caution. Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine.

Chemical IUPAC Name
[3S-[3R[E(1S,3S,4S)],4S,5R,8S,9E,12R,14R,15S,16R,18S,19S,26aR]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5, 19-dihydroxy-3- [2-(4-hydroxy-3-methoxycyclohexyl) -1-methylethenyl]-14, 16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15, 19-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclotricosine-1,7,20, 21(4H,23H)-tetrone, monohydrate

Chemical Formula
C44H69NO12

Half Life
11.3 hours (range from 3.5 to 40.6 hrs)

Drug Type
Approved Drug

# Accession No
APRD00276

CAS Registry Number
104987-11-3