Tacrolimus

TACROLIMUS- tacrolimus capsule
KAISER FOUNDATION HOSPITALS

Rx Only

WARNING

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe tacrolimus capsules. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

DESCRIPTION

Tacrolimus capsules are available for oral administration containing the equivalent of 1 mg of anhydrous tacrolimus. In addition, each capsule contains the following inactive ingredients: croscarmellose sodium, hypromellose, lactose monohydrate, and magnesium stearate.

The tacrolimus capsule shell for 1 mg strength consists of black iron oxide, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide.

Tacrolimus capsules are printed with edible black ink. The black ink is comprised of ammonia, black iron oxide, butyl alcohol, potassium hydroxide, propylene glycol, and shellac.

Tacrolimus, previously known as FK506, is the active ingredient in tacrolimus capsules. Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. Chemically, tacrolimus is designated as [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.

The chemical structure of tacrolimus is:

chemical structure
(click image for full-size original)

Tacrolimus has a molecular formula of C44 H69 NO12 •H2 O and a formula weight of 822.03. Tacrolimus appears as white crystals or crystalline powder. It is practically insoluble in water, freely soluble in ethanol, and very soluble in methanol and chloroform.

CLINICAL PHARMACOLOGY

Mechanism of Action

Tacrolimus prolongs the survival of the host and transplanted graft in animal transplant models of liver, kidney, bone marrow, small bowel and pancreas, lung and trachea, skin, cornea, and limb.

In animals, tacrolimus has been demonstrated to suppress some 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.

Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that tacrolimus binds 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 inhibited. This effect may prevent 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 (such as interleukin-2, gamma interferon). The net result is the inhibition of T-lymphocyte activation (i.e., immunosuppression).

Pharmacokinetics

Tacrolimus activity is primarily due to the parent drug. The pharmacokinetic parameters (mean±S.D.) of tacrolimus have been determined following intravenous (IV) and/or oral (PO) administration in healthy volunteers, and in kidney transplant, and liver transplant patients. (See table below.)

* not applicable; † Corrected for individual bioavailability; ‡ AUC0-120; § AUC0-72 ; ¶ AUC0 -inf; # not available
Population N Route (Dose) Parameters

Cmax

(ng/mL)

Tmax

(hr)
AUC (ng•hr/mL) t 1/2 (hr) CI (L/hr/kg)

V

(L/kg)
Healthy Volunteers 8

IV

* *

598‡

34.2

0.04

1.91

16

PO

29.7 ± 7.2

1.6

243§ ±73

34.8

0.041†

1.94†

Kidney Transplant Pts 26

IV

* * 294¶ ±262

18.8

0.083

1.41

PO

19.2

3

203¶

# # #

PO

24.2

1.5

288¶

# # #
Liver Transplant Pts 17

IV

* *

3300¶

11.7

0.053

0.85

PO

68.5

2.3

519¶

# # #

Due to intersubject variability in tacrolimus pharmacokinetics, individualization of dosing regimen is necessary for optimal therapy. (See DOSAGE AND ADMINISTRATION). Pharmacokinetic data indicate that whole blood concentrations rather than plasma concentrations serve as the more appropriate sampling compartment to describe tacrolimus pharmacokinetics.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.