Tìm theo
Tacrolimus
Các tên gọi khác (6 ) :
  • (-)-FK 506
  • 8-DEETHYL-8-[but-3-enyl]-ascomycin
  • FK 506
  • FK506
  • Prograf
  • Tacrolimus anhydrous
Thuốc Gốc
Small Molecule
CAS: 104987-11-3
ATC: D11AH01, L04AD02
ĐG : Astellas Pharma Inc. , http://www.astellas.com
CTHH: C44H69NO12
PTK: 804.0182
Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It was discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C44H69NO12
Phân tử khối
804.0182
Monoisotopic mass
803.481976677
InChI
InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1
InChI Key
InChIKey=QJJXYPPXXYFBGM-LFZNUXCKSA-N
IUPAC Name
(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(1E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-(prop-2-en-1-yl)-11,28-dioxa-4-azatricyclo[22.3.1.0^{4,9}]octacos-18-ene-2,3,10,16-tetrone
Traditional IUPAC Name
(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(1E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-(prop-2-en-1-yl)-11,28-dioxa-4-azatricyclo[22.3.1.0^{4,9}]octacos-18-ene-2,3,10,16-tetrone
SMILES
CO[C@@H]1C[C@@H](CC[C@H]1O)\C=C(/C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@H](C[C@@H](C)C\C(C)=C\[C@@H](CC=C)C(=O)C[C@H](O)[C@H]1C)OC
Độ tan chảy
126 °C
Độ hòa tan
Insoluble
logP
3.3
logS
-5.3
pKa (strongest acidic)
9.96
pKa (Strongest Basic)
-2.9
PSA
178.36 Å2
Refractivity
215.62 m3·mol-1
Polarizability
87.41 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
11
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Tacrolimus is a macrolide antibiotic. It acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Although this activity is similar to cyclosporine studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporine. Tacrolimus has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment.
Cơ Chế Tác Dụng : Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It was discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription. The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that 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.
Dược Động Học :
▧ Absorption :
Absorption of tacrolimus from the gastrointestinal tract after oral administration is incomplete and variable. The absolute bioavailability in adult kidney transplant patients is 17±10%; in adults liver transplant patients is 22±6%; in healthy subjects is 18±5%. The absolute bioavailability in pediatric liver transplant patients was 31±24%. Tacrolimus maximum blood concentrations (Cmax) and area under the curve (AUC) appeared to increase in a dose-proportional fashion in 18 fasted healthy volunteers receiving a single oral dose of 3, 7, and 10 mg. When given without food, the rate and extent of absorption were the greatest. The time of the meal also affected bioavailability. When given immediately after a meal, mean Cmax was reduced 71%, and mean AUC was reduced 39%, relative to the fasted condition. When administered 1.5 hours following the meal, mean Cmax was reduced 63%, and mean AUC was reduced 39%, relative to the fasted condition.
▧ Volume of Distribution :
* 2.6 ± 2.1 L/kg [pediatric liver transplant patients] * 1.07 ± 0.20 L/kg [patients with renal impairment, 0.02 mg/kg/4 hr dose, IV] * 3.1 ± 1.6 L/kg [Mild Hepatic Impairment, 0.02 mg/kg/4 hr dose, IV] * 3.7 ± 4.7 L/kg [Mild Hepatic Impairment, 7.7 mg dose, PO] * 3.9 ± 1.0 L/kg [Severe hepatic impairment, 0.02 mg/kg/4 hr dose, IV] * 3.1 ± 3.4 L/kg [Severe hepatic impairment, 8 mg dose, PO]
▧ Protein binding :
~99% bound to human plasma protein, primarily to albumin and alpha-1-acid glycoprotein. This is independent of concentration over a range of 5-50 ng/mL.
▧ Metabolism :
Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.
▧ Route of Elimination :
In man, less than 1% of the dose administered is excreted unchanged in urine. When administered IV, fecal elimination accounted for 92.6±30.7%, urinary elimination accounted for 2.3±1.1%.
▧ Half Life :
The elimination half life in adult healthy volunteers, kidney transplant patients, liver transplants patients, and heart transplant patients are approximately 35, 19, 12, 24 hours, respectively. The elimination half life in pediatric liver transplant patients was 11.5±3.8 hours, in pediatric kidney transplant patients was 10.2±5.0 (range 3.4-25) hours.
▧ Clearance :
* 0.040 L/hr/kg [healthy subjects, IV] * 0.172 ± 0.088 L/hr/kg [healthy subjects, oral] * 0.083 L/hr/kg [adult kidney transplant patients, IV] * 0.053 L/hr/kg [adult liver transplant patients, IV] * 0.051 L/hr/kg [adult heart transplant patients, IV] * 0.138 ± 0.071 L/hr/kg [pediatric liver transplant patients] * 0.12 ± 0.04 (range 0.06-0.17) L/hr/kg [pediatric kidney transplant patients] * 0.038 ± 0.014 L/hr/kg [patients with renal impairment, 0.02 mg/kg/4 hr dose, IV] * 0.042 ± 0.02 L/hr/kg [Mild Hepatic Impairment, 0.02 mg/kg/4 hr dose, IV] * 0.034 ± 0.019 L/hr/kg [Mild Hepatic Impairment, 7.7 mg dose, PO] * 0.017 ± 0.013 L/hr/kg [Severe hepatic impairment, 0.02 mg/kg/4 hr dose, IV] * 0.016 ± 0.011 L/hr/kg [Severe hepatic impairment, 8 mg dose, PO]
Độc Tính : Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD50=134-194 mg/kg (rat).
Chỉ Định : For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.
Tương Tác Thuốc :
  • Abarelix Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Abatacept Avoid combination due to enhanced toxic effects of immunosuppressants.
  • ado-trastuzumab emtansine Avoid combination due to the increase in immunosuppressant side effects.
  • Amikacin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Amikacin. Use caution during concomitant therapy.
  • Amiodarone Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Amitriptyline Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Amoxapine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Amphotericin B Additive renal impairment may occur during concomitant therapy with Amphotericin B. Use caution during concomitant therapy.
  • Amprenavir The protease inhibitor, Amprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Amprenavir therapy is initiated, discontinued or altered.
  • Antithymocyte globulin Avoid combination due to increased immunosuppressive effects
  • Apomorphine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Apramycin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Apramycin. Use caution during concomitant therapy.
  • Arsenic trioxide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir The protease inhibitor, Atazanavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Atazanavir therapy is initiated, discontinued or altered.
  • Belatacept Avoid combination due to enhanced immunosuppressive effect.
  • Belimumab Avoid combination due to enhanced adverse effects of immunosuppressants.
  • Bleomycin Tacrolimus (Topical) may enhance the adverse/toxic effect of Immunosuppressants. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Boceprevir Boceprevir increases levels of tacrolimus by affecting CYP3A4 metabolism. Concomitant therapy requires close monitoring.
  • Brentuximab vedotin Avoid combination due to the potential enhancement of toxic effects of immunosuppressants.
  • Bromocriptine Bromocriptine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Bromocriptine therapy is initiated, discontinued or altered.
  • Carbamazepine Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
  • Carboplatin Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Carmustine Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carmustine. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Caspofungin Caspofungin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Caspofungin therapy is initiated, discontinued or altered.
  • Chlorambucil Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants sucb as chlorambucil. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Chloramphenicol Chloramphenicol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Chloramphenicol therapy is initiated, discontinued or altered.
  • Chlorpromazine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Cimetidine Cimetidine may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Cimetidine therapy is initiated, discontinued or altered.
  • Cisapride Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Cisapride may also increase the concentration of Tacrolimus in the blood.
  • Cisplatin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Cisplatin. Use caution during concomitant therapy.
  • Cladribine Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as tacrolimus. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Clarithromycin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, Clarithromycin, may also increase the blood concentration of Tacrolimus.
  • Clofarabine Tacrolimus (topical) may enhance the adverse/toxic effect of immunosuppressants such as clofarabine. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
  • Clomipramine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Clotrimazole The antifungal, Clotrimazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Clotrimazole therapy is initiated, discontinued or altered.
  • Conivaptan The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Conivaptan is initiated, discontinued or dose changed.
  • Crizotinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Cyclosporine Additive renal impairment may occur during concomitant therapy with cyclosporine. Combination therapy should be avoided.
  • Danazol Danazol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Danazol therapy is initiated, discontinued or altered.
  • Darunavir The protease inhibitor, Darunavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Darunavir therapy is initiated, discontinued or altered.
  • Dasatinib Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Delavirdine The strong CYP3A4 inhibitor, Delavirdine, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Delavirdine is initiated, discontinued or dose changed.
  • Desipramine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Diltiazem Diltiazem may increase the serum concentration of tacrolimus by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of tacrolimus if diltiazem therapy is initiated, discontinued or dose changed.
  • Disopyramide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Dofetilide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Dolasetron Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Domperidone Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Doxepin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Dronedarone Tacrolimus is a CYP3A substrate with a narrow therapeutic index thus concomitant therapy with dronedarone will increase plasma levels of tacrolimus. Monitor plasma concentrations and adjust dose accordingly.
  • Droperidol Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Erythromycin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The macrolide antibiotic, erythromycin, may also increase the blood concentration of tacrolimus.
  • Etanercept Avoid combination due to enhanced immunosuppressive effects
  • Ethinyl Estradiol Ethinyl estradiol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ethinyl estradiol therapy is initiated, discontinued or altered.
  • Felodipine Felodipine increases tacrolimus levels
  • Flecainide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Fluconazole Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. The antifungal, fluconazole, may also increase serum concentrations of tacrolimus.
  • Fluoxetine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Flupentixol Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Fosamprenavir The protease inhibitor, Fosamprenavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Fosamprenavir therapy is initiated, discontinued or altered.
  • Foscarnet Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Fosphenytoin The hydantoin decreases the effect of tacrolimus
  • Gatifloxacin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Gemtuzumab ozogamicin Avoid combination of adverse effects of immunosuppressants.
  • Gentamicin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Gentamicin. Use caution during concomitant therapy.
  • Glatiramer Acetate Avoid combination due to enhanced adverse effects of immunosuppressants.
  • golimumab Avoid combination due to the enhancement of side effects from immunosuppressants.
  • Halofantrine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Haloperidol Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Homoharringtonine Avoid combination as there is potential to increase immunosuppressant adverse effects.
  • Ibritumomab Avoid combination due to enhanced adverse effects of immunosuppressants.
  • Ibutilide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Imatinib The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Imatinib is initiated, discontinued or dose changed.
  • Imipramine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Indapamide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Indinavir The protease inhibitor, Indinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Indinavir therapy is initiated, discontinued or altered.
  • Infliximab Avoid combination because of risk of enhance adverse effects of immunosuppressants
  • Isoniazid The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Isoniazid is initiated, discontinued or dose changed.
  • Isradipine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Itraconazole The antifungal, Itraconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Itraconazole therapy is initiated, discontinued or altered.
  • Ketoconazole The antifungal, Ketoconazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ketoconzole therapy is initiated, discontinued or altered.
  • Lapatinib Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Levofloxacin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Lopinavir The protease inhibitor, Lopinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Lopinavir therapy is initiated, discontinued or altered.
  • Loxapine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Maprotiline Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Mefloquine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Mesoridazine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Methadone Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Methylprednisolone Methylprednisone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Methylprednisone therapy is initiated, discontinued or altered.
  • Metoclopramide Metoclopramide may increase the concentration of Tacrolimus in the blood. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Metoclopramide therapy is initiated, discontinued or altered.
  • Metronidazole Metronidazole increases the levels/toxicity of tacrolimus
  • Mibefradil The calcium channel blocker, Mibefradil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Mibefradil therapy is initiated, discontinued or altered.
  • Miconazole The strong CYP3A4 inhibitor, Miconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Miconazole is initiated, discontinued or dose changed.
  • Moxifloxacin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Mycophenolate mofetil Tacrolimus may increase the plasma concentration of Mycophenolic acid. Monitor and adjust the dose of Mycophenolate mofetil to the therapeutic range.
  • Natalizumab Tacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
  • Nefazodone Nefazodone may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nefazodone therapy is initiated, discontinued or altered.
  • Nelfinavir The protease inhibitor, Nelfinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nelfinavir therapy is initiated, discontinued or altered.
  • Neomycin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Neomycin. Use caution during concomitant therapy.
  • Netilmicin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Netilmicin. Use caution during concomitant therapy.
  • Nicardipine The calcium channel blocker, Nicardipine, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nicardipine therapy is initiated, discontinued or altered.
  • Nifedipine The calcium channel blocker, Nifedipine, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Nifedipine therapy is initiated, discontinued or altered.
  • Nilotinib May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Norfloxacin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Nortriptyline Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Obinutuzumab Avoid combination due to enhanced adverse effects of immunosuppressants.
  • Octreotide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Omalizumab Avoid combination due to enhanced adverse toxic effects.
  • Omeprazole Omeprazole may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Omeprazole therapy is initiated, discontinued or altered.
  • Paclitaxel Avoid combination of topical tacrolimus due to the potential enhancement of adverse effects of immunosuppressants.
  • Pegaspargase Tacrolimus enhances adverse effects of pegaspargase therefore the combination should be avoided.
  • Pentamidine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Perflutren Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Phenobarbital Phenobarbital may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenobarbital therapy is initiated, discontinued or altered.
  • Phenytoin Phenytoin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenytoin therapy is initiated, discontinued or altered.
  • Pimozide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Posaconazole The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Posaconazole is initiated, discontinued or dose changed.
  • Probucol Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Procainamide Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Propafenone Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Protriptyline Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Quetiapine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Quinidine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Quinidine, a strong CYP3A4 inhibitor, may also increase the serum concentration of Tacrolimus by inhibiting its metabolism and clearance.
  • Quinupristin This combination presents an increased risk of toxicity
  • Ranolazine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Rifabutin Carbamazepine may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Carbamazepine therapy is initiated, discontinued or altered.
  • Rifampicin Rifampin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Rifampin therapy is initiated, discontinued or altered.
  • Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
  • Risperidone Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Ritonavir The protease inhibitor, Ritonavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Ritonavir therapy is initiated, discontinued or altered.
  • Saquinavir The protease inhibitor, Saquinavir, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Saquinavir therapy is initiated, discontinued or altered.
  • Silodosin The p-glycoprotein inhibitor, Tacrolimus, may increase the bioavailability of Silodosin. Increased Silodosin exposure may result in Silodosin toxicity. Concurrent use if not recommended.
  • Sirolimus Sirolimus may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Sirolimus therapy is initiated, discontinued or altered.
  • Sotalol Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Sparfloxacin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • St. John's Wort St. John's Wort may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if St. John's Wort therapy is initiated, discontinued or altered.
  • Streptomycin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Streptomycin. Use caution during concomitant therapy.
  • Sunitinib Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Must monitor levels closely with concomitant therapy.
  • Telithromycin Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Telithromycin, a strong CYP3A4 inhibitor, may also increase the serum concentration of Tacrolimus by inhibiting its metabolism and clearance.
  • Temsirolimus Temsirolimus may decrease the blood concentration of Tacrolimus. Concomitant therapy may increase the adverse/toxic effects of both agents. Concomitant therapy should be avoided.
  • Teriflunomide Avoid combination due to the increased toxic effects of immunosuppressants.
  • Tetrabenazine May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
  • Thioridazine May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Thiothixene Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Tipranavir Tipranavir may decrease the metabolism and clearance of Tacrolimus. Dose adjustments may be required. Monitor for Tacrolimus efficacy and toxicity during concomitant therapy.
  • Tobramycin Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Tobramycin. Use caution during concomitant therapy.
  • Tofacitinib Avoid combination due to the potential increase in immunosuppressant associated adverse effects.
  • Topotecan The p-glycoprotein inhibitor, Tacrolimus, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Trimipramine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Troleandomycin The macrolide antibiotic, Troleandomycin, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Troleandomycin therapy is initiated, discontinued or altered.
  • Verapamil The calcium channel blocker, Verapamil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Verapamil therapy is initiated, discontinued or altered.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of tacrolimus by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of tacrolimus if voriconazole is initiated, discontinued or dose changed.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Capsule - Oral - 0.5 mg, 1 mg, 3 mg, 5 mg
Injection, solution - Intravenous - 5 mg/mL
Ointment - Topical - 0.03%, 0.1%
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Advagraf
  • Công ty :
    Sản phẩm biệt dược : Hecoria
  • Công ty :
    Sản phẩm biệt dược : Prograf
  • Công ty :
    Sản phẩm biệt dược : Protopic
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00864
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=445647
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506004
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01375
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00107
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0469-0607-73
PharmGKB
http://www.pharmgkb.org/drug/PA451578
Wikipedia
http://en.wikipedia.org/wiki/Tacrolimus
RxList
http://www.rxlist.com/cgi/generic2/tacrolimus.htm
Drugs.com
http://www.drugs.com/cdi/tacrolimus.html
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