Peringatan Keamanan

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).

Tacrolimus

DB00864

small molecule approved investigational

Deskripsi

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 inhibits calcineurin which inhibits T-lymphocyte signal transduction and IL-2 transcription.

Struktur Molekul 2D

Berat 804.0182
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (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.
Volume Distribusi * 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]
Klirens (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]

Absorpsi

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.

Metabolisme

The metabolism of tacrolimus is predominantly mediated by CYP3A4 and secondarily by CYP3A5.A38786,L8162 Tacrolimus is metabolized into 8 metabolites: 13-demethyl tacrolimus, 31-demethyl tacrolimus, 15-demethyl tacrolimus, 12-hydroxy tacrolimus, 15,31-didemethyl tacrolimus, 13,31-didemethyl tacrolimus, 13,15-didemethyl tacrolimus, and a final metabolite involving O-demethylation and the formation of a fused ring.A38786 The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus.L8162 In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.L8162

Rute Eliminasi

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%.

Farmakogenomik

2 Varian
CYP3A5 (None)

Patients with this genotype in CYP3A5 are extensive metabolizers and require higer doses of tacrolimus to attain the therapeutic effect.

ABCB1 (rs2032582)

The presence of this genotype in ABCB1 may indicate an increased risk of drug-induced neurotoxicity when treated with tacrolimus.

Interaksi Makanan

6 Data
  • 1. Avoid alcohol. Consuming alcohol may increase the rate of tacrolimus release from extended-release formulations.
  • 2. Avoid grapefruit products.
  • 3. Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of tacrolimus; therefore, monitoring tacrolimus whole blood trough concentrations may be warranted.
  • 4. Take at the same time every day.
  • 5. Take on an empty stomach. Take at least 1 hour before or 2 hours after a meal as coadministration with food decreases the rate and extent of absorption.
  • 6. Take separate from antacids. Coadministration of tacrolimus with aluminum or magnesium hydroxide antacids may increase the serum levels of tacrolimus, which poses a risk for toxicity.

Interaksi Obat

1999 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tacrolimus.
Natalizumab The risk or severity of immunosuppression can be increased when Tacrolimus is combined with Natalizumab.
Roflumilast The serum concentration of Roflumilast can be increased when it is combined with Tacrolimus.
Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Tacrolimus.
Afatinib The serum concentration of Afatinib can be increased when it is combined with Tacrolimus.
Modafinil The metabolism of Tacrolimus can be increased when combined with Modafinil.
Armodafinil The metabolism of Tacrolimus can be increased when combined with Armodafinil.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Tacrolimus.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Tacrolimus.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Tacrolimus.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Tacrolimus.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Tacrolimus.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Tacrolimus.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Tacrolimus.
Silodosin The excretion of Silodosin can be decreased when combined with Tacrolimus.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Tacrolimus.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Tacrolimus.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Tacrolimus.
Cilostazol The metabolism of Cilostazol can be decreased when combined with Tacrolimus.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Tacrolimus.
Fentanyl Tacrolimus may decrease the excretion rate of Fentanyl which could result in a higher serum level.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Tacrolimus.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Tacrolimus.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Tacrolimus.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Tacrolimus.
Eszopiclone The metabolism of Eszopiclone can be decreased when combined with Tacrolimus.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Tacrolimus.
Lovastatin The metabolism of Lovastatin can be decreased when combined with Tacrolimus.
Metreleptin The metabolism of Tacrolimus can be increased when combined with Metreleptin.
Alfuzosin The metabolism of Alfuzosin can be decreased when combined with Tacrolimus.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Tacrolimus.
Foscarnet The risk or severity of nephrotoxicity can be increased when Tacrolimus is combined with Foscarnet.
Mannitol The risk or severity of nephrotoxicity can be increased when Mannitol is combined with Tacrolimus.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Tacrolimus.
Tenofovir Tacrolimus may increase the nephrotoxic activities of Tenofovir.
Tenofovir disoproxil Tacrolimus may increase the nephrotoxic activities of Tenofovir disoproxil.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Tacrolimus.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Tacrolimus.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Tacrolimus.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Tacrolimus.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Tacrolimus.
(S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Tacrolimus.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Tacrolimus.
Caspofungin The serum concentration of Tacrolimus can be decreased when it is combined with Caspofungin.
Cinacalcet The serum concentration of Tacrolimus can be decreased when it is combined with Cinacalcet.
Ertapenem The serum concentration of Tacrolimus can be increased when it is combined with Ertapenem.
Itraconazole The serum concentration of Tacrolimus can be increased when it is combined with Itraconazole.
Phenytoin The serum concentration of Tacrolimus can be decreased when it is combined with Phenytoin.
Fosphenytoin The serum concentration of Tacrolimus can be decreased when it is combined with Fosphenytoin.
Clozapine The serum concentration of Tacrolimus can be increased when it is combined with Clozapine.
Dronedarone The serum concentration of Tacrolimus can be increased when it is combined with Dronedarone.
Azelastine The metabolism of Tacrolimus can be decreased when combined with Azelastine.
Dabrafenib The serum concentration of Tacrolimus can be increased when it is combined with Dabrafenib.
Viloxazine The serum concentration of Tacrolimus can be increased when it is combined with Viloxazine.
Methylene blue The serum concentration of Tacrolimus can be increased when it is combined with Methylene blue.
Aldesleukin The serum concentration of Tacrolimus can be increased when it is combined with Aldesleukin.
Octreotide The serum concentration of Tacrolimus can be increased when it is combined with Octreotide.
Fluvoxamine The serum concentration of Tacrolimus can be increased when it is combined with Fluvoxamine.
Fluconazole The serum concentration of Tacrolimus can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Tacrolimus can be increased when it is combined with Erythromycin.
Citalopram The serum concentration of Tacrolimus can be increased when it is combined with Citalopram.
Nelfinavir The serum concentration of Tacrolimus can be increased when it is combined with Nelfinavir.
Indinavir The serum concentration of Tacrolimus can be increased when it is combined with Indinavir.
Cabergoline The serum concentration of Tacrolimus can be increased when it is combined with Cabergoline.
Diethylstilbestrol The serum concentration of Tacrolimus can be increased when it is combined with Diethylstilbestrol.
Isradipine The serum concentration of Tacrolimus can be increased when it is combined with Isradipine.
Valproic acid The serum concentration of Tacrolimus can be increased when it is combined with Valproic acid.
Acetaminophen The serum concentration of Tacrolimus can be increased when it is combined with Acetaminophen.
Dihydroergotamine The serum concentration of Tacrolimus can be increased when it is combined with Dihydroergotamine.
Methadone The serum concentration of Tacrolimus can be increased when it is combined with Methadone.
Terfenadine The serum concentration of Tacrolimus can be increased when it is combined with Terfenadine.
Diltiazem The serum concentration of Tacrolimus can be increased when it is combined with Diltiazem.
Methylergometrine The serum concentration of Tacrolimus can be increased when it is combined with Methylergometrine.
Mefloquine The serum concentration of Tacrolimus can be increased when it is combined with Mefloquine.
Mirtazapine The serum concentration of Tacrolimus can be increased when it is combined with Mirtazapine.
Sorafenib The serum concentration of Tacrolimus can be increased when it is combined with Sorafenib.
Nitric Oxide The serum concentration of Tacrolimus can be increased when it is combined with Nitric Oxide.
Cerivastatin The serum concentration of Tacrolimus can be increased when it is combined with Cerivastatin.
Teniposide The serum concentration of Tacrolimus can be increased when it is combined with Teniposide.
Chloramphenicol The serum concentration of Tacrolimus can be increased when it is combined with Chloramphenicol.
Quinine The serum concentration of Tacrolimus can be increased when it is combined with Quinine.
Raloxifene The serum concentration of Tacrolimus can be increased when it is combined with Raloxifene.
Cimetidine The serum concentration of Tacrolimus can be increased when it is combined with Cimetidine.
Haloperidol The serum concentration of Tacrolimus can be increased when it is combined with Haloperidol.
Ritonavir The serum concentration of Tacrolimus can be increased when it is combined with Ritonavir.
Erlotinib The serum concentration of Tacrolimus can be increased when it is combined with Erlotinib.
Ciprofloxacin The serum concentration of Tacrolimus can be increased when it is combined with Ciprofloxacin.
Zafirlukast The serum concentration of Tacrolimus can be increased when it is combined with Zafirlukast.
Vinblastine The serum concentration of Tacrolimus can be increased when it is combined with Vinblastine.
Fluticasone propionate The serum concentration of Tacrolimus can be increased when it is combined with Fluticasone propionate.
Thiopental The serum concentration of Tacrolimus can be increased when it is combined with Thiopental.
Imatinib The serum concentration of Tacrolimus can be increased when it is combined with Imatinib.
Nicardipine The serum concentration of Tacrolimus can be increased when it is combined with Nicardipine.
Efavirenz The serum concentration of Tacrolimus can be increased when it is combined with Efavirenz.
Astemizole The serum concentration of Tacrolimus can be increased when it is combined with Astemizole.
Dextropropoxyphene The serum concentration of Tacrolimus can be increased when it is combined with Dextropropoxyphene.
Verapamil The serum concentration of Tacrolimus can be increased when it is combined with Verapamil.
Epinephrine The serum concentration of Tacrolimus can be increased when it is combined with Epinephrine.
Aprepitant The serum concentration of Tacrolimus can be increased when it is combined with Aprepitant.
Tamoxifen The serum concentration of Tacrolimus can be increased when it is combined with Tamoxifen.

Target Protein

Protein phosphatase 3 catalytic subunit alpha PPP3CA
Peptidyl-prolyl cis-trans isomerase FKBP1A FKBP1A

Referensi & Sumber

Synthesis reference: Pan Sup Chang, Hoon Cho, "Water soluble polymer-tacrolimus conjugated compounds and process for preparing the same." U.S. Patent US5922729, issued April, 1997.
Artikel (PubMed)
  • PMID: 2445721
    Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, Okuhara M, Kohsaka M, Aoki H, Imanaka H: FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1987 Sep;40(9):1249-55.
  • PMID: 15896681
    Pritchard DI: Sourcing a chemical succession for cyclosporin from parasites and human pathogens. Drug Discov Today. 2005 May 15;10(10):688-91.
  • PMID: 1715244
    Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL: Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15.
  • PMID: 16702731
    Fukatsu S, Fukudo M, Masuda S, Yano I, Katsura T, Ogura Y, Oike F, Takada Y, Inui K: Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. Drug Metab Pharmacokinet. 2006 Apr;21(2):122-5.
  • PMID: 16021174
    Hanifin JM, Paller AS, Eichenfield L, Clark RA, Korman N, Weinstein G, Caro I, Jaracz E, Rico MJ: Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol. 2005 Aug;53(2 Suppl 2):S186-94.
  • PMID: 17965516
    Iwasaki K: Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet. 2007 Oct;22(5):328-35.

Contoh Produk & Brand

Produk: 262 • International brands: 0
Produk
  • Ach-tacrolimus
    Capsule • 1 mg • Oral • Canada • Generic • Approved
  • Ach-tacrolimus
    Capsule • 5 mg • Oral • Canada • Generic • Approved
  • Ach-tacrolimus
    Capsule • 0.5 mg • Oral • Canada • Generic • Approved
  • Advagraf
    Capsule, extended release • 0.5 mg • Oral • Canada • Approved
  • Advagraf
    Capsule, extended release • 1 mg • Oral • Canada • Approved
  • Advagraf
    Capsule, extended release • 5 mg • Oral • Canada • Approved
  • Advagraf
    Capsule, extended release • 3 mg • Oral • Canada • Approved
  • Advagraf
    Capsule, extended release • 0.5 mg • Oral • EU • Approved
Menampilkan 8 dari 262 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul