Contents

Search

tacrolimus; FK506; fujimycin (Prograf, Advagraf, Envarsus XR)

Also tacrolimus. Tradename Prograf. Indications: - prophylaxis of organ transplantation rejection in patients receiving allogeneic liver transplantation - renal graft rejection - lung transplantation [7] - used concomitantly with glucocorticoids - immunosuppressive agent used for maintenance of immunosuppression after cardiac transplantation & for treatment of refractory transplantation rejection - lichen sclerosus, atopic dermatitis (topical) [4] Contraindications: - concurrent use of cyclosporine; separate use by at least 24 hours Dosage: 1) IV continuous infusion: 0.05-1 mg/kg/day until oral dose is tolerated starting no sooner than 6 hours after transplantation 2) oral: 0.15-0.3 mg/kg/day divided every 12 hours Tabs: 1 mg, 5 mg. Injection: 5 mg/mL (1 mL). Topical: 0.1% Monitor: - tacrolimus in serum/plasma - CYP3A5 gene mutation may expedite achieving therapeutic levels [NGC] Pharmacokinetics: 1) absorption is highly variable; food decreases absorption 2) volume of distribution (Vd) = 17 L/kg [6] 3) extensively metabolized in the liver by predominantly by CYP3A5 & to a lesser extent CYP3A5 4) eliminated primarily via the bile 5) protein binding 75-99% Adverse effects: not common (1-10%) 1) nephrotoxicity with hyperkalemia, elevated serum creatinine & hypertension 2) neurotoxicity including insomnia, mild tremors, headache, photophobia, hyperesthesia, confusion, seizures, dysarthria, persistent coma 3) infections & malignant complications including post-transplant lymphoproliferative disorder, bacterial infections, viral infection, & fungal infections 4) hyperglycemia including new onset diabetes mellitus 5) dyslipidemia [2] 6) gastrointestinal symptoms including nausea/vomiting, abdominal pain 7) peripheral edema at high to toxic levels 8) BK virus-associated nephropathy in renal transplant patients [5] Drug interactions: 1) separate antacids from tacrolimus by at least 2 hours 2) agents which may increase plasma tacrolimus - erythromycin, clotrimazole, flucanozole, methylprednisolone, ketoconazole, itraconazole, diltiazem, verapamil, nicardipine, cimetidine, clarithromycin, danazol, metoclopramide, bromocryptine 3) cyclosporine is associated with synergistic immunosuppression & increased nephrotoxicity 4) nephrotoxic antibiotics & amphotericin B increase nephrotoxicity 5) agents which may decrease plasma tacrolimus - rifampin, rifabutin, carbamazepine, phenytoin, phenobarbital 6) any drug that inhibits CYP3A4 or CYP3A5 may increase levels of tacrolimus 7) any drug that induces CYP3A4 or CYP3A5 may diminish levels of tacrolimus Mechanism of action: 1) inhibits calcineurin [4] 2) inhibits formation of interleukin-2 Origin: Produced by Streptomyces tsukubaensis.

Interactions

drug interactions drug adverse effects (more general classes) monitor with immunosuppressive agents

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) FK506-binding protein 1A (12 kD FK506-binding protein, immunophilin FKBP12, FKBP1A) FK506-binding protein 2 (13 kD FK506-binding protein, FKBP2) FK506-binding protein 3, 25 kD FK506-binding protein or rapamycin-selective 25 kD immunophilin sirolimus; rapamycin (Rapamune) tacrolimus in blood tacrolimus toxicity

Specific

tacrolimus topical (Protopic)

General

calcineurin inhibitor heterocyclic compound, 3 rings immunosuppressive agent lactone prokaryote-specific molecule

Properties

MISC-INFO: elimination route LIVER protein-binding 75-99% elimination by hemodialysis - 1/2life 4-40 HOURS pregnancy-category C

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
  3. Department of Veterans Affairs, VA National Formulary
  4. Hengge UR et al, Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus. Br J Dermatol 2006, 155:1021 PMID: 17034535
  5. FDA Medwatch http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm171828.htm
  6. The Drug Monitor Tacrolimus http://www.thedrugmonitor.com/tacro.html
  7. Deprecated Reference
  8. Wikipedia: Tacrolimus https://en.wikipedia.org/wiki/Tacrolimus

Component-of

calcitriol/fluticasone/tacrolimus