II. Indications

  1. See Tacrolimus Ointment for use in Atopic Dermatitis
  2. FDA Approved indications
    1. Allogenic Organ Transplant (Kidney, Liver, Heart)
      1. Used in combination with other immunosupressants (e.g. Mycophenolate)
  3. Other Non-FDA approved indications
    1. Other organ transplant (Cornea, Pancreas, Kidney)
    2. Lupus Nephritis
    3. Crohns Disease
    4. Membranous Glomerulonephritis
    5. Myasthenia Gravis

III. Mechanism

  1. See Calcineurin Inhibitor
  2. Tacrolimus is a Macrolide isolated from the Bacteria Streptomyces tsukubaensis
  3. Tacrolimus is a Calcineurin Inhibitor via binding the FKBP 12 Protein

IV. Medications

  1. Tacrolimus capsules: 0.5 mg, 1 mg, 5 mg
  2. Tacrolimus extended release capsules (Astagraf XL): 0.5 mg, 1 mg, 5 mg
  3. Tacrolimus extended release tablets (Envarsus XR): 0.75 mg, 1 mg, 4 mg

V. Dosing

  1. See other references for specific dosing regimens per indication
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring of Tacrolimus
  3. Decrease dose in renal dysfunction, and adjust doses based on serum levels

VI. Adverse Effects

  1. Nephrotoxicity
  2. Hepatotoxicity
  3. Cardiovascular adverse effects
    1. Hypertension
    2. QTc Prolongation
    3. Myocardial hypertrophy
  4. Neurologic adverse effects
    1. Headaches
    2. Tremor
    3. Neuropathy
    4. Seizures
  5. Gastrointestinal (more prominent than Cyclosporine)
    1. Nausea or Vomiting
    2. Diarrhea
    3. Abdominal Pain
    4. Anorexia
  6. Secondary Malignancy
    1. Squamous cell cancer
    2. Lymphoproliferative disorders
  7. Miscellaneous adverse effects
    1. Hyperkalemia
    2. Diabetes Mellitus
    3. Alopecia
    4. Serious infections (Bacterial, viral, fungal)

VII. Safety

  1. Pregnancy Category C
  2. Avoid in Lactation per drug label
    1. However thought to be safe in Lactation based on registry data
    2. https://pubmed.ncbi.nlm.nih.gov/30000743/
  3. Monitoring
    1. Renal Function
    2. Blood Pressure

VIII. Pharmacokinetics

  1. Hepatic Metabolism (CYP3A4)
  2. Biliary excretion (95%)

IX. Drug Interactions

  1. See Calcineurin Inhibitor
  2. Nephrotoxic Drugs (e.g. Aminoglycosides, Amphotericin B)
    1. Avoid in combination with Tacrolimus (combination increases nephrotoxicity)
  3. Numerous Drug Interactions (see other references)
    1. Tacrolimus is CYP3A4 metabolized
    2. Many medications alter Tacrolimus absorption and serum levels

X. Efficacy

  1. Similar efficacy and more potent than Cyclosporine in Solid Organ Transplant

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

tacrolimus (on 11/2/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
TACROLIMUS 0.03% OINTMENT Generic $0.73 per gram
TACROLIMUS 0.1% OINTMENT Generic $1.91 per gram
TACROLIMUS 0.5 MG CAPSULE (IMMEDIATE RELEASE) Generic $0.19 each
TACROLIMUS 1 MG CAPSULE (IMMEDIATE RELEASE) Generic $0.28 each
TACROLIMUS 5 MG CAPSULE (IMMEDIATE RELEASE) Generic $1.55 each
prograf (on 1/12/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
PROGRAF 0.5 MG CAPSULE Generic $0.19 each
PROGRAF 1 MG CAPSULE Generic $0.28 each
astagraf xl (on 1/12/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ASTAGRAF XL 1 MG CAPSULE $4.96 each
envarsus xr (on 12/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ENVARSUS XR 1 MG TABLET $6.19 each

Ontology: Tacrolimus (C0085149)

Definition (NCI_NCI-GLOSS) A drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants.
Definition (NCI) A macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.
Definition (MSH) A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
Definition (PDQ) A macrolide isolated from the fungus Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42009&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42009&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1311" NCI Thesaurus)
Concepts Organic Chemical (T109)
MSH D016559
SnomedCT 395305001, 109129008, 386975001
LNC LP15182-6, MTHU001849
English 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, 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)-, monohydrate, (3S-(3R*(E(1S*,3S*,4S*)),4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*))-, Tacrolimus, 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, Fujimycin, TACROLIMUS, 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, 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-p, Tacrolimus [Chemical/Ingredient], tacrolimus, Tacrolimus [skin], Tacrolimus [skin] (product), tacrolimus (medication), immunosuppressives tacrolimus, Tacrolimus (product), Tacrolimus (substance)
Swedish Takrolimus
Czech takrolimus, FK-506
Finnish Takrolimuusi
German Tacrolimus
Russian TAKROLIMUS, FK-506, ТАКРОЛИМУС
Japanese プログラフ, タリムス, タクロリムス水和物, タクロリムス, プロトピック, アドバグラフ, グラセプター
Spanish tacrolimús, tacrolimus, tacrolimus (producto), tacrolimús (producto), tacrolimús (sustancia), tacrolimus (piel), tacrolimus (piel) (producto), Tacrolimús, tacrolimus (sustancia), Tacrolimus
French Tacrolimus
Polish Takrolimus, FK-506
Portuguese Tacrolimus, Tacrolimo
Italian Tacrolimus