Pharm

Tacrolimus

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Tacrolimus, Prograf, Astagraf XL, Hecoria, Envarsus XR, FK 506

  • See Also
  1. Tacrolimus Ointment
  2. Calcineurin Inhibitor
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • Pharmacokinetics
  1. Hepatic Metabolism (CYP3A4)
  2. Biliary excretion (95%)
  • 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
  • Efficacy
  1. Similar efficacy and more potent than Cyclosporine in Solid Organ Transplant
  • Resources
  1. Tacrolimus Capsules (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=45af3eda-caaa-4478-9372-95aa65adc9b3
  2. Calcineurin Inhibitors (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK558995/