Tacrolimus

Tacrolimus

  • Pregnancy category C
  • Macrolide immunosuppressant derived from soil bacterium

  • 1-2 mg PO twice daily

Binds FK506 binding proteins (similar to cyclophilin function), which binds calcineurin, inhibiting its ability to dephosphorylate Nuclear factor of activated T-cells 1 (NFAT-1) decreasing Interleukin-2, T cell activation & proliferation

  • Graft versus host disease prophylaxis
  • Pyoderma gangrenosum
  • Psoriasis
  • Sarcoidosis

Absolute

  • Significant renal insufficiency 
  • Uncontrolled hypertension
  • Allergy to Cyclosporine or ingredients
  • Cured or persistent malignancy (except non-melanoma skin cancer)
  • Cutaneous T-cell lymphoma

Relative

  • Age <18 or >64 years
  • Pregnancy or lactation
  • Unreliable patients
  • Controlled hypertension
  • Active infection
  • Immune suppression
  • Planning to receive a live vaccine
  • Concomitant nephrotoxic treatment or medication interaction with Cyclosporine
  • Concomitant phototherapy, methotrexate, or immune- suppressant medication

Immunosuppression

  • Posterior reversible encephalopathy syndrome
  • Hypertension
  • Renal dysfunction 
  • Diabetes mellitus (Tacrolimus > Cyclosporine)
  • Hyperlipidemia
  • Hyperkalemia (especially when combined with Angiotensin-converting-enzyme inhibitor)

  •  Other nephro-toxic drugs

  • Lower dose or discontinue if Creatinine increased by >30% of baseline

Baseline

  • History & physical exam (blood pressure at least 2 readings, 2 days apart)
  • complete blood count, liver function tests, creatinine/ blood urea nitrogen, urinalysis, lipid profile, magnesium, potassium, uric acid
  • Tuberculin skin test
  • Pneumococcal & Influenza vaccine

Follow-up

  • Blood pressure at every visit
  • Creatinine & blood urea nitrogen q2weeks x 2 months then q4 weeks 
  • complete blood count, liver function tests, urinalysis, lipid profile, magnesium, potassium, uric acid qmonthly 
  • Glomerular filtration rate after 1 year of continuous therapy

Therapeutic guidelines

  • For severe disease, flares & recalcitrant disease: start with a higher dose: 5mg/kg/day & once patient is stable, decrease by 1mg/kg/day q2weeks till minimum effective dose
  • For moderate disease: start with 2.5-3mg/kg/day then increase by 0.5-1mg/kg/day q2weeks till effective dose
  • Insufficient response after 3 month: add another immunosuppressant & taper Cyclosporine to discontinue 

Risk factors for developing non-melanoma skin cancer while on Cyclosporine

  • Treatment > 2years 
  • Concurrent immunosuppressive medications 
  • Previous treatment with psoralen + ultraviolet-A radiation (PUVA)
  • Baseline multiple Squamous cell carcinoma
  • Transplant patients 

Sequential therapy

  • Sequential use of Cyclosporine & Acitretin: fast onset (Cyclosporine) & good maintenance (acitretin) 
  • Cyclosporine & Methotrexate: not yet determined to be safe but is used in rheumatology patients