Pharm

Cyclosporine

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Cyclosporine, Sandimmune, Neoral, Gengraf

  • See Also
  1. Ophthalmic Cyclosporine
  2. Calcineurin Inhibitor
  • Indications
  1. See Ophthalmic Cyclosporine
  2. FDA Approved (adults)
    1. Solid Organ Transplant (Kidney, heart, liver, and Bone Marrow)
      1. Immunosuppression (maintenance prevention of rejection)
      2. Cyclosporine is typically combined with Corticosteroids when used for organ transplant
    2. Refractory Rheumatoid Arthritis
      1. May be used in combination with Methotrexate
    3. Refractory Plaque Psoriasis
  3. Other Non-FDA approved Indications
    1. Graft versus host disesase
    2. Autoimmune Conditions (Behcet's Disease, Vasculitis, Myopathy)
    3. Psoriatuc Arthritis
    4. Thrombocytopenia (chronic, idiopathic, refractory)
    5. Solid Organ Transplant in children
  • Mechanism
  1. See Calcineurin Inhibitor
  2. Cyclosporine is a cyclic polypeptide isolated from the fungus Beauveria nivea
  3. Cyclosporine is a Calcineurin Inhibitor via binding cytophilin
  • Medications
  1. Cyclosporine is available in both microemulsion (Neoral, Gengraf) and original formulation (Sandimmune)
    1. Original formulation has variable absorption due to dependence on GI bile acid concentrations
    2. Microemulsion has more consistent Bioavailability as it is not dependent on bile acids
    3. Monitor levels closely if switching between formulations
  2. Cyclosporine capsules: 25 mg, 100 mg
  3. Cyclosporine: 100 mg/ml
  • Dosing
  1. See other references for specific dosing regimens per indication
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring of Cyclosporine
  3. Decrease dose in renal dysfunction, and adjust doses based on serum levels
  • Adverse Effects
  1. See Calcineurin Inhibitor
  2. Nephrotoxicity
  3. Venous Thromboembolism
  4. Hepatotoxicity
  5. Hypertension
  6. Hyperlipidemia
  7. Gingival Hyperplasia
  8. Hirsutism
  9. Serious infections (Bacterial, viral, fungal)
  10. Gastrointestinal (less prominent than with Tacrolimus)
    1. Nausea or Vomiting
    2. Diarrhea
    3. Abdominal Pain
    4. Anorexia
  11. Neurotoxicity
    1. Seizures
    2. Headaches
    3. Encephalopathy (rare)
  12. Secondary Malignancy
    1. Squamous cell cancer
    2. Lymphoproliferative disorders
  • Pharmacokinetics
  1. Hepatic metabolism (CYP3A4)
  2. No renal dose adjustments needed
  • Safety
  1. Pregnancy Category C
    1. Associated wirh preterm delivery and low birth weight
    2. Preeclampsia risk
  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. Cyclosporine blood concentrations (frequent)
    2. Monitoring of renal and hepatic function
  • Drug Interactions
  1. See Calcineurin Inhibitor
  2. Numerous Drug Interactions (see other references)
    1. Cyclosporine is CYP3A4 metabolized
  3. Nephrotoxic Drugs (e.g. Aminoglycosides, Amphotericin B)
    1. Avoid in combination with Cyclosporine (combination increases nephrotoxicity)
  • Resources
  1. Cylcosporine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bfca7088-fe93-abb9-3ec3-e6f5710a69c6
  2. Calcineurin Inhibitors (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK558995/