Liposomal Doxorubicin

Aka: Liposomal Doxorubicin, Doxorubicin Hydrochloride Liposome, Pegylated Liposomal Doxorubicin, Liposomal Adriamycin, Doxil, Lipodox 50

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II. Indications

  1. FDA Approved
    1. Kaposi Sarcoma (associated with AIDS)
    2. Multiple Myeloma
    3. Ovarian Cancer
  2. Off-Label
    1. Breast Cancer
    2. Hodgkin Lymphoma
    3. Cutaneous T-Cell Lymphoma
    4. Soft Tissue Sarcoma
    5. Uterine Sarcoma

III. Mechanism

  1. See Antibiotic Chemotherapy
  2. This formulation is a liposome-encapsulated preparation of Doxorubicin
    1. See Non-Liposomal Doxorubicin
    2. Liposomal delivery of Doxorubicin has several benefits
      1. Increases Doxorubicin penetration into tumors
      2. Decreases Doxorubicin clearance resulting in longer duration of effects
      3. Decreases Doxorubicin-associated toxicity (esp. cardiotoxicity)
  3. Doxorubicin is a derivative of Daunorubicin, an anthracycline Aminoglycoside antineoplastic
    1. Daunorubicin is isolated from the bacterium Streptomyces peucetius (Caesius variety)
    2. Doxorubicin is a hydroxylated form of Daunorubicin
  4. Doxorubicin inserts between adjacent DNA base pairs
    1. Blocks DNA Transcription by RNA Polymerase
  5. Doxorubicin also inhibits Topoisomerase 2
    1. Inhibits normal Nucleotide strand ligation during DNA Replication
  6. Doxorubicin also induces free radical formation with several secondary effects
    1. Lipid peroxidation of cell membrane lipids (cytotoxic effects)
    2. Toxic effects (esp. cardiovascular adverse effects)

IV. Medications

  1. Liposomal Doxorubicin IV Solution: 20 mg and 50 mg vials

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Adverse Effects

  1. Severe skin and soft tissue necrosis on extravasation
    1. Doxorubicin is a strong Vesicant (causes Blistering)
  2. Cardiotoxicity (esp. children)
    1. Risk of Congestive Heart Failure (esp. with multiple doses)
  3. Myelosuppression
  4. Hyperuricemia
  5. Infusion reactions (severe)
  6. Alopecia
  7. Mucositis
  8. Necrotizing colitis
  9. Palmar-Plantar erythrodysesthesia
  10. Carcinogenic (risk of secondary malignancy)
  11. Urine Discoloration (transient red coloration)

VII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
    2. Liver Function Tests
    3. Renal Function Tests
    4. Serum Uric Acid
    5. Echocardiogram with ejection fraction

VIII. Resources

  1. Liposomal Doxorubicin Injection Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5910862-f565-a685-2f3e-9d6e676c381b
  2. Doxorubicin (StatPearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK459232/

IX. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia

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