Adriamycin
Synonym :
Doxorubicin
Mechanism :
The cytotoxic effect of doxorubicin on malignant cells are thought to be related to nucleotide base intercalation and cell membrane lipid binding activities of doxorubicin. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin with topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin cytocidal activity. Doxorubicin cellular membrane binding may affect a variety of cellular functions.
Indication :
- Various types of malignancies
Contraindications :
Doxorubicin therapy is contraindicated in patients who have marked myelosuppression induced by previous treatment with other antitumor agents or by radiotherapy. Doxorubicin treatment is contraindicated in patients who received previous treatment with complete cumulative doses of doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenes.
Dosing :
Current treatment protocol to be consulted always for details of dosage and scheduling.
35-75 mg/m² IV every 21 days or 20-30 mg/m²/dose every week or 60-90 mg/m² IV infused over 96 hour every 3-4 weeks.
Dose adjustment in hepatic impairment:
If Bilirubin is 1.2-3 mg/dl: Decrease dose by 50%.
If Bilirubin is 3.1-5 mg/dl: Decrease dose by 75%.
If Bilirubin is >5: Avoid use.
Adverse Effect :
Congestive heart failure, delayed cardiac toxicity (doxorubicin induced cardiomyopathy), hyperpigmentation of nailbeds and dermal crease, onycholysis, nausea and vomiting, phlebosclerosis, facial flushing, secondary acute myeloid leukemia, fever, chills and urticaria.Severe cellulitis, vesication and tissue necrosis will occur if extravasation of doxorubicin occurs during administration.
Interaction :
Actinomycin, mithramycin: Cardiomyopathy.
Mercaptopurine: Increased hepatotoxicity.
Mitomycin: Increased late congestive cardiac failure.
Barbiturates: Increased doxorubicin clearance.
Verapamil: Increased doxorubicin plasma levels, reversal of doxorubicin resistance.
Propranolol: Increased cardiotoxicity.
cyclosporin: Increased doxorubicin plasma levels, modulation of doxorubicin resistance, increased myelotoxicity.
Carbamazepine, phenytoin and sodium valproate: Altered anticonvulsant plasma levels.
Warfarin: increased warfarin effect.
Cimetidine, ranitidine: Increased doxorubicin toxicity.
Interferon-alfa: Altered doxorubicin disposition, doxorubicin dose reduction.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
Serum bilirubin 1.2 to 3 mg/dL: Administer 50% of dose.
Serum bilirubin 3.1 to 5 mg/dL: Administer 25% of dose.
Transaminases 2 to 3 times upper limit of normal (ULN): Administer 75% of dose.
Transaminases >3 times ULN: Administer 50% of dose.
Severe hepatic impairment: Use is contraindicated.