Etoposide
Mechanism :
Etoposide is a semisynthetic derivative of podophyllotoxin used in the treatment of certain neoplastic diseases. Its effect appears to be at the G2 portion of the cell cycle in mammalian cells. It acts by lysis of cells entering mitosis and cells are inhibited from entering prophase. It also acts by the induction of DNA strand breaks by an interaction with DNA topoisomerase II or the formation of free radicals.
Indication :
Contraindications :
Contraindicated in patients who have known hypersensitivity to etoposide or any component of the formulation. Full blood count, renal and hepatic function should be assessed before each course.
Dosing :
Under 3 years:
3.3 mg/kg/day continuous intravenous infusion for 4 days.
Above 3 years:
100 mg/m²/day continuous intravenous infusion for 4 days.
Adverse Effect :
Myelosuppression, anaphylactic-like reactions, nausea and vomiting, transient hypotension following rapid intravenous administration, reversible alopecia, constipation, abdominal pain, asthenia, fatigue, malaise, somnolence, dysphagia, optic neuritis, transient cortical blindness, interstitial pneumonitis/pulmonary fibrosis, fever, seizure.
Interaction :
Warfarin: May lead to increased prothrombin time.
Phenobarbital: May increase etoposide clearance.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 60 | 85% of dose |
| 45-60 | 80% of dose |
| 30-45 | 75% of dose |
| <30 | 50% of dose, based on clinical response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<30 mL/min |
| HD | Not dialysed. Dose as in GFR<30 mL/min |
| HDF/High flux | Not dialysed. Dose as in GFR<30 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in GFR<30 mL/min |
Hepatic Dose :
Dose adjustment in hepatic impairment: Although there are no guidelines available for changing dosage in hepatic impairment, dosage adjustments are recommended.
Hepatic dosage adjustments:
Bilirubin level of 1.5 to 3 mg/dL or AST level greater than 3-times the upper limit of normal (ULN): Decrease etoposide dose by 50%.
Bilirubin level of 3 to 5 mg/dL: Decrease etoposide dose by 75%.
Bilirubin level greater than 5 mg/dL: Avoid use of etoposide till bilirubin level drops below 5 md/dL.