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etoposide (Vepesid, VP-16)

Tradename: VP-16. Indications: - testicular cancer - prostate cancer [6] - lung cancer - stomach cancer - lymphomas (including Hodgkin's disease) - sarcomas - Ewing's sarcoma - rhabdomyosarcoma - Wilm's tumor - acute non-lymphocytic leukemia - acute myeloid leukemia - neuroblastoma - brain tumors - ovarian carcinoma - stem cell transplantation [6] Dosage: 1) 50-120 mg/m2 IV for 3-5 days 2) 50 mg/m2/day PO divided BID for 21 days - round to nearest 50 mg 3) adjustment of dose in renal failure a) creatinine clearance 10-50 mL, give 75% of dose b) < 10 mL/min, give 50% of the dose 4) adjustment of dose in liver failure - total bilirubin 1.5-3 mg/dL, give 50% of dose 5) infuse over 30-60 minutes to reduce risk of hypotension 6) injection may be used for oral administration: a) mix with orange juice, apple juice or lemonade to concentration of 0.4 mg/mL or less b) use within 3 hours Capsule: 50 mg Injection: 20 mg/mL (5 mL, 25 mL) Stability is concentration-dependent: 1) intact vial remains stable for 2 years at room temp 2) 0.2 mg/mL stable for 96 hours; 2 mg/mL stable for 1 hour Pharmacokinetics: 1) oral absorption varies 2) highly protein bound 3) metabolized by liver by cyt P450 3A4 4) eliminated in bile & urine 5) 1/2life is 7-14 hours Adverse effects: 1) common (> 10%) - alopecia (reversible) - myelosuppression - nausea (mild to moderate, more common with oral dose) - mucositis 2) less common (1-10%) - diarrhea, abdominal pain, stomatitis, fatigue, elevated serum transaminases, hypotension (infusion rate related) 3) uncommon (< 1%) - pain at site of injection, anaphylaxis, neuritis, neuropathy, thrombophlebitis, tachycardia, somnolence, fever/chills, headache 4) other - metallic taste - toxic hepatitis with high doses - may cause permanent sterility - acute myeloid leukemia (AML) with t11q23 (MLL) [5] Drug interactions: 1) warfarin: increased prothrombin time (PT) 2) any drug that inhibits cyt P450 3A4 may increase levels of etoposide 3) any drug that induces cyt P450 3A4 may diminish levels of etoposide Mechanism of action: 1) plant alkaloid 2) derivative of podophyllotoxins 3) inhibits DNA synthesis by inhibiting DNA topoisomerase II 4) active G2 & S phase 5) PRMT7 may be involved in etoposide-induced cytotoxicity

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

antimitotic agent; mitotic inhibitor (antineoplastic agent) epipodophyllotoxin

Properties

INHIBITS: topoisomerase MISC-INFO: pregnancy-category D safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
  6. Deprecated Reference