etoposide (Vepesid, VP-16)
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Introduction
Tradename: VP-16.
Indications
- testicular cancer
- prostate cancer[6]
- lung cancer
- stomach cancer
- lymphomas (including Hodgkin's disease)
- sarcomas
- acute non-lymphocytic leukemia
- neuroblastoma
- brain tumors
- ovarian carcinoma
- stem cell transplantation[6]
Dosage
- 50-120 mg/m2 IV for 3-5 days
- 50 mg/m2/day PO divided BID for 21 days
- round to nearest 50 mg
- adjustment of dose in renal failure
- creatinine clearance 10-50 mL, give 75% of dose
- < 10 mL/min, give 50% of the dose
- adjustment of dose in liver failure
- total bilirubin 1.5-3 mg/dL, give 50% of dose
- infuse over 30-60 minutes to reduce risk of hypotension
- injection may be used for oral administration:
- mix with orange juice, apple juice or lemonade to concentration of 0.4 mg/mL or less
- use within 3 hours
Capsule: 50 mg
Injection: 20 mg/mL (5 mL, 25 mL)
Stability is concentration-dependent:
- intact vial remains stable for 2 years at room temp
- 0.2 mg/mL stable for 96 hours; 2 mg/mL stable for 1 hour
Pharmacokinetics
- oral absorption varies
- highly protein bound
- metabolized by liver by cyt P450 3A4
- eliminated in bile & urine
- 1/2life is 7-14 hours
Adverse effects
- common (> 10%)
- alopecia (reversible)
- myelosuppression
- nausea (mild to moderate, more common with oral dose)
- mucositis
- less common (1-10%)
- diarrhea, abdominal pain, stomatitis, fatigue, elevated serum transaminases, hypotension (infusion rate related)
- uncommon (< 1%)
- pain at site of injection, anaphylaxis, neuritis, neuropathy, thrombophlebitis, tachycardia, somnolence, fever/chills, headache
- other
- metallic taste
- toxic hepatitis with high doses
- may cause permanent sterility
- acute myeloid leukemia (AML) with t11q23 (MLL)[5]
Drug interactions
- warfarin: increased prothrombin time (PT)
- any drug that inhibits cyt P450 3A4 may increase levels of etoposide
- any drug that induces cyt P450 3A4 may diminish levels of etoposide
Mechanism of action
- plant alkaloid
- derivative of podophyllotoxins
- inhibits DNA synthesis by inhibiting DNA topoisomerase II
- active G2 & S phase
- PRMT7 may be involved in etoposide-induced cytotoxicity
More general terms
Additional terms
References
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
- ↑ 6.0 6.1 6.2 Deprecated Reference
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=36462
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=439525
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3310
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5284558
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=284997