VEPESID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEPESID (VEPESID).
Topoisomerase II inhibitor; induces DNA strand breaks by stabilizing the topoisomerase II-DNA complex, inhibiting DNA relegation and causing cell cycle arrest at G2 phase.
| Metabolism | Hepatic metabolism via CYP3A4 and glucuronidation; also metabolized by catechol-O-methyltransferase (COMT). |
| Excretion | Renal (45-50% as unchanged drug), biliary/fecal (40-50% as metabolites and unchanged drug). |
| Half-life | Terminal elimination half-life: 4-11 hours (mean 8 hours). Clinically, no dose adjustment for mild renal impairment but caution in severe renal impairment (CrCl <10 mL/min) due to prolonged half-life. |
| Protein binding | 95-97% bound to albumin. |
| Volume of Distribution | 7-17 L/kg (mean 10 L/kg). Large Vd indicates extensive tissue distribution, crossing blood-brain barrier minimally. |
| Bioavailability | Oral: 50% (range 25-75%). IV: 100%. |
| Onset of Action | IV: 5-10 minutes (myelosuppression and antineoplastic effect); oral: 1-2 hours (clinical response may take days). |
| Duration of Action | Myelosuppression: 7-14 days (nadir); antineoplastic effect: variable, typically 2-3 weeks between cycles. |
| Molecular Weight | 588.56 |
50-100 mg/m2 IV once daily on days 1-5, OR 100 mg/m2 IV once daily on days 1, 3, and 5, repeated every 3-4 weeks. Oral dose: 50-100 mg/m2 once daily for 14-21 days, repeated every 4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment. CrCl 15-50 mL/min: reduce dose by 25%. CrCl <15 mL/min: reduce dose by 50%, or consider alternate therapy. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended. |
| Pediatric use | 100-150 mg/m2 IV once daily for 3 days, or 50-75 mg/m2 IV once daily for 5 days, repeated every 3-4 weeks. Oral: 50-100 mg/m2 once daily for 14-21 days. |
| Geriatric use | Start at lower end of dosing range (50 mg/m2 IV daily) due to increased risk of myelosuppression; monitor renal function closely. |
| 1st trimester | Etoposide is teratogenic in animal studies, causing fetal malformations and embryolethality. Human data are limited; however, use in first trimester is contraindicated due to risk of fetal harm. |
| 2nd trimester | Etoposide can cause fetal harm; use only if benefit outweighs risk. Potential risks include low birth weight, preterm birth, and neonatal toxicity. |
| 3rd trimester | Etoposide may cause adverse effects such as neonatal myelosuppression and infection. Avoid use near term due to risk of neonatal hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for VEPESID (VEPESID).
| Placental transfer | Etoposide crosses the placenta in humans; reported cord blood levels are 30-40% of maternal plasma levels. |
| Breastfeeding | Etoposide is excreted in human milk; breastfeeding is not recommended during treatment and for at least 2 weeks after last dose due to potential serious adverse reactions in the nursing infant. |
■ FDA Black Box Warning
Severe myelosuppression with fatal infections and bleeding; risk of secondary acute myeloid leukemia (especially with alkylating agents); hypersensitivity reactions including anaphylaxis; hypotension with rapid infusion.
| Serious Effects |
Hypersensitivity to etoposide or any excipientSevere hepatic impairmentSevere renal impairment (creatinine clearance <10 mL/min)
| Precautions | Monitor complete blood counts due to myelosuppression; risk of secondary leukemia; hypersensitivity reactions (including anaphylaxis); hypotension with rapid administration; renal and hepatic impairment require dose adjustment; extravasation risk. |
| Food/Dietary | No specific food interactions documented. Take oral etoposide on an empty stomach to minimize variability; avoid grapefruit juice as it may affect CYP3A4 metabolism. |
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| Lactation Rating | L5 (Contraindicated) per LactMed |
| Teratogenic Risk | FDA Pregnancy Category D. Etoposide is embryotoxic and teratogenic in animal studies. First trimester: high risk of major malformations, including craniofacial defects, neural tube defects, and skeletal anomalies. Second and third trimesters: risk of intrauterine growth restriction, fetal myelosuppression, and neonatal pancytopenia. Use only if clearly needed and potential benefits outweigh risks. |
| Fetal Monitoring | Complete blood counts (CBC) with differential prior to each dose; monitor for myelosuppression. Fetal growth ultrasound every 4-6 weeks if used in second/third trimester. Assess for fetal anomalies via targeted ultrasound if exposed in first trimester. Monitor liver and renal function tests. Neonatal CBC after delivery. |
| Fertility Effects | Potential for gonadal suppression, azoospermia, and amenorrhea in males and females. Risk of permanent infertility, especially with cumulative doses. Consider fertility preservation options (e.g., sperm or oocyte cryopreservation) prior to treatment. |
| Clinical Pearls | Vepesid (etoposide) is a topoisomerase II inhibitor used in small-cell lung cancer, testicular cancer, and certain lymphomas. Administer IV over 30-60 minutes to avoid hypotension; oral bioavailability is variable (50-75%) and requires dose adjustment. Monitor for myelosuppression (nadir at 7-14 days), anaphylaxis (risk higher with rapid infusion), and secondary leukemia (acute promyelocytic leukemia). Premedicate with antiemetics due to moderate emetic risk. Dose reduction needed in renal impairment (CrCl <50 mL/min). Hypersensitivity reactions may occur with first dose; have resuscitation equipment available. |
| Patient Advice | Take oral capsules on an empty stomach with a full glass of water; do not crush or chew. · Report signs of infection (fever, sore throat), bleeding (easy bruising, black stool), or unusual tiredness. · Avoid pregnancy; use effective contraception during and for at least 6 months after treatment. · Discuss potential hair loss and temporary taste changes. · Do not receive live vaccines during therapy. |