Schedule H

Intravenous, Oral

• Injection: 50 mg/2.5 mL vial (concentrate for IV infusion)

• Injection: 100 mg/5 mL vial (concentrate for IV infusion)

• Capsules: 50 mg

• Capsules: 100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Small Cell Lung Cancer (SCLC) — Adults

(Combined with cisplatin or carboplatin — EP/EC regimen)

Intravenous Administration:

Parameter Recommendation

Starting dose 100 mg/m² IV on Days 1–3 of each 21-day cycle

Titration Not applicable

Usual maintenance dose 100 mg/m² IV daily × 3 days every 21 days

Maximum dose 100 mg/m²/day; adjust for myelosuppression

Oral Administration (Alternative):

Parameter Recommendation

Starting dose 200 mg/m² orally daily × 5 days (double IV dose due to ~50% bioavailability)

Titration Not applicable

Usual maintenance dose 200 mg/m² orally daily × 5 days every 21 days

Maximum dose 200 mg/m²/day orally

Duration: 4–6 cycles

Clinical Notes:

• Infuse IV over minimum 30–60 minutes to avoid hypotension

• Oral bioavailability approximately 50% — hence double dose compared to IV

• May divide oral daily dose into two doses if GI tolerance poor

• Moderate emetogenic potential — antiemetic prophylaxis required

1. Testicular Germ Cell Tumours — Adults

(Part of BEP regimen: Bleomycin, Etoposide, Cisplatin)

Parameter Recommendation

Starting dose 100 mg/m² IV on Days 1–5 of each 21-day cycle

Titration Not applicable

Usual maintenance dose 100 mg/m² IV daily × 5 days every 21 days

Maximum dose 100 mg/m²/day

Duration: 3–4 cycles (good-risk); 4 cycles (intermediate/poor-risk)

Clinical Notes:

• Administer with cisplatin 20 mg/m²/day Days 1–5 and bleomycin 30 units weekly

• Monitor cumulative bleomycin dose for pulmonary toxicity

• Assess tumour markers (AFP, β-hCG) for response

1. Refractory/Relapsed Non-Hodgkin Lymphoma and Hodgkin Lymphoma — Adults

(Part of salvage regimens: ESHAP, ICE, DHAP)

Parameter Recommendation

Starting dose 40–100 mg/m² IV on Days 1–4 (regimen-dependent)

Titration Not applicable

Usual maintenance dose Per specific salvage protocol

Maximum dose 200 mg/m²/day in some intensified regimens

Duration: 2–4 cycles before stem cell transplant evaluation

Clinical Notes:

• ESHAP: Etoposide 40–60 mg/m² IV Days 1–4 with methylprednisolone, cytarabine, cisplatin

• ICE: Etoposide 100 mg/m² IV Days 1–3 with ifosfamide, carboplatin

• Requires intensive haematological monitoring

1. Acute Myeloid Leukaemia (AML) — Induction/Re-induction — Adults

Parameter Recommendation

Starting dose 100 mg/m² IV on Days 1–3 or 1–5 (protocol-dependent)

Titration Not applicable

Usual maintenance dose Per induction protocol (MEC, FLAG-IDA, etc.)

Maximum dose 100 mg/m²/day typically

Duration: Per institutional AML protocol

Clinical Notes:

• MEC regimen: Etoposide with mitoxantrone and cytarabine

• Specialist haemato-oncology supervision mandatory

• Prolonged myelosuppression expected

Secondary Indications — Adults (Off-label)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Neuroblastoma

Parameter Recommendation

Starting dose 100–150 mg/m² IV on Days 1–3 or 1–5 per protocol

Titration Not applicable

Usual maintenance dose 100–150 mg/m²/day × 3–5 days per cycle

Maximum dose 150 mg/m²/day

Cycle frequency: Every 21–28 days as per induction protocol

Clinical Notes:

• Part of multi-agent protocols (e.g., COJEC, N5 rapid induction)

• Combined with cisplatin, cyclophosphamide, vincristine, doxorubicin

1. Ewing Sarcoma / Primitive Neuroectodermal Tumour (PNET)

Parameter Recommendation

Starting dose 100 mg/m² IV on Days 1–5

Titration Not applicable

Usual maintenance dose 100 mg/m²/day × 5 days alternating cycles

Maximum dose 100 mg/m²/day

Cycle frequency: Every 21 days (VDC/IE alternating regimen)

Clinical Notes:

• Part of VDC/IE regimen (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide)

• Intensive myelosuppression expected

1. Wilms Tumour (Nephroblastoma) — High-Risk/Relapsed

Parameter Recommendation

Starting dose 100–150 mg/m² IV on Days 1–3

Titration Not applicable

Usual maintenance dose Per SIOP/COG salvage protocols

Maximum dose 150 mg/m²/day

Clinical Notes:

• Used in high-risk histology or relapsed disease

• Combined with carboplatin, ifosfamide (ICE regimen)

1. Paediatric Acute Myeloid Leukaemia

Parameter Recommendation

Starting dose 100–150 mg/m² IV on Days 1–3 or 1–5

Titration Not applicable

Usual maintenance dose Per institutional AML protocol

Maximum dose 150 mg/m²/day

Clinical Notes:

• Part of ADE or MRC-based induction protocols

• Intensified consolidation may use higher cumulative doses

1. Retinoblastoma (Intravenous Chemoreduction)

Parameter Recommendation

Starting dose 150 mg/m² IV on Day 1

Titration Not applicable

Usual maintenance dose 150 mg/m² IV every 21–28 days

Maximum dose 150 mg/m² per cycle

Duration: 6 cycles typically (VEC regimen)

Clinical Notes:

• Part of VEC regimen with vincristine and carboplatin

• NPCB protocol for retinoblastoma chemoreduction

Safety Monitoring (All Paediatric Indications):

• CBC with differential before each cycle and at nadir (Days 10–14)

• Serum creatinine and LFTs before each cycle

• Monitor for infection during neutropenic period

• Blood pressure during IV infusion

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

CrCl (mL/min) Dose Recommendation

50 Full dose (100%)

15–50 Reduce dose by 25% (give 75% of calculated dose)

<15 Reduce dose by 50% (give 50% of calculated dose)

Haemodialysis:

• Etoposide is not significantly dialysed (high protein binding ~94%)

• Administer after dialysis session

• Reduce dose by 50%; monitor toxicity closely

Peritoneal Dialysis:

• Limited data — reduce dose by 50%; specialist supervision recommended

Note: Etoposide is hepatically metabolised (CYP3A4) — impaired metabolism leads to increased toxicity.

• Known hypersensitivity to etoposide or polysorbate 80 (excipient in IV formulation)

• Severe pre-existing myelosuppression (ANC <500/mm³ or platelets <50,000/mm³) unless life-threatening malignancy

• Severe uncontrolled active infection

• Severe hepatic impairment (bilirubin >3× ULN) — relative contraindication

• Pre-existing myelosuppression — dose-limiting toxicity; delay cycle if counts not recovered

• Renal impairment — dose reduction required

• Hepatic impairment — increased toxicity risk

• Elderly patients — reduced bone marrow reserve

• Concurrent radiation therapy — enhanced myelosuppression

• Previous extensive chemotherapy — cumulative marrow damage

• History of hypersensitivity reactions to chemotherapy

• Low serum albumin — increased free drug fraction and toxicity risk

• Rapid IV infusion — hypotension risk; infuse over ≥30–60 minutes

Parameter Information

Risk Category Category D — documented fetal harm; teratogenic and embryotoxic

Overall Safety Avoid during pregnancy, especially first trimester

Preferred Alternatives Delay chemotherapy until after delivery if clinically feasible

When May Be Used Life-threatening malignancy in 2nd/3rd trimester where no alternative exists — joint oncology-perinatology decision with documented informed consent

Monitoring Detailed fetal anomaly scan; fetal growth surveillance; neonatal CBC after delivery

Parameter Information

Compatibility Contraindicated — breastfeeding must be stopped

Expected Milk Levels Unknown; presumed significant due to cytotoxicity

Preferred Alternatives None — breastfeeding must be discontinued

Decision Stop breastfeeding during therapy and for at least 1 week after last dose

Infant Monitoring Not applicable — exposure must be avoided

Parameter Recommendation

Starting dose Lower end of dose range (80–100 mg/m²/day)

Titration Not applicable

Special considerations Age-related decline in renal and hepatic function; calculate CrCl before dosing

Extra monitoring CBC more frequently; renal function before each cycle

Risk factors Increased susceptibility to myelosuppression; slower marrow recovery; higher infection risk; polypharmacy

Interacting Drug Effect & Mechanism Management

Cyclosporine Increases etoposide AUC by 50–80% (P-glycoprotein inhibition) — enhanced toxicity Reduce etoposide dose by 50% if concurrent use essential; monitor for severe myelosuppression

Cisplatin Decreases etoposide renal clearance; enhanced myelosuppression Standard combination — but monitor CBC closely; sequence matters

Strong CYP3A4 inducers (phenytoin, carbamazepine, phenobarbital, rifampicin) Reduced etoposide levels — decreased efficacy Avoid concurrent use if possible; if essential, consider dose increase with close monitoring

Warfarin Enhanced anticoagulant effect — bleeding risk Monitor INR frequently; anticipate warfarin dose reduction

Live vaccines Risk of disseminated infection due to immunosuppression Avoid live vaccines during and for 3–6 months after treatment

Interacting Drug Effect Management

Moderate CYP3A4 inhibitors (fluconazole, erythromycin) Increased etoposide levels Monitor for toxicity; may need dose reduction

Amphotericin B Additive nephrotoxicity (affects etoposide clearance) Monitor renal function; adjust etoposide dose if CrCl declines

Fluoroquinolones Additive myelosuppression Monitor CBC closely

Antiepileptics (valproate) Possible altered etoposide metabolism Monitor for efficacy and toxicity

Grapefruit juice May increase oral etoposide absorption Avoid grapefruit during oral etoposide therapy

Other myelosuppressive agents Additive bone marrow toxicity Standard in combination protocols — adjust doses per protocol and monitor CBC

• Myelosuppression (neutropenia, leukopenia, thrombocytopenia, anaemia) — dose-limiting; nadir Days 10–14

• Nausea and vomiting (moderate emetogenic potential)

• Alopecia (common, reversible)

• Mucositis and stomatitis

• Anorexia

• Diarrhoea or constipation

• Fatigue

• Fever (may be non-infectious)

• Transient hypotension (during IV infusion if too rapid)

Adverse Effect Clinical Action

Severe myelosuppression with febrile neutropenia Hospitalisation; broad-spectrum antibiotics; G-CSF support; delay next cycle

Anaphylaxis / Severe hypersensitivity (to polysorbate 80) Immediate discontinuation; resuscitation; do not rechallenge

Severe hypotension (rapid IV infusion) Stop infusion; fluid resuscitation; restart at slower rate

Secondary acute myeloid leukaemia / Myelodysplastic syndrome Typically occurs years after therapy; haematology referral

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (rare) Immediate discontinuation; dermatology/ICU referral

Hepatotoxicity (transaminase elevation, cholestasis) Monitor LFTs; dose adjustment or discontinuation

Tumour lysis syndrome Prophylactic hydration and allopurinol/rasburicase in high tumour burden

Before each cycle CBC with differential (ANC ≥1500/mm³, platelets ≥100,000/mm³ for full dose); renal and hepatic function

During cycle CBC at nadir (Days 10–14); blood pressure monitoring during IV infusion

If neutropenic Daily temperature monitoring; assess for signs of infection

Long-term Monitor for signs of secondary malignancy (MDS/AML) if prolonged or repeated courses (>6 cycles)

• Posid (Intas)

• Eposide (Cipla)

• Lastet (Nippon Kayaku/Zydus)

• Etoposide (Dr. Reddy's)

• Etosid (Alkem)

• Oncotecan (RPG Life Sciences)

• Etoford (Neon)

• VP-16 (Generic — multiple manufacturers)

• Etoposide IP (Fresenius Kabi, Celon Labs)

FDCs: Not applicable

Note: Included in NLEM 2022 (injection form); prices may be NPPA-controlled. Available in government cancer centres under national cancer programmes. Significant price variation between brands.

• IV infusion rate is critical — infuse over minimum 30–60 minutes to avoid hypotension; monitor blood pressure during infusion

• Oral bioavailability is ~50% — when converting from IV to oral, double the dose; oral absorption is variable, so IV preferred for critical disease

• Myelosuppression is dose-limiting — nadir typically at Days 10–14; ensure adequate count recovery (ANC >1500, platelets >100,000) before next cycle

• Secondary leukaemia risk — topoisomerase II inhibitors associated with therapy-related AML/MDS, typically presenting 2–5 years after treatment; patients receiving multiple cycles require long-term surveillance

• Hypersensitivity reactions may occur — often related to polysorbate 80 excipient; premedication may be considered in patients with history of reactions to polysorbate-containing drugs

• Always use in combination protocols — etoposide is rarely used as monotherapy; efficacy depends on synergistic combinations

Etoposide; VP-16; topoisomerase II inhibitor; antineoplastic; small cell lung cancer; testicular cancer; BEP regimen; germ cell tumour; paediatric oncology; myelosuppression; secondary leukaemia; NLEM India

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022

• ICMR Guidelines — Management of Lung Cancer

• AIIMS Oncology Protocols

• Tata Memorial Centre Chemotherapy Protocols

• National Cancer Grid India — Chemotherapy Protocol Compendium

• National Programme for Control of Blindness (NPCB) — Retinoblastoma Protocols

• IAP Paediatric Oncology Guidelines

• API Textbook of Medicine, 11th Edition

• Harrison's Principles of Internal Medicine, 21st Edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition

• RCT/meta-analysis for off-label Kaposi sarcoma indication