Schedule H

Intravenous, Intravesical (selected indications)

• Injection: 10 mg/5 mL vial (solution for injection)

• Injection: 50 mg/25 mL vial (solution for injection)

• Injection: 10 mg vial (lyophilised powder for reconstitution)

• Injection: 50 mg vial (lyophilised powder for reconstitution)

• Liposomal injection (pegylated): 20 mg/10 mL vial

• Liposomal injection (pegylated): 50 mg/25 mL vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Breast Cancer (AC Regimen, CAF, and Other Combination Protocols) — Adults

Parameter Recommendation

Starting dose 60 mg/m² IV on Day 1 of each cycle

Titration Not applicable

Usual maintenance dose 60 mg/m² IV every 21 days (with cyclophosphamide)

Maximum dose 60 mg/m² per cycle; cumulative lifetime dose 450–550 mg/m²

Duration: 4–6 cycles as per protocol

Clinical Notes:

• Part of AC regimen (with cyclophosphamide) or CAF regimen (with cyclophosphamide, 5-FU)

• Baseline and periodic cardiac monitoring mandatory

• Reduce cumulative dose limit to 400 mg/m² if prior chest radiation or concurrent cardiotoxic therapy

1. Hodgkin Lymphoma (ABVD Regimen) — Adults

Parameter Recommendation

Starting dose 25 mg/m² IV on Days 1 and 15 of each 28-day cycle

Titration Not applicable

Usual maintenance dose 25 mg/m² IV on Days 1 and 15

Maximum dose 50 mg/m² per cycle; cumulative lifetime dose applies

Duration: 6–8 cycles as per staging and response

Clinical Notes:

• Part of ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine)

• Monitor CBC before each dose; delay cycle if significant neutropenia

1. Non-Hodgkin Lymphoma (CHOP Regimen) — Adults

Parameter Recommendation

Starting dose 50 mg/m² IV on Day 1 of each 21-day cycle

Titration Not applicable

Usual maintenance dose 50 mg/m² IV every 21 days

Maximum dose 50 mg/m² per cycle; cumulative lifetime dose 450–550 mg/m²

Duration: 6–8 cycles

Clinical Notes:

• Part of CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisolone)

• R-CHOP (with rituximab) for CD20+ B-cell lymphomas

1. Acute Leukaemias (ALL/AML — Induction Protocols) — Adults

Parameter Recommendation

Starting dose 25–45 mg/m²/day IV for 2–3 consecutive days

Titration Not applicable

Usual maintenance dose Protocol-specific; varies by regimen

Maximum dose 45 mg/m²/day; cumulative lifetime dose applies

Duration: Per induction protocol (typically 1–2 induction cycles)

Clinical Notes:

• Part of multi-agent induction chemotherapy (e.g., 7+3 regimen for AML)

• Intensive myelosuppression expected — ensure supportive care

1. Ovarian Cancer (Combination Regimens) — Adults

Parameter Recommendation

Starting dose 40–60 mg/m² IV every 21–28 days

Titration Not applicable

Usual maintenance dose 50 mg/m² IV per cycle

Maximum dose 60 mg/m² per cycle; cumulative lifetime dose 450–550 mg/m²

Duration: 6 cycles typically

Clinical Notes:

• Liposomal doxorubicin (pegylated) preferred for platinum-resistant/refractory disease

• Liposomal formulation: 40–50 mg/m² IV every 28 days

1. AIDS-Related Kaposi Sarcoma — Adults

Liposomal Doxorubicin (Pegylated):

Parameter Recommendation

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Acute Lymphoblastic Leukaemia (ALL) — Paediatric Induction/Intensification

Parameter Recommendation

Starting dose 25–30 mg/m² IV (protocol-specific)

Titration Not applicable

Usual maintenance dose 25–30 mg/m² IV per dose as per protocol schedule

Maximum dose 45 mg/m² per dose; cumulative lifetime dose 300–450 mg/m²

Clinical Notes:

• Part of multi-agent induction (e.g., BFM, MCP-841 protocols)

• Paediatric oncology supervision mandatory

1. Wilms Tumour (Nephroblastoma)

Parameter Recommendation

Starting dose 45 mg/m² IV on Day 1

Titration Not applicable

Usual maintenance dose 45 mg/m² IV every 21 days

Maximum dose 45 mg/m² per dose

Duration: As per SIOP or COG protocol (typically 4–6 cycles depending on stage)

Clinical Notes:

• Given with dactinomycin and vincristine

• Dose modifications for hepatic dysfunction

1. Ewing Sarcoma / Osteosarcoma

Parameter Recommendation

Starting dose 25–37.5 mg/m²/day IV for 2–3 consecutive days per cycle

Titration Not applicable

Usual maintenance dose Protocol-specific (total per cycle: 50–75 mg/m²)

Maximum dose Cumulative lifetime dose 375–450 mg/m²

Duration: 12–18 weeks of neoadjuvant/adjuvant therapy

1. Neuroblastoma

Parameter Recommendation

Starting dose 30–40 mg/m² IV per cycle

Titration Not applicable

Usual maintenance dose Protocol-specific

Maximum dose Cumulative lifetime dose limits apply

Safety Monitoring (All Paediatric Indications):

• Baseline and periodic echocardiography (LVEF, shortening fraction)

• CBC with differential before each cycle

• Liver function tests

• Strict vesicant precautions — central line preferred

• Growth and developmental monitoring long-term

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

Hepatoblastoma 30 mg/m² IV as part of PLADO regimen Per protocol OFF-LABEL • Specialist only

Rhabdomyosarcoma 30 mg/m² IV per cycle Per IRS/COG protocols OFF-LABEL • Specialist only

Age Restrictions:

• No absolute minimum age — used in infants for specific malignancies

• All paediatric use must be under specialist paediatric oncology supervision with appropriate protocols

• Cumulative dose limits lower in children due to lifelong cardiac risk

Notes:

• Primary elimination is hepatobiliary; renal impairment has minimal direct impact

• Monitor for enhanced toxicity if concurrent hepatic impairment

Doxorubicin is primarily metabolised and excreted via the hepatobiliary system — dose reduction essential in hepatic impairment

Serum Bilirubin Dose Recommendation

1.2–3.0 mg/dL Reduce dose to 50% of standard

3.1–5.0 mg/dL Reduce dose to 25% of standard

5.0 mg/dL Avoid use; if essential, use ≤25% dose under specialist supervision

AST Elevation Dose Recommendation

2–3× ULN Consider 25–50% dose reduction

3× ULN Avoid or use with extreme caution

• Known hypersensitivity to doxorubicin or other anthracyclines

• Severe myocardial insufficiency or decompensated heart failure (NYHA Class IV)

• Recent myocardial infarction (within 6 months)

• Severe persistent myelosuppression from prior therapy

• Cumulative lifetime dose already reached (≥550 mg/m² conventional; ≥900 mg/m² liposomal)

• Severe hepatic impairment (bilirubin >5 mg/dL) — relative contraindication

• Active severe infection with haemodynamic compromise

• Pre-existing cardiac disease or borderline LVEF — baseline echocardiography mandatory

• Prior anthracycline exposure — calculate cumulative lifetime dose carefully

• Prior or concurrent mediastinal/cardiac radiation — increased cardiotoxicity risk; lower cumulative threshold

• Active infection — treat before initiating chemotherapy

• Concurrent use of other cardiotoxic agents (trastuzumab, cyclophosphamide)

• Extravasation risk — severe vesicant; use central venous access where feasible

• Elderly patients — enhanced susceptibility to cardiotoxicity and myelosuppression

• Hepatic impairment — dose reduction essential

• Concurrent live vaccine administration — avoid

Parameter Information

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

Overall Safety Avoid during first trimester; may be considered in 2nd/3rd trimester for life-threatening malignancy

Preferred Alternatives No safer alternative for most indications; delay treatment if clinically feasible

When May Be Used Life-threatening malignancy requiring immediate treatment — joint oncology-perinatology decision with documented informed consent

Monitoring Detailed fetal anomaly scan; fetal echocardiography if exposed; fetal growth surveillance; amniotic fluid assessment

Parameter Information

Compatibility Contraindicated — do not breastfeed during treatment

Expected Milk Levels Doxorubicin excreted in breast milk; potentially harmful to infant

Preferred Alternatives None — breastfeeding must be discontinued

Decision Stop breastfeeding during therapy and for at least 7–10 days after last dose

Infant Monitoring Not applicable — exposure must be avoided

Parameter Recommendation

Starting dose Lower end of dose range (e.g., 40–50 mg/m²)

Titration Not applicable

Special considerations Significantly increased cardiotoxicity risk; lower cumulative dose threshold recommended (≤400 mg/m²)

Extra monitoring Baseline and frequent echocardiography; renal and hepatic function assessment

Risk factors Reduced cardiac reserve; age-related decline in hepatic function; polypharmacy; myelosuppression more pronounced

Interacting Drug Effect & Mechanism Management

Trastuzumab Synergistic cardiotoxicity; increased risk of heart failure Avoid concurrent administration; separate by at least 7 weeks if sequential; monitor LVEF closely

Paclitaxel Increased doxorubicin levels and toxicity (altered hepatic clearance) Administer doxorubicin before paclitaxel; monitor for enhanced myelosuppression

Cyclophosphamide Additive cardiotoxicity and myelosuppression Standard combination in AC regimen but requires careful dose modification and cardiac monitoring

Verapamil Inhibits P-glycoprotein efflux; increases doxorubicin levels and cardiotoxicity Avoid combination if possible; if essential, monitor closely

Ciclosporin Increases doxorubicin AUC; enhanced toxicity Avoid or reduce doxorubicin dose

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) May increase doxorubicin exposure Monitor for toxicity; consider dose adjustment

Interacting Drug Effect Management

Phenytoin, Phenobarbital Enzyme induction may reduce doxorubicin efficacy Monitor treatment response; avoid if possible

Digoxin Doxorubicin-induced mucositis may reduce digoxin absorption Monitor digoxin levels

Warfarin Variable effect on INR due to altered hepatic function Monitor INR frequently during chemotherapy

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

6-Mercaptopurine Increased hepatotoxicity risk Monitor LFTs closely

Radiation therapy Enhanced local toxicity ("radiation recall") Avoid concurrent administration to same site if possible

• Myelosuppression (neutropenia, thrombocytopenia, anaemia) — nadir typically 10–14 days

• Nausea and vomiting (moderately-high emetogenic potential)

• Alopecia (near-universal; reversible)

• Mucositis and stomatitis

• Red/orange discolouration of urine (benign; warn patients)

• Skin hyperpigmentation (especially over veins, nail beds)

• Fatigue

• Diarrhoea

• Anorexia

Adverse Effect Clinical Action

Cardiotoxicity — acute (arrhythmias, ECG changes, pericarditis-myocarditis) Monitor; usually reversible; supportive care

Cardiotoxicity — chronic/delayed (cardiomyopathy, heart failure, reduced LVEF) Irreversible; discontinue permanently; cardiology referral; cumulative dose-related

Extravasation necrosis Immediate discontinuation; dexrazoxane antidote if available; cold compresses; surgical consultation for severe cases

Severe neutropenic sepsis Hospitalisation; broad-spectrum antibiotics; G-CSF support

Secondary malignancies (AML, MDS) Long-term surveillance; especially with alkylating agents

Tumour lysis syndrome Hydration; urate-lowering therapy; monitor electrolytes

Severe hepatotoxicity Discontinue; supportive care

Before each cycle CBC with differential, LFTs, clinical cardiac assessment

Cardiac monitoring LVEF assessment every 3 cycles or earlier if symptoms; mandatory if cumulative dose approaching limits

During infusion Monitor infusion site for extravasation; vital signs

Long-term (survivors) Annual cardiac assessment for childhood cancer survivors; lifelong surveillance for late cardiotoxicity

Conventional Doxorubicin:

• Adriamycin (Pfizer)

• Adrim (Fresenius Kabi)

• Doxorubicin (Cipla, Zydus, Neon)

• Doxorubin (Biochem)

• Cadria (Cadila)

• Oncodox (United Biotech)

Liposomal Doxorubicin (Pegylated):

• Lipodox (Sun Pharma)

• Caelyx (Janssen) — limited availability

• Pegadria (Intas)

FDCs: Not applicable

Note: Conventional doxorubicin included in NLEM 2022; prices may be NPPA-controlled. Liposomal formulations not under NLEM; significant price variation. Available in government cancer centres under national programmes.

• Cumulative dose tracking is critical — cardiotoxicity risk increases sharply beyond 450 mg/m²; maintain lifetime dose records accessible across institutions

• Red urine is expected and harmless — warn patients proactively to prevent unnecessary alarm; lasts 1–2 days post-dose

• Vesicant precautions are non-negotiable — preferentially use central venous access; if peripheral, verify patency before and during infusion; have dexrazoxane available for extravasation management

• Liposomal formulation reduces cardiotoxicity — consider for patients with pre-existing cardiac disease, prior anthracycline exposure, or when higher cumulative doses anticipated; cost is limiting factor

• Pre-medication for emesis is essential — doxorubicin is moderately-highly emetogenic; use 5-HT3 antagonist + dexamethasone ± NK1 antagonist

• Cardiac surveillance extends beyond treatment — childhood cancer survivors require lifelong cardiac follow-up for late-onset cardiomyopathy

Doxorubicin; anthracycline; oncology; breast cancer; lymphoma; CHOP; ABVD; cardiotoxicity; vesicant; extravasation; cumulative dose limit; liposomal; NLEM India; myelosuppression

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022

• ICMR Guidelines — Breast Cancer Management; Paediatric ALL

• AIIMS Chemotherapy Protocols

• API Textbook of Medicine, 11th Edition

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Paediatric Oncology Guidelines

• Tata Memorial Centre Chemotherapy Protocols

• WHO Model List of Essential Medicines