Schedule H

Intravenous

• Injection: 1 mg/mL solution (10 mL vial — 10 mg)

• Injection: 1 mg/mL solution (50 mL vial — 50 mg)

• Injection: 1 mg/mL solution (100 mL vial — 100 mg)

• Lyophilised powder for reconstitution: 10 mg vial

• Lyophilised powder for reconstitution: 50 mg vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Metastatic Testicular Cancer (BEP Regimen) — Adults

Parameter Recommendation

Starting dose 20 mg/m² IV daily on Days 1–5 of each 21-day cycle

Titration Not applicable

Usual maintenance dose 20 mg/m²/day × 5 days per cycle

Maximum dose 100 mg/m² per cycle; cumulative lifetime dose <400 mg/m²

Duration: 3–4 cycles

Clinical Notes:

• Part of BEP regimen (bleomycin, etoposide, cisplatin)

• Mandatory aggressive pre- and post-hydration (minimum 1–2 L NS with electrolyte supplementation)

• Triple antiemetic prophylaxis essential (5-HT3 antagonist + dexamethasone + NK1 antagonist)

1. Advanced Ovarian Cancer — Adults

Combination Therapy:

Parameter Recommendation

Starting dose 75–100 mg/m² IV on Day 1

Titration Not applicable

Usual maintenance dose 75–100 mg/m² IV every 21 days

Maximum dose 100 mg/m² per cycle

Monotherapy:

Parameter Recommendation

Starting dose 100 mg/m² IV on Day 1

Titration Not applicable

Usual maintenance dose 100 mg/m² IV every 28 days

Maximum dose 100 mg/m² per cycle

Duration: 6 cycles typically

Clinical Notes:

• Commonly combined with paclitaxel or cyclophosphamide

• Consider carboplatin if renal function borderline or in elderly

1. Advanced Bladder Cancer (Urothelial Carcinoma) — Adults

Parameter Recommendation

Starting dose 70 mg/m² IV on Day 1

Titration Not applicable

Usual maintenance dose 70 mg/m² IV every 21–28 days

Maximum dose 100 mg/m² per cycle

Duration: 4–6 cycles

Clinical Notes:

• Part of GC regimen (gemcitabine + cisplatin) or MVAC (methotrexate, vinblastine, doxorubicin, cisplatin)

• Cisplatin eligibility criteria: CrCl ≥60 mL/min, ECOG PS 0–1, no significant comorbidities

1. Head and Neck Squamous Cell Carcinoma — Concurrent Chemoradiation — Adults

High-Dose Regimen (Standard):

Parameter Recommendation

Starting dose 100 mg/m² IV on Day 1 of radiation

Titration Not applicable

Usual maintenance dose 100 mg/m² IV on Days 1, 22, and 43 during radiotherapy

Maximum dose 100 mg/m² per dose; 300 mg/m² total during radiation

Weekly Regimen (Alternative):

Parameter Recommendation

Starting dose 30–40 mg/m² IV weekly

Titration Not applicable

Usual maintenance dose 40 mg/m² IV weekly × 6–7 weeks during radiotherapy

Maximum dose 40 mg/m² per week

Clinical Notes:

• High-dose regimen preferred for definitive chemoradiation

• Weekly regimen used if high-dose not tolerable

• Intensive supportive care required — mucositis, dehydration, nephrotoxicity common

Secondary Indications — Adults (Off-label)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Germ Cell Tumours (Testicular, Ovarian, Extragonadal)

Parameter Recommendation

Starting dose 20 mg/m²/day IV for 5 consecutive days

Titration Not applicable

Usual maintenance dose 20 mg/m²/day × 5 days per cycle (100 mg/m² per cycle)

Maximum dose 100 mg/m² per cycle

Cycle frequency: Every 21 days

1. Osteosarcoma (Adjuvant/Neoadjuvant Protocols)

Parameter Recommendation

Starting dose 60 mg/m² IV on Day 1 OR 100–120 mg/m² IV with dose fractionation

Titration Not applicable

Usual maintenance dose Protocol-specific (60–120 mg/m² per cycle)

Maximum dose 120 mg/m² per cycle

Clinical Notes:

• Given with doxorubicin and high-dose methotrexate in MAP protocol

• Intensive hydration and electrolyte monitoring mandatory

1. Neuroblastoma (High-Risk Protocols)

Parameter Recommendation

Starting dose 50 mg/m² IV on Day 1 OR 25 mg/m²/day × 4 days

Titration Not applicable

Usual maintenance dose 50–100 mg/m² per cycle

Maximum dose Protocol-specific

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

1. Hepatoblastoma (PLADO/SIOPEL Protocols)

Parameter Recommendation

Starting dose 80 mg/m² IV continuous infusion over 24 hours

Titration Not applicable

Usual maintenance dose 80 mg/m² per cycle

Maximum dose 80 mg/m² per cycle

Cycle frequency: Every 14–21 days

Safety Monitoring (All Paediatric Indications):

• Baseline audiometry — mandatory before first cycle

• Repeat audiometry every 2–3 cycles or at first symptom

• Serum creatinine and electrolytes (Mg²⁺, K⁺, Ca²⁺) before every dose

• CBC with differential before each cycle

• 24-hour urine creatinine clearance if renal function declining

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

Medulloblastoma (Post-operative Chemotherapy) 75 mg/m² IV per cycle Protocol-specific OFF-LABEL • Specialist only • Part of multi-agent CNS tumour protocols • Paediatric neuro-oncology supervision

Ewing Sarcoma 100 mg/m² IV per cycle (fractionated) Per protocol OFF-LABEL • Specialist only • VDC/IE alternating regimen

Age Restrictions:

• Not recommended in infants <6 months except under specialist paediatric oncology protocols

• Ototoxicity risk is significantly higher in young children — vigilant audiological monitoring essential

• All paediatric use requires institutional paediatric oncology supervision

CrCl (mL/min) Dose Recommendation

≥60 Full dose with standard hydration

46–59 Consider 25% dose reduction OR switch to carboplatin

30–45 Reduce dose by 50% OR switch to carboplatin (preferred)

<30 Avoid cisplatin — use carboplatin if platinum indicated

Haemodialysis: Cisplatin is not effectively dialysable (high protein binding, large volume of distribution). Avoid use in dialysis patients.

Notes:

• Calculate CrCl before every cycle

• Cumulative nephrotoxicity — monitor for progressive decline

• Aggressive hydration (pre- and post-infusion) reduces nephrotoxicity risk

Note: Cisplatin is not primarily hepatically metabolised — hepatic impairment is less critical than renal impairment.

• Known hypersensitivity to cisplatin or other platinum compounds

• Severe renal impairment (CrCl <30 mL/min)

• Pre-existing significant sensorineural hearing loss (unless treatment is potentially curative and no alternative)

• Severe pre-existing myelosuppression (ANC <1500/mm³ or platelets <100,000/mm³ at baseline)

• Dehydrated patients unable to receive adequate pre-hydration

• Active severe infection with haemodynamic compromise

• Pre-existing renal dysfunction (CrCl 30–60 mL/min) — dose modification or consider carboplatin

• Pre-existing hearing impairment or tinnitus — baseline audiometry mandatory

• Prior platinum-based chemotherapy — cumulative toxicity risk

• Concurrent or recent use of other nephrotoxic agents (aminoglycosides, NSAIDs, vancomycin)

• Concurrent or recent use of other ototoxic agents (aminoglycosides, loop diuretics)

• Elderly patients with reduced functional reserve

• Pre-existing peripheral neuropathy

• High tumour burden — tumour lysis syndrome risk

• Inadequate venous access for hydration protocols

Parameter Information

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

Overall Safety Avoid during pregnancy, especially first trimester

Preferred Alternatives No safer platinum alternative; delay treatment if feasible; non-platinum regimens if available

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; amniotic fluid assessment; neonatal audiology post-delivery

Parameter Information

Compatibility Contraindicated — do not breastfeed during treatment

Expected Milk Levels Unknown; presumed significant due to low molecular weight and cytotoxicity

Preferred Alternatives None — breastfeeding must be discontinued

Decision Stop breastfeeding during therapy and for at least 14 days after last dose

Infant Monitoring Not applicable — exposure must be avoided

Parameter Recommendation

Starting dose Lower end of dose range (e.g., 60–75 mg/m²); consider carboplatin as alternative

Titration Not applicable

Special considerations Age-related decline in renal function — calculate CrCl (Cockcroft-Gault) before every cycle

Extra monitoring Baseline and serial audiometry; electrolytes; renal function before each dose

Risk factors Enhanced susceptibility to nephrotoxicity, ototoxicity, neurotoxicity, and myelosuppression; polypharmacy; dehydration risk

Interacting Drug Effect & Mechanism Management

Aminoglycosides (amikacin, gentamicin, tobramycin) Synergistic nephrotoxicity and ototoxicity Avoid combination; if essential, monitor renal function and audiometry intensively

Loop diuretics (furosemide) Increased ototoxicity risk Avoid concurrent use unless clinically essential; use alternative diuretics for hydration management

Vancomycin Additive nephrotoxicity Avoid if possible; monitor renal function closely

Paclitaxel Sequence-dependent toxicity — cisplatin before paclitaxel reduces paclitaxel clearance Administer paclitaxel before cisplatin when used in combination

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

Amphotericin B Additive nephrotoxicity Avoid concurrent use if possible; if essential, use liposomal formulation and monitor closely

Interacting Drug Effect Management

Phenytoin Reduced phenytoin absorption/levels; seizure risk Monitor phenytoin levels; adjust dose as needed

NSAIDs Increased nephrotoxicity Avoid concurrent use during cisplatin cycles; use paracetamol for analgesia

Methotrexate Additive myelosuppression and nephrotoxicity Monitor CBC and renal function; ensure adequate methotrexate clearance before cisplatin

Taxanes (docetaxel) Additive myelosuppression and neurotoxicity Monitor peripheral neuropathy; dose modification if severe

5-HT3 antagonists (ondansetron, granisetron) QT prolongation risk (additive with cisplatin-induced hypomagnesaemia) Monitor ECG in high-risk patients; correct electrolyte abnormalities

Ifosfamide Additive nephrotoxicity Ensure adequate hydration; monitor renal function

• Nausea and vomiting (near-universal without prophylaxis — highly emetogenic)

• Nephrotoxicity (dose-related; prevented by hydration)

• Electrolyte disturbances (hypomagnesaemia, hypokalaemia, hypocalcaemia)

• Myelosuppression (leukopenia, thrombocytopenia — nadir Days 14–21)

• Ototoxicity (high-frequency hearing loss, tinnitus)

• Peripheral neuropathy (cumulative; sensory predominant)

• Anorexia and taste alterations

• Fatigue

• Alopecia (mild compared to other agents)

Adverse Effect Clinical Action

Severe nephrotoxicity (acute kidney injury, chronic renal impairment) Hold therapy; aggressive hydration; consider switch to carboplatin for subsequent cycles

Irreversible ototoxicity (permanent sensorineural hearing loss) Discontinue cisplatin; audiological rehabilitation; switch to carboplatin if further platinum indicated

Severe anaphylaxis/hypersensitivity (especially on repeat exposure) Immediate discontinuation; resuscitation; avoid rechallenge; consider desensitisation protocols only in specialised centres

Febrile neutropenia Hospitalisation; broad-spectrum antibiotics; G-CSF support

Severe hypomagnesaemia (with tetany, arrhythmias) IV magnesium replacement; cardiac monitoring

Posterior reversible encephalopathy syndrome (PRES) Discontinue; supportive care; blood pressure control

Optic neuritis / Visual loss (rare) Discontinue immediately; ophthalmology referral

Tumour lysis syndrome Prophylactic hydration and allopurinol/rasburicase; electrolyte monitoring

Pre-infusion (each cycle) Serum creatinine, CrCl, electrolytes, CBC — do not administer if CrCl <60 mL/min without dose modification

During infusion Ensure adequate hydration (minimum 1–2 L pre-infusion, 1 L post-infusion); monitor for infusion reactions

Post-infusion Electrolytes (especially magnesium) at 24–48 hours; encourage oral hydration

Every cycle CBC with differential (nadir Days 14–21); renal function; electrolytes

Periodic (every 2–3 cycles) Audiometry; neurological examination for peripheral neuropathy

Cumulative dose tracking Document total cisplatin dose; increased vigilance for ototoxicity and nephrotoxicity beyond 300–400 mg/m²

• Platinex (Khandelwal)

• Cisplat (Fresenius Kabi)

• Cytoplatin (Neon)

• Platin (Sun Pharma)

• Cisteen (Celon)

• Kemoplat (Dabur)

• Oncoplatin (Zydus)

• Uniplatin (United Biotech)

• Cizcan (Biochem)

FDCs: Not applicable

Note: Not included in NLEM 2022 (carboplatin is included). Prices variable between government procurement and private retail. Available in government cancer centres under national programmes.

• Hydration is non-negotiable — administer minimum 1–2 L normal saline before cisplatin infusion with potassium chloride (20 mEq/L) and magnesium sulfate (1–2 g); continue post-infusion hydration

• Cisplatin is the most emetogenic chemotherapy agent — mandatory triple antiemetic prophylaxis (5-HT3 antagonist + dexamethasone + NK1 antagonist) starting before infusion

• Audiometry at baseline is essential — ototoxicity may be irreversible and can occur suddenly; repeat every 2–3 cycles or at first symptom (tinnitus, hearing difficulty)

• Carboplatin is often a safer alternative — consider switching in elderly, renal impairment (CrCl <60 mL/min), pre-existing neuropathy, or when cumulative dose limits approached

• Sequence matters with paclitaxel — always administer paclitaxel before cisplatin to avoid reduced paclitaxel clearance and enhanced toxicity

• Cumulative dose awareness — nephrotoxicity and ototoxicity increase significantly beyond 300–400 mg/m² total; document lifetime cisplatin exposure

Cisplatin; platinum; antineoplastic; chemotherapy; nephrotoxicity; ototoxicity; testicular cancer; ovarian cancer; head and neck cancer; bladder cancer; BEP regimen; concurrent chemoradiation; highly emetogenic; paediatric oncology

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• AIIMS Chemotherapy Protocols (Head-Neck, Germ Cell Tumours)

• API Textbook of Medicine, 11th Edition

• Tata Memorial Centre Chemotherapy Protocols

• National Cancer Grid India — Chemotherapy Protocol Compendium

• ICMR Guidelines (Cervical Cancer Management)

• IAP Paediatric Oncology Guidelines

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Model List of Essential Medicines