BLACK BOX WARNING
- nephrotoxicity (cumulative renal toxicity)
- myelosuppression
- ototoxicity
- anaphylactic reactions
cisplatin
Brand: Platinol
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: platinum-based alkylating agent
Drug Family: antineoplastic
Subclass: first-generation platinum antineoplastic
Organ Systems: hematology-oncology
Mechanism of Action
Undergoes hydrolysis to form reactive platinum species; forms intrastrand and interstrand DNA cross-links (primarily at adjacent guanine residues), distorting DNA helix; triggers apoptosis via p53 pathway; cells in all phases of cell cycle are susceptible.
DNA (intrastrand and interstrand cross-links)
Indications
- testicular cancer (curative)
- ovarian cancer
- bladder cancer
- lung cancer (NSCLC and SCLC)
- head and neck cancer
- cervical cancer
Contraindications
- cisplatin hypersensitivity
- pre-existing significant renal impairment
- pre-existing severe hearing loss (ototoxicity)
- myelosuppression
Adverse Effects
Common
- severe nausea/vomiting (most emetogenic of all chemotherapies)
- nephrotoxicity
- peripheral neuropathy
- electrolyte wasting (hypomagnesemia, hypokalemia, hypocalcemia)
Serious
- nephrotoxicity (dose-limiting, cumulative)
- ototoxicity (irreversible high-frequency hearing loss)
- peripheral neuropathy (cumulative, sometimes irreversible)
- myelosuppression
- severe nausea and vomiting (most emetogenic agent)
- anaphylaxis
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | extensively binds to plasma proteins (>90%) and tissue proteins; distributes widely |
| Metabolism | non-enzymatic conversion to reactive species in plasma |
| Excretion | renal (primarily platinum — 90% within 24 hours of administration); dose reduction with renal impairment |
| Half-life | 58–73 hours (terminal) |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | variable per cycle |
| Protein Binding | >90% |
| Vd | moderate-large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| aminoglycosides/vancomycin/loop diuretics | additive ototoxicity and nephrotoxicity | major |
| NSAIDs | increase nephrotoxicity risk by reducing renal prostaglandin-mediated vasodilation | major |
| phenytoin | cisplatin reduces phenytoin absorption and increases metabolism; subtherapeutic phenytoin levels | major |
Nursing Considerations
- Pre-hydration with at least 1–2 L of 0.9% NaCl over 2–4 hours before and after cisplatin is mandatory to prevent nephrotoxicity; maintain urinary output >100 mL/hr during infusion.
- Aggressive antiemetic prophylaxis is required — the most emetogenic chemotherapy regimen demands a 5-HT3 antagonist + NK1 antagonist + dexamethasone combination.
- Monitor BMP (electrolytes, creatinine) before each cycle; replace magnesium aggressively (hypomagnesemia is universal and can be severe).
- Audiogram testing at baseline and periodically; instruct patients to report tinnitus, decreased hearing, or dizziness immediately.
Clinical Pearls
- Cisplatin's discovery was accidental — an American researcher studying the effects of electric current on bacterial growth noticed that platinum electrodes were producing platinum compounds that inhibited bacterial division, leading to its development as an anti-cancer drug.
- The combination of bleomycin, etoposide, and cisplatin (BEP) is curative for advanced testicular cancer in >80% of cases — one of oncology's greatest success stories and a testament to cisplatin's importance.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.