Cisplatin !

A platinum drug that cross-links DNA. Key in testicular, ovarian and bladder cancer; known for kidney damage, hearing loss and severe vomiting.

Updated 2026-11-01

Class: Platinum compounds
Target: DNA (N7 of adjacent guanines)
ATC code: L01XA01
WHO Model List of Essential Medicines

Also called: cis-diamminedichloroplatinum (II), CDDP

DNA (N7 of adjacent guanines)Cisplatin

The crystal shows a DNA double helix carrying the main cisplatin adduct: platinum bridging two neighbouring guanines on one strand.

Target in 3D: DNA (N7 of adjacent guanines). PDB structure 1AIO (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Cisplatin is stable while the surrounding chloride is high (blood, saline). Inside the cell, where chloride is low, its two chloride ligands are replaced by water and the platinum becomes reactive. It binds the N7 atom of guanine, mostly linking two adjacent guanines on the same strand, and also forms interstrand cross-links. The bent DNA cannot be copied or transcribed, and the damage triggers apoptosis, most strongly in the S phase. Testicular tumours are especially sensitive.

Low chloride inside the cell: water replaces chloride
Reactive platinum binds N7 of guanine
Intrastrand and interstrand DNA cross-links
Replication and transcription stop: apoptosis

Pharmacokinetics

Absorption: Intravenous only.
Distribution: Platinum binds plasma proteins irreversibly and reaches high levels in liver, prostate and kidney; little reaches the brain.
Metabolism: Not metabolised by enzymes: the chloride ligands are displaced chemically by water and sulfhydryl groups.
Elimination: Mainly in the urine, partly by active tubular secretion; platinum stays in tissues for months.
Half-life: The parent drug disappears from plasma within about half an hour; protein-bound platinum lingers for days.

Indications

Metastatic testicular tumours, in combination regimens. Testicular cancer →
Metastatic ovarian tumours, in combination or as second-line single agent. Ovarian cancer →
Advanced transitional-cell bladder cancer. Bladder cancer →
Lung cancer, in combination regimens and with radiotherapy. Lung cancer →
Head and neck squamous cell carcinoma, often with radiotherapy. Head and neck squamous cell carcinoma (oral cavity and oropharynx, HPV) →
Cervical cancer, often with radiotherapy. Cervical cancer →

Adverse effects

Common

Severe nausea and vomiting, both acute and delayed
Low magnesium, calcium, potassium and sodium
Tinnitus and high-frequency hearing loss
Myelosuppression
Peripheral sensory neuropathy (stocking-glove)

Contraindications

Pre-existing kidney impairment
Myelosuppression
Hearing impairment
Allergy to cisplatin or other platinum compounds

Key interactions

Aminoglycosides: Add to cisplatin's kidney damage and ototoxicity.
Other ototoxic drugs (e.g. vancomycin): Higher risk of hearing loss.
Anticonvulsants: Their blood levels may fall below the therapeutic range.
Paclitaxel: Giving paclitaxel after cisplatin slows paclitaxel clearance and deepens myelosuppression; paclitaxel is given first.
Bleomycin: Cisplatin-induced kidney damage reduces bleomycin clearance and raises the risk of bleomycin lung toxicity.

What is monitored

Creatinine, BUN and creatinine clearance before each course
Magnesium, calcium, potassium and sodium
Audiometry before starting and before each dose (and for years after in children)
Blood counts and neurological examination

Administration and safety

Look-alike risk: cisplatin and carboplatin are checked by full name; confusing them can cause an overdose.
Given with intravenous hydration before and after; it is not diluted in dextrose alone.
Never prepared or given with needles or sets that contain aluminium: aluminium makes it precipitate and lose potency.
Strong antiemetic prophylaxis is started before the dose (for acute and delayed vomiting).
Hazardous drug: prepared and given following hazardous-drug handling procedures (impervious gloves, no skin contact) and disposed of as cytotoxic waste.

Nursing care

Independent double check of drug, patient, route and cycle before giving it (high-alert medicine).
Strict intake and output and daily weight; check that urine output is adequate before and during the infusion.
Watch the infusion site for infiltration and the patient for flushing, wheeze or low blood pressure in the first minutes.
Ask about ringing in the ears, hearing change, tingling of hands and feet, and muscle cramps (low magnesium).
Teaching: drink fluids as advised, report vomiting that prevents drinking, and avoid pregnancy and breastfeeding.

Pregnancy and breastfeeding

Can cause fetal harm; pregnancy is avoided during treatment, and breastfeeding is not advised because cisplatin passes into milk.

Test yourself

Think of the answer, then tap the question to see it.

What is the dose-limiting toxicity of cisplatin, and how is it reduced?

Cumulative nephrotoxicity; it is reduced with intravenous saline hydration (chloride diuresis), sometimes with mannitol, and amifostine.

Which electrolyte disturbance is typical of cisplatin and can cause tetany?

Hypomagnesaemia (often with hypocalcaemia), from renal tubular damage.

Which test is done before each cisplatin dose in children, and why?

Audiometry, because cisplatin ototoxicity is cumulative and more frequent in children.

Why must aluminium needles not be used with cisplatin?

Aluminium reacts with cisplatin, forming a precipitate and reducing its potency.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - CISPLATIN injection (DailyMed (U.S. National Library of Medicine), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 70 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).

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Representative model, for educational purposes only.