CISPLATIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Platinum-based alkylating-like agent that forms intrastrand and interstrand DNA crosslinks, inhibiting DNA replication and transcription, leading to cell cycle arrest and apoptosis.
| Metabolism | Undergoes nonenzymatic conversion to inactive metabolites. The majority of platinum is irreversibly bound to plasma proteins. Elimination is primarily renal via glomerular filtration and tubular secretion. |
| Excretion | Renal excretion accounts for 70-90% of cisplatin elimination, with approximately 20-50% excreted unchanged in the urine within 24 hours. Biliary/fecal excretion is minimal (<5%). |
| Half-life | The terminal elimination half-life is 20-30 hours (range 10-40 hours) in patients with normal renal function. This prolonged half-life is due to slow release of platinum from tissue binding and is clinically relevant for cumulative nephrotoxicity and ototoxicity. |
| Protein binding | Cisplatin is >90% bound to plasma proteins, primarily albumin and gamma-globulins. Binding is irreversible and extensive, resulting in a non-dialyzable platinum pool. |
| Volume of Distribution | The volume of distribution is 11-12 L/m² (approximately 0.3-0.6 L/kg), indicating extensive tissue binding, particularly in liver, kidney, and skin. |
| Bioavailability | Not applicable for oral route (inactive due to first-pass metabolism and low absorption). By intraperitoneal route, bioavailability is approximately 50-100% relative to IV. Intratumoral administration yields variable bioavailability. |
| Onset of Action | Intravenous: Clinical effects (antitumor activity) begin within 1-2 hours following IV administration, as DNA cross-linking occurs rapidly after cellular uptake. |
| Duration of Action | The duration of action (antitumor effect) extends for weeks to months following a single dose, as DNA adducts persist. Clinically, cycles are repeated every 3-4 weeks to allow recovery from toxicity. |
50-100 mg/m² IV every 3-4 weeks; or 20 mg/m² IV daily for 5 days every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl ≥60 mL/min: full dose; CrCl 45-59 mL/min: give 75% of dose; CrCl 30-44 mL/min: give 50% of dose; CrCl <30 mL/min: consider alternative therapy. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh class C) due to potential toxicity; consider dose reduction based on bilirubin and transaminases. |
| Pediatric use | 3 mg/kg IV every 3-4 weeks (generally lower than adult weight-based dosing; adjust for renal function). |
| Geriatric use | Start at lower end of dosing range (e.g., 50 mg/m² IV every 3-4 weeks) with close monitoring of renal function and myelosuppression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Nephrotoxic drugs enhance cisplatin-induced kidney damage Ototoxicity is cumulative and may be severe and irreversible.
| Breastfeeding | Cisplatin is excreted into human breast milk; the milk-to-plasma ratio is unknown. Due to potential severe adverse reactions in nursing infants, including nephrotoxicity, neurotoxicity, and myelosuppression, breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Cisplatin is embryotoxic and teratogenic in animals. First trimester exposure is associated with increased risk of major congenital malformations, including central nervous system, skeletal, and genitourinary defects. Second and third trimester exposure may cause intrauterine growth restriction, low birth weight, and fetal myelosuppression. Use is contraindicated in pregnancy unless life-threatening. |
■ FDA Black Box Warning
Cisplatin should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Cumulative renal toxicity, severe neurotoxicity, severe nausea and vomiting, myelosuppression, anaphylactic-like reactions, and ototoxicity may occur. Cisplatin can cause fetal harm when administered to a pregnant woman. It has been associated with secondary leukemia.
| Common Effects | Nephrotoxicity |
| Serious Effects |
["History of severe hypersensitivity to cisplatin or other platinum-containing compounds","Preexisting severe renal impairment (creatinine clearance < 30 mL/min)","Severe myelosuppression","Hearing impairment (severe)","Breastfeeding (discontinue nursing)"]
| Precautions | ["Nephrotoxicity: Monitor renal function; maintain adequate hydration and diuresis.","Ototoxicity: Tinnitus and high-frequency hearing loss; audiometry monitoring recommended.","Neurotoxicity: Peripheral neuropathy; may be dose-limiting.","Myelosuppression: Leukopenia, thrombocytopenia, anemia; monitor CBC.","Electrolyte disturbances: Hypomagnesemia, hypocalcemia, hypokalemia.","Anaphylactic reactions: Have resuscitation equipment available.","Hemolytic uremic syndrome (HUS): Rare but serious.","Hepatotoxicity: Monitor liver function.","Vascular events: Arterial thrombosis in patients with vascular risk factors.","Carcinogenicity: Risk of secondary leukemia."] |
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| Fetal Monitoring | Pregnant patients: Frequent fetal ultrasound for growth assessment and anomaly detection. Maternal monitoring includes complete blood count (CBC) with differential, renal function (serum creatinine, BUN, creatinine clearance), electrolytes (particularly magnesium, potassium, calcium), liver function tests, and auditory evaluation. In neonates: monitoring for myelosuppression, renal function, and hearing loss if exposed in utero. |
| Fertility Effects | Cisplatin is highly gonadotoxic. In males, it causes oligospermia, azoospermia, and elevated FSH, often irreversible. In premenopausal females, it induces ovarian failure, amenorrhea, and reduced anti-Müllerian hormone, leading to premature ovarian insufficiency and infertility. Fertility preservation consultation is recommended before therapy. |