Cisplatin (3 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- CISPLATIN
- PLATINOL
- PLATINOL-AQ
Boxed Warning
• Nephrotoxicity: cisplatin for injection can cause severe renal toxicity, including acute renal failure. Severe renal toxicities are dose-related and cumulative. Ensure adequate hydration and monitor renal function and electrolytes. Consider dose reductions or alternative treatments in patients with renal impairment [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. • Peripheral Neuropathy: cisplatin for injection can cause dose-related peripheral neuropathy that becomes more severe with repeated courses of the drug [see Warnings and Precautions (5.2)]. • Nausea and Vomiting: cisplatin for injection can cause severe nausea and vomiting. Use highly effective antiemetic premedication [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)]. • Myelosuppression: cisplatin for injection can cause severe myelosuppression with fatalities due to infections. Monitor blood counts accordingly. Interruption of therapy may be required [see Warnings and Precautions (5.4)].
Contraindications
Cisplatin for injection is contraindicated in patients with severe hypersensitivity to cisplatin [see Warnings and Precautions (5.4)].
Adverse Reactions
The following adverse reactions are described in greater detail, in other sections: •Nephrotoxicity [see Warnings and Precautions (5.1)] •Peripheral Neuropathy [see Warnings and Precautions (5.2)] •Nausea and vomiting [see Warnings and Precautions (5.3)] •Myelosuppression [see Warnings and Precautions (5.4)] •Hypersensitivity reactions [see Warnings and Precautions (5.5)] •Ototoxicity [see Warnings and Precautions (5.6] •Ocular toxicity [see Warnings and Precautions (5.7)] •Secondary malignancies [see Warnings and Precautions (5.8)] •Injection site reactions [see Warnings and Precautions (5.10)] Common adverse reactions are nephrotoxicity, peripheral neuropathy, nausea and vomiting myelosuppression, and ototoxicity. The following adverse reactions have been identified from clinical trials or post-marketing surveillance. Blood and lymphatic system disorders: Coombs‑positive hemolytic anemia. hemolytic uremic syndrome, thrombotic thrombocytopenic purpura Cardiovasculardisorders: Venous thromboembolism, arterial thromboembolism, myocardial infarction, cerebrovascular accident, thrombotic microangiopathy, cerebral arteritis, pericardial effusion, cardiac failure, ventricular dysfunction, Raynaud’s phenomenon Eye disorders: Optic neuritis, papilledema, cortical blindness, blurred vision, color blindness, retinal pigmentation Gastrointestinal disorders: Nausea, vomiting, anorexia, diarrhea, stomatitis, gastrointestinal perforation, pancreatitis, hiccups General disorders: Asthenia, malaise Hepatobiliary disorders: Elevations of aminotransferases, lactate dehydrogenase, and bilirubin; hepatic failure Hypersensitivity: Anaphylaxis, facial edema, wheezing, tachycardia, and hypotension Local Site Reactions: Tissue cellulitis, fibrosis, necrosis, pain, edema, and erythema Metabolism and nutrition disorders: Hypomagnesemia, often requiring magnesium supplementation; hyperuricemia, other electrolyte abnormalities (hypocalcemia, hyponatremia, hypokalemia, and hypophosphatemia), S
Drug Interactions
The following drug interactions are described in other sections: •Nephrotoxic drugs [see Warnings and Precautions (5.1)] •Ototoxic drugs [see Warnings and Precautions (5.6)]
Mechanism of Action
The main mechanism of the cytotoxic action involves the binding of cisplatin to genomic DNA in the cell nucleus to form interstrand and intrastrand cross-links. This interferes with normal transcription and/or DNA replication mechanisms and triggers cytotoxic processes that lead to cell death.
Overdosage
Acute overdosage with cisplatin for injection may result in renal failure, hepatic failure, hearing loss, ocular toxicity, myelosuppression, nausea and vomiting, and neuritis. In addition, death can occur following overdosage. Management of overdosage should include general supportive measures to sustain the patient through any period of toxicity that may occur. Important measures include renal protection by intravenous hydration with or without the use of an osmotic diuretic. Hemodialysis is not effective because of the high degree of protein binding of cisplatin for injection. Plasmapheresis has been used to treat cases of cisplatin for injection overdosage, but the optimal treatment regimen has not been established. For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.