CISPLATIN

What it is

DBL Cisplatin Injection is a solution for injection. Each mL contains 1 mg cisplatin. Cisplatin is an antineoplastic agent. Cisplatin is a platinum compound with biochemical properties similar to those of bifunctional alkylating agents, and the drug inhibits DNA synthesis by producing intrastrand and interstrand crosslinks in DNA.

Approved indications

— Palliative treatment of metastatic non-seminomatous germ cell carcinoma — Palliative treatment of advanced-stage refractory ovarian carcinoma — Palliative treatment of advanced-stage refractory bladder carcinoma — Palliative treatment of refractory squamous cell carcinoma of the head and neck

Dosing overview

The usual dose in adults and children when used as single agent therapy is 50–100 mg/m² as a single intravenous infusion every 3–4 weeks, or 15–20 mg/m² as a daily intravenous infusion for 5 days every 3–4 weeks. The dosage of cisplatin must be based on the clinical, renal and haematologic status of the patient.

Key safety warnings

Cisplatin is a highly toxic drug with a relatively narrow therapeutic index, and a therapeutic effect is unlikely to occur without some evidence of toxicity. Cisplatin should be administered only under constant supervision by physicians experienced in therapy with cytotoxic agents and only when potential benefits of cisplatin therapy outweigh the possible risks. Cisplatin displays high tissue uptake in the kidneys, exhibits dose related and cumulative nephrotoxicity, and is excreted mainly in the urine. In addition, the plasma elimination half-life of cisplatin is prolonged in renal failure. Patients should be adequately hydrated before and for 24 hours after administration of cisplatin to ensure good urinary output and minimise nephrotoxicity. Ototoxicity is cumulative and occurs mainly with high dose regimes. Tinnitus or occasional decreased ability to hear normal conversation are indications of ototoxicity, which have been frequently observed. Audiometric testing should be performed, if possible prior to initiation of therapy and at regular intervals thereafter, particularly if the clinical symptoms of tinnitus or hearing impairment occur. Myelosuppression may occur in patients treated with cisplatin. Haematological toxicity is dose-related and cumulative. Marked nausea and vomiting occur in almost all patients treated with cisplatin and are occasionally so severe that dosage reduction or discontinuance of treatment is necessary.

Contraindications

Use of cisplatin is contraindicated in renal impairment, hearing disorders, bone marrow depression, generalised infections, during pregnancy or lactation, and in patients with a history of hypersensitivity to cisplatin or platinum-containing compounds.

Regulatory history

Cisplatin (DBL formulation, sponsored by Pfizer Australia Pty Ltd) received initial approval on 31 January 1994. Multiple cisplatin formulations from Accord Healthcare and Intas were first listed on the Australian Register of Therapeutic Goods on 9 July 2018, available in strengths of 10 mg/10 mL, 25 mg/25 mL, 50 mg/50 mL and 100 mg/100 mL concentrated injection vials.