AVACIS 50

Indications

• Testicular cancer
• Ovarian cancer
• Bladder cancer
• Non-small cell lung cancer
• Head and neck cancers

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines as it varies based on the type of cancer and treatment protocol.

Mechanism of action

Cisplatin enters cells through passive diffusion and active transport mechanisms. Once inside, it forms reactive platinum-DNA adducts, which cross-link DNA strands. This cross-linking inhibits DNA replication and transcription, leading to cell cycle arrest and triggering programmed cell death or apoptosis. The primary pathway involves the formation of 1,2-intrastrand cross-links between adjacent guanines in the DNA, particularly at the N7 position.

Pharmacodynamics

Cisplatin exhibits dose-dependent cytotoxicity against a variety of tumor cells. Its effectiveness is influenced by the rate of drug uptake, the extent of DNA damage, and the ability of cells to repair that damage. Tumors that have upregulated DNA repair mechanisms may be less sensitive to cisplatin. Additionally, the drug can induce various cellular stress responses, influencing the overall effectiveness of treatment.

Pharmacokinetics

Cisplatin is administered intravenously, with peak plasma concentrations occurring shortly after infusion. It has a volume of distribution that suggests extensive tissue uptake. The drug is primarily eliminated through the kidneys, with renal clearance being a significant route of excretion. Its half-life varies, ranging from 30 minutes to several hours, depending on the formulation and patient factors. The nephrotoxicity associated with cisplatin is a major concern, necessitating careful monitoring of renal function during treatment.

Contra-indications

• Hypersensitivity to cisplatin or any of its components
• Severe renal impairment
• Myelosuppression
• Pregnancy

Adverse effects

• Nausea and vomiting
• Nephrotoxicity
• Ototoxicity
• Peripheral neuropathy
• Myelosuppression
• Electrolyte imbalances
• Anemia
• Fatigue

Interactions

• Other nephrotoxic agents (e.g., aminoglycosides, NSAIDs)
• Myelosuppressive agents
• Live vaccines
• Radiation therapy

Precautions

• Renal function should be monitored prior to and during treatment
• Electrolyte levels should be monitored, especially magnesium and potassium
• Hearing should be assessed regularly due to risk of ototoxicity
• Use with caution in patients with pre-existing hearing loss or renal impairment

Pregnancy

Cisplatin is classified as category D. It can cause fetal harm and should be avoided during pregnancy.

Breast-feeding

It is not known whether cisplatin is excreted in human milk. Caution is advised, and breastfeeding should be discontinued during treatment.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Cisplatin injection for intravenous use