CISPLATINUM INJECTION 50MG/ML

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 paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Cisplatin exerts its antitumor effects primarily through three mechanisms: it attaches alkyl groups to DNA bases, leading to fragmentation by repair enzymes, it forms cross-links between DNA strands preventing their separation for replication and transcription, and it induces mispairing of nucleotides resulting in mutations.

Pharmacodynamics

As an alkylating agent, cisplatin interferes with DNA synthesis and transcription by cross-linking guanine bases within the DNA double helix. This disruption is critical as it prevents DNA strands from uncoiling and separating, thereby halting cell division. Cisplatin can also lead to the incorporation of alkyl groups onto various biomolecules, further inhibiting their normal function and contributing to cytotoxicity. It is classified as cell cycle-nonspecific, affecting cells irrespective of their stage in the cell cycle.

Pharmacokinetics

Cisplatin is administered intravenously and is widely distributed in body tissues. It undergoes rapid renal excretion, with approximately 80% of the drug eliminated in the urine within 24 hours. The drug has a terminal half-life of about 30 minutes to 2 hours, although its effects can persist much longer due to covalent bonding with cellular macromolecules. Renal function is a critical factor influencing cisplatin clearance, and dosage adjustments may be necessary in patients with compromised renal function.

Contra-indications

• Hypersensitivity to cisplatin or any component of the formulation
• Severe renal impairment
• Myelosuppression
• Pregnancy

Adverse effects

• Nausea and vomiting
• Nephrotoxicity
• Ototoxicity
• Peripheral neuropathy
• Bone marrow suppression
• Anemia
• Leukopenia
• Thrombocytopenia
• Hypomagnesemia
• Hypokalemia

Interactions

• Potentially increased nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides, vancomycin, or non-steroidal anti-inflammatory drugs (NSAIDs)
• May interact with anticoagulants, leading to increased bleeding risk
• Caution with live vaccines as immunosuppression may occur

Precautions

• Monitor renal function before and during therapy
• Monitor blood counts regularly due to risk of myelosuppression
• Ensure hydration to reduce nephrotoxicity risk
• Use with caution in patients with pre-existing hearing loss due to ototoxicity risk

Pregnancy

Cisplatin is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Cisplatin is not recommended during breastfeeding as it may affect the infant.

Storage

Store at room temperature, protected from light. Keep out of reach of children.

Formulations

• Cisplatin injection solution for intravenous use

Mechanism of action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Pharmacodynamics

Cisplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.