Cisplatin modifies cell cycle by interfering with DNA structure and function. Effects are most prominent during the S phase but cells are killed at all stages. Cisplatin synergises with other anticancer drugs e.g. fluorouracil. It has a narrow therapeutic margin and is highly toxic.

Absorption
Well absorbed (intraperitoneal).

Distribution
Concentrated in the liver, kidneys, large and small intestines; poor penetration into the CNS.

Excretion
Urine. Elimination half-life: 25-49 minutes (initial), 58-73 hours (terminal).

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Severe nausea and vomiting. Serious toxic effects on the kidneys, bone marrows and ears. Hypomagnesaemia, hypocalcaemia, hyperuricaemia. Peripheral neuropathies, papilloedema, optic neuritis, seizures. Ototoxicity (children) manifested as tinnitus, loss of hearing, deafness or vestibular toxicity.

Potentially Fatal: Rarely, renal damage due to inadequate hydration during therapy. Very rarely life-threatening myelosuppression. Anaphylactoid reactions (rare) and cardiac abnormalities.

Warnings

Overdose/confusion with carboplatin
Doses above 100 mg/m 2 /cycle once every 3 to 4 weeks rarely used. Avoid confusion with carboplatin or prescribing practices that fail to differentiate daily doses from total dose per cycle.

GI
Marked nausea and vomiting occur in almost all patients and are occasionally so severe that the drug must be discontinued.

Hematologic
Myelosuppression occurs in 25% to 30% of patients. Leukopenia and thrombocytopenia are more pronounced at doses above 50 mg/m 2 . Anemia (decrease of 2 g hemoglobin/dL) occur at the same frequency and with the same timing as leukopenia and thrombocytopenia.

Hypersensitivity
Anaphylactic-like reactions have occurred.

Ototoxicity
Has occurred in no more than 31% of patients given a single dose of 50 mg/m 2 . It is manifested by tinnitus or loss of high frequency hearing, and occasionally deafness. May be pronounced in children.

Renal toxicity
Dose-related and cumulative renal insufficiency is the major dose-limiting toxicity. This is manifested by elevations in BUN and creatinine, serum uric acid, or a decrease in Ccr. Renal toxicity becomes more severe and prolonged with repeated courses; therefore, renal function must return to normal before another dose can be given. Amifostine can be used to reduce renal toxicity in patients with advanced ovarian cancer receiving repeated doses of cisplatin.

Patients with renal or hepatic disorder, myelosuppression. Monitor renal, neurological and auditory function. Perform blood counts regularly. Maintain adequate hydration before and 24 hours after admin to minimise nephrotoxicity.

Synergistic with 5-fluorouracil and etoposide. Efficacy increased and toxicity reduced when combined with radioprotecting agent WR 2721. At doses ≤100 mg, cisplatin is an ideal drug to combine with other cytotoxic drugs; unlike other antineoplastic drugs, it causes little myelosuppression.

Potentially Fatal: Potentiates nephrotoxicity with aminoglycosides. Increased toxicity when combined with other cytotoxic drugs.

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Intravenous
Metastatic ovarian cancer
Adult: As monotherapy: 100 mg/m2 per cycle, given as a single dose infused in 0.9% sodium chloride or glucose once every 4 weeks.
For combination therapy with cyclophosphamide: 75-100 mg/m2 on day 1 of every 4-week cycle.
Child:
Renal impairment: Dose adjustment may be needed.

Intravenous
Metastatic testicular tumours
Adult: 20 mg/m2 BSA daily for 5 days per cycle.
Renal impairment: Dose adjustment may be needed.

Intravenous
Advanced bladder cancer
Adult: 50-70 mg/m2 per cycle once every 3-4 weeks, depending on the extent of prior exposure to radiation and/or chemotherapy treatment. An initial dose of 50 mg/m2 every 4 weeks may be used in heavily pre-treated patients.
Renal impairment: Dose adjustment may be needed.

Incompatibility
Y-site incompatibility: Thiotepa, cefepime, amphotericin B, amifostine, piperacillin/tazobactam, cholesteryl sulfate complex.
Admixture incompatibility: Mesna, thiotepa, fluorouracil.

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Contraindicated in pregnancy.

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindicated in lactation

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Patients with severe renal or auditory disorder, known hypersensitivity, severe bone marrow suppression, peripheral neuropathy, pregnancy, lactation.

Intravenous
Store at 15-25°C.

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