Cytosplat

Each 10 mL contains: Cisplatin, BP 10 mg.
Each 50 mL contains: Cisplatin, BP 50 mg.

Pharmacology: Pharmacodynamics: Cisplatin has biochemical properties similar to those of bifunctional alkylating agents. The drug inhibits DNA synthesis by producing intrastrand and interstrand cross links in DNA. Protein and RNA synthesis are also inhibited to a lesser extent.
Although the principal mechanism of action of cisplatin appears to be inhibition of DNA synthesis, other mechanisms, including enhancement of tumour immunogenicity, may be involved in its antineoplastic activity. Cisplatin also has immunosuppressive, radiosensitising, and antimicrobial properties.
Cisplatin does not appear to be cell cycle specific.
Pharmacokinetics: There is good uptake of cisplatin by the kidneys, liver and intestine. More than 90% of platinum containing species remaining in the blood are bound (possibly irreversibly) to plasma proteins.
Penetration into the CSF is poor although significant amounts of cisplatin can be detected in intracerebral tumours.
The clearance of total platinum from plasma is rapid during the first four hours after intravenous administration, but then proceeds more slowly because of covalent binding to serum proteins. Levels of unbound platinum fall with a half-life of 20 minutes to 1 hour depending on the rate of drug infusion.
The elimination of intact drug and various platinum-containing biotransformation products is via the urine. About 15-25% of administered platinum is rapidly excreted in the first 2-4 hours after administration of cisplatin. This early excretion is mostly of intact cisplatin. In the first 24 hours after administration, 20-80% is excreted, the remainder representing drug bound to tissues or plasma protein.

Cisplatin is used for the treatment of metastatic testicular tumors, metastatic ovarian tumors, advanced bladder carcinoma, testicular neoplasms, ovarian neoplasms, head and neck cancer, cervical carcinoma, lung carcinoma and a wide variety of other neoplasms. The drug is often used as a component of combination chemotherapeutic regimens because of its relative lack of hematologic toxicity.

Cisplatin is administered by IV infusion. The drug has also been administered intraarterially and intraperitoneally.
Testicular Neoplasms, Bladder Cancer, Prostatic Cancer: The usual dosage of cisplatin is 15-20 mg/m² IV once daily for 5 consecutive days every 3 weeks, or administer 25-35 mg/m² once weekly according to patient's condition.
Ovarian Neoplasms: The usual dosage of cisplatin is 50-70 mg/m² once every 4 weeks, or administer following one method according to patient's condition.
Head and Neck Cancer: The usual dosage of cisplatin is 10-20 mg/m² once daily for 5 consecutive days every 3 weeks, or 50-70 mg/m² once every 4 weeks according to patient's condition.
Lung Carcinoma: The usual dosage of cisplatin is 70-90 mg/m² once every 4 weeks, or 20 mg/m² once daily for 5 consecutive days every 3 weeks according to patient's condition.
Esophageal Cancer: The usual dosage of cisplatin is 50-70 mg/m² once every 4 weeks, or 15-20 mg/m² once daily for 5 consecutive days every 3 weeks according to patient's condition.
Uterine and Neck Cancer: The usual dosage of cisplatin is 15-20 mg/m² once daily for 5 consecutive days every 3 weeks, or 70-90 mg/m² once every 4 weeks according to patient's condition.
Gastric Cancer: The usual dosage of cisplatin is 70-90 mg/m² once every 4 weeks.
Cisplatin should be added to an IV infusion fluid prior to administration; either Sodium Chloride 0.9% or Glucose 5% are suitable.
Remission of renal toxicity: Adults: Pre-treatment hydration with 1-2 liters of fluid infused for over 4 hours prior to cisplatin treatment.
Cisplatin should be added to 0.5-1 liter of an intravenous infusion fluid depending on the dosage for every 2 hours during administration; either 0.9% Sodium Chloride or Sodium Chloride 0.9% and Glucose 5%.
Adequate hydration with 1-2 liters of fluid infused for over 4 hours after cisplatin administration is recommended.
Diuresis may be aided by administration with mannitol and/or furosemide, if necessary.
Children: Pre-treatment hydration with 300-900 mL/m² of fluid infused for over 2 hours prior to cisplatin treatment.
Cisplatin should be added to 300-900 mL/m² of an intravenous infusion fluid depending on the dosage for every 2 hours during administration; either 0.9% Sodium Chloride or Sodium Chloride 0.9% and Glucose 5%.
Adequate hydration with 600 mL/m² of fluid infused for over 3 hours after cisplatin administration is recommended.
Diuresis may be aided by administration with mannitol and/or furosemide, if necessary.

An acute overdose of cisplatin may result in renal failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, untreatable nausea and vomiting and/or neuritis. An overdose may be fatal.
There is no specific antidote in the event of an overdosage of cisplatin. Even if haemodialysis is initiated 4 hours after the overdose it has little effect on the elimination of cisplatin from the body following a strong and rapid fixation of cisplatin to proteins.
Treatment in the event of an overdose consists of general support measures.

Patients with pre-existing renal impairment.
Patients with a history of hypersensitivity to Cisplatin.

Patients with renal impairment, hepatic impairment, depressed bone marrow function, or hearing disorder.
Infection and bleeding tendency should be considered.
Some adverse effects (e.g., ototoxicity) appear to be more severe in children.
The influence of cisplatin on human reproduction has not been determined. Cisplatin therapy might have an anti-fertility effect.
Needles or intravenous sets containing aluminum parts that may come in contact with cisplatin should not be used for preparation or administration. Aluminum reacts with cisplatin, causing precipitate formation and a loss of potency.
Should not be injected with other antitumor agents.
In vitro, cisplatin has been shown to be mutagenic in bacteria.
The drug has been shown to be carcinogenic in mice and rats. It has been reported that concomitant administration of other antitumor agents may cause cardiac infarction and cerebral infarction.
Others: Cardiac abnormalities (including conduction defects and congestive heart failure) and hypercalcemia reported to occur infrequently.
Use in pregnancy & lactation: Safe use in pregnancy has not been established.
Cisplatin should not be administered to patients who are pregnant or to mothers who are breast-feeding.

Safe use in pregnancy has not been established.
Cisplatin should not be administered to patients who are pregnant or to mothers who are breast-feeding.

Gastrointestinal: Marked nausea and vomiting occur in almost all patients treated with cisplatin and are occasionally so severe that the drug must be discontinued. Diarrhea, anorexia may occur. Occasionally, constipation, stomatitis may also occur.
Nephrotoxicity: Nephrotoxicity, which is dose related and can be severe, may occur in patients receiving cisplatin. Renal toxicity is manifested by an increase in serum creatinine clearance and glomerular filtration rate.
Hematological: Myelosuppression may occur in patients treated with cisplatin. Leucopenia and thrombocytopenia are more pronounced at higher doses. Anemia occurs at approximately the same frequency and with the same timing as leucopenia and thrombocytopenia.
Ototoxicity: Ototoxicity, manifested as tinnitus, with or without clinical hearing loss, and occasional deafness, may occur in patients receiving cisplatin and may be more severe in children than in adults. Rarely, temporary unilateral otalgia and recruitment have also occurred.
Careful monitoring by audiometry should be performed prior to initiation of therapy and prior to subsequent doses of cisplatin.
Hypersensitivity: Anaphylactic-like reactions, rash may occur.
Neurotoxicity: Neurotoxicity, usually characterized by peripheral neuropathies, has occurred in some patients. Loss of taste and seizures have also been reported.
Neuropathies resulting from cisplatin treatment may occur after prolonged therapy; however, neurological symptoms have been reported to occur after a single dose.
Cisplatin therapy should be discontinued when the symptoms are first observed. Preliminary evidence suggests peripheral neuropathy may be irreversible in some patients.
Hepatic: Mild and transient elevations of serum AST (SGOT), ALT (SGPT), and bilirubin concentrations may occur in patients receiving cisplatin.
Cardiovascular: Occasionally congestive heart failure, palmus, tachycardia, atrial fibrillation occurred.
Electrolyte: Cisplatin may cause serious electrolyte disturbances; sodium, potassium, chromium, calcium, phosphorus, magnesium.
Others: Other adverse effects associated with cisplatin include mild alopecia or thinning of the hair, hiccups, myalgia, pyrexia, and gingival platinum line.
Severe adverse effects such as renal impairment, depressed bone marrow function may occur, therefore, therapy should be monitored periodically and clinical examinations should also be performed regularly; renal function, hematologic, hepatic function tests.

Concomitant administration of other antitumor agents and radiation exposure may increase depressed bone marrow function.
Concomitant administration of aminoglycoside antibiotics may result in increased ototoxicity or nephrotoxicity.

Administration: Should be administered only by or under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents.
Preparation (Guidelines): Chemotherapeutic agents should be prepared for administration only by professionals who have been trained in the safe use of the preparation.
Operations such as reconstitution, dilution and transfer to syringes should be carried out only in the designated area.
The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.
Pregnant personnel are advised not to handle chemotherapeutic agents.
Contamination: In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of skin. Medical advice should be sought if the eyes are affected.
In the event of spillage, operators should put on gloves and mop up the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and seal it.
Disposal: Syringes, container, absorbent materials, solution and any other contaminated material should be placed in a thick plastic bag or other impervious container and incinerated.

Store at temperatures not exceeding 30°C.
Preserve in sealed containers, protected from light.

Cytotoxic Chemotherapy

L01XA01 - cisplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.

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