NEW ZEALAND DATA SHEET - Medsafe

1 NEW ZEALAND DATA SHEETPage1of121 PRODUCT NAMECISPLATIN EBEWE 1 mg/mL Solution for injection2 QUALITATIVE AND QUANTITATIVE COMPOSITIONEach vial contains cisplatin 1 mg/mL10mg in 10mL, 50mg in 50mL and 100mg in 100mLExcipients with known effect: NoneFor the full list of excipients, see section PHARMACEUTICAL FORMS olution for colourless sterile aqueous CLINICAL indicationsCisplatin Ebewe is indicated as palliative therapy to be employed as follows:Metastatic Non-seminomatous Germ Cell Carcinoma:In established combination therapy with other approved chemotherapeutic agents in patientswith metastatic non-seminomatous germ cell tumours who have already received appropriatesurgical and/or radiotherapeutic Ovarian Tumours: cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients withmetastatic ovarian tumours refractory to standard chemotherapy who have not previouslyreceived cisplatin Ebewe and Refractory Carcinoma of the Bladder.

2 cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients withadvanced stage bladder cancer refractory to standard chemotherapy who have not previouslyreceived cisplatin Ebewe Cell Carcinoma of the Head and Neck (Refractory to StandardChemotherapy): cisplatin Ebewe, as a single agent, is indicated as secondary therapy in patients withsquamous cell carcinoma of the head and neck refractory to standard chemotherapy who havenot previously received cisplatin Ebewe ZEALAND DATA and method of administrationNote:Needles or intravenous sets containing aluminium parts that may come in contact withCisplatin Ebewe should not be used for preparation or administration. Aluminium reacts withCisplatin Ebewe, causing precipitate formation and a loss of solution should be used intravenously only and should be administered by infusiononly as recommended Non-seminomatous Germ Cell Carcinoma:The usual dosage of cisplatin Ebewe for the treatment of non-seminomatous carcinoma incombination with other approved therapeutic agents is:20 daily for 5 days (Days 1-5) every three weeks for three Ovarian Tumours:As a single agent, cisplatin Ebewe may be administered at a dose of 100 onceevery 4 and Refractory Carcinoma of the Bladder.

3 cisplatin Ebewe should be administered as a single agent at a dose of 50-70 onceevery 3 to 4 weeks depending on the extent of prior exposure to radiation therapy and/or priorchemotherapy. For heavily pretreated patients an initial dose of 50 mg/m repeated every 4weeks is Cell Carcinoma of the Head and Neck (Refractory to StandardChemotherapy):As a single agent, cisplatin Ebewe may be administered at a dose of 100 onceevery 4 following important principles should be taken into consideration when must be administered in an intravenous solution containing at least NaCl. This amount of chloride ion is essential to maintain cisplatin stability inintravenous solution. The medicine should be diluted in Sodium Chloride IntravenousInfusion ( ) or in 1/2 or 1/3 physiologic saline with 5 percent urine output of 100 mL/hr or greater will tend to minimise cisplatin can be accomplished by prehydration with 2 litres of an appropriate intravenoussolution, and similar post cisplatin hydration (recommended 2,500 mL/m /24 hours).

4 If vigorous hydration is insufficient to maintain adequate urinary output, an osmoticdiuretic may be administered ( mannitol). doses of 60 mg/m have been administered safely over 1-2 hours; dosesgreater than 60 mg/m should be administered over 6-8 hours with sufficient fluid tomaintain adequate urine output during administration and post administration has been associated with electrolyte imbalances includingsymptomatic hypomagnesaemia. Therefore monitoring of serum electrolytes, before,during and after every course of cisplatin is repeat course of cisplatin Ebewe should not be given until the serum creatinine is mg/100 mL and/or the BUN is below 25 mg/100 mL. A repeat course should not be givenNEW ZEALAND DATA SHEETPage3of12until circulating blood elements are at an acceptable level (platelets 100,000/mm3, WBC 4,000/mm3).

5 Subsequent doses of cisplatin Ebewe should not be given until an audiometricanalysis indicates that auditory acuity is within normal instructions on dilution of the medicine before administration, see section Ebewe is contraindicated in patients with pre-existing renal impairment. CisplatinEbewe should not be employed in myelosuppressed patients, in patients who are dehydratedand those with pre-existing renal impairment or patients with hearing Ebewe is contraindicated in patients with a history of allergic reactions to CisplatinEbewe or other platinum-containing is nephrotoxic and neurotoxic (in particular ototoxic). These toxicities may becumulative if disorders of this type receiving cisplatin should not administration of yellow fever vaccine is warnings and precautions for useCisplatin Ebewe should be administered only in a hospital under the supervision of aqualified physician experienced in the use of cancer chemotherapeutic agents.

6 Appropriatemanagement of therapy and complications is possible only when adequate diagnostic andtreatment facilities are readily with other platinum-based products, hypersensitivity reactions appearing in most casesduring perfusion may occur, and necessitate discontinuation of the perfusion and anappropriate symptomatic treatment. Cross reactions, sometimes fatal, have been reported withall the platinum compounds (See section and ). cisplatin produces cumulative nephrotoxicity. The serum creatinine, BUN, and creatinineclearance should be measured prior to initiating therapy, and prior to each subsequent the recommended dosage, cisplatin Ebewe should not be given more frequently than onceevery 3 to 4 weeks (see section ).

7 This can be accomplished by pre-hydration with 2 litersof an appropriate intravenous solution, and similar post cisplatin hydration (recommended2,500 mL/m2/24 hours). If vigorous hydration is insufficient to maintain adequate urinaryoutput, an osmotic diuretic may be administered (eg, mannitol).Anaphylactic-like reactions to cisplatin have been reported and include facial oedemabronchorestriction, tachycardia and hypotension. These reactions have occurred withinminutes of administration to patients with prior exposure to cisplatin , and have beenalleviated by administration of adrenaline, corticosteroids and are reports of severe neuropathies in patients in whom regimens are employed usinghigher doses of cisplatin or greater dose frequencies than those recommended.

8 Theseneuropathies may be irreversible and are seen as paresthesias in a stocking-glove distribution,areflexia, and loss of proprioception and vibratory sensation. A neurologic examination mustbe carried out at regular intervalsLoss of motor function has also been ototoxicity of cisplatin is cumulative, audiometric testing should be performed prior toinitiating therapy and prior to each subsequent dose of medicine (see section ). cisplatin has been found to have a carcinogenic potential in animals. The development ofNEW ZEALAND DATA SHEETPage4of12acute leukaemia co-incident with the use of cisplatin has been reported rarely in humans, as isgenerally associated with other leukemogenic agents.

9 In these reports, cisplatin was generallygiven in combination with other leukaemogenic blood counts should be monitored weekly. Liver function should be monitoredperiodically. Neurological examination should also be performed regularly (see section ).Neurologic examination should also be performed regularly (see section ). CisplatinEbewe should be administered only in a hospital under the supervision of a qualifiedphysician experienced in the use of cancer chemotherapy of its high protein binding cisplatin Ebewe may interfere with the distribution ofother protein bound cisplatin produces cumulative nephrotoxicity and ototoxicity, other nephrotoxic orototoxic medicines should be avoided during cisplatin therapy unless dilution of the solution cisplatin Ebewe undergoes varying degrees ofdecomposition, depending on the diluent used.

10 Normal Saline is the preferred diluent (seesection ).Injection site reactions may occur during the administration of cisplatin . Given the possibilityof extravasation, it is recommended to closely monitor the infusion site for possibleinfiltration during medicine administration. A specific treatment for extravasation reactions isunknown at this with other medicines and other forms of interactionPlasma levels of anticonvulsants may become subtherapeutic during cisplatin a randomised trial in advanced ovarian cancer, response duration was adversely affectedwhen pyridoxine was used with Altretamine (hexamethylmelamine) and renal toxicity of ifosfamide may be greater when used with cisplatin or in patients whohave previously been given may increase hearing loss due to anticoagulants.