Cisplatin Injection BP 10mg/20ml Vial Taj Pharma

  1. Name of the medicinal product
  2. Cisplatin Injection BP 10mg/10ml infusion Taj Pharma
    Cisplatin Injection BP 10mg/20ml infusion Taj Pharma
    Cisplatin Injection BP 50mg/50ml infusion Taj Pharma
    Cisplatin Injection BP 50mg/100ml infusion Taj Pharma
    Cisplatin Injection BP 100mg/100ml infusion Taj Pharma
    Cisplatin Injection BP 200mg/200ml infusion Taj Pharma

    1. Qualitative and quantitative composition

    a) Cisplatin Injection BP 10mg/10ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….1mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    b) Cisplatin Injection BP 10mg/20ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….0.5mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    c) Cisplatin Injection BP 50mg/50ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….1 mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    d) Cisplatin Injection BP 50mg/100ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….0.5mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    e)Cisplatin Injection BP 100mg/100ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….1mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    f) Cisplatin Injection BP 200mg/200ml infusion Taj Pharma
    Each ml contains:
    Cisplatin BP ……………….1mg
    Water for Injection……… Q.S.
    Excipients: ………………..Q.S.

    For the full list of excipients, see section 6.1.

    1. Pharmaceutical form

    Cisplatin solution for injection.

    1. Clinical particulars

    4.1 Therapeutic indications

    To be used as mono-therapy, or as part of an existing chemotherapy for advanced or metastatic tumours: testicular carcinoma (palliative and curative poly-chemotherapy) and ovary carcinoma (stages III and IV), and head and neck squamous-cell epithelioma (palliative therapy).

    In the treatment of small cell lung carcinoma.

    In the treatment of advanced non-small cell lung carcinoma.

    4.2 Posology and method of administration

    Posology

    Adults and children:

    The cisplatin dosage depends on the primary disease, the expected reaction, and on whether cisplatin is used for monotherapy or as a component of a combination chemotherapy. The dosage directions are applicable for both adults and children. For recommendations on the dosage applicable, based on the diagnosis and the clinical condition, the current medical literature should be consulted.

    For monotherapy, the following two dosage regimens are recommended:

    Single dose of 50 to 120 mg/m2 body surface every 3 to 4 weeks; 15 to 20 mg/m2/day for five days, every 3 to 4 weeks.

    If cisplatin is used in combination chemotherapy, the dose of cisplatin must be reduced. A typical dose is 20 mg/m2 or more once every 3 to 4 weeks unless in the combination therapy of small-cell and non-small-cell lung carcinoma, in which a typical dose of 80 mg/m2 is administered.

    Further dosage recommendations are to be based upon current medical insights, to be obtained from the literature or/and the appropriate working parties.

    For warnings and precautions to be considered prior to the start of the next treatment cycle, see section 4.4.

    In patients with renal dysfunction or bone marrow depression, the dose should be reduced adequately.

    Method of administration

    Cisplatin “Ebewe” 10mg/20ml Cisplatin solution for injection is to be diluted before use (see section 6.6.).

    The diluted solution should be administered only intravenously by injection (see below). For administration, any device containing aluminium that may come in contact with cisplatin (sets for intravenous injection, needles, catheters, syringes) must be avoided (see section 6.2.).

    The cisplatin solution for injection prepared according to instructions (see section 6.6.) should be administered by intravenous injection over a period of 6 to 8 hours.

    Adequate hydration must be maintained from 2 to 12 hours prior to administration until minimum 6 hours after the administration of cisplatin. Hydration is necessary to cause sufficient diuresis during and after treatment with cisplatin. It is realised by intravenous injection of one of the following solutions:

    sodium chloride solution 0.9%;

    mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1).

    Hydration prior to treatment with cisplatin:

    Intravenous injection of 100 to 200ml/hour for a period of 6 to 12 hours.

    Hydration after termination of the administration of cisplatin:

    Intravenous injection of another 2 litres at a rate of 100 to 200 ml per hour for a period of 6 to 12 hours.

    Forced diuresis may be required should the urine secretion be less than 100 to 200 ml/hour after hydration. Forced diuresis may be realised by intravenously administering 37.5g mannitol as a 10% solution (375 ml mannitol solution 10%), or by administration of a diuretic if the kidney functions are normal. The administration of mannitol or a diuretic is also required when the administrated cisplatin dose is higher than 60 mg/m2 of body surface.

    It is necessary that the patient drinks large quantities of liquids for 24 hours after the cisplatin injection to ensure adequate urine secretion.

    4.3 Contraindications

    Hypersensitivity to the active substance or other platinum containing compounds, or to any of the excipients listed in section 6.1.

    in dehydrated condition (pre- and post-hydration is required to prevent serious renal dysfunction);

    with myelosuppression;

    pre-existing renal impairment or hearing impairment due to the fact that cisplatin is nephrotoxic and neurotoxic (in particular ototoxic). These toxicities may be cumulative if disorders of this type pre-exist.who are pregnant or breastfeeding (see section 4.6.)

    in combination with yellow fever vaccine and phenytoin in prophylactic use (See section 4.5)

    4.4 Special warnings and precautions for use

    Cisplatin reacts with metallic aluminum to form a black precipitate of platinum. All aluminum containing IV sets, needles, catheters and syringes should be avoided.

    Cisplatin must be administered under close supervision by a qualified doctor specialized in the use of chemotherapeutic agents.

    Appropriate monitoring and management of the treatment and its complications are only possible if adequate diagnosis and exact treatment conditions are available.

    Nephrotoxicity

    Cisplatin causes severe cumulative nephrotoxicity. A urine output of 100 mL/hour or greater will tend to minimize cisplatin nephrotoxicity. This can be accomplished by pre-hydration with 2 liters of an appropriate intravenous solution, and similar post cisplatin hydration (recommended 2,500 mL/m2/24 hours). If vigorous hydration is insufficient to maintain adequate urinary output, an osmotic diuretic may be administered (eg, mannitol).

    Neuropathies

    Severe cases of neuropathies have been reported. These neuropathies may be irreversible and may manifest by paraesthesia, areflexia and a proprioceptive loss and a sensation of vibrations. A loss of motor function has also been reported. A neurologic examination must be carried out at regular intervals.

    Ototoxicity

    Ototoxicity has been observed in up to 31% of patients treated with a single dose of cisplatin 10mg/m2, and is manifested by tinnitus and/or hearing loss in the high frequency range (4000 to 8000Hz). Decreased ability to hear conversational tones may occur occasionally. Ototoxic effect may be more pronounced in children receiving cisplatin. Hearing loss can be unilateral or bilateral and tends to become more frequent and severe with repeated doses; however, deafness after initial dose of cisplatin has been reported rarely. Ototoxicity may be enhanced with prior simultaneous cranial irradiation and may be related to peak plasma concentration of cisplatin. It is unclear whether cisplatin induced ototoxicity is reversible. Careful monitoring by audiometry should be performed prior to initiation of therapy and prior to subsequent doses of cisplatin. Vestibular toxicity has also been reported (see section 4.8 Undesirable effects).

    Allergic phenomena

    As with other platinum-based products, hypersensitivity reactions appearing in most cases during perfusion may occur, and necessitate discontinuation of the perfusion and an appropriate symptomatic treatment. Cross reactions, sometimes fatal, have been reported with all the platinum compounds (see section 4.3 Contraindications and section 4.8 Undesirable effects).

    Hepatic function and hematological formula

    The hematological formula and the hepatic function must be monitored at regular intervals.

    Carcinogenic potential

    In humans, in rare cases the appearance of acute leukemia has coincided with use of cisplatin, which was in general associated with other leukemogenic agents.

    Cisplatin is a bacterial mutagen and causes chromosome aberrations in cultures on animal cells. Carcinogenicity is possible but has not been demonstrated. Cisplatin is teratogenic and embryotoxic in mice.

    Injection site reactions

    Injection site reactions may occur during the administration of cisplatin. Given the possibility of extravasation, it is recommended to closely monitor the injection site for possible infiltration during drug administration. A specific treatment for extravasation reactions is unknown at this time.

    Warning

    This cytostatic agent has a more marked toxicity than is usually found in antineoplastic chemotherapy.

    Renal toxicity, which is above-all cumulative, is severe and requires particular precautions during administration (see section 4.2 Posology and method of administration and section 4.8 Undesirable effects).

    Nausea and vomiting may be intense and require adequate antiemetic treatment.

    Close supervision must also be carried out with regard to ototoxicity, myelodepression and anaphylactic reactions (see section 4.8 Undesirable effects).

    Warning

    Preparation of the intravenous solution

    As with all other potentially toxic products, precautions are essential when handling the cisplatin solution. Skin lesions are possible in the event of accidental exposure to the product. It is advisable to wear gloves. In the event the cisplatin solution comes into contact with the skin or mucous membranes, wash the skin or mucous membranes vigorously with soap and water.

    Conforming to the procedures appropriate for the manipulation and elimination of cytostatic agents is recommended.

    Administering the solution to the patient, verify the clarity of the solution and the absence of particles.

    This medicinal product contains 35 mg sodium per 20ml vial, equivalent to 1.75% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

    This medicinal product contains 71 mg sodium per 20ml vial, equivalent to 3.55% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

    This medicinal product contains 177 mg sodium per 50ml vial, equivalent to 8.85% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

    This medicinal product contains 354 mg sodium per 100ml vial, equivalent to 17.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

    4.5 Interaction with other medicinal products and other forms of interaction

    Nephrotoxic substances

    Concomitant administration of nephrotoxic (e.g. cephalosporins, aminoglycosides, amphotericin B or contrast media) or ototoxic (e.g. aminoglycosides) medicinal products will potentiate the toxic effect of cisplatin on the kidneys. During or after treatment with cisplatin caution is advised with predominantly renally eliminated substances, e.g. cytostatic agents such as bleomycin and methotrexate, because of potentially reduced renal elimination.

    The renal toxicity of ifosfamide may be greater when used with cisplatin or in patients who have previously been given cisplatin.

    Reduction of the blood’s lithium values was noticed in a few cases after treatment with cisplatin combined with bleomycin and etoposide. It is therefore recommended to monitor the lithium values.

    Ototoxic substances

    Concomitant administration of ototoxic (e.g. aminoglycosides, loop diuretics) medicinal products will potentiate the toxic effect of cisplatin on auditory function. Except for patients receiving doses of cisplatin exceeding 60 mg/m2, whose urine secretion is less than 1000 ml per 24 hours, no forced diuresis with loop diuretics should be applied in view of possible damage to the kidney tract and ototoxicity.

    Ifosfamide may increase hearing loss due to cisplatin.

    Attenuated live vaccines

    Yellow fever vaccine is strictly contraindicated because of the risk of fatal systemic vaccinal disease (see section 4.3 Contraindications). In view of the risk of generalized illness, it is advisable to use an inactivated vaccine if available.

    Oral anticoagulants

    In the event of simultaneous use of oral anticoagulants, it is advisable regularly to check the INR.

    Antihistamines, Phenothiazines and others

    Simultaneous use of antihistamines, buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes or trimethobenzamides may mask ototoxicity symptoms (such as dizziness and tinnitus).

    Anticonvulsive substances

    Serum concentrations of anticonvulsive medicines may remain at sub-therapeutic levels during treatment with cisplatin.

    Pyridoxine + altretamine combination

    During a randomized study of the treatment of advanced ovarian cancer, the response time was unfavorably affected when pyridoxine in combination with altretamine (hexamethylmelamine) and cisplatin.

    Paclitaxel

    Treatment with cisplatin prior to an injection with paclitaxel may reduce the clearance of paclitaxel by 33% and therefore can intensify neurotoxicity.

    4.6 Fertility, pregnancy and lactation

    Pregnancy

    There are no adequate data from the use of cisplatin in pregnant women, but based on its pharmacological properties Cisplatin is suspected to cause serious birth defects. Studies in animals have shown reproductive toxicity and transplacental carcinogenicity (see section 5.3.). Cisplatin is contraindicated during the pregnancy period.

    Breast-feeding

    Cisplatin is excreted in human milk. Breastfeeding during the therapy is contraindicated.

    Fertility

    Both male and female patients must use effective contraceptive methods to prevent conception and/or reproduction during and for at least 6 months after treatment with cisplatin.

    Genetic consultation is recommended if the patient wishes to have children after ending the treatment. Since a treatment with cisplatin may cause irreversible infertility, it is recommended that men, who wish to become fathers in the future, ask for advice regarding cryoconservation of their sperm prior to the treatment.

     

    4.7 Effects on ability to drive and use machines

    Due to the possible side effects cisplatinhas minor or moderate influence on the ability to drive and use machines. Patients who suffer from these effects (eg feeling sleepy or vomiting) must avoid driving and operating machinery.

    4.8 Undesirable effects

    Undesirable effects depend on the used dose and may have cumulative effects.

    The most frequently reported adverse events (>10%) of Cisplatin were haematological (leukopenia, thrombocytopenia and anaemia), gastrointestinal (anorexia, nausea, vomiting and diarrhoea), ear disorders (hearing impairment), renal disorders (renal failure, nephrotoxicity, hyperuricaemia) and fever.

    Serious toxic effects on the kidneys, bone marrow and ears have been reported in up to about one third of patients given a single dose of cisplatin; the effects are generally dose-related and cumulative. Ototoxicity may be more severe in children.

    The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories:

    very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

    Table of Adverse Drug Events reported during clinical or post-marketing experience (MedDRA terms)

    Infections and infestations
    Common Sepsis
    Not known Infectiona
    Neoplasm benign, malignant, and unspecified
    Uncommon Acute leukemia
    Blood and lymphatic system disorders
    Very common Bone marrow failure, thrombocytopenia, leukopenia, anemia
    Not known Coombs positive hemolytic anemia
    Immune system disorders
    Uncommon Anaphylactoidb reactions
    Endocrine disorders
    Not known Blood amylase increased, inappropriate antidiurectic hormone secretion
    Metabolism and nutrition disorders
    Very common Hyponatremia
    Uncommon Hypomagnesemia
    Not known Dehydration, hypokalemia, hypophosphatemia, hyperuricemia, hypocalcemia, tetany
    Nervous system disorders
    Rare Convulsion, neuropathy peripheral, leukoencephalopathy, reversible posterior leukoencephalopathy syndrome
    Not known Cerebrovascular accident, hemorrhagic stroke, ischemic stroke, ageusia, cerebral arteritis, Lhermitte’s sign, myelopathy, autonomic neuropathy
    Eye disorders
    Not known Vision blurred, color blindness acquired, blindness cortical, optic neuritis, papilledema, retinal pigmentation
    Ear and labyrinth disorders
    Uncommon Ototoxicity
    Not known Tinnitus, deafness
    Cardiac disorders
    Common: Arrhythmia, bradycardia, tachycardia
    Rare Myocardial infarction
    Very rare Cardiac arrest
    Not known Cardiac disorder
    Vascular disorders
    Common Venous thromboembolism
    Not known Thrombotic microangiopathy (hemolytic uremic syndrome), Raynaud’s phenomenon
    Respiratory, thoracic and mediastinal disorders
    Not known Pulmonary embolism
    Gastrointestinal disorders
    Rare Stomatitis
    Not known Vomiting, nausea, anorexia, hiccups, diarrhea
    Hepatobiliary disorders
    Not known Hepatic enzymes increased, blood bilirubin increased
    Skin and subcutaneous tissue disorders
    Not known Rash, alopecia
    Musculoskeletal, connective tissue and bone disorders
    Not known Muscle spasms
    Renal and urinary disorders
    Not known Renal failure acute, renal failurec, renal tubular disorder
    Reproductive system and breast disorders
    Uncommon Abnormal spermatogenesis
    General disorders and administration site conditions
    Very common Pyrexia
    Not known Asthenia, malaise, injection site extravasationd

    a: Infectious complications have led to death in some patients.

    b: Symptoms reported for anaphylactoid reaction such as facial edema (PT-face oedema), wheezing, bronchospasm, tachycardia, and hypotension will be included in the parentheses for anaphylactoid reaction in the AE frequency table.

    c: Elevations in BUN and creatinine, serum uric acid, and/or a decrease in creatinine clearance are subsumed under renal insufficiency/failure.

    d: Local soft tissue toxicity including tissue cellulitis, fibrosis, and necrosis (common) pain (common), oedema (common) and erythema (common) as the result of extravasation.

    Reporting of suspected adverse reactions

    Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

    4.9 Overdose

    CAUTION IS ESSENTIAL IN ORDER TO PREVENT AN INADVERTENT OVERDOSE.

    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 a cisplatin overdose. Even if hemodialysis is initiated 4 hours after the overdose it has little effect on the elimination of cisplatin from the body due to a strong and rapid fixation of cisplatin to proteins.

    1. Pharmacological properties

    5.1 Pharmacodynamic properties

    Pharmacotherapeutic group: Antineoplastic agents / Platinum compounds

    Mechanism of action

    Cisplatin is an anorganic substance containing a heavy metal [cis-diamminedichloroplatinum(II)]. This substance inhibits the DNA synthesis by realising transverse connections within and between the DNA strings. The protein and RNA synthesis is inhibited to a lesser extent.

    Pharmacodynamic effects

    Although the primary activity of cisplatin seems to be the inhibition of DNA synthesis, the antineoplastic process includes other activities, such as enlargement of the tumour immunogenicity. Cisplatin’s oncolytic functions can be compared to the functions of alkylating substances. Cisplatin also offers immunosuppressive, radiosensitising and antibacterial features.

    Cisplatin does not seem to be cell cycle specific.

    The cytotoxic activities of cisplatin are caused by binding all DNA bases, with a preference for the N-7 position of guanine and adenosine.

    5.2 Pharmacokinetic properties

    Distribution

    After intravenous administration, cisplatin is rapidly distributed among all tissues. Following cisplatin doses of 20 to 120 mg/m2, the concentrations of platinum are highest in liver, prostate and kidney, somewhat lower in bladder, muscles, testicle, pancreas and spleen and lowest in bowel, adrenal, heart, lung, cerebrum and cerebellum.

    Biotransformation

    Over 90% of the total plasma cisplatin is bounded with protein after two hours following the administration. This process may be irreversible. The protein-bounded part is not antineoplastic active. Cisplatin is non-linearly pharmacokinetic. Cisplatin is converted by a non-enzymatic process into one or more metabolites. Elimination from the plasma is realised in two phases after intravenous bolus injection of 50-100 mg/m2 of cisplatin. The following half-life period have been registered for humans:

    t ½ (distribution): 10-60 minutes

    t ½ (terminal): approximately 2-5 days

    Elimination

    The considerable protein binding of the total platinum contents results in an extended or incomplete excretion phase with cumulative urine secretion ranging from 27 to 45% of the administered dose in a period from 84 to 120 hours. An extended injection results in the urine secretion of a larger part of the dose. The faecal secretion is minimal, and small amounts of platinum can be traced in the gallbladder and the large intestine. Dysfunctional kidneys increase the plasma half-life period, which may also increase theoretically in the presence of ascites caused by the highly protein binding activities of cisplatin.

    5.3 Preclinical safety data

    Chronic toxicity:

    Chronic toxicity models indicate kidney damage, bone marrow depression, gastro-intestine disorders and ototoxicity.

    Mutagenity and carcinogenity:

    Cisplatin is mutagenic in numerous in vitro and in vivo tests (bacterial test systems and chromosome defects in animal cells and tissue cultures). Long term studies of cisplatin on mice and rats evidenced the carcinogenic effects.

    Reproductive toxicity:

    Fertility: Gonadal suppression resulting in amenorrhoea or azoospermia may be irreversible and cause definitive infertility.

    Studies in rats showed that exposure during pregnancy produces tumours in the adult offspring.

    Pregnancy and lactation: Cisplatin is embryotoxic and teratogenic for mice and rats, and defects have been reported for both species. Cisplatin was found in the milk.

    1. Pharmaceutical particulars

    6.1 List of excipients

    Sodium chloride, Hydrochloric acid,Water for injections.

    6.2 Incompatibilities

    Cisplatin reacts with aluminium which results in production of a black platinum precipitate. Therefore any device containing aluminium that may come in contact with cisplatin (sets for intravenous injection, needles, catheters, syringes) must be avoided.

    This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

    The cisplatin 1 mg/ml concentrate must not be diluted with glucose solution 5% alone or mannitol solution 5% alone, but only with the mixtures containing additionally sodium chloride as stated in section 6.6.

    Antioxidants (such as sodium metabisulphite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil and paclitaxel may inactivate cisplatin in injection systems.

    6.3 Shelf life

    Medicinal product as packaged for sale:

    2 years

    Solution for injection after dilution (see section 6.6):

    Chemical and physical in-use stability has been demonstrated for 48 hours at 2 to 8°C when protected from light for solutions with a final cisplatin concentration of 0.1 mg/ml after dilution of the cisplatin 10mg/20ml concentrate with one of the following solutions:

    – sodium chloride solution 0.9%;

    – mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1);

    – mixture of sodium chloride solution 0.9% and mannitol solution 5% (1:1).

    From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution / dilution (etc) has taken place in controlled and validated aseptic conditions.

    6.4 Special precautions for storage

    Medicinal product as packaged for sale:

    Do not store above 25 °C. Do not refrigerate or freeze. Keep the vial in the outer carton.

    For storage conditions of the diluted medicinal product, see section 6.3.

    6.5 Nature and contents of container

    Packs of 1, 5 or 10 vial(s) containing 10ml, 20 ml, 50 ml or 100 ml Cisplatin solution for injection each.

    Not all pack sizes may be marketed.

    6.6 Special precautions for disposal and other handling

    Cisplatin 1 mg/ml Cisplatin solution for injection is to be diluted before use. For preparation of solution for injection, any device containing aluminium that may come in contact with cisplatin (sets for intravenous injection, needles, catheters, syringes) must be avoided (see section 6.2.).

    Preparation of solution for injection must take place in aseptic conditions.

    For dilution of the concentrate, one of the following solutions should be used:

    – sodium chloride solution 0.9%;

    – mixture of sodium chloride solution 0.9% and glucose solution 5% (1:1) (resulting final concentrations: sodium chloride 0.45%, glucose 2.5%).

    – Should hydration prior to the treatment with cisplatin be impossible, the concentrate may be diluted with:

    – mixture of sodium chloride solution 0.9% and mannitol solution 5% (1:1) (resulting final concentrations: sodium chloride 0.45%, mannitol 2.5%).

    Preparation of cisplatin solution for injection:

    The required amount (dose) of the cisplatin concentrate 1 mg/ml calculated according to the instructions in section 4.2. should be diluted in 1-2 litres of one of the above mentioned solutions.

    The diluted solution should be administered only by intravenous injection (see section 4.2.).

    Only clear and colourless to yellowish solutions without visible particles should be used.

    For single use only.

    Cytotoxic agents should be prepared for administration only by personnel who have been trained in the safe handling of the preparation.

    Refer to local cytotoxic handling guidelines.

    As any other cytotoxic agent, cisplatin should be used with extreme caution: gloves, face masks and protective clothing are required and vital. Cisplatin should be processed under a protective hood, if possible. Contact with skin and/or mucous membranes must be avoided. Pregnant hospital employees should not work with cisplatin.

    Skin contact: Rinse with large quantities of water. Apply an ointment if you have a temporary burning feeling. (Note: Some persons are sensitive to platinum and may experience a skin reaction).

    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. In the case of spillage all items coming into contact with Cisplatin should be handled and disposed in accordance to local cytotoxic guidelines.

    7. Manufactured in India By:
    TAJ PHARMACEUTICALS LIMITED
    at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
    ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

    Cisplatin Injection BP 10mg/20ml Vial Taj Pharma

    Package leaflet: Information for the user

    Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

    • Keep this leaflet. You may need to read it
    • If you have further questions, ask your doctor, pharmacist or
    • This medicine has been prescribed for you Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
    • If you get any side effects, talk to your doctor, pharmacist or This includes any possible side effects not listed in this leaflet. See section 4.

    What is in this leaflet:

    1. What Cisplatin Injection is and what it is used for
    2. What you need to know before you use Cisplatin Injection
    3. How to use Cisplatin Injection
    4. Possible side effects
    5. How to store Cisplatin Injection
    6. Contents of the pack and other information

    What Cisplatin Injection is and what it is used for

    Cisplatin forms part of a group of medicines called cytostatics, which are used in the treatment of cancer. Cisplatin can be used alone but more commonly Cisplatin is used in combination with other cytostatics.

    What is it used for?

    Cisplatin can destroy cells in your body that may cause certain types of cancer (tumour of testis, tumour of ovary, tumour of the bladder, head and neck epithelial tumour, lung cancer and for cervical cancer in combination with radiotherapy).

    Your doctor will be able to provide you with more information.

    1. What you need to know before you use Cisplatin Injection

    Do not take Cisplatin if:

    • you are allergic to cisplatin or to any of the other ingredients of this medicine (listed in section 6
    • you are allergic (hypersensitive) to any other medicine that contains platina compounds
    • you have kidney problems (renal dysfunction)
    • you suffer from dehydration
    • you suffer from severe suppression of bone marrow functionality, symptoms may be: extreme tiredness, easy bruising or bleeding, occurrence of infections
    • your hearing is impaired
    • you suffer from nervous disorders caused by cisplatin
    • you are breast-feeding
    • combined with live vaccines, including yellow fever
    • combined with phenytoin in prophylactic use (see “Other medicines and Cisplaitn” below).

    Warnings and precautions

    Your doctor will carry out tests in order to determine the levels of calcium, sodium, potassium and magnesium in your blood, as well as to check your blood picture and your liver and kidney functionality and neurological function.

    • Cisplatin should only be administered under the strict supervision of a specialist doctor experienced in administrating
    • Your hearing will be tested prior to each treatment with
    • If you suffer from a nervous disorder not caused by
    • If you have had radiation therapy to your head
    • If you suffer from an infection. Please consult your
    • If you intend to have children (see Pregnancy, breast-feeding and fertility
    • Tell your doctor if the above applies to you before this medicine is
    • With spillage of cisplatin the contaminated skin must immediately be washed with water and soap. If cisplatin is injected outside the blood vessels the administration must be stopped immediately. Infiltration of cisplatin in the skin can result in tissue damage (cellulitis, fibrosis and necrosis).

    Please consult your doctor, even if these statements were applicable to you at any time in the past.

    Other medicines and Cisplatin

    Please note that these statements may also apply to products used some time ago or at some time in the future. Tell your doctor or pharmacist if you are taking, or have recently taken, or might take any other medicine –

    • Simultaneous use of medicines that inhibit the bone marrow function or radiation can potentiate the adverse effects of cisplatin on the bone
    • Cisplatin toxicity may increase when administered simultaneously with other cytostatics (medicine for cancer treatment), such as bleomycin and
    • Agents to treat high blood pressure (antihypertensives containing furosemide, hydralazine, diazoxide, and propranolol) may increase the toxic effect of Cisplatin on kidneys.
    • Cisplatin toxicity may severely affect the kidneys when administered simultaneously with agents that may cause side effects in the kidneys, such as those for the prevention/ treatment of certain infections (antibiotics: cephalosporins, aminoglycosides, and/or amphotericin B) and contrast
    • Cisplatin toxicity may affect hearing faculties when administered simultaneously with agents that may have a side effect on hearing faculties, such as
    • If you use agents to treat gout during your treatment with cisplatin, then the dosage of such agents may need to be adjusted (e.g. allopurinol, colchicine, probenecid and/or sulfinpyrazone).
    • Administration of drugs that elevate your rate of bodily urine excretion (loop diuretics) combined with cisplatin (cisplatin dose: more than 60mg/m², urine secretion: less than 1000 ml per 24 hours) may result in toxic effects on kidneys and
    • The first signs of hearing damage (dizziness and/or tinnitus) may remain hidden when – during your treatment with cisplatin – you are also being administered agents to treat hypersensitivity (antihistamines, such as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes and/or trimethobenzamides).
    • Cisplatin given in combination with ifosphamide may result in hearing
    • The effects of treatment with cisplatin can be reduced through simultaneous administration of pyridoxine and hexamethylmelamine.
    • Cisplatin given in combination with bleomycin and vinblastine may result in paleness or blue coloration of the fingers and/or toes (Raynaud’s phenomenon).
    • Administration of cisplatin prior to treatment with paclitaxel or in combination with docetaxel may result in severe nerve
    • The combined use of cisplatin with bleomycin and etoposide may decrease lithium levels in the Therefore, lithium levels should be checked on a regular basis.
    • Cisplatin reduces the effects of phenytoin on the treatment of
    • Penicillamine may reduce the effectiveness of
    • Cisplatin may have an adverse impact on the effectivity of agents preventing coagulation (anticoagulants). Therefore, coagulation should be checked more often during combined
    • Concomitant use of cisplatin with ciclosporin can weaken the immune system, with the risk of increased production of white blood cells (lymphocytes)
    • You should not receive any vaccinations containing live viruses within three months after the end of treatment with
    • When undergoing treatment with cisplatin, you should not receive yellow fever vaccinations (also see “Do not take Cisplatin”).
    Pregnancy, breast-feeding and fertility

    If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

    Cisplatin must not be used during pregnancy unless clearly indicated by your doctor.

    You must use effective contraception during and at least 6 months after treatment with Cisplatin. You must not breastfeed while you are treated with Cisplatin.

    Male patients treated with Cisplatin are advised not to father a child during treatment and for up to 6 months after treatment. Further, men are advised to seek counseling on sperm preservation before starting treatment.

    Driving and using machines

    Cisplatin may cause side effects such as feeling sleepy and/or vomiting. If you suffer from either of these conditions, then you should not operate any machines that require your full attention.

    Cisplatin injection contains sodium

    Cisplatin contains 3.5 mg sodium per ml. This should be considered if you have to keep to a low sodium diet.

    1. How to use Cisplatin Injection

    Dosage and method of administration

    Cisplatin should only be given by a specialist in cancer treatment.

    The concentrate is diluted with a sodium chloride solution that contains glucose. Cisplatin is only given by injection into a vein (an intravenous infusion).

    Supportive equipment should be available to control anaphylactic reactions. Cisplatin should not come into contact with any materials that contain aluminium.

    The recommended dosage of Cisplatin depends on your well-being, the anticipated effects of the treatment, and whether or not cisplatin is given on its own (monotherapy) or in combination with other agents (combination chemotherapy).

    Cisplatin (monotherapy):

    The following dosages are recommended:

    • A single dosage of 50 to 120 mg/m² body surface, every 3 to 4
    • 15 to 20 mg/m² per day over a 5-day period, every 3 to 4 weeks

    Cisplatin in combination with other chemotherapeutical agents (combination chemotherapy):

    • 20 mg/m² or more, once every 3 to 4

    For treatment of cervical cancer cisplatin is used in combination with radiotherapy. A typical dose is 40 mg/m² weekly for 6 weeks.

    In order to avoid, or reduce, kidney problems, you are advised to drink copious amounts of water for a period of 24 hours following treatment with Cisplatin.

    If you take more Cisplatin than you should

    Your doctor will ensure that the correct dose for your condition is given. In case of overdose, you may experience increased side effects. Your doctor may give you symptomatic treatment for these side effects. If you think you received too much Cisplatin, immediately contact your doctor.

    If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

    1. Possible side effects

    Like all medicines, this medicine can cause side effects, although not everybody gets them

    If you experience any side effect it is important that you inform your doctor before your next treatment.

    Tell your doctor immediately, if you notice any of the following:

    • persistent or severe diarrhoea or vomiting
    • stomatitis/mucositis (sore lips or mouth ulcer)
    • swelling of the face, lips mouth or throat
    • unexplained respiratory symptoms such as non-productive cough, difficulty in breathing or crackles
    • difficulty in swallowing
    • numbness or tingling in your fingers or toes
    • extreme tiredness
    • abnormal bruising or bleeding
    • signs of infection, such as sore throat and high temperature
    • sensation of discomfort close to or at the injection site during the

    The following side effects may occur:

    Very common (may affect more than 1 in 10 people)

    Blood and lymphatic system: suppression of the bone marrow characterised by a severe decrease of white blood cells, which makes infections more likely (leukopenia), reduction in blood platelets, which increases the risk of bruising and bleeding (thrombocytopenia), as well as reduction in red blood cells, which can make the skin pale and cause weakness or breathlessness (anaemia).

    Nutrition and metabolism: reduced level of electrolytes (sodium)

    Gastrointestinal tract: loss of appetite (anorexia), nausea, vomiting, diarrhoea.

    Kidneys and urinary tracts: excessive uric acid levels (hyperuricaemia) in the blood (e.g. gout).

    General symptoms: fever.

    Common (may affect up to 1 in 10 people) Infections: blood-poisoning (sepsis).

    Heart: arrhythmia, including reduced heartbeat (bradycardia), accelerated heartbeat (tachycardia).

    Blood vessels: inflammation of a vein (phlebitis) at injection site.

    Respiratory disorders: difficulty of breathing (dyspnoea), inflammation of the lungs (pneumonia) and respiratory failure.

    Uncommon (may affect up to 1 in 100 people)

    Immune system: hypersensitivity reactions, including rash, eczema with severe itching and lump formation (urticaria), redness and inflammation of the skin (erythema) or itching (pruritus), (anaphylactoid reactions) with symptoms such as swelling of the face and fever, low blood pressure (hypotension), accelerated heartbeat (tachycardia), breathing difficulties (dyspnoea), distress as a result of muscle cramps in the airways (bronchospasms) Hearing: damage to the ear (ototoxicity)

    Nutrition and metabolism: reduced level of electrolytes (Magnesium)

    Gastrointestinal tract: metallic setting on the gums.

    Skin: loss of hair (alopecia).

    Reproductive system and breasts: dysfunctional spermatogenesis and ovulation, and painful breast growth in men (gynaecomastia).

    Rare (may affect up to 1 in 1,000 people)

    Immune system: severe hypersensitivity (anaphylactic reactions) with low blood pressure (hypotension), accelerated heartbeat (tachycardia), breathing difficulties (dyspnoea), distress as a result of muscle cramps in the airways (bronchospasms), swelling of the face and fever; suppression of the immune system (immunosuppression).

    Nervous system: loss of certain types of brain function, including brain dysfunction characterised by spasms and reduced levels of consciousness (encephalopathy), peripheral neuropathy of the sensory nerves (bilateral, sensory neuropathy), characterised by tickling, itching or tingling without cause and sometimes characterised by a loss of taste, touch, sight, sudden shooting pains from the neck through the back into the legs when bending forwards, attacks (seizures)..

    Hearing: unable to hold normal conversation, loss of hearing (in particular among children and elderly patients).

    Heart: increased blood pressure levels, coronary artery disease and heart attacks.

    Liver and bile: reduced albumin (protein) levels in blood

    Gastrointestinal tract: inflammation of mucous membranes of the mouth (stomatitis)

    General: Cisplatin, like other similar medicines, increases the risk of leukaemia (acute leukaemia).

    Very rare (may affect up to 1 in 10,000 people)

    Nutrition and metabolism: increased iron levels in the blood.

    Heart: heart(cardiac) arrest.

    Not known (frequency cannot be estimated from the available data)

    Infections: Infection

    Blood and lymphatic system:, haemolytic anaemia

    Hormones: insufficient production of the vasopressin hormone in the brain (SIADH), blood amylase (enzyme) increased.

    Nutrition and metabolism: reduced level of electrolytes (calcium, phosphate, potassium) in the blood with muscle cramping and/or changes in an electrocardiogram (ECG). Excessive cholesterol levels in the blood.

    Nervous system: spinal disease, brain dysfunction (confusion, slurred speech, sometimes blindness, memory loss, and paralysis);stroke, loss of taste (ageusia), as well as closure of the carotid artery.

    General symptoms: weakness (asthenia), malaise, dehydration, swelling (oedema), pain,redness and inflammation of the skin (erythema, skin ulcer)at the area of injection

    Kidneys and urinary tracts: kidney dysfunction, such as failure to produce urine (anuria) and urine poisoning of the blood (uraemia)

    Musculo skeletal: muscle spasms

    Skin and dermis: hair loss, rash

    Liver and bile: liver dysfunction, liver enzymes increased, bilirubin increased.

    Gastrointestinal tract: loss of appetite (anorexia), nausea, vomiting, diarrhoea, hiccups.

    Blood vessels: blood flow dysfunction, e.g. in the brain, but also in the fingers and toes (Raynaud’s syndrome), Thrombotic microangiopathy combined with haemolytic uraemic syndrome.

    Heart: cardiac disorder

    Hearing and balance function: loss of hearing combined with tinnitus (ringing in ears)

    Eyes: blurred vision, difficulties in colour perception and eye movement dysfunction. swelling (papilloedema), inflammation of the eye nerve combined with pain and reduced nerve function (optic neuritis), blindness as a result of brain dysfunction.

    Reporting of side effects

    If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

    1. How to store Cisplatin Injection

    Keep this medicine out of sight and reach of children.

    Keep the vial in the outer carton (to avoid exposure of Cisplatin to light).

    Concentrate for solution for infusion 1 mg/ml

    Keep container in the outer carton in order to protect from light. Do not refrigerate or freeze.

    Do not use this medicine after the expiry date which is stated on the vial and the outer carton after ‘exp’. The expiry date refers to the last day of that month. Do not use this medicine if you notice visible signs of deterioration.

    All materials that have been used for the preparation and administration, or which have been in contact with cisplatin in any way, must be disposed of according to local cytotoxic guidelines

    If you find the solution cloudy or a deposit that does not dissolve is noticed, the bottle should be discarded.

    1. Contents of the pack and other information

    What Cisplatin Injection contains:

    Cisplatin Injection contains the active ingredient cisplatin.
    Each 20 ml of solution contains 10 milligram (mg) of cisplatin.
    Each 50 ml of solution contains 50 milligram (mg) of cisplatin.
    Each 100 ml of solution contains 50 milligram (mg) of cisplatin.

     7. Manufactured in India By:
    TAJ PHARMACEUTICALS LIMITED
    at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
    ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

     

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.