Document: Carboplatin Cipla concentrate for solution for infusion ENG SmPC change

• Carboplatin Cipla concentrate for solution for infusion PL
• Carboplatin Cipla concentrate for solution for infusion ENG PL
• Carboplatin Cipla concentrate for solution for infusion SmPC
• Carboplatin Cipla concentrate for solution for infusion ENG SmPC
• Carboplatin Cipla concentrate for solution for infusion ENG PAR
• Carboplatin Cipla concentrate for solution for infusion sPAR
• Carboplatin Cipla concentrate for solution for infusion ENG sPAR

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SUMMARY OF PRODUCT CHARACTERISTICS

Carboplatin Cipla 10 mg/ml concentrate for solution for infusion

1 ml of concentrate for solution for infusion contains 10mg of carboplatin

Each 5 ml vial contains 50 mg carboplatin

Each 15 ml vial contains 150 mg carboplatin

Each 45 ml vial contains 450 mg carboplatin

Each 60 ml vial contains 600 mg carboplatin

For the full list of excipients, see section 6.1

Concentrate for solution for infusion

A Clear, colourless solution free from visible particles.

pH: 5.00 - 7.00

Carboplatin Cipla is indicated for the treatment of:

Dosage and Administration:

Carboplatin should be used by the intravenous route only.

The recommended dosage of carboplatin in previously untreated adult patients with normal kidney function, i.e. creatinine clearance > 60 ml/min is 400 mg/m² as a single short term IV dose administered by a 15 to 60 minutes infusion. Alternatively, the Calvert formula shown below may be used to determine dosage:

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]
Target AUC	Planned chemotherapy	Patient treatment status
5-7mg/ml .min	single agent carboplatin	Previously untreated
4-6 mg/ml .min	single agent carboplatin	Previously treated
4-6mg/ml .min	Carboplatin plus cyclophosphamide	Previously untreated

Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m². Calvert's formula should not be used in patients who have received extensive pretreatment**.

**Patients are considered heavily pretreated if they have received any of the following:

Therapy with carboplatin should be discontinued in the case of an unresponsive tumour, progressive disease and/or occurrence of not tolerable side effects.

Therapy should not be repeated until four weeks after the previous carboplatin course and/or until the neutrophil count is at least 2,000 cells/mm³ and the platelet count is at least 100,000 cells/mm³.

Reduction of the initial dosage by 20-25% is recommended for those patients who present with risk factors such as prior myelosuppressive treatment and low performance status (ECOG-Zubrod 2-4 or Karnofsky below 80).

Determination of the haematological nadir by weekly blood counts during the initial courses of treatment with carboplatin is recommended for dosage adjustment for subsequent courses of the therapy.

Needles or intravenous sets containing aluminum parts that may come in contact with carboplatin injection should not be used for preparation or administration. Aluminum reacts with carboplatin injection causing precipitate formation and/or loss of potency.

The safety measures for dangerous substances are to be complied with preparation and administration.

Preparation must be carried out by personnel who have been trained in the safe use while wearing protective gloves, face mask and protective clothes.

Renal Impairment

Patients with creatinine clearance values of less than 60 ml/min are at greater risk to develop myelosuppression.

The frequency of severe leukopenia, neutropenia, or thrombocytopenia has been maintained at about 25% with the following dosage recommendations:

Baseline Creatinine Clearance Initial Dose (Day 1)

41-59 mL/min 250 mg/m²I.V.

16-40 mL/min 200 mg/m²I.V.

Insufficient data exist on the use of carboplatin injection in patients with creatinine clearance of

15 mL/min or less to permit a recommendation for treatment.

All of the above dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance and to the acceptable level ofmyelosuppression.

Combination Therapy:

The optimal use of carboplatin in combination with other myelosuppressive agents requires dosage adjustments according to the regimen and schedule to be adopted.

Paediatric population:

There is insufficient information available to recommend a dosage in the paediatric population

Elderly patients:

In patients of more than 65 years of age, adjustment of the carboplatin dose to the general condition is necessary during the first and the subsequent therapeutic courses.

Dilution and Reconstitution:

The product must be diluted prior to infusion, see section 6.6

Carboplatin is contraindicated in patients with:

• hypersensitivity to the active substance, to anyof the excipients listed in section 6.1 or to other platinum containing compounds

• breast-feeding(see section 4.6)

• concomitant use with yellow fever vaccine

• patients with severe myelosuppression

• patients with bleeding tumors

• patients with pre-existing severe renal impairment (creatinine clearance of <30ml per minute)unless in the judgment of the physician and patient, the possible benefits of treatment outweigh the risks.

Carboplatin should be used only by physician experienced with cancer chemotherapeutic drugs. Blood counts as well as renal and hepatic function tests must be done regularly and the drug should be discontinued if abnormal depression of the bone marrow or abnormal renal or hepatic function is seen.

Hematologic Toxicity

Leukopenia, neutropenia, and thrombocytopenia are dose-dependent and dose-limiting. Peripheral blood counts should be monitored during carboplatin injection treatment frequently and, in case of toxicity, until recovery is achieved. Median day of nadir is day 21 in patients receiving single agent carboplatin injection and day 15 in patients receiving carboplatin injection in combination with other chemotherapeutic agents. In general, single intermittent courses of carboplatin injection should not be repeated until leukocyte, neutrophil, and platelet counts have returned to normal. Therapy should not be repeated until 4 weeks after the previous carboplatin injection course and/or until the neutrophil count is at least 2,000 cells/mm³and the platelet count is at least 100,000 cells/mm³.

Anemia is frequent and cumulative requiring very rarely a transfusion.

Severity of myelosuppression is increased in patients with prior treatment (in particular with cisplatin) and/or impaired kidney function. Initial carboplatin injection dosages in these groups of patients should be appropriately reduced (see section 4.2) and the effects carefully monitored through frequent blood counts between courses. Carboplatin injection combination therapy with other myelosuppressive forms of treatment must be planned very carefully with respect to dosages and timing in order to minimize additive effects.

Renal toxicity and hepatic function

Renal and hepatic function impairment may be encountered with carboplatin. Very high doses of carboplatin (≥ 5 times single agent recommended dose) have resulted in severe abnormalities in hepatic and/or renal function. It is not clear whether an appropriate hydration programme might overcome effects on renal function. Dose reduction or discontinuation of therapy is required in the presence of moderate to severe alteration in renal or hepatic function test. (See Section 4.8).

The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function before carboplatin treatment. Impairment of renal function is also more likely in patients who have previously experienced nephrotoxicity as a result of cisplatintherapy. In patients with impaired renal function, the effect of carboplatin on the haematopoietic system is more pronounced and longer-acting than in patients with normal renal function. In this risk group, therapy with Carboplatin must be performed with special caution (see section 4.2). Although no clinical evidence on compounding nephrotoxicity has been accumulated, it is recommended not to combine carboplatin with aminoglycosides or other nephrotoxic compounds.

Allergic Reactions

As with other platinum-based drugs, allergic reactions appearing most often during perfusion may occur and necessitate discontinuation of the perfusion and an appropriate symptomatic treatment.Rare cases of allergic reactions to carboplatin have been reported, for example, erythematous rash, fever with no apparent cause or pruritus. In rare cases, anaphylaxis, angiooedema and anaphylactoid reactions including bronchospasm, urticaria and facial oedema occurred. These reactions are similar to those observed after administration of other platinum containing compounds and may occur within minutes. The incidence of allergic reactions may increase with previous exposure to platinum therapy,but allergic reactions have been observed duringtheinitial exposure to carboplatin. Patients should be closely monitored for possible allergic reactions and managed with appropriate supportive therapy, including antihistamines, adrenaline and/or glucocorticoids. Cross reactions, sometimes fatal, have been reported with all the platinum compounds (see section 4.3 and 4.8).

Neurologic Toxicity:

Although peripheral neurologic toxicity is generally common and mild, limited to paresthesia and decrease of osteotendinous reflexes, its frequency is increased in patients older than 65 years and/or in patients previously treated with cisplatin. Monitoring and neurological examinations should be carried out at regular intervals.

Visual disturbances, including loss of vision, have been reported after the use of carboplatin injection in doses higher than those recommended in patients with renal impairment. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.

Geriatric Use

In studies involving combination therapy with carboplatin and cyclophosphamide, elderly patients treated with carboplatin were more likely to develop severe thrombocytopenia than younger patients. Because renal function is often decreased in the elderly, renal function should be considered when determining dosage (see section 4.2).

Other

Auditory defects have been reported during carboplatin therapy. Ototoxicity may be more pronounced in children. Cases of hearing loss with a delayed onset have been reported in paediatric patients. A long-term audiometric follow-up in this population is recommended.

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including carboplatin, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving carboplatin. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.

The carcinogenic potential of carboplatin has not been studied but compounds with similar mechanisms of action and mutagenicity have been reported to be carcinogenic (see section 5.3).

Safety and effectiveness of carboplatin administration in children are not proven.

Aluminium containing equipment should not be used during preparation and administration of carboplatin (see section 6.2).

Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or IV administration sets that contain aluminium parts which may come into contact with carboplatin, should not be used for the preparation or administration of the drug.

Due to the increase of thrombotic risk in case of tumoral diseases, the use of anticoagulative treatment is frequent.

The high intra-individual variability of the coagulabilty during diseases, and the eventuality of interaction between oral anticoagulants and anticancer chemotherapy, require, if it is decided to treat the patient with oral anticoagulants, to increase frequency of the control of the INR monitoring.

Concomitant use contraindicated

Concomitant use not recommended

• Live attenuated vaccines (except yellow fever): risk of systemic, possible fatal disease. This risk is increased in subjects who are already immunosuppressed by their underlying disease. Use an inactivated vaccine where this exists (poliomyelitis).

• Phenytoin, fosphenytoin: risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by the cytotoxic drug or risk of toxicity enhancement or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin.

• Concurrent administration of carboplatin and chelating agents should be avoided as it can theoretically lead to a decrease of the antineoplastic effect of carboplatin. However, the antineoplastic effect of carboplatin was not influenced by diethyl-dithiocarbamate in animal experiments or in clinical use.

Concomitant use to take into consideration

• Cyclosporin (and by extrapolation tacrolimus and sirolimus): excessive immunosuppression with risk of lymphoproliferation.

• Aminoglycosides: the concomitant use of carboplatin with aminoglycosides antibiotics should be taken into account due to the cumulative nephrotoxicity and ear toxicity, particularly in renal failure patient.

• Loop diuretics: the concomitant use of carboplatin with loop diuretic should be taken into account due to the cumulative nephrotoxicity and ear toxicity.

• Concurrent therapy with nephrotoxic drugs or ototoxic drugs such as amino glycoside, vancomycin, capreomycin and diuretics is not recommended, since this may lead to increased or exacerbated toxicity due to carboplatin induced changes in renal clearance of these substances.

• When combining carboplatin with other myelosuppressive compounds, the myelosuppressive effect of carboplatin and/or the other compounds may be more pronounced. Patients receiving concomitanttherapy with other nephrotoxic agents are likely to experience more severe and prolonged myelotoxicity due to decreased renal clearance of carboplatin.

Pregnancy

Carboplatin can cause fetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryotoxic and teratogenic in rats receiving the drug during organogenesis. No controlled studies in pregnant women have been conducted. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women with child-bearing potential should be advised to avoid becoming pregnant.

Breast-feeding:

It is not known whether carboplatin is excreted in human milk.

If treatment becomes necessary during the lactation period, breastfeeding must be stopped.

Fertility

Gonadal suppression resulting in amenorrhea or azospermia may occur in patients receiving antineoplastic therapy. These effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.

Men of sexually mature age treated with Carboplatin are recommended not to father a child during treatment and up to 6 month afterwards and to ask advice about spermatic preservation prior to initiation of the therapy because of the possibility of irreversible infertility due to therapy with carboplatin.

No studies on the effects on the ability to drive and use machines have been performed.

However, Carboplatin may cause nausea, vomiting, vision abnormalities and ototoxicity; therefore, patients should be warned on the potential effect of these events on the ability to drive or to use machines.

The frequency of adverse reactions reported is based on a cumulative database of 1,893 patients receiving single agent carboplatin injection and post-marketing experience.

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 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

System Organ Class	Frequency	MedDRA Term
Neoplasms, benign and Malignant(including cysts and polyps)	Not known	Treatment related secondary Malignancy
Infections and infestations	Common	Infections*
Blood and lymphatic system	Very common	Thrombocytopenia, neutropenia, leukopenia, anaemia
	Common	Haemorrhage*
	Not known	Bone marrow failure, febrile neutropenia, hemolytic-uraemic syndrome
Immune system disorders	Common	Hypersensitivity, anaphylactoid type reaction
Metabolism and nutrition disorders	Not known	Dehydration, anorexia, hyponatraemia
Nervous system disorders	Common	Neuropathy peripheral, paraesthesia, decrease of osteotendinous reflexes, sensory disturbance, dysgeusia
	Not known	Cerebrovascular accident*
Eye disorders	Common	Visual disturbance, rare cases of loss of vision
Ear and labyrinth disorders	Common	Ototoxicity
Cardiac disorders	Common	Cardiovascular disorder*
	Not known	Cardiac failure*
Vascular disorders	Not known	Embolism*, hypertension, hypotension
Respiratory, thoracic and mediastinal disorders	Common	Respiratory disorder, interstitial lung disease, bronchospasm
Gastrointestinal disorders	Very common	Vomiting, nausea, abdominal pain
	Common	Diarrhoea, constipation, mucous membrane disorder
	Not known	Stomatitis
Skin and subcutaneous tissue disorders	Common	Alopecia, skin disorder
	Not known	Urticaria, rash, erythema, pruritus
Musculoskeletal and Connective tissue disorders	Common	Musculoskeletal disorder
Renal and urinary disorders	Common	Urogenital disorder
General disorders and administration site conditions	Common	Asthenia
	Not known	Injection site necrosis, injection site reaction, injection site extravasation, injection site erythema, malaise
Investigation	Very common	Creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver funtion test abnormal, blood sodium decreased, blood potassium decreased, blood calcium decreased, blood magnesium decreased.
	Common	Blood bilirubin increased, blood creatinine increased, blood uric acid increased

* Fatal in < 1%, fatal cardiovascular events in <1% included cardiac failure, embolism, and cerebrovascular accident combined.

Description of selected adverse reactions

Haematologic:

Myelosuppression is the dose-limiting toxicity of carboplatin injection. In patients with normal baseline values, thrombocytopenia with platelet counts below 50,000/mm³occurs in 25% of patients, neutropenia with granulocyte counts below 1,000/mm³in 18% of patients, and leukopenia with WBC counts below 2,000/mm³in 14% of patients. The nadir usually occurs on day 21. Myelosuppression can be worsened by combination of carboplatin injection with other myelosuppressive compounds or forms of treatment.

Myelotoxicity is more severe in previously treated patients, in particular in patients previously treated with cisplatin and in patients with impaired kidney function. Patients with poor performance status have also experienced increased leukopenia and thrombocytopenia. These effects, although usually reversible, have resulted in infectious and hemorrhagic complications in 4% and 5% of patients given carboplatin injection, respectively. These complications have led to death in less than 1% of patients.

Anaemia with haemoglobin values below 8 g/dl has been observed in 15% of patients with normal baseline values. The incidence of anaemia is increased with increasing exposure to carboplatin injection.

Gastrointestinal:

Vomiting occurs in 65% of patients, in one-third of whom it is severe. Nausea occurs in an additional 15%. Previously treated patients (in particular patients previously treated with cisplatin) appear to be more prone to vomiting. These effects usually disappear within 24 hours after treatment and are generally responsive to or prevented by antiemetic medication. Vomiting is more likely when carboplatin injection is given in combination with other emetogenic compounds.

The other gastro-intestinal complaints corresponded to pain in 8% of patients, diarrhoea, and constipation in 6% of patients.

Neurologic:

Peripheral neuropathy (mainly paresthesias and decrease of osteotendinous reflexes) has occurred in 4% of patients administered carboplatin injection. Patients older than 65 years and patients previously treated with cisplatin, as well as those receiving prolonged treatment with carboplatin injection, appear to be at increased risk.

Clinically significant sensory disturbances (ie, visual disturbances and taste modifications) have occurred in 1% of patients.

The overall frequency of neurologic side effects seems to be increased in patients receiving carboplatin injection in combination. This may also be related to longer cumulative exposure.

Ototoxicity:

Auditory defects out of the speech range with impairments in the high-frequency range (4,000-8,000 Hz) were found in serial audiometric investigations with a frequency of 15%. Very rare cases of hypoacusia have been reported.

In patients with a hearing organ predamaged due to cisplatin, a further exacerbation in the hearing function sometimes occurs during treatment with carboplatin.

Renal:

When given in usual doses, development of abnormal renal function has been uncommon, despite the fact that carboplatin injection has been administered without high-volume fluid hydration and/or forced diuresis. Elevation of serum creatinine occurs in 6% of patients, elevation of blood urea nitrogen in 14%, and of uric acid in 5% of patients. These are usually mild and are reversible in about one-half the patients. Creatinine clearance has proven to be the most sensitive renal function measure in patients receiving carboplatin injection. Twenty-seven percent (27%) of patients who have a baseline value of 60 ml/min or greater, experience a reduction in creatinine clearance during carboplatin injection therapy.

Electrolytes:

Decreases in serum sodium, potassium, calcium, and magnesium occur in 29%, 20%, 22%, and 29% of patients, respectively. In particular, cases of early hyponatraemia have been reported. The electrolyte losses are minor and mostly take a course without any clinical symptoms.

Hepatic:

Modification of liver function in patients with normal baseline values was observed, including elevation of total bilirubin in 5%, SGOT in 15%, and alkaline phosphatase in 24% of patients. These modifications were generally mild and reversible in about one-half the patients. In a limited series of patients receiving very high dosages of carboplatin injection and autologous bone marrow transplantation, severe elevation of liver function tests has occurred.

Cases of an acute, fulminant liver cell necrosis occurred after high-dosed administration of carboplatin.

Allergic Reactions:

Anaphylactic-type reactions, sometimes fatal, may occur in the minutes following injection of the product: facial oedema, dyspnoea, tachycardia, low blood pressure, urticaria, anaphylactic shock, bronchospasm.

Other undesirable effects:

Secondary acute malignancies after cytostatic combination therapies containing carboplatin have been reported.

Alopecia, fever and chills, mucositis, asthenia, malaise as well as dysgeusia have occasionally been observed.

In isolated cases, a haemolytic-uraemic syndrome occurred.

Isolated cases of cardiovascular incidents (cardiac insufficiency, embolism) as well as isolated cases of cerebrovascular accidents have been reported.

Cases of hypertension have been reported.

Local reactions:

Reactions at the site of injection (burning, pain, reddening, swelling, urticaria, necrosis in connection with extravasation) have been reported.

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V

Symptoms

Carboplatin was administered in Phase I studies at a dosage of up to 1600 mg/m²i.v. per course. At this dosage, life-threatening haematological side effects with granulocytopenia, thrombocytopenia and anaemia were observed. The granulocyte, thrombocyte and haemoglobin nadir were observed between days 9-25 (median: days 12-17). The granulocytes had reached values of ≥ 500/µl after 8-14 days (median: 11) and the thrombocytes values of ≥ 25,000/µl after 3-8 days (median: 7).

The following non-haematological side effects also occurred: renal function disturbances with a 50% drop in the glomerular filtration rate, neuropathy, ototoxicity, sight loss, hyperbilirubinaemia, mucositis, diarrhoea, nausea and vomiting with headache, alopesia, erythema, and severe infection. In the majority of cases, hearing disturbances were transient and reversible.

Management

There is no known antidote for carboplatin over dosage. The anticipated complications of over dosage would be related to myelosuppression as well as impairment of hepatic, auditory and renal function. Bone marrow transplantation and transfusions (thrombocytes, blood) can be effective measures of managing haematological side effects.Use of higher than recommended doses of carboplatin injection has been associated with loss of vision (see section 4.4).

Pharmacotherapeutic group: Antineoplastic agents, Platinum compounds

ATC code: L01X A02

Carboplatin is an antineoplastic agent. Its activity has been demonstrated against several murine and human cell lines.

Carboplatin exhibited comparable activity to cisplatin against a wide range of tumours regardless of implant site.

Alkaline elution techniques and DNA binding studies have demonstrated the qualitatively similar modes of action of carboplatin and cisplatin. Carboplatin, like cisplatin, induces changes in the superhelical conformation of DNA, which is consistent with a "DNA shortening effect".

Paediatric patients: safety and efficacy in children have not been established

Following administration of carboplatin in man, linear relationships exist between dose and plasma concentrations of total and free ultrafilterable platinum. The area under the plasma concentration versus time curve for total platinum also shows a linear relationship with the dose when creatinine clearance ≥ 60 ml/min.

Repeated dosing during four consecutive days did not produce an accumulation of platinum in plasma. After a 1-hour infusion (20-520 mg/m²), plasma levels of total platinum and free (ultrafilterable) platinum decay biphasically following first order kinetics.For free platinum, the initial phase (t alpha) half life is approximately 90 minutes and the later phase (t beta) half life approximately 6 hours. All free platinum is in the form of carboplatin in the first 4 hours after administration. Protein binding of carboplatin reaches 85-89% within 24 hours of administration, although during the first 4 hours, only up to 29% of the dose is protein bound.Carboplatin is excreted primarily in the urine, with recovery of approximately 65% of the administered platinum within 24 hours. Most of the drug is excreted in the first 6 hours. Approximately 32% of a given dose of carboplatin is excreted unchanged. Total body and renal clearances of free ultrafilterable platinum correlate with the rate of glomerular filtration but not tubular secretion. Patients with poor renal function may require dosage adjustments due to altered pharmacokinetics of carboplatin.

Carboplatin clearance has been reported to vary by 3- to 4- fold in paediatric patients. As for adult patients, literature data suggest that renal function may contribute to the variation in carboplatin clearance.

Carboplatin has been shown to be embryotoxic and teratogenic in rats. It is mutagenic in vivo and in vitro and although the carcinogenic potential of carboplatin has not been studied, compounds with similar mechanisms of action and mutagenicity have been reported to be carcinogenic.

Water for injections

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

Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or IV administration sets containing aluminium parts that may come into contact with carboplatin should not be used for preparation or administration of carboplatin. Precipitation can lead to a reduction of the antineoplastic activity.

Unopened vials: 2 years.

After dilution

Chemical and physical in-use stability has been demonstrated after dilution with infusion fluids described in section 6.6 for 24 hours at room temperature (25°C) or 24 hours under refrigeration (2-8°C).

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.

Keep the vial in the outer carton in order to protect from light.

After dilution

For the storage condition of diluted medicinal product see section 6.3.

Clear vials of Type I glass, packed in a carton.

Vials are closed with a fluororesin laminate bromobutyl rubber stopper with an aluminium crimp cap with a polypropylene flip-off lid.

Packs of 1 vial containing 50 mg/5ml of carboplatin. (Red flip-off lid)
Packs of 1 vial containing 150 mg/15ml of carboplatin. (Dark Green flip-off lid)
Packs of 1 vial containing 450 mg/45ml of carboplatin. (Blue flip-off lid)
Packs of 1 vial containing 600 mg/60ml of carboplatin. (Red flip-off lid)

Not all pack sizes may be marketed.

This product is for single dose use only.

Solutions should only be used if clear and particle free.

Disposal:

Any unused product or waste material should be disposed of in accordance with local requirements.

Dilution:

The product must be diluted before use. It may be diluted with 5% Glucose Injection, or 0.9% Sodium Chloride Injection, to concentrations from 2.0 mg/ml and as low as 0.4 mg/ml (400 micrograms/ml).

Guidelines for the safe handling of anti-neoplastic agents:

Cipla Europe NV,

Uitbreidingstraat 80,

2600 Antwerp,

Belgium.

[To be completed nationally]

2015-09-17

[To be completed nationally]

2015-09-17

[To be completed nationally]