Carboplatin Injection BP 150mg/15mL Taj Pharma

  1. Name of the medicinal product

Carboplatin Injection BP 50mg/5mL Taj Pharma
Carboplatin Injection BP 150mg/15mL Taj Pharma
Carboplatin Injection BP 450mg/45mL Taj Pharma
Carboplatin Injection BP 600mg/60mL Taj Pharma

  1. Qualitative and quantitative composition

a) Carboplatin Injection BP 50mg/5mL Taj Pharma
Each 1 ml contains
Carboplatin BP                          10 mg
Water for Injection BP                  q.s.

b) Carboplatin Injection BP 150mg/15mL Taj Pharma
Each 1 ml contains
Carboplatin BP                          10 mg
Water for Injection BP                  q.s. 

c) Carboplatin Injection BP 450mg/45mL Taj Pharma
Each 1 ml contains
Carboplatin BP                          10 mg
Water for Injection BP                  q.s.

d) Carboplatin Injection BP 600mg/60mL Taj Pharma
Each 1 ml contains
Carboplatin BP                          10 mg
Water for Injection BP                  q.s.

For the full list of excipients, see 6.1

  1. Pharmaceutical form

Solution for Injection.

  1. Clinical particulars

4.1 Therapeutic indications

Antineoplastic agent indicated in the treatment of:

  • ovarian carcinoma of epithelial origin
  • small cell lung carcinoma.

4.2 Posology and method of administration

Posology

The recommended dose of carboplatin in previously untreated adults with normal renal function is 400 mg/m2, given as a single short term intravenous Injection over 15 to 60 minutes. 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
5-7 mg/ml.min single agent carboplatin previously untreated
4-6 mg/ml.min single agent carboplatin previously treated
4-6 mg/ml.min carboplatin plus cyclophosphamide previously untreated

Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.

Therapy should not be repeated until 4 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.

Initial dosage should be reduced by 20-25% in patients with risk factors such as previous myelosuppressive therapy and/or poor performance status (ECOG-Zubrod 2-4 or Karnofsky below 80).

Determination of hematologic nadir by weekly blood counts during initial courses is recommended for future dosage adjustment and scheduling of carboplatin.

Needles or intravenous sets containing aluminium parts that may come in contact with carboplatin injection should not be used for preparation or administration. Aluminium 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.

Impaired renal function: In patients with impaired renal function, dosage of carboplatin should be reduced (refer to Calvert formula) and haematological nadirs and renal function monitored.

Patients with creatinine clearance values below 60 ml/min are at increased risk of severe 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/m2 I.V.
16-40 ml/min 200 mg/mI.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 of myelosuppression.

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.

Elderly population

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.

Paediatric population

There is insufficient information to support a dosage recommendation in the paediatric population.

Method of administration

Carboplatin injection should be used by the intravenous route only.

4.3 Contraindications

Carboplatin is contraindicated in:

– hypersensitivity to the active substance or to any of the excipients listed in 6.1

– patients with severe myelosuppression

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

– patients with bleeding tumours

– concomitant use with yellow fever vaccine (see section 4.5)

– patients with a history of severe allergic reaction to carboplatin or other platinum containing compounds.

Dosage adjustment may allow use in the presence of mild renal impairment (see section 4.2).

4.4 Special warnings and precautions for use

Warnings:

Myelosuppression

Myelosuppression as a result of carboplatin treatment is closely related to the renal clearance of the drug. Therefore, in patients with abnormal renal function, or who are receiving concomitant therapy with nephrotoxic drugs, myelosuppression, especially thrombocytopenia, may be more severe and prolonged.

The occurrence, severity and protraction of toxicity is likely to be greater in patients who have received extensive prior treatment with the drug for their disease or with cisplatin, have poor performance status and are advanced in years. Renal function parameters should be assessed prior to, during and after carboplatin therapy Initial carboplatin 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. Myelosuppressive effects may be additive to those of concomitant chemotherapy.

Peripheral blood counts (including platelets, white blood cells and haemoglobin) should be followed during and after therapy. Combination therapy with other myelosuppressive drugs may require modification of dosage/timing of schedules in order to minimise additive effects.

Carboplatin courses should not, in general, be repeated more frequently than every 4 weeks in order to ensure that the nadir in blood counts has occurred and there has been recovery to a satisfactory level.

Patients with severe and persistent myelosuppression are at high risk of infectious complications including fatal outcomes (see section 4.8). If any of these events occurs, carboplatin should be interrupted and dose modification or discontinuation should be considered.

Allergic Reactions

As with other platinum-based drugs, allergic reactions appearing most often during administration may occur and necessitate discontinuation of Injection. Patients should be observed carefully and an appropriate symptomatic treatment (including antihistamines, adrenaline and/or glucocorticoids) must also be initiated in such cases. Cross reactions, sometimes fatal, have been reported with all the platinum compounds (see sections 4.3 and 4.8).

The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.

Renal Toxicity

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).

Precautions:

Carboplatin should only be administered under the supervision of a qualified physician who is experienced in the use of chemotherapeutic agents. Diagnostic and treatment facilities should be readily available for management of therapy and possible complications.

Peripheral blood counts, renal and hepatic function tests should be monitored closely. Blood counts should be performed prior to commencement of carboplatin therapy and at weekly intervals thereafter. 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 treatment. This will monitor toxicity and help determine the nadir and recovery of haematological parameters and assist in subsequent dosage adjustments. Median day of nadir is day 21 in patients receiving single agent carboplatin and day 15 in patients receiving carboplatin in combination with other chemotherapeutic agents. In general, single intermittent courses of carboplatin should not be repeated until leukocyte, neutrophil, and platelet counts have returned to normal. Lowest levels of platelets are generally seen between days 14 and 21 of initial therapy. A greater reduction is seen in patients who previously received extensive myelosuppressive chemotherapy. Lowest levels of white cells occur generally between days 14 and 28 of initial therapy. If neutrophil levels fall below 2000 cells/mm3 or platelets are less than 100,000 cells/mm3 then postponement of carboplatin therapy until bone barrow recovery is evident, should be considered. This recovery usually takes 5 to 6 weeks. Transfusions may be necessary and dosage reductions recommended for subsequent treatment.

Anaemia is frequent and cumulative, however rarely requires a transfusion.

Haemolytic-uremic syndrome (HUS)

Haemolytic-uremic syndrome (HUS) is a life-threatening side effect. Carboplatin should be discontinued at the first signs of any evidence of micro-angiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or LDH. Renal failure may not be reversible with discontinuation of therapy and dialysis may be required.

Renal toxicity

The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function before carboplatin treatment. It is not clear whether an appropriate hydration programme might overcome such an effect but dosage reduction or discontinuation of therapy is required in the presence of severe alteration in renal function test. Impairment of renal function is more likely in patients who have previously experienced nephrotoxicity as a result of cisplatin therapy.

Neurologic Toxicity

Although peripheral neurologic toxicity is generally common and mild, limited to paresthesia and decreases in 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 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.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

Cases of Reversible Posterior Leukoencephalopathy Syndrome (RPLS) have been reported in patients receiving carboplatin in combination chemotherapy. RPLS is a rare, reversible (after treatment discontinuation), rapidly evolving neurological condition, which can include seizure, hypertension, headache, confusion, blindness, and other visual and neurological disturbances (see section 4.8). Diagnosis of RPLS is based upon confirmation by brain imaging, preferably MRI (Magnetic Resonance Imaging).

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.

Other

Auditory defects have been reported during carboplatin therapy. Ototoxicity may be more pronounced in children and is more likely seen in patients previously treated with cisplatin. Cases of hearing loss with a delayed onset have been reported in pediatric 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.

Aluminium-containing equipment should not be used during preparation and administration of carboplatin (see section 4.5).

4.5 Interaction with other medicinal products and other forms of interaction

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 cases of tumoral diseases, the use of anticoagulative treatment is frequent. The high intra-individual variability of the coagulabilty during diseases, and the possibility of interaction between oral anticoagulants and anticancer chemotherapy, may require an increase in frequency of INR monitoring if a patient is treated with oral anticoagulants.

Concomitant use contraindicated

Yellow fever vaccine: risk of generalised disease mortal (see section 4.3).

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 exist (poliomyelitis).

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

Concomitant use to take into consideration

– Ciclosporin (and by extrapolation tacrolimus and sirolimus): Excessive immunosuppression with risk of lymph proliferation.

– Concurrent therapy with nephrotoxic or ototoxic drugs such as aminoglycosides, vancomycin, capreomycin and diuretics, may increase or exacerbate toxicity, particularly in renal failure patients, due to carboplatin induced changes in renal clearance.

– Loop diuretics: The concomitant use of carboplatin with loop diuretic should be approached with caution due to the cumulative nephrotoxicity and ototoxicity.

Combination therapy with other myelosuppressive agents may require dose changes or rescheduling of doses in order to minimise the additive myelosuppressive effects.

4.6 Fertility, pregnancy and lactation

Pregnancy

Carboplatin can cause foetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryo toxic and teratogenic in rats receiving the drug during organogenesis. No controlled studies in pregnant women have been conducted.

Safe use of carboplatin in pregnancy has not been established. Both men and women receiving carboplatin should be informed of the potential risk of adverse effects on reproduction (see section 5.3). Women of childbearing potential should be fully informed of the potential hazard to the foetus should they become pregnant during carboplatin therapy. Carboplatin should not be used in pregnant women or women of childbearing potential who might become pregnant unless the potential benefits to the mother outweigh the possible risks to the foetus.

Breast-feeding

It is not known whether carboplatin is excreted in breast milk. To avoid possible harmful effects in the infant, breast-feeding must be stopped during carboplatin therapy.

Fertility

Gonadal suppression resulting in amenorrhoea or azoospermia 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 functional 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 advised not to father a child during treatment and up to 6 months afterwards. Male patients should seek advice about sperm preservation prior to initiation of the therapy because of the possibility of irreversible infertility due to therapy with carboplatin.

4.7 Effects on ability to drive and use machines

No studies of 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 of the potential effect of these events on the ability to drive or to use machines.

4.8 Undesirable effects

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

System Organ Class Frequency MedDRA Term
Neoplasms, benign and malignant and unspecified (incl cysts and polyps) Not known Treatment related secondary malignancy
Infections and infestations Common Infections*
Not known Pneumonia
Blood and lymphatic system disorders Very common Thrombocytopenia, neutropenia, leukopenia, anaemia
Common Haemorrhage*
Not known Bone marrow failure, febrile neutropenia, haemolytic-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*, encephalopathy, Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Eye disorders Common Visual disturbance (incl. 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, pancreatitis
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
Investigations Very Common Creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver function 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.

Blood and lymphatic system disorders:

Myelosuppression is the dose-limiting toxicity of carboplatin injection. In patients with normal baseline values, thrombocytopenia with platelet counts below 50,000/mm3 occurs in 25% of patients, neutropenia with granulocyte counts below 1,000/mm3 in 18% of patients, and leukopenia with WBC counts below 2,000/mm3 in 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.

Neoplasms, benign, malignant and unspecified (including cysts and polyps):

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

Respiratory, thoracic and mediastinal disorders:

Pulmonary fibrosis has been reported very rarely, manifested by tightness of the chest and dyspnoea. This should be considered if a pulmonary hypersensitivity state is excluded (see General disorders below).

Gastrointestinal disorders:

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. Nausea and vomiting are generally delayed until 6 to 12 hours after administration of carboplatin, are readily controlled or prevented with antiemetics and disappear within 24 hours. Vomiting is more likely when carboplatin injection is given in combination with other emetogenic compounds.

The other gastrointestinal complaints corresponded to pain in 8% of patients, diarrhoea, and constipation in 6 % of patients. Cramps have also been reported.

Nervous system disorders:

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. Parasthesias present prior to treatment, especially if caused by cisplatin, may persist or worsen during carboplatin therapy (see section 4.4).

Eye disorders:

Visual disturbances, including sight loss, are usually associated with high dose therapy in renally impaired patients.

Ear and labyrinth disorders:

A subclinical decrease in hearing acuity in the high frequency range (4000-8000 Hz), determined by audiogram, occurred in 15% of patients. Very rare cases of hypoacusia have been reported.

Tinnitus was also commonly reported. Hearing loss as a result of cisplatin therapy may give rise to persistent or worsening symptoms. At higher than recommended doses, in common with other ototoxic agents, clinically significant hearing loss has been reported to occur in paediatric patients when carboplatin is administered.

Hepatobiliary disorders:

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-dose administration of carboplatin.

Renal and urinary disorders:

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. Impairment of renal function is more likely in patients who have previously experienced nephrotoxicity as a result of cisplatin therapy.

Immune system disorders:

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.

Fever with no apparent cause has also been reported.

Skin and subcutaneous tissue disorders:

Erythematous rash, fever and pruritis have been observed. These were reactions similar to those seen after cisplatin therapy but in a few cases no cross-reactivity was present.

Investigations:

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.

Cardiac disorders:

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

General disorders and administration site conditions:

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

Fever, chills and mucositis have occasionally been observed.

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

There is no known antidote for carboplatin overdosage. No overdosage occurred during clinical trials. If necessary, however, the patient may need supportive treatment relating to myelosuppression, renal, hepatic and auditory function impairment. Reports of doses up to 1600mg/m2 indicate patients feeling extremely ill with diarrhoea and alopecia developing. Use of higher than recommended doses of carboplatin has been associated with loss of vision (see section 4.4).

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antineoplastic agent.

Carboplatin, like Cisplatin, interferes with DNA intra-strand and inter-strand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.

Paediatric population

Safety and efficacy in children have not been established.

5.2 Pharmacokinetic properties

Absorption

After a 1-hour Injection (20-520mg/m2), plasma levels of total platinum and free (ultra filterable) 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.

Distribution

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. Patients with poor renal function may require dosage adjustments due to altered pharmacokinetics of carboplatin.

Elimination

Carboplatin is excreted primarily by glomerular filtration in urine, with recovery of 65% of a dose within 24 hours. Most of the drug is excreted within the first 6 hours. Approximately 32% of a given dose of carboplatin is excreted unchanged.

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.

5.3 Preclinical safety data

Carboplatin has been shown to be embryo toxic 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.

  1. Pharmaceutical particulars

6.1 List of excipients

Water for injections BP.

6.2 Incompatibilities

Aluminium-containing equipment should not be used (see section 4.5).

6.3 Shelf life

2 years

In use:

Carboplatin solution for Injection may be further diluted in Glucose 5% and administered as an intravenous Injection. Chemical and physical in-use stability has been demonstrated for 56 days to final concentrations of 0.2 mg/ml and 3.5mg/ml when stored at 2-8 °C in non-PVC (polyolefin) Injection bags when protected from light.

Carboplatin solution for Injection may also be further diluted in Sodium Chloride 0.9% and administered as an intravenous Injection. The Injection solution is chemically stable for up to 24 hours when stored at 2-8°C and up to 8 hours when stored at 22°C.

From a microbiological point of view however, 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 dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Clear glass and Onco-Tain® vials;

Do not store above 25°C. Keep the vial in the outer carton in order to protect from light.

Onco-Vials®;

Store in a refrigerator (2-8°C). Keep the vial in the outer carton in order to protect from light.

6.5 Nature and contents of container

Carboplatin Intravenous Injection is supplied in individually packed clear glass, Onco-Tain® vials and Onco-Vials®, containing either 5 ml, 15 ml, 45 ml or 60 ml of a sterile solution of carboplatin 10 mg per ml.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particular matter is observed, shake and re-inspect. Vials with visible particulate matter should not be used.

Handling:

Carboplatin should be prepared for administration only by professionals who have been trained in the safe use of chemotherapeutic agents.

Contamination

In the event of contact of carboplatin with eyes or skin, wash affected area with copious amounts of water or normal saline. A bland cream may be used to treat transient stinging of skin. Medical advice should be sought if the eyes are affected.

In the event of a spillage, two operators should put on gloves and mop up the spilled material with a sponge kept for that purpose. In the event of a powder spillage, cover with a cloth and moisten with water before mopping up. Rinse the area twice with water. Put all solutions and sponges in a plastic bag, seal and label with the words ‘CYTOTOXIC WASTE’ and incinerate.

 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).

Carboplatin Injection BP 150mg/15mL 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 any further questions, ask your doctor or
  • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section
What is in this leaflet
  1. What Carboplatin Intravenous Injection is and what it is used for
  2. What you need to know before you use Carboplatin Intravenous Injection
  3. How to use Carboplatin Intravenous Injection
  4. Possible side effects
  5. How to store Carboplatin Intravenous Injection
  6. Contents of the pack and other information
1.  What Carboplatin Intravenous Injection is and what it is used for

Carboplatin Intravenous Injection is an anti-cancer medicine. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Carboplatin is used in the treatment of some types of lung cancer and ovarian cancer.

2.  What you need to know before you use Carboplatin Intravenous Injection Do not use Carboplatin Intravenous Injection
  • if you are allergic to carboplatin or to any of the ingredients of this medicine (listed in section 6)
  • if you have had hypersensitivity to similar platinum containing medicines in the past
  • if you have severe kidney disease
  • if you have fewer blood cells than normal (your doctor will check this with a blood test)
  • if you have a tumour that bleeds
  • if you plan to receive a yellow fever vaccination or have just received one Tell your doctor if any of the above applies to you before this medicine is
Warnings and Precautions

Talk to your doctor, pharmacist or nurse before using Carboplatin Intravenous Injection

  • if you are pregnant or if there is a chance you may be
  • if you are breast-feeding.
  • if you have mild renal disease. Your doctor will want to monitor you more
  • if you are elderly (over 65 years old).
  • if you have been treated with cisplatin or similar anti-cancer medicines in the past, carboplatin may cause abnormalities in your nervous system, such as pins and needles or hearing and vision problems. Your doctor may regularly assess
  • if you have headache, altered mental functioning, seizures and abnormal vision (from blurriness to vision loss).
  • if you develop extreme tiredness and shortness of breath with decreased number of red blood cells, (haemolytic anaemia), alone or combined with low platelet count, abnormal bruising (thrombocytopenia) and kidney disease where you pass little or no urine (symptoms of Haemolytic-uraemic syndrome).
  • if you have fever (temperature greater than or equal to 38oC), or chills, which could be signs of infection. You may be at risk of getting an infection of the
Other medicines and Carboplatin Intravenous Injection

Tell your doctor, pharmacist or nurse if you taking, have recently taken or might take any other medicines, for example:

  • medicines which can reduce the number of cells in your blood, at the same time as carboplatin, may require changes to the dosage and frequency of your carboplatin treatment
  • some antibiotics called aminoglycosides, vancomycin or capreomycin, at the same time as carboplatin, may increase the risk of kidney or hearing problems
  • some water tablets (diuretics), at the same time as carboplatin, may increase the risk of kidney or hearing problems
  • live or live-attenuated vaccines (for yellow fever vaccine see section 2, Do not use Carboplatin Intravenous Injection)
  • blood thinning medicines e.g. warfarin, at the same time as carboplatin, may require an increase in frequency of blood coagulation monitoring
  • phenytoin and fosphenytoin (used to treat various types of convulsions and seizures), at the same time as carboplatin, may increase the risk of a seizure
  • other medicines which decrease the activity of the immune system (e.g.ciclosporin, tacrolimus, sirolimus)
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 for advice before taking this medicine.

Due to the possible risk of birth defects, female patients of childbearing potential should take contraceptive measures before and during treatment with carboplatin.

Men treated with this medicine are advised not to father a child during, and up to 6 months after treatment. Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility.

Treatment with carboplatin may temporarily or permanently reduce fertility in men and women. Tell your doctor if you have concerns.

Driving and using machines

Do not drive or use machines if you experience any side effect which may lessen your ability to do so such as nausea, vomiting, worsening of eyesight, or changes to your vision and hearing.

The Carboplatin Intravenous Injection vial stopper contains dry natural rubber

The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.

  1. How to use Carboplatin Intravenous Infusion

This medicine will be given by infusion (drip) into a vein over 15-60 minutes.

Dose

Your doctor will work out the correct dose of carboplatin for you and how often it must be given.

The recommended dose will depend on your medical condition, your size and how well your kidneys are working. Your doctor will tell how well your kidneys are working using blood or urine samples.

You will have regular blood tests after your dose of carboplatin. You may also have checks for nerve damage and hearing loss.

There is likely to be about 4 weeks between each dose of carboplatin.

If you are given too much Carboplatin Intravenous Infusion than you should

This medicine will be given to you in a hospital, under the supervision of a doctor. It is unlikely that you will be given too much or too little, however, tell your doctor or nurse if you have any concerns.

  1. Possible side effects

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

If any of the following happen, tell your doctor immediately:

  • abnormal bruising, bleeding, or signs of infection such as a sore throat and high temperature
  • severe allergic reaction (anaphylaxis/anaphylactic reactions) – you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint
  • haemolytic-uraemic syndrome (a disease characterised by acute kidney failure), decreased urination or blood in the urine

These are serious side effects. You may need urgent medical attention.

Very common: may affect more than 1 in 10 people

  • tiredness, shortness of breath and paleness caused by anaemia (a condition in which there is a decreased number of red blood cells)
  • feeling sick (nausea) or being sick (vomiting)
  • stomach pain and cramp

Tests may also show:

  • changes in your red and white blood cells and platelets (myelosuppresion)
  • increase in the level of urea in your blood
  • decrease in the level of sodium, potassium, calcium and magnesium in your blood
  • decrease in renal creatinine clearance
  • abnormal liver enzyme levels

Common: may affect up to 1 in 10 people

  • signs of infection such as fever or sore throat
  • flu-like symptoms
  • symptoms of severe allergic reaction include sudden wheeziness or tightness of chest, swelling of the eyelids, face or lips, facial flushing, low blood pressure, rapid heart beat, hives, shortness of breath, dizziness and anaphylactic shock
  • tingling or numbness in your hands, feet, arms or legs
  • burning or prickling sensation
  • decreased tendon reflex
  • taste disturbance or loss of taste
  • temporary worsening of eyesight or changes to your vision
  • ringing in the ears or changes in your hearing
  • heart disorders
  • tightness of the chest or wheezing
  • interstitial lung disease (a group of lung disorders in which the deep lung tissues become inflamed)
  • diarrhoea or constipation
  • sore lips or mouth ulcers (mucous membrane disorders)
  • hair loss
  • rash and/or itchy skin
  • pain or discomfort in your bones, joints, muscles, or surrounding structures (musculoskeletal disorder)
  • problems with your kidneys or urine
  • extreme tiredness/weakness (asthenia)

Tests may also show:

  • increased level of bilirubin and creatinine in your blood
  • increased level of uric acid in your blood which may lead to gout

Rare: may affect up to 1 in 1,000 people

  • temporary sight loss

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

  • scarring of the lungs which causes shortness of breath and/or cough (pulmonary fibrosis)

Not known: frequency cannot be estimated from available data

  • cancers caused by treatment with carboplatin (secondary malignancies)
  • feeling unwell with high temperature due to low levels of white blood cells (febrile neutropenia)
  • a group of symptoms such as headache, altered mental functioning, seizures and abnormal vision (from blurriness to vision loss). These are symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder
  • dry mouth, tiredness, and headache due to excessive loss of body water (dehydration)
  • loss of appetite, anorexia
  • pancreatitis
  • stroke (sudden numbness or weakness in the face, arm, or leg, especially on one side of the body)
  • severely impaired liver function, damage or death of liver cells
  • heart failure
  • obstruction in blood vessel (embolism), swelling or tenderness of leg/arm
  • changes in blood pressure (hypertension or hypotension)
  • skin disorders such as hives, rash, skin redness (erythema), and itching
  • swelling or soreness where the injection was given
  • lung infection

Carboplatin may lead to problems with your blood, liver and kidneys. Your doctor will take blood samples to check for these problems.

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Carboplatin Intravenous Infusion

Keep this medicine out of the sight and reach of children.

Expiry

Do not use this medicine after the expiry date which is stated on the vial label and carton after ‘EXP’. Where only a month and year is stated, the expiry date refers to the last day of that month.

Storage

This medicine comes in two types of vial, ONCO-VIAL® and standard vials.

ONCO-VIAL® – store in a refrigerator (2 to 8°C). Keep the vial in the outer carton in order to protect from light.

Standard vials – Do not store above 25°C. Keep the vial in the outer carton in order to protect from light.

If Carboplatin for Intravenous Infusion is diluted before use, the diluted solution should be used immediately. If not used immediately it should not normally be stored for longer than 24 hours at 2 to 8ºC.

  1. Contents of the pack and other information What Carboplatin Intravenous Infusion contains

The active substance is carboplatin. Each millilitre (ml) of solution contains 10 milligrams (mg) of carboplatin.

The other ingredient is water for injections BP.

What Carboplatin Intravenous Infusion looks like and contents of the pack

Carboplatin Intravenous Infusion is a clear, colourless solution for infusion which comes in glass containers called vials.

 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).

Related Products

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.