Carboplatin is indicated for the treatment of:
1. Advanced Ovarian Carcinoma of Epithelial Origin in:
 first-line therapy
 second-line therapy, after other treatments have failed
2. Small Cell Carcinoma of the Lung

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 > 60ml/min is 400mg/m2 given as a single short-term intravenous 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
5-7 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.
Calvert Formula should not be used in patients who have received extensive pre-treatment**.
**Patients are considered heavily pre-treated if they have received any of the following:
 Mitomycin C
 Nitrosourea
 Combination therapy with Doxorubicin/Cyclophosphamide/Cisplatin
 Combination therapy with 5 or more agents
 Radiotherapy ≥ 4,500 rad, focused on a 20 x 20cm field or on more than one field of therapy

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 future dosage adjustment and scheduling of Carboplatin.
Needles or intravenous sets containing aluminium parts that may come in contact with Carboplatin should
not be used for preparation or administration. Aluminium reacts with Carboplatin 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 of less than 60ml/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)
41-59ml/min 250mg/m2 I.V.
16-40ml/min 200mg/m2 I.V.
Insufficient data exist on the use of Carboplatin injection in patients with creatinine clearance of 15ml/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
In patients of more than 65 years of age, adjustment of the Carboplatin dose to the general condition and
renal function is necessary during the first and the subsequent therapeutic courses.
Paediatric population
The safety and efficacy of carboplatin in children has not yet been established. No data are available.
Method of administration
Dilution and Reconstitution
The product must be diluted prior to infusion, see Section 6.6.

Carboplatin is contraindicated in:  hypersensitivity to the active substance or to any of the excipients listed in Section 6.1  patients with severe myelosuppression  patients with pre-existing severe renal impairment (with creatinine clearance of ≤ 30ml/min), unless in the judgment of the physician and patient, the possible benefits of treatment outweigh the risks  patients with bleeding tumors  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

Carboplatin is contraindicated in:
 hypersensitivity to the active substance or to any of the excipients listed in Section 6.1
 patients with severe myelosuppression
 patients with pre-existing severe renal impairment (with creatinine clearance of ≤ 30ml/min), unless
in the judgment of the physician and patient, the possible benefits of treatment outweigh the risks
 patients with bleeding tumors
 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 impairment (see Section 4.2).

Precautions
Carboplatin should be administered by individuals under the supervision of a qualified physician who is
experienced in the use of anti-neoplastic therapy. 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.
Diagnostic and treatment facilities should be readily available for management of therapy and possible
complications.
Warnings
Haematological 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 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.
Supportive transfusional therapy may be required in patients who suffer severe myelosuppression.
Haemolytic anaemia with the presence of serologic drug-induced antibodies has been reported in patients
treated with Carboplatin. This event can be fatal.
Acute promyelocytic leukaemia and myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)
have been reported years after therapy with Carboplatin and other antineoplastic treatments.
Hepatic and/or renal insufficiency
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).
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 (see Section 4.5).
The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function
before carboplatin treatment. Impairment of renal function is more likely in patients who have previously
experienced nephrotoxicity as a result of Cisplatin therapy.
Venoocclusive liver disease
Cases of hepatic venoocclusive disease (sinusoidal obstruction syndrome) have been reported, some of
which were fatal. Patients should be monitored for signs and symptoms of abnormal liver function or
portal hypertension which do not obviously result from liver metastases.
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. Infrequent

allergic reactions to Carboplatin have been reported, e.g. erythematous rash, fever with no apparent cause
or pruritus. Rarely anaphylaxis, angio-oedema and anaphylactoid reactions including bronchospasm,
urticaria and facial oedema have occurred.
Patients should be observed carefully for possible allergic reactions and managed with appropriate
supportive therapy, including antihistamines, adrenaline and/or glucocorticoids. The occurrence and
severity of toxicity is likely to be greater in patients who have received extensive prior treatment for their
disease, have poor performance status and are advanced in years. Renal function parameters should be
assessed prior to, during and after Carboplatin therapy.
Cross reactions, sometimes fatal, have been reported with all the Platinum compounds (see Section 4.3
and Section 4.8).
The vial stopper contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
Neurotoxicity
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.
Ototoxicity
Auditory defects have been reported during Carboplatin therapy.
Ototoxicity in children
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 paediatric patients. A
long-term audiometric follow-up in this population is recommended.
Tumour Lysis Syndrome (TLS)
In post-marketing experience Tumour Lysis Syndrome (TLS) has been reported in patients following the
use of Carboplatin alone or in combination with other chemotherapeutic agents. Patient at high risk of
TLS, such as patients with high proliferative rate, high tumor burden, and high sensitivity to cytotoxic
agents, should be monitored closely and appropriate precaution taken.
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).
Vaccinations
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.
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 minimize additive effects.
Carboplatin courses should not, in general, be reported 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.
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).
Haemolytic-Uraemic Syndrome (HUS)
Haemolytic-Uraemic Syndrome (HUS) is a life threatening side effect. Carboplatin should be discontinued
at the first signs of any evidence of microandiopathic haemolytic anaemia, such as rapidly falling
haemoglobin with concomitant thrombocytopaenia, elevation of serum bilirubin, serum creatine, blood
urea nitrogen, or LDH. Renal failure may not be reversible with discontinuation of therapy and dialysis
may be required.
Other
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. Carboplatin can cause nausea and
vomiting. Premedication with antiemetics has been reported to be useful in reducing the incidence and
intensity of these effects.
Aluminium containing equipment should not be used during preparation and administration of Carboplatin
(see Section 6.2). Aluminium reacts with Carboplatin injection causing precipitate formation and/or loss
of potency.

When combining Carboplatin with other myelosuppressive compounds or radiation therapy, the
myelosuppressive effect of Carboplatin and/or the other compounds may be more pronounced. Patients
receiving concomitant therapy with other nephrotoxic agents are likely to experience more severe and
prolonged myelotoxicity due to decreased renal clearance of Carboplatin.
Combination therapy with other myelosuppressive agents may require dose changes or rescheduling of
doses in order to minimize the additive myelosuppressive effects.

Concomitant use contraindicated
 Yellow fever vaccine: Risk of generalized vaccinal disease mortality (see Section 4.3.)
Concomitant use not recommended
 Live attenuated vaccines (except yellow fever): Risk of systemic, possible fatal disease. This is
increased in subjects who are already immunosuppressed by their underlying disease. Use 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 be taken into consideration
 Chelating agents - decreasing effect of Carboplatin
 Ciclosporin (and by extrapolation Tacrolimus and Sirolimus): Excessive immunosuppression with
risk of lymphoproliferation
 Aminoglycosides, Vancomycin, Capreomycin: The concomitant use of Carboplatin with
aminoglycosides, Vancomycin, Capreomycin should be taken into account due to the cumulative
nephrotoxicity and ear toxicity, particularly in patients with severe renal impairment.
 Loop diuretics: The concomitant use of Carboplatin with loop diuretic should be approached with
caution due taken into account due to the cumulative nephrotoxicity and ear ototoxicity.
 Due to increase of thrombotic risk in cases of tumoral diseases, the use of anticoagulative treatment
is frequent. The high intra-individual variability of the coagulability during diseases, and the
eventuality of interaction between oral anticoagulants and anticancer chemotherapy, may require, if
it is decided to treat patients with VKA, to increase the frequency of the control of the INR
monitoring. if a patient is treated with oral anticoagulants. Caution and more frequent INR monitoring
is recommended with concomitant treatment of warfarin with Carboplatin, as increased INR has been
reported.
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.

Pregnancy
Carboplatin can cause foetal 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.
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.
Breastfeeding
It is not known whether Carboplatin is excreted in breast milk.
To avoid possible harmful effects in the infant, breastfeeding must be stopped during Carboplatin therapy.
Fertility
Gonadal suppression resulting in amenorrhoea 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 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 further 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.

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.

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)

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 8g/dl has been observed in 15% of patients with normal baseline
values. The incidence of anaemia is increased with increasing exposure to Carboplatin injection.
Myelosuppression may be more severe and prolonged in patients with impaired renal function, extensive
prior treatment, poor performance status and age above 65.
At maximum tolerated dosages of Carboplatin administered as a single agent, thrombocytopenia, with
nadir platelet counts of less than 50 x 109/l, occurs in about a third of the patients. The nadir usually occurs
between days 14 and 21, with recovery within 35 days from the start of therapy.
Leukopenia has also occurred in approximately 20% of patients but its recovery from the day of nadir
(day 14-28) may be slower and usually occurs within 42 days from the start of therapy. Neutropenia with
granulocyte counts below 1 x 109/l occurs in approximately one fifth of patients. Haemoglobin values
below 9.5 mg/100ml have been observed in 48%of patients with normal baseline values.
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
Very rare: Pulmonary fibrosis 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 24hours.
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
Very common: A subclinical decrease in hearing acuity in the high frequency range (4000-8000 Hz),

10
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 8g/dl has been observed in 15% of patients with normal baseline
values. The incidence of anaemia is increased with increasing exposure to Carboplatin injection.
Myelosuppression may be more severe and prolonged in patients with impaired renal function, extensive
prior treatment, poor performance status and age above 65.
At maximum tolerated dosages of Carboplatin administered as a single agent, thrombocytopenia, with
nadir platelet counts of less than 50 x 109/l, occurs in about a third of the patients. The nadir usually occurs
between days 14 and 21, with recovery within 35 days from the start of therapy.
Leukopenia has also occurred in approximately 20% of patients but its recovery from the day of nadir
(day 14-28) may be slower and usually occurs within 42 days from the start of therapy. Neutropenia with
granulocyte counts below 1 x 109/l occurs in approximately one fifth of patients. Haemoglobin values
below 9.5 mg/100ml have been observed in 48%of patients with normal baseline values.
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
Very rare: Pulmonary fibrosis 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 24hours.
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
Very common: A subclinical decrease in hearing acuity in the high frequency range (4000-8000 Hz),
11
determined by audiogram, occurred in 15% of patients. Very rare cases of hypoacusia have been reported.
Common: 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 60ml/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.
Very common: Renal toxicity is usually not dose-limiting in patients receiving Carboplatin, nor does it
require preventive measures such as high-volume fluid hydration or forced diuresis.
Common: Renal function impairment, as defined by a decrease in the creatinine clearance below
60ml/min.
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.
Hepatobiliary disorders
Very common: The alkaline phosphatase level is increased more frequently than SGOT, SGPT or total
bilirubin. The majority of these abnormalities regress spontaneously during the course of treatment.
Rare: Severe hepatic dysfunction (including acute liver necrosis) has been reported after administration of
higher than recommended carboplatin dosages.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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 to The National Pharmacovigilance Centre (NPC).
To report any side effect(s) in Saudi Arabia, please contact:
p
The National Pharmacovigilance Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Ext: 2317-2356-2340
SFDA Call Centre: 19999
E-mail : npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa/

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).

Pharmacotherapeutic group: Antineoplastic agent, Platinum compounds
ATC group: 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

Distribution
Repeated dosing during four consecutive days did not produce an accumulation of Platinum in plasma.
Biotransformation
After a 1-hour infusion (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.
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.
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 clearance has been reported to vary by 3- to 4- fold in paediatric patients (see Section 4.2 and
4.4). As for adult patients, literature data suggest that renal function may contribute to the variation in
Carboplatin clearance.
Linearity/non-linearity
Following administration of Carboplatin in man, linear relationships exist between dose and plasma
concentrations of total and free ultra-filterable Platinum. The area under the plasma concentration versus
time curve for total Platinum also shows a linear relationship with the dose when creatinine clearance ≥
60ml/min.

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 Injection

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
intravenous 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.

24months Shelf life after dilution In use: Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature and 30 hours at 2°C to 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°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Keep out of sight and reach of children.
Do not store above 30°C. Do not refrigerate or freeze.
Keep vial in the outer carton in order to protect from light.
Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to the
last day of that month.
For storage conditions of the diluted medicinal product, see Section 6.3.

Cartinum 10mg/ml concentrate for Solution for Infusion is filled in Type-I amber glass vial sealed with
rubber stopper and flip-off cap.
Pack sizes:
1 × 5ml vial (50mg/5ml)
1 × 15ml vial (150mg/15ml)
1 X 45ml vial (450mg/45ml)
1 × 60ml vial (600mg/60ml)
Not all pack sizes may be marketed.

This product is for single-dose use only. Discard any unused portion.
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.
Disposal
Any unused product or waste material should be disposed of in accordance with local requirement.
Dilution
The product must be diluted prior to infusion, with 5% dextrose solution or 0.9% sodium chloride solution,
to concentrates as low as 0.5mg/ml.
Special precautions for administration
This product is a concentrate and must be diluted before use. After first opening, the product should be
used immediately. Discard any unused portion.