Consumer medicine information

Carboplatin Injection (Pfizer)

Carboplatin

BRAND INFORMATION

Brand name

Pfizer (Australia) Carboplatin

Active ingredient

Carboplatin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Carboplatin Injection (Pfizer).

What is in this leaflet

This leaflet answers some common questions about Carboplatin Injection.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Carboplatin Injection against the benefits it is expected to have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Carboplatin Injection is used for

Carboplatin belongs to a group of anticancer medicines known as platinum complexes. Carboplatin works by preventing the growth of cancer cells and eventually destroying them. It is used for cancer of the ovary.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

Before you are given Carboplatin Injection

When you must not be given it

Do not use Carboplatin Injection if:

  • you have an allergy to carboplatin, other medicines containing platinum (cisplatin)
  • you have severe kidney disease or poor kidney function (your dose may be reduced with some milder conditions)
  • you have a low blood count
  • severe bleeding

Females: Do not use this medicine if you are pregnant or planning to become pregnant. Avoid becoming pregnant by using effective contraception during treatment and up to 6 months after therapy. It may affect your developing baby if you take it during pregnancy.

Males: Tell your doctor or pharmacist if your partner intends to become pregnant while you are being given Carboplatin Injection, or shortly after you have stopped treatment with carboplatin.

Carboplatin may cause birth defects if either the male or female is using it at the time of conception. It is recommended that you use some kind of birth control while you are using Carboplatin Injection and for at least 3 months after you stop treatment. A barrier method of birth control, such as a condom, should be used while you are being given carboplatin and for the 3-month period after your last dose. Your doctor will discuss this with you.

Do not breast feed if you are using this medicine.

If you are not sure you should be given Carboplatin, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant.

Tell your doctor if you are breast-feeding or plan to breast-feed.

Tell your doctor if you have or have had any of the following medical conditions:

  • any sort of infection e.g. sinusitis, tooth abscess, etc
  • abnormal, heavy bleeding or problems with blood clotting
  • bleeding gums
  • unusual tiredness
  • poor kidney function
  • problems with hearing
  • low levels of red blood cells, white blood cells or platelets
  • problems with the nervous system such as numbness, tingling, weakness of limbs; headache, seizures, confusion, vision disturbances
  • herpes zoster infections (also known as shingles)
  • chicken pox (now or recently), or if you have been in recent contact with someone who has chicken pox.

Tell your doctor if you have had previous treatment with cisplatin.

Tell your doctor if you have an infection or high temperature. Your doctor may decide to delay your treatment until the infection has gone. A mild illness, such as a cold, is not usually a reason to delay treatment.

Tell your doctor if you are going to be vaccinated (have an injection to prevent a certain disease).

If you have not told your doctor about any of the above, tell him/her before you are given Carboplatin.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Carboplatin may interfere with each other. These include:

  • other anticancer drugs (such as paclitaxel and cyclophosphamide), radiation therapy or any other treatment which weakens your immune system
  • drugs that affect the kidneys such as some antibiotics
  • some vaccinations (injections to prevent you getting a certain disease).
  • phenytoin/fosphenytoin

You may need different amounts of your medicines or you may need to take different medicines. Your doctor will advise you.

How Carboplatin is given

Carboplatin is given by slow injection into a vein. It must only be given by a doctor or a nurse.

Your doctor will decide what dose, how often and how long you will receive it.

This depends on your condition and other factors, such as your weight, age, blood tests, how well your kidneys are working and whether or not other medicines are being given at the same time.

If you are given too much (overdose)

Overdose is unlikely as treatment is given in hospital under the supervision of a doctor.

However, if you are given too much Carboplatin, you may experience some of the effects listed under "Side Effects" below.

Ask your doctor if you have any concerns. Your doctor has information on how to recognise and treat an overdose.

While you are being treated with Carboplatin

Things you must do

Keep all of your doctor's appointments so that your progress can be checked.

You will also have blood pressure checks, blood and hearing tests to check for side effects.

Tell any other doctors, dentists and pharmacists who treat you that you are using this medicine.

If you become pregnant while using this medicine, tell your doctor immediately.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are using Carboplatin Injection.

Like other medicines, Carboplatin can cause some side effects. If they occur, most are likely to be minor or temporary. However, some may be serious and need medical attention.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • taste abnormalities
  • pain and redness at site of injection
  • weakness, tiredness or fatigue
  • joint pain, muscle pain
  • diarrhoea, constipation
  • mild nausea and vomiting
  • hair loss, especially of the scalp.

Tell your doctor or nurse as soon as possible if you notice any of the following:

  • hearing loss or ringing in the ears (tinnitus)
  • muscle irritability or cramps
  • tingling or a loss of sensation in the fingers or toes
  • blurred vision
  • flaking or peeling of the skin, rash or itchy rash.

Tell your doctor or nurse immediately if you notice any of the following or go to Accident and Emergency at your nearest hospital:

  • signs of an allergic reaction (such as shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin; dizziness or light-headedness)
  • signs of infection, such as fever and chills, sore throat, sweats or feel generally unwell
  • headaches, changes in mental status (confusion, thinking abnormal, altered consciousness) or seizures
  • visual disturbances or loss
  • shortness of breath
  • tremor
  • looking pale and yellowing of the skin and/or eyes
  • rapid breathing or rapid heart rate
  • bleeding, unusual bruising, bleeding gums, blood in the urine or stools, or pinpoint red spots
  • rash, fever or itching
  • swollen face or limbs, abdominal pain or swelling
  • mouth ulcers or sore mouth
  • severe nausea, vomiting
  • a feeling of tiredness
  • chest pain, stroke, a feeling of tightness, pressure or heaviness in the chest
  • decrease in urine.

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

Other side effects not listed above may also occur in some patients.

Tell your doctor if you notice any other effects.

Some side effects may only be seen by your doctor.

Product description

What it looks like

Carboplatin Injection is a clear, colourless solution in a plastic vial.

It comes in three sizes: 50 mg of carboplatin in 5 mL, 150 mg in 15 mL and 450 mg in 45 mL.

Ingredients

Carboplatin Injection contains carboplatin as the active ingredient.

It also contains Water for Injections. It does not contain a preservative.

Supplier

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Numbers

50 mg / 5 mL - AUST R 42853

150 mg / 15 mL - AUST R 49348

450 mg / 45 mL - AUST R 49349

Date of preparation

This leaflet was prepared in August 2022.

Published by MIMS October 2022

BRAND INFORMATION

Brand name

Pfizer (Australia) Carboplatin

Active ingredient

Carboplatin

Schedule

S4

 

1 Name of Medicine

Carboplatin.

2 Qualitative and Quantitative Composition

Carboplatin Injection is a sterile, hypotonic, preservative-free solution containing carboplatin 10 mg/mL in water for injections.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of advanced ovarian carcinoma of epithelial origin.

4.2 Dose and Method of Administration

Dosage.

The recommended dosage for previously untreated adults (with normal renal function) is 400 mg/m2 as a single intravenous infusion over 15-60 minutes. Therapy should not be repeated again until four weeks have elapsed.
In patients with risk factors, such as previous myelosuppressive therapy or in the aged, the initial dosage may need to be reduced by 20-25%.
Determination of the haematological nadir by weekly blood counts is recommended for adjusting future doses and scheduling of carboplatin therapy.

Method of administration.

Prior to administration, carboplatin solutions should be inspected visually for particulate matter. Dilutions may be made in Glucose 5% Intravenous Infusion to concentrations as low as 0.1 mg/mL. The product and admixture contain no antimicrobial agent. In order to reduce microbiological hazards it is recommended that further dilution should be effected immediately prior to use and infusion commenced as soon as practicable after preparation of the admixture. Infusion should be completed within 24 hours of preparation and any residue discarded (see Section 6.6 Special Precautions for Disposal).
Aluminium reacts with carboplatin causing precipitate formation and loss of potency, therefore aluminium-containing equipment should not be used for preparation or administration of carboplatin.

Dosage adjustment.

Renal impairment.

As carboplatin is excreted by the kidney and is nephrotoxic, the optimum dosage should be determined by frequent monitoring of the haematological nadir and renal function.
The suggested dosage schedule for patients with impaired renal function based on creatinine clearance is shown in Table 1.

Paediatric.

Insufficient information is available to make specific recommendations.

Combination therapy.

Carboplatin has been used in combination with other antineoplastic agents and the dosage varies according to the protocol used.
Dosage adjustments should be made according to the treatment regimen adopted and the results obtained from haematological monitoring.

Handling precautions.

As with all antineoplastic agents, trained personnel should prepare Carboplatin Injection. This should be performed in a designated area (preferably a cytotoxic laminar flow cabinet). Protective gown, mask, gloves and appropriate eye protection should be worn when handling carboplatin. Where solution accidentally contacts skin or mucosa, the affected area should be immediately washed thoroughly with soap and water. It is recommended that pregnant personnel not handle cytotoxic agents such as carboplatin.
Luer-Lock fitting syringes are recommended in the assembly of syringes and giving sets to avoid leakage. Large bore needles are recommended to minimise pressure and possible formation of aerosols. Aerosols may also be reduced by using a venting needle during preparation.
Items used to prepare carboplatin, or articles associated with body waste, should be disposed of by placing in a double sealed polythene bag and incinerating at 1100°C (see Section 6.6 Special Precautions for Disposal).

4.3 Contraindications

Carboplatin Injection is contraindicated in the following conditions:
Pre-existing severe renal impairment; dose adjustment may allow use in the presence of mild renal impairment (see Section 4.2 Dose and Method of Administration).
Severe myelosuppression.
Hypersensitivity to carboplatin or other platinum-containing compounds (e.g. cisplatin).
Severe bleeding.
During pregnancy or lactation.

4.4 Special Warnings and Precautions for Use

Carboplatin should be administered only under constant supervision by physicians experienced in therapy with cytotoxic agents and only when potential benefits of carboplatin therapy outweigh the possible risks. Appropriate facilities should be available for adequate management of complications should they arise, particularly in the case of administration of high drug dosages.
Carboplatin is a highly toxic drug with a narrow therapeutic index and a therapeutic effect is unlikely to occur without some evidence of toxicity.

Myelosuppression.

Bone marrow suppression (leucopenia, neutropenia and thrombocytopenia) is dose dependent and is the dose-limiting toxicity of carboplatin. Peripheral blood cell counts should be performed at frequent intervals (e.g. on a weekly basis) in patients receiving carboplatin.
At the recommended drug doses, the haematologic toxicity of carboplatin is usually moderate and reversible. Myelosuppression associated with carboplatin is closely related to the renal clearance of the drug; therefore patients with impaired renal function are more susceptible.
Myelosuppression, particularly thrombocytopenia (reduction in platelet count), will also be more severe in patients receiving concomitant therapy with other nephrotoxic drugs such as aminoglycoside antibiotics, other myelosuppressive drugs or radiation therapy. Toxicity is more likely to be prolonged and more severe in patients who have undergone previous chemotherapy, are more advanced in age, or who are debilitated. Dosage reductions may be necessary in these cases. Treatment of severe haematologic toxicity may consist of supportive care, anti-infective agents for complicating infections, transfusions of blood products, autologous bone marrow rescue, peripheral stem cell transplantation and haematopoietic agents (colony-stimulating factors).
The nadir for platelets (peak detrimental effect) is usually between days 14-21 following initial treatment and days 14-28 for white blood cells. Minimum counts should be 50,000/mm3 for platelets and 2,000/mm3 for white blood cells. If counts fall below this level, therapy should be suspended until recovery is complete, usually five to six weeks. Supportive transfusional therapy may be necessary in severe cases.
It is important, therefore, that the assessment of renal function and peripheral blood counts (including white blood cells, platelets and haemoglobin) be made prior to, during and following treatment with carboplatin. In order to ensure that the peak detrimental effect on blood cells has occurred, repeat courses of treatment with carboplatin should not be given more frequently than monthly under normal circumstances.

Blood and lymphatic system disorders.

Haemolytic anaemia with the presence of serologic drug-induced antibodies has been reported in patients treated with carboplatin. This event can be fatal.
Haemolytic uremic syndrome (HUS) is a potentially life-threatening side effect. Carboplatin should be discontinued at the first sign of any evidence of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or lactate dehydrogenase (LDH). Renal failure may not be reversible with discontinuation of therapy and dialysis may be required.

Secondary leukaemia.

Acute promyelocytic leukaemia (APL) and myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) have been reported years after therapy with carboplatin and other antineoplastic treatments.

Hepatobiliary disease.

Cases of hepatic veno-occlusive disease (sinusoidal obstructive syndrome) have been reported. Some of them were fatal.

Central nervous system (CNS)/hearing functions.

Neurological evaluations and auditory monitoring should be performed regularly during and after carboplatin therapy, particularly in patients previously treated with cisplatin and in patients over 65 years of age.
Ototoxicity is cumulative, and frequency and severity of hearing disorder increases with high dose regimens and repeated doses, or prior treatment with cisplatin (also ototoxic). Auditory function should be monitored prior to initiating therapy and regularly during treatment or when auditory symptoms occur. Clinically important deterioration of auditive function may require dosage modifications or discontinuation of therapy. The risk of ototoxicity may be increased by concomitant administration of other ototoxic drugs (e.g. aminoglycosides) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Delayed onset hearing loss has been reported in paediatric patients. Long-term audiometric follow-up in this population is recommended.

Reversible posterior leukoencephalopathy syndrome (RPLS).

Cases of 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. Diagnosis of RPLS is based upon confirmation by brain imaging, preferably MRI.

Tumour lysis syndrome (TLS).

Patients at high risk of TLS such as patients with high proliferative rate, high tumour burden and high sensitivity to cytotoxic agents should be monitored closely and appropriate precaution taken.

Gastrointestinal effects.

Carboplatin can induce emesis. The incidence and severity of emesis may be reduced by pre-treatment with antiemetics or by carboplatin administration as a continuous IV infusion over 24 hours, or as IV administration of divided doses over 5 consecutive days rather than as a single infusion. Selective inhibitors of type 3 (5-HT3), serotonergic receptors (e.g. ondansetron) or substituted benzamides (e.g. metoclopramide) may be particularly effective antiemetics and combination therapy may be considered for patients experiencing severe or refractory emetogenic effects.

Hypersensitivity reactions.

As in the case of other platinum complexed compounds, allergic reactions to carboplatin have been reported. Patients should be monitored for possible anaphylactoid reactions and appropriate equipment and medication should be readily available to treat such reactions (e.g. antihistamines, corticosteroids, adrenaline (epinephrine), oxygen) whenever carboplatin is administered.

Immunosuppressant effects/ increased susceptibility to infections.

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.
Carboplatin should be administered with caution to patients with herpes zoster, existing or recent chicken pox, or recent exposure to chicken pox, due to the risk of severe generalised disease. It should also be administered with caution to patients with other infections.
The myelosuppressive effects of carboplatin may adversely affect dental procedures, resulting in an increased incidence of microbial infection, delayed healing and gingival bleeding. Where possible, dental work should be completed prior to initiation of carboplatin therapy, or deferred until blood counts have returned to normal. Patients should be instructed on proper oral hygiene during treatment, including caution in the use of toothbrushes, dental floss and toothpicks.

Aluminium.

Aluminium-containing equipment should not be used (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 6.2 Incompatibilities).

Use in renal impairment.

Renal toxicity is not usually dose-limiting. Unlike cisplatin therapy, pre-treatment and post-treatment hydration is not necessary as the drug has a relatively low nephrotoxic potential, although some patients may show a decrease in creatinine clearance. Renal impairment is more likely to be seen in patients who have previously experienced nephrotoxicity as a result of chemotherapy.
Previous therapy with cisplatin or concomitant administration of other nephrotoxic drugs (e.g. aminoglycoside antibiotics) may increase the risk of nephrotoxicity (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Carboplatin is excreted primarily in the urine and renal function should be assessed prior to and during therapy. (See Section 4.2 Dose and Method of Administration; Section 4.3 Contraindications). Creatinine clearance appears to be the most sensitive measure of kidney function in patients receiving carboplatin. Dose adjustment criteria for patients with impaired renal function are provided in Section 4.2 Dose and Method of Administration.

Use in the elderly.

See Section 4.8 Adverse Effects (Undesirable Effects).

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Carboplatin is mostly used in combination with antineoplastic drugs having similar cytotoxic effects. In these circumstances additive toxicity is likely to occur. The combination of carboplatin therapy and other myelosuppressive agents may warrant dosage adjustments in order to avoid cumulative toxic effects. Concomitant use of carboplatin and other myelosuppressive agents or radiation therapy may potentiate the haematologic toxicity.
In patients who have previously received cisplatin, neurotoxicity such as paraesthesias, decreased deep tendon reflexes, and ototoxicity are more likely to be seen. The frequency and severity of hearing disorder increases with prior treatment with cisplatin (as cisplatin is also ototoxic). Paraesthesias present prior to treatment, especially if caused by cisplatin, may persist or worsen during carboplatin therapy.
In patients receiving carboplatin concomitantly with paclitaxel, myalgias and arthralgias commonly occur. Fatigue has also been reported in patients receiving this combination.
Pain, most likely related to tumour size, and asthenia occur frequently in patients receiving carboplatin in conjunction with cyclophosphamide. Visual disturbances have been reported in patients receiving usual dosages of carboplatin in conjunction with cyclophosphamide.
Concomitant administration of carboplatin and aminoglycosides results in an increased risk of nephrotoxicity and/or ototoxicity, and the drugs should be used concurrently with caution. The use of other nephrotoxic drugs results in a potentiation of renal effects by carboplatin.
Carboplatin interacts with aluminium to form a black precipitate of platinum and loss of potency. Aluminium-containing IV sets, needles, catheters and syringes should not be used for administration (see Section 6.2 Incompatibilities).
An increased incidence of emesis has been reported when carboplatin and other emetogenic drugs are given concurrently or carboplatin is administered to patients who previously received emetogenic therapy.
Vaccination with a live vaccine should be avoided in patients receiving carboplatin.
A decrease in phenytoin serum levels has been observed with concurrent administration of carboplatin and phenytoin/fosphenytoin. This may lead to exacerbation of seizures.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Women of childbearing potential should be advised to avoid becoming pregnant while receiving carboplatin and to use effective contraception during treatment with carboplatin and for at least six months after the last dose. Men with female partners of childbearing potential should be advised to use effective contraception during treatment with carboplatin and for at least three months after the last dose.
Male and female fertility may be impacted by treatment with carboplatin. Both men and women should seek advice for fertility preservation before treatment with carboplatin.
(Category D)
Carboplatin has been shown to be embryo-toxic and mutagenic, and its use in pregnant women is not recommended. Women of child-bearing potential should use adequate contraception, and carboplatin should only be used in women of child-bearing potential if the expected benefits outweigh the risks of such therapy.
If the patient becomes pregnant whilst receiving the drug she should be advised of the potential hazard to the fetus.
 It is not known whether or not carboplatin is excreted in breast milk. However, because of the potential for serious adverse reactions in infants should the drug pass into the milk, breast feeding should be discontinued during carboplatin therapy in lactating women.

4.7 Effects on Ability to Drive and Use Machines

The effect of carboplatin on the ability to drive or use machinery has not been systematically evaluated.

4.8 Adverse Effects (Undesirable Effects)

Many side effects of carboplatin therapy are unavoidable due to the pharmacological actions of the drug. However, the adverse effects are generally reversible if detected early.
Adverse reactions as reported for the various organ systems are as follows.

Blood and lymphatic system disorders.

Haematological toxicity is the most common dose-limiting toxicity, with leucopenia in 55% of patients, thrombocytopenia in 62% of patients, anaemia in up to 59% of patients and neutropenia. Myelosuppression is dose-related. When used as single agent therapy, toxicity is not usually cumulative and is reversible, although transfusional therapy may be necessary in severe cases.
Platelet and leukocyte/granulocyte nadirs usually occur two to three weeks from drug administration. Recovery is generally adequate to allow the administration of the subsequent carboplatin dose four weeks after a previous administration. Anaemia (haemoglobin less than 11 g/dL), which may be symptomatic, occurs in a substantial proportion of patients. This effect may be cumulative and transfusions may be needed particularly in patients receiving prolonged therapy (e.g. more than 6 cycles).
Haemolytic anaemia (sometimes fatal) has also been reported.
Clinical sequelae of bone marrow/haematologic toxicity such as fever, infections, sepsis/septic shock and haemorrhage may be expected.
Haemolytic uraemic syndrome has been reported.

Neoplasms - benign, malignant and unspecified.

There have been rare reports of acute myelogenous leukaemias and myelodysplastic syndromes arising in patients who have been treated with carboplatin, mostly when given in combination with other potentially leukaemogenic agents.

Renal and urinary disorders.

Manifests as reduced creatinine clearance, mild and transient elevations of serum creatinine, blood urea nitrogen and uric acid levels. Acute renal failure has been reported rarely. Risk of carboplatin-induced nephrotoxicity (e.g. impaired creatinine clearance) becomes more prominent at relatively high dosages or in patients previously treated with cisplatin.

Gastrointestinal disorders.

Nausea and vomiting: Onset may be delayed for 6-12 hours after administration of carboplatin and usually disappears within 24 hours, but may persist for up to 3 days in some patients. Vomiting may be delayed for 24 hours or longer after treatment in some patients. Antiemetic medication can be used to adequately control these effects. Stomatitis, mucositis, diarrhoea, constipation and abdominal pain have been reported with carboplatin therapy.

Hepatobiliary disorders.

Mild and usually transient elevations of serum alkaline phosphatase, aspartate aminotransferase or bilirubin concentrations may occur. Substantial abnormalities in liver function test have been reported in patients treated with carboplatin at high doses and autologous bone marrow transplantation. Abnormalities of liver function tests have been reported in up to 30% of patients. These changes are normally only transient in nature and disappear spontaneously.

Ear and labyrinth disorders.

Manifests as tinnitus and hearing loss in the higher frequency range. Hearing impairment may persist or worsen with carboplatin therapy.

Eye disorders.

Visual abnormalities, such as transient sight loss (which can be complete for light and colours) or other disturbances may occur in patients treated with carboplatin. Improvement and/or total recovery of vision usually occurs within weeks after the drug is discontinued. Cortical blindness has been reported in patients with impaired renal function receiving high-dose carboplatin.

Cardiac disorders.

Cardiac failure, ischaemic coronary artery disorders (e.g. myocardial infarction, cardiac arrest, angina, myocardial ischaemia), Kounis syndrome.

Vascular disorders.

Cerebrovascular events.

Immune system disorders.

Allergic reactions to carboplatin have been reported. These include anaphylaxis/anaphylactoid reactions, hypotension, bronchospasm and pyrexia. Hypersensitivity reactions may occur within a few minutes after IV administration of carboplatin. Erythematous rash, fever and pruritus may occur (less than 2% of patients).

Skin and subcutaneous tissue disorders.

Exfoliative dermatitis may rarely occur. Erythematous rash, pruritus, urticaria, and alopecia have also been reported in association with carboplatin.

Musculoskeletal and connective tissue disorders.

Myalgia/arthralgia. This can commonly occur in patients receiving carboplatin together with paclitaxel (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Nervous system disorders.

In the majority of patients, neurotoxicity manifests mainly as paraesthesias and decreased deep tendon reflexes. The effect, more common in patients over 65 years of age, appears to be cumulative, occurring mainly in patients receiving prolonged therapy and/or in those who have received prior cisplatin therapy. Central nervous system effects may also occur. Pre-existing paraesthesias (especially those related to previous cisplatin treatment) may worsen during carboplatin therapy. Fatigue has been reported in patients receiving carboplatin concomitantly with paclitaxel. Dysgeusia has been reported in patients taking carboplatin.

Metabolism and nutrition disorders.

Electrolyte abnormalities (hypokalaemia, hypocalcaemia, hyponatraemia and/or hypomagnesaemia).

General disorders and administration site conditions.

Asthenia, flu-like symptoms (1%) and reactions at injection site (< 1%). Taste abnormalities, and adverse respiratory and genitourinary effects have also been reported. Pain, most likely related to tumour size occur frequently in patients receiving carboplatin in conjunction with cyclophosphamide.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

There are no known antidotes for carboplatin overdosage, thus every possible measure should be taken to avoid an overdose; this includes full awareness of the potential danger of an overdose, careful calculation of the dose to be administered and availability of adequate diagnostic and treatment facilities. Acute overdosage with carboplatin may result in an enhancement of its expected toxic effects (e.g. severe myelosuppression, intractable nausea and vomiting, severe neurosensorial toxicities, liver failure, kidney failure, etc.). Death may follow. Haemodialysis is only effective, even then partially, up to 3 hours after administration because of the rapid and extensive binding of platinum to plasma proteins. Signs and symptoms of overdosage should be managed with supportive measures.
The patient may need to be sustained through complications relating to myelosuppression, renal and hepatic impairment. Diarrhoea and alopecia may develop.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Class: Antineoplastic agent.
Carboplatin has an inorganic heavy metal complex containing a central atom of platinum. It is an analogue of cisplatin. Carboplatin has biochemical properties similar to those of cisplatin. It is believed to bind to DNA to produce intra- and inter-strand (predominantly) crosslinks which modify structure and inhibit DNA synthesis.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Distribution.

Protein binding is less than with cisplatin. Initially protein binding is low, with up to 29% of carboplatin bound during the first 4 hours. After 24 hours 85-89% is protein bound.

Elimination.

After intravenous infusion of a single dose over one hour, plasma concentrations of total platinum and free platinum decline biphasically following first order kinetics. For free platinum, reported value for the initial phase of the half-life (t alpha½) is about 90 minutes and in the later phase the half-life (t beta½) is about 6 hours. Total platinum elimination has a similar initial half-life, while in the later phase the half-life of total platinum may be greater than 24 hours.

Excretion.

Carboplatin is mainly excreted by the kidneys. Most excretion occurs within the first 6 hours of administration with 50-70% excreted within 24 hours. 32% of the dose is excreted as unchanged drug. A reduction in dosage is recommended for patients with poor renal function.

5.3 Preclinical Safety Data

Genotoxicity.

Animal studies demonstrate that carboplatin is mutagenic and teratogenic.

Carcinogenicity.

The carcinogenic potential of carboplatin has not been studied; however, compounds with a similar mechanism of action have been reported to be carcinogenic.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections.

6.2 Incompatibilities

Carboplatin interacts with the aluminium containing components of needles, syringes, catheters and intravenous administration sets to form a black precipitate so these items should not be used for the administration of carboplatin injections.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light. Single use only. Discard unused portion.

6.5 Nature and Contents of Container

AUST R 42853: Carboplatin Injection 50 mg in 5 mL (sterile) Plastic Vial.
AUST R 49348: Carboplatin Injection 150 mg in 15 mL (sterile) Plastic Vial.
AUST R 49349: Carboplatin Injection 450 mg in 45 mL (sterile) Plastic Vial.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

Spills and disposal.

If spills occur, restrict access to the affected area. Wear two pairs of gloves (latex rubber), a respirator mask, a protective gown and safety glasses. Limit the spread of the spill by covering with a suitable material such as absorbent towel or adsorbent granules. Spills may also be treated with 3 M sulphuric acid with 0.3 M potassium permanganate (2:1) or 5% sodium hypochlorite. Collect up absorbent/adsorbent material and other debris from spill and place in a leak proof plastic container and label accordingly. Cytotoxic waste should be regarded as hazardous or toxic and clearly labelled 'Cytotoxic waste for incineration at 1100°C'. Waste material should be incinerated at 1100°C for at least 1 second. Cleanse the remaining spill area with copious amounts of water.
In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Molecular Formula: C6H12N2O4Pt.
Molecular Weight: 371.3.

CAS number.

41575-94-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes