Consumer medicine information

Carboplatin Accord

Carboplatin

BRAND INFORMATION

Brand name

Carboplatin Accord

Active ingredient

Carboplatin

Schedule

SUMMARY CMI

CARBOPLATIN ACCORD

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Carboplatin Accord?

Carboplatin Accord contains the active ingredient carboplatin. Carboplatin Accord is used for the treatment of ovarian cancer, cancer of the testes, some types of lung cancer, cancer of the brain and/or spinal cord, cancer of the head and neck, neuroblastoma (a cancer of the nerves and adrenal glands), a type of cancer called sarcoma.

For more information, see Section 1. Why am I using Carboplatin Accord? in the full CMI.

2. What should I know before I use Carboplatin Accord?

Do not use if you have ever had an allergic reaction to an any medicine containing carboplatin, other platinum-containing compounds (cisplatin or oxaliplatin) or mannitol, or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Carboplatin Accord? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Carboplatin Accord and affect how it works.

See Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Carboplatin Accord?

Carboplatin Accord is an injection and will be given to you by your doctor or nurse.

More instructions can be found in Section 4. How do I use Carboplatin Accord? in the full CMI.

5. What should I know while using Carboplatin Accord?

Things you should do

Tell any other doctors, dentists, and pharmacists who are treating you that you are being treated with Carboplatin Accord
If you become pregnant while taking this medicine, tell your doctor immediately
Keep all your doctor's appointments so that your progress can be checked.
Avoid people with infections.
Check with your doctor immediately if you notice any unusual bleeding or bruising, black stools, blood in urine or stools or pinpoint red spots on your skin
Be careful when using a regular toothbrush, dental floss or toothpick.
Be careful not to cut yourself when you are using sharp objects such as a safety razor or nail cutters
Avoid contact sports or other situations where you may get bruised or injured

Driving or using machines

Be careful driving or operating machinery until you know how Carboplatin Accord affects you. This medicine may cause dizziness, light-headedness, tiredness and drowsiness in some people. Be careful when drinking alcohol while you are taking this medicine. If you drink alcohol, dizziness or light-headedness may be worse.

For more information, see Section 5. What should I know while using Carboplatin Accord? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

Some of the common, serious and very serious side effects are included in full below in the CMI. Speak to your doctor if you have any of these side effects and they worry you.

The very serious side effects are:

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, chills, sore throat or mouth ulcers
headaches, changes in mental status (confusion, thinking abnormal, altered consciousness) or seizures
visual disturbances or loss
shortness of breath
rapid breathing or rapid heart rate
tremor
unusual bleeding or bruising, blood in urine or stools
problems with urination e.g. pain or difficulty
yellowing of the skin or eyeballs
severe nausea and vomiting
a feeling of tightness, pressure or heaviness in the chest

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

CARBOPLATIN ACCORD

Active ingredient: carboplatin

Consumer Medicine Information (CMI)

This leaflet provides important information about using Carboplatin Accord. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Carboplatin Accord.

Where to find information in this leaflet:

1. Why am I using Carboplatin Accord?
2. What should I know before I use Carboplatin Accord?
3. What if I am taking other medicines?
4. How do I use Carboplatin Accord?
5. What should I know while using Carboplatin Accord?
6. Are there any side effects?
7. Product details

1. Why am I using Carboplatin Accord?

Carboplatin Accord contains the active ingredient carboplatin. Carboplatin belongs to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear of these being called chemotherapy medicines. This medicine is classified as a platinum-complex cytotoxic.

It works by killing cancer cells and/or stopping cancer cells from growing and multiplying.

Carboplatin Accord is used for the treatment of:

ovarian cancer
cancer of the testes
some types of lung cancer
cancer of the brain and/or spinal cord
cancer of the head and neck
neuroblastoma (a cancer of the nerves and adrenal glands)
a type of cancer called sarcoma.

Carboplatin is often used in combination with other medicines to treat cancer.

2. What should I know before I use Carboplatin Accord?

Warnings

Do not use Carboplatin Accord if:

you are allergic to carboplatin or any of the ingredients listed at the end of this leaflet
always check the ingredients to make sure you can use this medicine

Check with your doctor if you have or have had:

an allergy to any medicine containing carboplatin, other platinum-containing compounds (cisplatin or oxaliplatin) or mannitol
allergies to any other medicines, foods, preservatives or dyes
very low numbers of white blood cells, red blood cells or platelets
if you have had previous treatment with cisplatin
severe kidney problems (your dose may be reduced with some milder conditions)
hearing problems
bleeding problems or problems with blood clotting
neurological problems (problems with the nervous system)
herpes zoster infections (also known as shingles)
chicken pox, or if you have been in recent contact with someone who has chicken pox
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.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

As with many medicines, Carboplatin Accord may harm your developing or breastfeeding baby.

Use an effective method of contraception during treatment with Carboplatin Accord and for up to six months after discontinuation of Carboplatin Accord.

Males: tell your doctor if your partner intends to become pregnant while you are using Carboplatin Accord or shortly after you have stopped using Carboplatin Accord.

Use barrier methods of contraception (e.g. condoms) during treatment and for up to 12 weeks after discontinuation of Carboplatin Accord.

3. What if I am taking other medicines?

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

Some medicines and Carboplatin Accord may interfere with each other.

other medicines used to treat cancer (such as paclitaxel and cyclophosphamide), radiation therapy or any other treatment which weakens your immune system
some antibiotics used to treat serious infections, including aminoglycosides (such as gentamicin, tobramycin or amikacin)
phenytoin/fosphenytoin
some vaccines (Do not have any vaccinations without your doctor's approval while you are being treated with Carboplatin Accord, and for up to 12 months after you stop treatment with it)

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Carboplatin Accord.

4. How do I use Carboplatin Accord?

How much to use

Carboplatin Accord is diluted in a fluid bag and then given as an infusion (drip) into your veins, over 15 to 60 minutes. It must only be given by a doctor or nurse.

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight, height, kidney function, blood counts and other chemotherapy medicines you are being given.

Carboplatin may be given alone or in combination with other drugs.

Several courses of carboplatin therapy may be needed depending on your response to treatment.

Additional treatment may not be repeated until your blood cell numbers return to acceptable levels and any unwanted effects have been controlled.

When to use Carboplatin Accord

It is very important that you continue to receive Carboplatin Accord for as long as your doctor prescribes it.

You will have blood tests before you begin treatment with Carboplatin Accord and weekly thereafter.

Carboplatin is usually given as a single infusion on one day. This is called one ‘cycle’ of chemotherapy. A cycle is usually repeated 4 weeks after the previous cycle. Your doctor will decide how many of these cycles you need.

If you use too much Carboplatin Accord

It is very unlikely that you will receive an overdose of Carboplatin Accord because a trained nurse or doctor will give it. If you think that you have been given too much Carboplatin Accord, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Carboplatin Accord?

Things you should do

Tell any other doctors, dentists, and pharmacists who are treating you that you are being treated with Carboplatin Accord
If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being treated with this medicine
If you are going to have surgery, tell the surgeon or anaesthetist you are being given this medicine
If you become pregnant while taking this medicine, tell your doctor immediately
Keep all your doctor's appointments so that your progress can be checked. Your doctor will do some tests e.g. blood pressure, blood tests, hearing test at regular intervals to make sure the medicine is working and to prevent any unwanted side effects
Avoid people with infections. Check with your doctor immediately if you think you are getting an infection, or if you get a fever or chills, cough or hoarseness, lower back or side pain, or find it painful or difficult to urinate
Check with your doctor immediately if you notice any unusual bleeding or bruising, black stools, blood in urine or stools or pinpoint red spots on your skin
Be careful when using a regular toothbrush, dental floss or toothpick. Your doctor or nurse may recommend other ways to clean your teeth and gums. Check with your doctor before having any dental work done
Be careful not to cut yourself when you are using sharp objects such as a safety razor or nail cutters
Avoid contact sports or other situations where you may get bruised or injured

Carboplatin and its breakdown products may be excreted in body fluids and waste, including blood, urine, faeces, vomitus and semen. In general, precautions to protect other people should be taken while you are receiving chemotherapy and for one week after the treatment period.

Flush the toilet twice to dispose of any body fluids and waste
Wear gloves to clean any spill of body fluid or waste. Use paper towels or old rags, a strong solution of non-bleaching detergent and large amounts of water to mop up the spill. Discard the towels or rags into a separate waste bag and dispose of fluids in the toilet.
Wash linen or clothing that is heavily contaminated by body fluids or waste separately from other items. Use a strong solution of non-bleaching detergent and large amounts of water.
Place soiled disposable nappies and other pads in a plastic bag, seal and dispose into the garbage.
For sexual intercourse, use a barrier method such as a condom

Driving or using machines

Be careful driving or operating machinery until you know how Carboplatin Accord affects you.

This medicine may cause dizziness, light-headedness, tiredness and drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery, or do anything else that could be dangerous.

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, dizziness or light-headedness may be worse.

Looking after your medicine

The hospital will store Carboplatin Accord under the correct conditions.

Getting rid of any unwanted medicine

Your doctor or pharmacist will dispose of any Carboplatin Accord that may be left over.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Common side effects

Common side effects	What to do
mild nausea or vomiting diarrhoea or constipation weakness, tiredness or fatigue sore muscles or joints pain or irritation at the injection site taste abnormalities	Speak to your doctor if you have any of these common side effects and they worry you

Temporary loss of hair, particularly that on the scalp is a less common but upsetting side effect of carboplatin and occurs in a small number of patients (about 2 patients per 100 treated). The severity of hair loss will depend on the dose of carboplatin given. It is more common when other anticancer medicines are used together with carboplatin.

Serious side effects

Serious side effects	What to do
hearing problems muscle irritability or cramps blurred vision or other visual disturbances tingling in the fingers or toes flaking or peeling of the skin, rash or itchy rash	Call your doctor straight away

Very Serious side effects

Very Serious side effects

What to do

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, chills, sore throat or mouth ulcers
headaches, changes in mental status (confusion, thinking abnormal, altered consciousness) or seizures
visual disturbances or loss
shortness of breath
rapid breathing or rapid heart rate
tremor
unusual bleeding or bruising, blood in urine or stools
problems with urination e.g. pain or difficulty
yellowing of the skin or eyeballs
severe nausea and vomiting
a feeling of tightness, pressure or heaviness in the chest

Call your doctor straight away or go straight to the Emergency Department at your nearest hospital

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Carboplatin Accord contains

Active ingredient (main ingredient)	carboplatin
Other ingredients (inactive ingredients)	water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What Carboplatin Accord looks like

Carboplatin Accord is a is a clear colourless solution supplied in a vial in single packs.

(50 mg/5 mL: AUST R 215852, 150 mg/15 mL: AUST R 215853, 450 mg/45 mL: AUST R 215854).

Who distributes Carboplatin Accord

Accord Healthcare Pty Ltd
Level 24, 570 Bourke Street
Melbourne, VIC, 3000
Australia

This leaflet was prepared in January 2022.

Published by MIMS April 2022

BRAND INFORMATION

Brand name

Carboplatin Accord

Active ingredient

Carboplatin

Schedule

1 Name of Medicine

Carboplatin.

2 Qualitative and Quantitative Composition

1 mL contains 10 mg carboplatin.
1 vial of 5 mL solution for injection contains 50 mg carboplatin.
1 vial of 15 mL solution for injection contains 150 mg carboplatin.
1 vial of 45 mL solution for injection contains 450 mg carboplatin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Carboplatin Accord solution for injection is a clear colourless to slightly pale-yellow solution containing carboplatin.

4 Clinical Particulars

4.1 Therapeutic Indications

Carboplatin is indicated in the treatment of: advanced stage ovarian cancer of epithelial origin, small cell lung carcinoma, carcinoma of the head and neck, carcinoma of the testis, paediatric cerebral tumours, soft tissue sarcoma, neuroblastoma.

4.2 Dose and Method of Administration

Adult.

The recommended dose of carboplatin in previously untreated adults with normal renal function is 400 milligrams/m² given as a single intravenous (IV) infusion over 15 to 60 minutes. Therapy should not be repeated until four weeks after the previous carboplatin course.
It is recommended that according to clinical circumstances the initial dosage may require reduction by 20 to 25% in patients with risk factors such as increasing age, previous myelosuppressive therapy and poor performance status.
Dosage modification may be required when carboplatin is used in combination with other myelosuppressive medicines, or radiation therapy, to minimise additive myelosuppressive effects.
Determination of haematologic nadir by weekly blood counts during initial courses is recommended for future dosage adjustment and scheduling of carboplatin.

Children.

Sufficient usage of carboplatin in paediatrics has not occurred to allow specific dosage recommendations to be made. Physicians are advised to refer to recently published literature for information on the current dosing regimens for particular tumours.

Impaired renal function.

In patients with initial impaired renal function reduction of dosage of carboplatin may be required. Haematological nadirs and renal function should be monitored in these circumstances.
A suggested dosage schedule in patients with impaired renal function based on creatinine clearance is as follows (see Table 1):

Preparation of carboplatin solution.

Equipment containing aluminium components should be avoided (see Section 4.4 Special Warnings and Precautions for Use).
Carboplatin Solution for Injection is a ready to use solution containing 10 mg/mL carboplatin in water for injections.
The injections may be further diluted in 5% glucose intravenous infusion. To minimise microbiological hazard, use as soon as practicable after preparation. If storage is necessary, hold at 2-8°C for not more than 24 hours.
Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.
These products contain no antimicrobial agent. However, in order to reduce microbiological contamination hazard, infusion should be commenced as soon as practicable after preparation. Infusion should be completed within 24 hours of preparation and any residue discarded.

Handling.

Warning: Carboplatin is a cytotoxic agent.
1. Carboplatin should be prepared for administration only by professionals who have been trained in the safe use of the preparation.
2. Operations such as transfer to syringes should be carried out only in the designated area.
3. The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.
4. Pregnant personnel are advised not to handle chemotherapeutic agents.

Contamination.

(a) In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat transient stinging of the skin. Medical advice should be sought if the eyes are affected.
(b) In the event of spillage, operators should put on gloves and mop up the spilled material with a sponge kept in the area for that purpose. Rinse the area twice with water. Put all solutions and sponges into a plastic bag and then seal it. The bag should be prominently labelled with the words "Cytotoxic Waste" or similar.

Compatibilities.

Carboplatin has been found to be stable for 24 hours when admixed with 5% glucose in water. Slow degradation of carboplatin has been observed in 0.9% sodium chloride, therefore dilution in 0.9% sodium chloride is not recommended.

4.3 Contraindications

Carboplatin is contraindicated in patients with the following conditions:
severe myelosuppression;
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);
history of severe allergic reactions to carboplatin, other platinum-containing compounds (e.g. cisplatin) or mannitol;
severe bleeding;
pregnancy or lactation.

4.4 Special Warnings and Precautions for Use

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

Bone marrow function.

Carboplatin should be administered with caution to patients with significant bleeding or with bone marrow depression.
Bone marrow suppression (leucopenia, neutropenia and thrombocytopenia) is dose dependent and is the dose-limiting toxicity of carboplatin. Although at the recommended drug doses, the haematologic toxicity of carboplatin is usually moderate and reversible, severe myelosuppression (especially thrombocytopenia) may occur in patients with renal impairment and in patients who are concurrently receiving (or have received) other myelosuppressive drugs or radiation therapy.
Peripheral blood counts and renal function should be monitored closely. Blood counts should be performed prior to commencement of carboplatin therapy and weekly thereafter. Aside from monitoring toxicity, this practice will help determine the nadir and recovery of the haematological parameters and assist in subsequent dose adjustments. Lowest levels in white cells and platelets are generally seen between days 14 and 28, and days 14 and 21 respectively after initial therapy. A greater reduction in platelets is seen in patients who previously received extensive myelosuppressive chemotherapy than non-treated patients. White blood cell counts less than 2 x 10⁹ cells/L (2,000 cells/mm³) or platelets less than 50 x 10⁹ cells/L (50,000 cells/mm³) should cause consideration of postponement of carboplatin therapy until bone marrow recovery is evident, which is usually 5 to 6 weeks. Transfusions may be required.
The occurrence, severity and protraction of toxicity are likely to be greater in patients who have received extensive prior treatment for their disease, have poor performance status and who are more advanced in age. Dosage reduction may be necessary in cases of severe toxicity. 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).
Carboplatin courses should not, in general, be repeated more frequently than every four weeks in order to ensure that the nadir in blood counts has occurred and that there has been recovery to a satisfactory level.

Hypersensitivity reactions.

Hypersensitivity and anaphylactic reactions to carboplatin have been reported. These allergic reactions have been similar in nature and severity to those reported with other platinum containing compounds. Symptoms include rash, urticaria, erythema, pruritus, bronchospasm and hypotension.
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, oxygen) whenever carboplatin is administered.

Central nervous system (CNS)/hearing functions.

Neurotoxicity, such as paraesthesias and decreased deep tendon reflexes, and ototoxicity are more likely to be seen in patients who have received cisplatin previously. Routine neurologic examination is advisable during carboplatin therapy, particularly in patients previously treated with cisplatin and in patients over 65 years of age. Ototoxicity is cumulative. The frequency and severity of hearing disorder increases with high dose regimens and repeated doses, or prior treatment with cisplatin (as cisplatin is also ototoxic). Assessment of hearing should be performed 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.

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 leukemia (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.

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 a single infusion. Selective inhibitors of type 3 (5HT-3), 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.

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.

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.

Carboplatin is excreted primariliy in the urine and renal function should be assessed prior to and during therapy. 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 Dose and Method of Administration.
Myelosuppression as a result of carboplatin treatment is closely related to the renal clearance of the medicine. Therefore, in patients who have abnormal renal function or who are receiving concomitant therapy with nephrotoxic medicines myelosuppression, especially thrombocytopenia, may be more severe and prolonged.
Renal toxicity is not usually dose-limiting. Pre-treatment and post-treatment hydration is not necessary. However, about 25% of patients show decreases in creatinine clearance and, less frequently, rises in serum creatinine and blood urea nitrogen may be seen. Impairment of renal function is more likely to be seen in patients who have previously experienced nephrotoxicity as a result of cisplatin therapy. 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).

Use in the elderly.

Carboplatin-induced peripheral neuropathy appears to be more common in those over 65 years of age than in younger patients. Elderly patients may have decreased renal and haematopoietic function, and may be more susceptible to other effects of the medicine (see Section 4.8 Adverse Effects (Undesirable Effects)).

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or IV administration sets that contain aluminium parts which may come in contact with carboplatin should not be used for preparation or administration of the drug (see Section 6.2 Incompatibilities).
Concurrent therapy with nephrotoxic medicines may increase or exacerbate renal toxicity due to carboplatin-induced changes in renal clearance. Patients receiving aminoglycoside antibiotics or other nephrotoxic medicines should not be treated with carboplatin.
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 is mostly used in combination with antineoplastic drugs having similar cytotoxic effects. In these circumstances additive toxicity is likely to occur. Combination therapy with other myelosuppressive medicines may require modification of the dose or timing of carboplatin therapy to minimise additive myelosuppressive effects. Dosage reduction is recommended if carboplatin is administered concurrently with radiation therapy.
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 with other emetogenic medicines or administration to patients who have previously received emetogenic medicines has increased the incidence of nausea and vomiting.
Vaccination with a live vaccine should be avoided in patients receiving carboplatin (see Section 4.4 Special Warnings and Precautions for Use).
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.

Both men and women receiving carboplatin should be informed of the potential risk of adverse effects on reproduction. Women of childbearing potential should be advised to avoid becoming pregnant by using effective contraception during treatment and up to 6 months after therapy. For women who are pregnant or become pregnant during therapy, genetic counselling should be provided.
Carboplatin is genotoxic. Men being treated with carboplatin are advised not to father a child during and up to three months after treatment.
Male and female fertility may be impacted by treatment with carboplatin. Most forms of chemotherapy have been associated with reduction of oogenesis and spermatogenesis and patients receiving carboplatin should be warned of this potential. Although not reported with carboplatin, this has been reported with other platinum agents. Recovery of fertility after exposure can occur but is not guaranteed. Both men and women should seek advice for fertility preservation before treatment with carboplatin.
(Category D)
This category specifies medicines which have caused or may be expected to cause an increased incidence of human fetal malformations or irreversible damage. These medicines may also have adverse pharmacological effects.
Carboplatin has been shown to be embryotoxic and mutagenic. Use in pregnancy 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 while being treated with carboplatin, she should be advised of the potential hazard to the fetus.
It is not known whether carboplatin is excreted in breast milk. To avoid possible harmful effects in the infant, breast-feeding should be discontinued during carboplatin therapy.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Myelosuppression is the dose-limiting toxicity of carboplatin. It is generally reversible and is not cumulative when carboplatin is used as single agent and at the recommended frequencies of administration.
Adverse effects which have been observed in studies to date can be grouped under the following organ systems.

Blood and lymphatic system disorders.

Leucopenia (55%), thrombocytopenia (32%), anaemia (59%). Myelosuppression is dose-related, and appears to be most common and more severe in patients who have received prior antineoplastic therapy (especially cisplatin), those who have received or who are currently receiving other myelosuppressive medicines or radiation therapy, and those with renal impairment. Transfusional support has been required in about one-fifth of patients.
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 uremic syndrome has been reported.

Gastrointestinal disorders.

Nausea and vomiting (53%), nausea only (25%), diarrhoea (6%), constipation (3%). Nausea and vomiting generally are delayed 6 to 12 hours after administration of carboplatin and disappear 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. Nausea and vomiting are readily controlled (or may be prevented) with antiemetic medication. Gastrointestinal pain, mucositis and stomatitis have also been reported.

Renal and urinary disorders.

Decrease in creatinine clearance (25%); increases in uric acid (25%), blood urea nitrogen (16%) and serum creatinine (7%). 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.

Investigations.

Decreases in serum magnesium (37%), potassium (16%) and, rarely, calcium (5%). Carboplatin may also cause decreases in serum sodium levels. These changes have not been severe enough to cause clinical symptoms.

Nervous system disorders.

Peripheral neuropathy (6%) which was mild, and dysgeusia (< 1%). 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 neurotoxicity has also been reported, although this may be related to concomitant antiemetic therapy. Fatigue has been reported in patients receiving carboplatin concomitantly with paclitaxel. Dysgeusia has been reported in patients taking carboplatin.

Ear and labyrinth disorders.

Subclinical decrease in hearing acuity as determined by audiogram, in the high frequency (4,000 to 8,000 Hz) range (15%); clinical ototoxicity, usually manifested as tinnitus (1%). Pre-existing hearing impairment may persist or worsen with carboplatin therapy. In patients who developed hearing loss as a result of cisplatin therapy, the impairment may persist or worsen.

Hepatobiliary disorders.

Increases in liver enzymes have been transient in the majority of cases. Alkaline phosphatase (ALP) (30%), aspartate aminotransferase (AST) (15%), bilirubin (4%). Substantial abnormalities in liver function test have been reported in patients treated with carboplatin at high doses and autologous bone marrow transplantation.

Immune system disorders.

In less than 2% of patients, reactions similar to those seen after cisplatin have been observed. Erythematous rash, fever, perioral tingling, urticaria, pruritus, bronchospasm, hypotension, hypoxia and pyrexia have been observed. Anaphylaxis and anaphylactoid reactions have also occurred, while exfoliative dermatitis has been reported rarely. In a few cases, no cross-reactivity was present. The frequency of allergic reactions is higher in patients who receive carboplatin in conjunction with other antineoplastic agents. Hypersensitivity reactions may occur within a few minutes after IV administration of carboplatin.

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 medicine is discontinued. Cortical blindness has been reported in patients with impaired renal function receiving high-dose carboplatin.

Neoplasms - benign, malignant and unspecified.

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

Cardiac disorders.

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

Vascular disorders.

Cerebrovascular events.

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).

Metabolism and nutrition disorders.

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

General disorders and administration site conditions.

Alopecia (2%), flu-like syndrome (1%), reaction at injection site (< 1%). Taste abnormalities, and adverse respiratory and genitourinary effects have also been reported. Haemolytic uraemic syndrome has occurred rarely. Pain, most likely related to tumour size, and asthenia 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 http://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. 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.

Carboplatin, an analogue of cisplatin, is an antineoplastic agent which interferes with DNA intrastrand and interstrand crosslinks in cells exposed to the medicine. DNA reactivity has been correlated with cytotoxicity.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Distribution.

Initially protein binding is low. During the first 4 hours after administration 0 to 29% of carboplatin is protein bound. By 24 hours 85 to 89% is protein bound.

Elimination.

After a one-hour infusion of the medicine (dose range 20 to 520 milligrams/m²) plasma levels of total platinum and ultrafilterable (free) platinum decay biphasically following first order kinetics. For ultrafilterable platinum reported values for the initial phase of the half life (t_{alpha 1/2}) are about 90 minutes and in the later phase the half life (t_{beta 1/2}) 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. Carboplatin is a stable molecule. All free platinum is in the form of carboplatin in the first 4 hours.
65% of the carboplatin dose is eliminated in the urine within 24 hours of administration with 32% of the dose being excreted as unchanged medicine. Most of the medicine is excreted in the first 6 hours.

Excretion.

Excretion of carboplatin is by glomerular filtration. Patients with poor renal function have a higher Area Under Curve for total platinum and a reduction in dosage is recommended.

5.3 Preclinical Safety Data

Genotoxicity.

Carboplatin has been shown to be mutagenic in mammalian cells. Patients should be advised of its mutagenic potential and should use effective contraception for an adequate duration of time after ceasing therapy.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections.

6.2 Incompatibilities

Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or intravenous administration sets that contain aluminium parts which may come in contact with carboplatin should not be used for preparation or administration of the medicine.
Parenteral drugs should be inspected visually for particulate matter and discolouration, prior to administration, whenever solution and container permit. If particulate matter is observed, shake and re-inspect. Vials with visible particulate matter should not be used.

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. Do not freeze. Protect from light.

6.5 Nature and Contents of Container

Three strengths are available as follows: 50 mg/5 mL, 150 mg/15 mL and 450 mg/45 mL in glass vials in packs of 1.

6.6 Special Precautions for Disposal

Syringes, containers, absorbent materials, solution and any other material which has come into contact with carboplatin should be placed in a thick plastic bag or other impervious container and incinerated at 1000°C or more. The bag or container should be prominently labelled with the words "Cytotoxic Waste" or similar.

6.7 Physicochemical Properties

Carboplatin is (SP-4-2)-diammines[cyclobutan-1,1-dicarboxylato(2-)-0,0']platin. It is a colourless, crystalline powder, sparingly soluble in water, very slightly soluble in acetone and in alcohol.
Molecular Formula: C₆H₁₂N₂O₄Pt.
Molecular Weight: 371.3.

Chemical structure.

CAS number.

41575-94-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

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