Consumer medicine information

DBL Carboplatin Injection

Carboplatin

BRAND INFORMATION

Brand name

DBL Carboplatin Injection

Active ingredient

Carboplatin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Carboplatin Injection.

What is in this leaflet

This leaflet answers some common questions about DBL 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 taking carboplatin against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What DBL Carboplatin Injection is used for

This medicine is used to treat:

  • 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 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.

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

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 not addictive.

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

Before you take are given DBL Carboplatin Injection

When you must not be given it

You should not be given DBL Carboplatin Injection if you have an allergy to:

  • any medicine containing carboplatin
  • other platinum-containing compounds such as cisplatin or oxaliplatin
  • mannitol

Some of the symptoms of an allergic reaction may include:

  • 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.

Females: Tell your doctor or pharmacist if you are pregnant or intend to become pregnant.

Like most cytotoxic medicines, carboplatin is not recommended for use during pregnancy. Avoid becoming pregnant by using effective contraception during treatment and up to 6 months after therapy. If there is any need to consider carboplatin during your pregnancy, your doctor or pharmacist will discuss the benefits and risks of using it.

Males: Tell your doctor or pharmacist if your partner intends to become pregnant while you are being given DBL 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 DBL Carboplatin Injection and for at least 12 weeks 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 12-week period after your last dose. Your doctor will discuss this with you.

Do not breast-feed if you are taking this medicine. It is not known whether carboplatin passes into breast milk and there is a possibility that the breast-fed baby may be affected.

You must not be given this medicine if you have any of the following conditions:

  • very low numbers of white blood cells (WBC), red blood cells (RBC) or platelets
  • severe kidney problems (your dose may be reduced with some milder conditions)
  • severe bleeding

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.

If you are not sure whether you should start taking this medicine, 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 have or have had any of the following medical conditions:

  • kidney problems
  • hearing problems
  • condition of the blood with a reduced number of red blood cells, white blood cells, or platelets
  • bleeding problems or problems with blood clotting
  • neurological problems (problems with the nervous system)
  • 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.

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

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

  • 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)
  • some vaccines (ask your doctor)
  • phenytoin/fosphenytoin.

These medicines may be affected by carboplatin or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Do not have any vaccinations (immunisations) without your doctor's approval while you are being treated with DBL Carboplatin Injection, and for up to 12 months after you stop treatment with it. Carboplatin may lower your body's resistance to infection and there is a chance that you may get the infection the immunisation is meant to prevent.

In addition, other people living in your household should not take oral polio vaccine (Sabin) since there is a chance they could pass the polio virus on to you.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How DBL Carboplatin Injection is given

How much is given

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.

DBL Carboplatin Injection 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.

Ask your doctor if you want to know more about the dose of carboplatin you receive.

How it is given

DBL Carboplatin Injection 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.

How long it is given for

DBL Carboplatin Injection 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 receive too much (overdose)

As DBL Carboplatin Injection is given to you under the supervision of your doctor, it is very unlikely that you will receive an overdose. However, if you experience any severe side effects after being given DBL Carboplatin Injection, tell your doctor immediately or go to Accident and Emergency at the nearest hospital.

In case of overdose, immediately contact the Poisons Information Centre for advice (telephone 13 11 26 in Australia) Symptoms of an overdose may include the side effects listed below in the 'Side Effects' section, but are usually of a more severe nature.

Ask your doctor, nurse or pharmacist if you have any concerns.

While you are being given DBL Carboplatin Injection

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given carboplatin.

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine.

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

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may want to check your blood pressure and do some blood, hearing and other tests from time to time to check on your progress and detect any unwanted side effects.

Keep follow up appointments with your doctor. It is important to have your follow-up cycles of carboplatin at the appropriate times to get the best effects from your treatments.

Carboplatin can lower the number of white blood cells and platelets in your blood. This means that you have an increased chance of getting an infection or bleeding. The following precautions should be taken to reduce your risk of infection or bleeding:

  • 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.

While you are being given carboplatin, your doctor should order regular tests to check the number of blood cells in your blood. The results of these tests will be used to determine the amount of carboplatin you will be given for your next dose.

Things to be careful of

Be careful driving or operating machinery until you know how carboplatin 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.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with carboplatin. Like other medicines, carboplatin may have unwanted side effects, some of which may be serious. You may need medical attention if you get some of the side effects.

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

Ask your doctor or pharmacist to answer any questions you may have.

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

  • mild nausea or vomiting
  • diarrhoea or constipation
  • weakness, tiredness or fatigue
  • sore muscles or joints
  • pain or irritation at the injection site
  • taste abnormalities.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

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 anti-cancer medicines are used together with carboplatin.

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

  • 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

The above list includes serious side effects that may require medical attention.

If any of the following happen, tell your doctor or nurse immediately 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, 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
  • swollen face or limbs, abdominal pain or swelling
  • a feeling of tightness, pressure or heaviness in the chest.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

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

Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

The benefits and side effects of carboplatin may take some time to occur. Therefore, even after you have finished receiving your carboplatin treatment you should tell your doctor immediately if you notice any of the side effects listed above.

After you have been given DBL Carboplatin Injection

Storage

DBL Carboplatin Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Product description

What it looks like

DBL Carboplatin Injection is a concentrated colourless or slightly yellow solution which will be diluted in a fluid bag and given as an infusion (‘drip’).

Ingredients

DBL Carboplatin Injection contains carboplatin as the active ingredient. It also contains:

  • Water for Injection

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Hospira Australia Pty Ltd
Melbourne VIC 3000
Australia

DBL Carboplatin Injection is available in the following strengths and pack sizes:

  • 50 mg in 5 mL, single glass
  • vials AUST R 12880
  • 150 mg in 15 mL, single glass vials AUST R 46845
  • 450 mg in 45 mL, single glass vials AUST R 46846

™ = Trademark

This leaflet was updated in April 2020.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

DBL Carboplatin Injection

Active ingredient

Carboplatin

Schedule

S4

 

1 Name of Medicine

Carboplatin.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

41575-94-4.

2 Qualitative and Quantitative Composition

DBL Carboplatin Injection is a sterile solution of carboplatin in Water for Injections and is presented in vials containing 5, 15 or 45 mL of 10 mg/mL carboplatin.
Each mL of DBL Carboplatin Injection contains carboplatin 10 mg.

3 Pharmaceutical Form

Solution for injection.
DBL Carboplatin Injection is a clear, colourless or slightly yellow solution free from particulates. The solution does not contain any preservatives. The pH of the injection ranges between 4.0 to 7.0.

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 drug. 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.

Excretion.

After a one hour infusion of the drug (dose range 20 to 520 mg/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 (talpha ½) are about 90 minutes and in the later phase the half-life (tbeta ½) 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 drug. Most of the drug 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.

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.

4.3 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 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 chemotherapeutic agents. Diagnostic and treatment facilities should be readily available for appropriate management of therapy and possible complications.

Bone marrow function.

Carboplatin should be administered with caution to patients with significant bleeding or with bone marrow depression.
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.
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 on a regular basis. 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.

Blood and lymphatic system disorders.

Haemolytic anemia with the presence of serologic drug-induced antibodies has been reported in patients treated with carboplatin. This event can be fatal.
Haemolytic-uraemic syndrome (HUS) is a potentially life-threatening side effect. Carboplatin should be discontinued at the first sign of any evidence of microangiopathic hemolytic 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 pretreatment 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.

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.

Renal function should be assessed prior to and during therapy. Myelosuppression as a result of carboplatin treatment is closely related to the renal clearance of the drug. Therefore, in patients who have abnormal renal function or who are receiving concomitant therapy with nephrotoxic drugs, 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 drug (see Section 4.8 Adverse Effects (Undesirable Effects)).

Paediatric use.

Safety and efficacy in children have not been established.

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 drugs should not be treated with carboplatin.
Concomitant administration of carboplatin and aminoglycosides results in an increased risk of ototoxicity, and the drugs should be used concurrently with caution.
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 drugs, or administration to patients who have previously received emetogenic drugs, has increased the incidence of nausea and vomiting.
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.

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. 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.

4.8 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 drugs or radiation therapy, and those with renal impairment. Transfusional support has been required in about one-fifth of patients.
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.

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 paraethesias 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 drug 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 myelodysplastic 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).

Others.

Alopecia (2%), flu-like syndrome (1%), reaction at injection site (< 1%). Taste abnormalities, and adverse respiratory and genitourinary effects have also been reported. 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 www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Adult.

The recommended dose of carboplatin in previously untreated adults with normal renal function is 400 mg/m2 given as a single intravenous 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 drugs 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.

Dosage adjustment.

Renal impairment.

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.

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.

Method of administration.

Preparation of carboplatin solution.

Equipment containing aluminium components should be avoided (see Section 4.4 Special Warnings and Precautions for Use).
DBL Carboplatin 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 reduce 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.

Compatibilities.

Carboplatin has been found to be stable for 24 hours when admixed with 5% glucose in water.

Handling guidelines.

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.

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 1,000°C or more.

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.

4.9 Overdose

No overdosage occurred during clinical trials. Should it occur, the patient may need to be sustained through complications relating to myelosuppression, renal impairment and hepatic impairment. From reports in which doses up to 1600 mg/m2 were used, patients were said to feel extremely unwell and developed diarrhoea and alopecia.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

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 drug.
Parenteral drugs should be inspected visually for particulate matter and discolouration, prior administration, whenever solution and container permit. If particulate matter observed, shake and reinspect. 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

DBL Carboplatin Injection is available as per Table 2.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes