Consumer medicine information

Carboplatin Kabi Injection

Carboplatin

BRAND INFORMATION

Brand name

Carboplatin Kabi

Active ingredient

Carboplatin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

What is in this leaflet

This leaflet answers some common questions about Carboplatin Kabi.

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 Kabi 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 in a safe place. You may need to read it again.

What Carboplatin Kabi is used for

Carboplatin Kabi is used to treat various types of cancer, such as.

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

Carboplatin Kabi belongs to a group of medicines called antineoplastic or cytotoxic medicines. You may also hear of these being called chemotherapy medicines. Carboplatin belongs to the group of anticancer medicines called the platinum complexes.

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

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

Your doctor may have prescribed Carboplatin Kabi for another reason.

Ask your doctor if you have any questions about why Carboplatin Kabi has been prescribed for you.

Carboplatin Kabi is not addictive.

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

Before you are given Carboplatin Kabi

When you must not be given it

Do not have Carboplatin Kabi if you have an allergy to Carboplatin Kabi or any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction to Carboplatin Kabi may include:

  • shortness of breath, wheezing, difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching, hives or flushed, red skin
  • dizziness or lightheadedness

Do not have Carboplatin Kabi if you have any of the following medical conditions:

  • severe kidney problems
  • condition of the blood with a reduced number of red blood cells, white blood cells or platelets

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.

Females: tell your doctor or pharmacist if you are pregnant or intend to become pregnant. Like most cytotoxic medicines Carboplatin Kabi is not recommended for use during pregnancy. If there is any need to consider Carboplatin Kabi during your pregnancy, your doctor or pharmacist will discuss with you the benefits and risks of using it.

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

Carboplatin Kabi may cause birth defects if either the male or female is using it at the time of conception. It is recommended that you use some kind of birth control while you are using Carboplatin Kabi and for at least 12 weeks after you stop using it. Your doctor will discuss this with you.

Do not breastfeed while taking Carboplatin Kabi. It is not known whether carboplatin passes into breast milk and therefore there is a possibility that the breast-fed baby may be affected.

If you are not sure whether you should start having Carboplatin Kabi, talk to your doctor or pharmacist.

Before you are given it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

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

  • kidney problems
  • peripheral neuropathy, which you may notice as numbness or weakness in your arms and legs
  • condition of the blood with a reduced number of red / white blood cells / platelets
  • bleeding problems
  • hearing problems
  • 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 about any other treatments you have had for cancer, including radiation treatment.

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

If you have not told your doctor about any of the above, tell them before you start having Carboplatin Kabi.

Taking other medicines

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

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

  • other medicines used to treat cancer, such as paclitaxel and cyclophosphamide
  • some antibiotics used to treat serious infections
  • some vaccines (ask your doctor)

These medicines may be affected by Carboplatin Kabi, or may affect how well it works. You may need different amounts of your medicine, or you may need to have different medicines. Your doctor or pharmacist will advise you.

Do not have any vaccinations (immunisations) without your doctor’s approval while you are being treated with carboplatin, 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 that the immunisation is intended to prevent.

In addition, other people living in the same 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 may have more information on medicines to be careful with or avoid while having Carboplatin Kabi.

How Carboplatin Kabi 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, kidney function, blood counts and other chemotherapy medicines you are being given.

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

Several courses of Carboplatin Kabi 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 uncontrolled effects have been controlled.

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

How it is given

Carboplatin Kabi is diluted into a fluid bag and given as an infusion (drip) into your veins, usually over 15 to 60 minutes.

Carboplatin Kabi must only be given by a doctor or nurse.

How long it is given

Carboplatin Kabi is usually given as a single infusion on one day. This is called one cycle of chemotherapy. Cycles are usually repeated about 4 weeks apart. Your doctor will decide how many of these cycles you will need.

Overdose

As Carboplatin Kabi is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given Carboplatin Kabi, tell your doctor immediately or go to Accident and Emergency at your nearest hospital. You may need urgent medical attention.

Symptoms of a Carboplatin Kabi overdose include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

While you are being given Carboplatin Kabi

Things you must do

Be sure to keep all your doctor’s appointments so your progress can be checked. Your doctor may want to do some blood 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 Kabi at the appropriate times to get the best effects from your treatments.

Tell any other doctors, dentists, and pharmacists who are treating you that you are having Carboplatin Kabi.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being treated with Carboplatin Kabi.

If you plan to have surgery that needs a general anaesthetic, tell your surgeon or anaesthetist that you are having Carboplatin Kabi.

If you become pregnant while being treated with Carboplatin Kabi, tell your doctor immediately.

Carboplatin Kabi 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. Take the following precautions to reduce your risk of infection or bleeding:

  • Avoid people who have infections. Check with your doctor immediately if you think you may be getting an infection, or if you get a fever, chills, cough, hoarse throat, lower back or side pain or find it painful or difficult to urinate.
  • Be careful when using a toothbrush, toothpick or dental floss. Your doctor, dentist, nurse or pharmacist may recommend other ways to clean your teeth and gums. Check with your doctor before having any dental work.
  • Be careful not to cut yourself when you are using sharp objects such as a razor or nail cutters.
  • Avoid contact sports or other situations where you may bruise or get injured.

Things you must not do

Do not give Carboplatin Kabi to anyone else, even if they have the same condition as you.

Do not have Carboplatin Kabi to treat any other complaints unless your doctor or pharmacist tells you to.

Things to be careful of

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

As with other medicines, Carboplatin Kabi may cause dizziness or tiredness in some people. Make sure you know how you react to Carboplatin Kabi before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive. If you drink alcohol, dizziness or light-headedness may be worse.

Side effects

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

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

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

  • nausea or vomiting
  • diarrhoea or constipation
  • stomach pain
  • sore mouth
  • tiredness or weakness
  • sore muscles or joints
  • pain at the injection site
  • unusual hair loss or thinning
  • taste disturbance or loss of taste

These are the more common or less serious side effects of Carboplatin Kabi.

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

  • hearing problems
  • buzzing or ringing or other persistent noise in the ears
  • blurred vision or other changes in vision
  • tingling in the fingers or toes
  • tiredness, headaches, being short of breath when exercising, looking pale

These may be serious side effects. You may need 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 infection such as fever, chills, sore throat, mouth ulcers
  • bleeding or bruising more easily than normal
  • problems with urination such as pain or difficulty
  • severe nausea or vomiting
  • signs of an allergic reaction such as difficulty breathing, swelling of the face, lips, tongue or other parts of the body, skin rash

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

Other side effects not listed above may occur in some patients. Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

The benefits and side effects of Carboplatin Kabi may take some time to occur. Therefore even after you have finished your Carboplatin Kabi treatment you should tell your doctor immediately if you notice any of the side effects listed in this section.

Storage

Carboplatin Kabi 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

Carboplatin Kabi is a clear, colourless to pale yellow solution in a glass vial.

Ingredients

Active ingredient:

  • carboplatin

Other ingredients:

  • water for injections

Carboplatin Kabi does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Fresenius Kabi Australia Pty Limited
964 Pacific Highway
Pymble NSW 2073
Australia.
Telephone: (02) 9391 5555

Carboplatin Kabi is available in the following sizes:
50 mg/5 mLAUST R 171244
150 mg/15 mLAUST R 171243
450 mg/45 mLAUST R 171241

Date of preparation of this leaflet:
07 October 2011

Published by MIMS January 2012

BRAND INFORMATION

Brand name

Carboplatin Kabi

Active ingredient

Carboplatin

Schedule

S4

 

Name of the medicine

Carboplatin.

Excipients.

Water for Injections BP. The solution does not contain any preservatives.

Description

The chemical name of carboplatin is (SP-4-2)-diamine cyclobutane-1,1-dicarboxylato (2-)-O, O’platin and the CAS registry number is 41575-94-4.
Carboplatin has a molecular weight of 371.26 and a molecular formula of C6H12N2O4Pt. It is a colourless, crystalline powder, sparingly soluble in water, very slightly soluble in acetone and in alcohol.
Carboplatin Kabi injection is a sterile solution of carboplatin in Water for Injections BP. It is presented in vials containing 50 mg/5 mL, 150 mg/15 mL and 450 mg/45 mL. The solution does not contain any preservatives. The pH of the injection ranges between 5.0 to 7.0.

Pharmacology

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.

Pharmacokinetics.

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 (tα½) are about 90 minutes and in the later phase the half life (tβ½) 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.
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 of carboplatin is by glomerular filtration. Patients with poor renal function have a higher AUC for total platinum and a reduction in dosage is recommended.

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.

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 Dosage and Administration).
History of severe allergic reactions to carboplatin, other platinum-containing compounds.
Severe bleeding.
Pregnancy or lactation.

Precautions

Warning: This product is cytotoxic and adequate care should be taken by all staff handling the product.
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.

Myelosuppression.

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 had 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.
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.
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.
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.

Nephrotoxicity.

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.

Neurotoxicity and ototoxicity.

Neurotoxicity, such as paraesthesias and decreased deep tendon reflexes, and ototoxicity are more likely to be seen in patients who have received cisplatin previously. 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). Neurological evaluations and an assessment of hearing should be performed on a regular basis.

Gastrointestinal.

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 as a single infusion. Selective inhibitors of type 3 (5-HT3) serotonergic receptors (e.g. ondansetron) or substituted benzamides (e.g. metoclopramide) may be particularly effective antiemetics and combination therapy may be considered for patients experiencing severe or refractory emetogenic effects.

Hypersensitivity reactions.

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. These reactions may occur within minutes of administration and should be managed with appropriate supportive therapy, including standard adrenaline, corticosteroid, oxygen and antihistamine therapy.

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.

Mutagenicity.

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.
Aluminium-containing equipment should not be used (See Interactions with Other Medicines).

Use in pregnancy.

Category D
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 foetus.
Category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

Use in lactation.

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.

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.

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.

Effects on ability to drive or operate machinery.

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

Interactions

Concurrent therapy with nephrotoxic drugs 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.
Combination therapy with other myelosuppressive drugs 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 been reported to increase the incidence of nausea and vomiting.
Live or killed virus vaccines should not be given during carboplatin therapy, or for 3 months to 1 year after carboplatin is discontinued. The immunosuppressive effect of carboplatin may potentiate viral replication and increase the adverse effects of live virus vaccines, and decrease the patient's antibody response to live or killed virus vaccines. In addition, immunisation with oral polio virus vaccine should be postponed in people who are in close contact with the patient, particularly family members.

Adverse Effects

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

Haematopoietic system.

Leucopenia (55%), thrombocytopenia (62%), anaemia (59%) and neutropenia. 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.

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.

Gastrointestinal system.

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 system.

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. Haemolytic uraemic syndrome. Risk of carboplatin-induced nephrotoxicity (e.g. impaired creatinine clearance) becomes more prominent at relatively high dosages or in patients previously treated with cisplatin.

Biochemistry.

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.

Neurotoxicity.

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. Paraesthesias present prior to treatment, especially if caused by cisplatin, may persist or worsen during prolonged carboplatin therapy (See Interactions with Other Medicines). 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.

Ototoxicity.

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.

Hepatic system.

Increases in liver enzymes have been mild and usually 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. Abnormalities of liver function tests have been reported in up to 30% of patients. These changes are normally only transient in nature and disappear spontaneously.

Allergic reactions.

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 and hypoxia 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.

Ocular effects.

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. Blurred vision may occur rarely. Visual disturbances have been reported in patients receiving usual dosages of carboplatin in conjunction with cyclophosphamide (See Interactions with Other Medicines). Loss of vision has been reported rarely in patients receiving carboplatin in doses higher than those usually recommended; improvement and/or total recovery of vision occurred within weeks after the drug was discontinued. Cortical blindness has been reported in patients with impaired renal function receiving high-dose carboplatin.

Cardiac disorders.

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

Vascular disorders.

Cerebrovascular events.

Metabolism and nutrition disorders.

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

Other.

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. Myalgias and arthralgias commonly occur in patients receiving carboplatin together with paclitaxel (See Interactions with Other Medicines).

Dosage and Administration

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

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.

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).

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.

Preparation of carboplatin solution.

Equipment containing aluminium components should be avoided (See Precautions).
Carboplatin Kabi injection is a ready to use solution containing 10 mg/mL carboplatin in Water for Injections BP.
The injections may be further diluted in 5% glucose intravenous infusion or 0.9% sodium chloride intravenous infusion BP. Slow degradation has been observed in 0.9% sodium chloride, therefore dilution with 5% glucose is recommended.
To reduce microbiological hazard, use as soon as practicable after preparation. If storage is necessary, hold at 2 to 8°C for not more than 24 hours.
Carboplatin Kabi injection contains an overfill to allow withdrawal of the stated volumes.

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.
Luer-lok fitting syringes are recommended. Large bore needles are recommended to minimise pressure and possible formation of aerosols. Aerosols may also be reduced by using a venting needle during preparation.

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 1000°C or more.

Overdosage

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.
If overdosage does occur, the Poisons Information Centre (telephone 131 126) should be contacted immediately.

Presentation

Compatibilities.

Carboplatin has been found to be stable for 24 hours when admixed with 0.9% sodium chloride or 5% glucose in water. Dilution with 0.9% sodium chloride is not recommended.
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.
Carboplatin Kabi is available in three strengths, with all strengths available as a single glass vial in an outer carton pack.
Carboplatin Kabi 50 mg/5 mL Injection AUST R 171244.
Carboplatin Kabi 150 mg/15 mL Injection AUST R 171243.
Carboplatin Kabi 450 mg/45 mL Injection AUST R 171241.

Storage

Store below 25°C. Protect from light. Do not freeze.

Poison Schedule

S4.