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Logo ASPEN CARBOPLATIN (Concentrate for solution for infusion)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ASPEN CARBOPLATIN (Concentrate for solution for infusion)

ASPEN CARBOPLATIN 50 mg (Concentrate for solution for infusion).
ASPEN CARBOPLATIN 150 mg (Concentrate for solution for infusion).
ASPEN CARBOPLATIN 450 mg (Concentrate for solution for infusion).

COMPOSITION:
ASPEN CARBOPLATIN 50 mg:
Each vial contains
carboplatin 50 mg/5 mL (10 mg/mL).
ASPEN CARBOPLATIN 150 mg:
Each vial contains carboplatin 150 mg/15 mL (10 mg/mL).
ASPEN CARBOPLATON 450 mg:
Each vial contains carboplatin 450 mg/45 mL (10 mg/mL).
Dextrose free

Excipients:
Water for injection, medicinal air.

PHARMACOLOGICAL CLASSIFICATION:
A 26 Cytostatic agents.

PHARMACOLOGICAL ACTION:
Pharmacodynamics:
Carboplatin [cis-diamine (1,1-cyclobutane-dicarboxylato) platinum] is a platinum co-ordination compound with antitumour properties. It is soluble in water at concentrations below 15 mg/mL.
Carboplatin has biochemical properties similar to those of cisplatin, thus producing
predominantly interstrand and intrastrand DNA cross links.
Pharmacokinetics: In patients with creatinine clearances of 60 mL/min or greater given carboplatin at doses of 300 to 500 mg/mL2, the plasma concentrations of carboplatin decay in a biphasic manner with mean alpha and beta half-lives of 1,6 h and 3,0 h, respectively. The total body clearance, apparent volume of distribution, and mean residence time for carboplatin are 73 mL/min, 16L and 3,5 h, respectively. Carboplatin exhibits linear, dose-dependent pharmacokinetics patients with creatinine clearances >60 mL/min.
The major route of elimination of carboplatin is renal excretion. Patients with creatinine clearances of 60 mL/min or greater, excrete 70% of the dose of carboplatin in the urine, with most of this occurring within 12 to 16 h.
In patients with creatinine clearances of less than 60 mL/min, carboplatin renal and total body clearances decreases progressively. Doses of carboplatin, therefore, should be reduced in patients with creatinine clearance <60 mL/min (see “DOSAGE AND DIRECTIONS FOR USE”).

INDICATIONS:
ASPEN CARBOPLATIN is indicated for the treatment of:
1. Advanced Ovarian carcinoma of epithelial origin in:
  a) First line therapy.
  b) Second line therapy, after other treatments have failed.
2. Limited evidence in support of the following:
  a) Small cell carcinoma of the lung.
  b) The treatment of squamous cell carcinoma of the head and neck.

CONTRAINDICATIONS:
ASPEN CARBOPLATIN is contraindicated in patients with a history of severe hypersensitivity reactions to carboplatin or other platinum-containing compounds.
ASPEN CARBOPLATIN should not be used in patients with severe pre-existing renal impairment (creatinine clearance at or below 20 mL/min).
ASPEN CARBOPLATIN should not be employed in severely myelosuppressed patients and/or in patients with localised tumoral bleeding.
Pregnancy and lactation (see “PREGNANCY AND LACTATION”).

WARNINGS:
Hypersensitivity reactions to ASPEN CARBOPLATIN have been reported. These may occur within minutes of administration and should be managed with appropriate supportive therapy. There is an increased risk of allergic reactions, including anaphylaxis in patients previously exposed to platinum therapy (see “CONTRAINDICATIONS” and “SIDE EFFECTS: Allergic Reactions”).
ASPEN CARBOPLATIN should be administered under the supervision of a medical practitioner experienced in the use of cancer chemotherapeutic agents.
Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Blood counts as well as renal and hepatic function tests must be done regularly and the medicines should be discontinued if abnormal depression of the bone marrow or abnormal renal or hepatic function is seen.
Haematological Toxicity:
Myelosuppression (leucopenia, neutropenia, thrombocytopenia) is dose-dependent and dose limiting. Peripheral blood counts should be monitored frequently and until recovery is achieved. Median day of nadir is day 21 in patients receiving single agent ASPEN CARBOPLATIN and day 15 in patients receiving ASPEN CARBOPLATIN in combination with other chemotherapeutic agents. Single intermittent courses of ASPEN CARBOPLATIN should not be repeated until leucocyte, neutrophil and platelet counts have returned to normal.
Transfusional support is frequently needed during treatment with ASPEN CARBOPLATIN, particularly in patients receiving prolonged therapy, since anaemia is cumulative.
Myelosuppression is increased in patients with prior treatment (in particular with cisplatin) and/or impaired kidney function. Initial ASPEN CARBOPLATIN dosages in these groups of patients should be appropriately reduced (see “DOSAGE AND DIRECTIONS FOR USE”) and the effects carefully monitored through frequent blood counts between courses. ASPEN CARBOPLATIN combination therapy with other myelosuppressive forms of treatment must be planned very carefully with respect to dosages and timing in order to minimise additive effects.
Neurologic Toxicity:
Although peripheral neurologic toxicity is generally rare and mild, its incidence is increased in patients older than 65 years and/or in patients previously treated with platinum components. Visual disturbances, including loss of vision, have been reported less frequently after the use of ASPEN CARBOPLATIN in doses higher than those recommended in patients with renal impairment.
Other:
Very high dosages of ASPEN CARBOPLATIN (up to five times the recommended single agent dose or more) have resulted in severe abnormalities in hepatic and renal function.
ASPEN CARBOPLATIN carcinogenic potential has not been studied, but compounds with similar mechanisms of action and mutagenicity have been reported to be carcinogenic.
Note: ASPEN CARBOPLATIN interacts with aluminium to form a black precipitate and/or loss of potency. It is important not to use IV sets, needles, catheters or syringes containing aluminium parts while mixing or administering ASPEN CARBOPLATIN.

INTERACTIONS:
The use of ASPEN CARBOPLATIN with nephrotoxic compounds is not recommended. Concomitant treatment with aminoglycosides has resulted in episodes of increased renal and audiologic toxicity. Hearing loss has been reported to occur in paediatric patients when ASPEN CARBOPLATIN was administered in combination with other ototoxic agents.
ASPEN CARBOPLATIN can induce nausea and vomiting, which can be more severe in previously treated patients (in particular in patients previously pre-treated with cisplatin).

PREGNANCY AND LACTATION:
Pregnancy is a contraindication. ASPEN CARBOPLATIN has been shown to be an embryotoxin and mutagen. It is recommended that patients of child-bearing or conceiving potential who are receiving ASPEN CARBOPLATIN exercise adequate contraception control.
Safety in lactation has not been established. It is not known whether this medicine is excreted in human milk.

DOSAGE AND DIRECTIONS FOR USE:
FOR INTRAVENOUS USE ONLY.
ASPEN CARBOPLATIN should be used by the intravenous route only.
The recommended dosage of ASPEN CARBOPLATIN in previously untreated adult patients with normal kidney function is 400 mg/m2 as a single IV dose administered by a short-term (15 to 60 minutes) infusion. Therapy should not be repeated until four weeks after the previous ASPEN CARBOPLATIN course and/or until the neutrophil count is at least 2000 cells/mm3 and the platelet count is at least 100 000 cells/mm3.
Reduction of the initial dosage by 20 –25% is recommended for those who present with risk factors such as prior myelosuppressive treatment and low performance status (ECOG-Zubrod 2 – 4 or karnofsky below 80). For patients aged 65 and over, dosage adjustment, initially or subsequently, may be necessary, depending on the physical condition of the patient. Determination of the haematological nadir by weekly blood counts during the initial courses of treatment with ASPEN CARBOPLATIN is recommended for future dosage adjustment.
Impaired Renal Function:
The optimal use of ASPEN CARBOPLATIN in patients presenting with impaired renal function required adequate dosage adjustments and frequent monitoring of both haematological nadirs and renal function.
Patients with creatinine clearance values below 60 mL/min are at increased risk of severe myelosuppression. The frequency of severe leucopenia, neutropenia, or thrombocytopenia has been maintained at about 25% with the following dosage recommendations:
ASPEN CARBOPLATIN 250 mg/m2 IV on day 1 in patients with baseline creatinine clearance values between 41 –59 mL/min.
ASPEN CARBOPLATIN 200 mg/m2 IV on day 1 in patients with baseline creatinine clearance values between 20 –40 mL/min.
Insufficient data exists on the use of ASPEN CARBOPLATIN in patients with creatinine clearance of 20 mL/min or less to permit a recommendation for treatment.
All of the above dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted accordingly to the patient’s tolerance and to the acceptable level of myelosuppression.
Combination Therapy:
The optimal use of ASPEN CARBOPLATIN in combination with other myelosuppressive agents requires dosage adjustments according to the regimen and schedule to be adopted.
Paediatrics:
Safety and efficacy in paediatrics have not been established.
Elderly:
Dosage adjustments, initially or subsequently, may be necessary depending on the physical condition of the patient.
Preparation of IV Solution:
Note above warning regarding interaction of ASPEN CARBOPLATIN with aluminium. ASPEN CARBOPLATIN solution may be further diluted with sufficient volumes of dextrose 5% in water or 0,9% sodium chloride to concentrations as low as 0,5 mg/mL.
When reconstituted as directed, ASPEN CARBOPLATIN solutions are stable for eight hours at room temperature (25ºC).
Note:
This is single dose vials, discard any unused concentrate portions.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Side effects:
Central Nervous System:
Frequent: Clinical ototoxicity, and other sensory disturbances (including visual disturbances and taste modification).
Less Frequent: Paraesthesia.
Gastrointestinal System:
Frequent: Nausea and vomiting.
Less Frequent: Pain, diarrhoea, constipation and anorexia.
Haematological System Disorders:
Frequent: Myelosuppression, thrombocytopenia, leucopenia, anaemia, haemorrhagic complications.
Hepatic System Disorders:
The following side-effects have been reported and frequencies are unknown:
The alkaline phosphatase level is increased more frequently than ALT, AST or total bilirubin.
Hypersensitivity reactions:
Less Frequent: Anaphylaxis, angioedema, and anaphylactoid reactions, including rash, urticaria, erythema, pruritus, bronchospasm, hypotension and facial oedema.
Renal System disorders:
Frequent: Elevation of serum creatinine, elevation of blood urea, and of uric acid.
Other:
The following side-effects have been reported and frequencies are unknown:
Second malignancies have been reported in association with multi-medicine therapy; however the relationship to ASPEN CARBOPLATIN is unclear. Respiratory, cardiovascular, mucosal, genitorurinary, cutaneous and musculoskeletal side-effects have occurred. Although death occurred because of cardiovascular events (cardiac failure, embolism, cerebrovascular accident) it is unclear whether this was related to chemotherapy rather than general patient conditions. Hypertension has been reported.
Among miscellaneous side-effects, asthenia and alopecia are the most frequent. Haemolyticuremic syndrome has been reported less frequently. Malaise has also been reported.
Serum electrolytes:
Frequent: Decreases in serum electrolytes (sodium, magnesium, potassium, calcium) have been reported after treatment with ASPEN CARBOPLATIN. Several cases of hyponatremia have been reported.
Paediatric Use:
Safety and effectiveness in paediatric patients have not been systemically studied (see “WARNINGS”).
Special Precautions:
Frequent hearing tests should be done on patients treated with ASPEN CARBOPLATIN.
Effects on ability to drive and use machines:
ASPEN CARBOPLATIN has no or negligible influence on the ability to drive and use machines.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
There is no known antidote for ASPEN CARBOPLATIN overdosage. The anticipated complications of overdosage would be related to myelosuppression as well as impairment of hepatic and renal function. Use of higher than recommended doses of ASPEN CARBOPLATIN has been associated with a loss of vision.

IDENTIFICATION:
A clear, colourless solution, free from visible particles.

PRESENTATION:
ASPEN CARBOPLATIN 50 mg: A single dose 8 mL Type I, clear, colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 50 mg of carboplatin as a 10 mg/mL solution in an outer carton.
ASPEN CARBOPLATIN 150 mg: A single dose 20 mL Type I, clear, colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 150 mg of carboplatin as a 10 mg/mL solution in an outer carton.
ASPEN CARBOPLATIN 450 mg: A single dose 50 mL Type I, clear, colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 450 mg of carboplatin as a 10 mg/mL solution in an outer carton.

STORAGE INSTRUCTIONS:
Store at or below 25ºC. Protect from light. Keep in outer carton until required for use.
When reconstituted as directed, ASPEN CARBOPLATIN solutions are stable for 8 hours at room temperature at 25ºC. Since the formulation contains no antibacterial preservatives, it is recommended that any solution remaining after 8 hours be discarded.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
Aspen Carboplatin 50 mg: 41/26/0608
Aspen Carboplatin 150 mg: 41/26/0609
Aspen Carboplatin 450 mg: 41/26/0610

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Pharmacare Limited
Building 12
Healthcare Park
Woodlands Drive
Woodmead
2191

DATE OF PUBLICATION OF THE PACKAGE INSERT
20 April 2012

APPROVED PATIENT INFORMATION LEAFLET
Read all sections of this leaflet carefully before you receive ASPEN CARBOPLATIN:
•        Keep this leaflet. You may need to read it again.
•        If you have further questions, please ask your doctor or your pharmacist.
•        ASPEN CARBOPLATIN has been prescribed for you personally and you should not share your medicine with other people. It may harm them, even if their symptoms are the same as yours.

Schedule 4

ASPEN CARBOPLATIN 50 mg
(concentrate for solution for infusion).
ASPEN CARBOPLATIN 150 mg
(concentrate for solution for infusion).
ASPEN CARBOPLATIN 450 mg
(concentrate for solution for infusion).

1. WHAT ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg CONTAINS:
The active substance is carboplatin:
ASPEN CARBOPLATIN 50 mg:
Each vial contains carboplatin 50 mg/5 mL (10 mg/mL).
ASPEN CARBOPLATIN 150 mg:
Each vial contains carboplatin 150 mg/15 mL (10 mg/mL).
ASPEN CARBOPLATON 450 mg:
Each vial contains carboplatin 450 mg/45 mL (10 mg/mL).
Dextrose free

The other ingredients are:
Water for injection and medicinal air.

2. WHAT ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg IS USED FOR:
The active ingredient in ASPEN CARBOPLATIN belongs to the group of medicines known as platinum-containing compounds (alkylating agents); it slows or stops the growth of cancer cells in your body. The length of treatment depends on the types of medicines you are taking, how well your body responds to them, and the type of cancer you have.
ASPEN CARBOPLATIN is used to treat ovarian and lung cancer.

3. BEFORE YOU RECEIVE ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg
You should not receive ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg if:
You are allergic to carboplatin, or any other platinum-containing compound.
You have renal or hearing or bone marrow depression.
You are pregnant or breastfeeding.

Take special care with ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg:
ASPEN CARBOPLATIN is to be administered only by or under the immediate supervision of your doctor.
Before receiving ASPEN CARBOPLATIN tell your doctor what prescription and nonprescription medications you are taking.
Hypersensitivity reactions to ASPEN CARBOPLATIN have been reported. These may occur within minutes of administration and your doctor will manage these symptoms. There is an increased risk in patients who has taken platinum therapy (used in the treatment of cancer) in the past.
Your doctor will do regular blood tests, liver function tests and kidney function tests. Depending on the results, your doctor will decide if you must continue with ASPEN CARBOPLATIN therapy.
ASPEN CARBOPLATIN can cause a decrease in the ability of the bone marrow to produce blood cells (myelosuppression). This can result in a decrease in white blood cells and platelets. Your doctor will do frequent blood tests.
If you experience visual disturbances, including loss of vision.
If you have renal disease.
If you have been treated with cisplatin or similar anti-cancer medicines in the past.
ASPEN CARBOPLATIN’s cancer-causing properties have not been studied, but compounds with similar mechanisms of action have been reported to cause cancer.
ASPEN CARBOPLATIN interacts with aluminium. Your healthcare providers should not use IV sets, needles, catheters or syringes that contain aluminium while mixing or administrating ASPEN CARBOPLATIN.
Your doctor will send you for frequent hearing tests to monitor your hearing.

Pregnancy and Breastfeeding:
If you are pregnant or breastfeeding your baby while receiving ASPEN CARBOPLATIN, please consult your doctor, pharmacist or other health care professional for advice.
ASPEN CARBOPLATIN may not be used at any time during pregnancy or whilst breastfeeding.

Driving and using machinery:
ASPEN CARBOPLATIN has no or negligible influence on the ability to drive and use machines
If you are unable to concentrate or remain alert after receiving ASPEN CARBOPLATIN, then do not drive or operate machinery or perform any activity for which you need to be attentive.

Taking other medicines with ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg:
If you are taking other medicines on a regular basis, including complementary or traditional medicines, the use of ASPEN CARBOPLATIN with these medicines may cause undesirable interactions. Please consult your doctor, pharmacist or other healthcare professional, for advice.
When receiving ASPEN CARBOPLATIN it is especially important that your health care professional know if you are taking any of the following:
Medication that increases the risk of kidney or hearing problems e.g. aminoglycosides like vancomycin taken at the same time as ASPEN CARBOPLATIN as this may increase the risk of kidney or hearing problems.
If you have been treated with cisplatin or similar anti-cancer medicines in the past.
Ask your doctor if you need further information on these types of medicine.

4. HOW ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg is ADMINISTERED:
ASPEN CARBOPLATIN is to be administered only by or under the immediate supervision of your doctor
Method of administration:
ASPEN CARBOPLATIN is for intravenous (administration directly into a vein) use only.
Dosage and frequency:
The dose of ASPEN CARBOPLATIN will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's size, and whether or not other medicines are also being taken.
If you have any questions about the proper dose of ASPEN CARBOPLATIN, ask your doctor.
Your doctor will monitor your blood counts and kidney function tests closely. Your doctor will perform blood counts at the beginning of your therapy and weekly to ensure that you are on the correct dose of ASPEN CARBOPLATIN. Regular clinical assessments will be done to detect any abnormalities of your nervous system.
It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

If you have received more ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg than you should:
ASPEN CARBOPLATIN is administered by a doctor experienced in the oncology field and overdosage is unlikely. However, use of higher than recommended dose for ASPEN CARBOPLATIN has been associated with a loss of vision. The anticipated complications of overdosage will be related to a decrease in the ability of the bone marrow to produce blood cells i.e. white blood cells and platelets. Symptoms will include, but are not limited to, bruising, nosebleeds or bleeding in the mouth and gums, rash.
If you notice any of these symptoms in yourself or any one else that has possibly received more APEN CARBOPLATIN than prescribed, please contact your doctor, pharmacist or nearest hospital immediately.

5. POSSIBLE SIDE-EFFECTS
ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg and ASPEN CARBOPLATIN 450 mg can have side effects.
If you experience any of the following symptoms, contact your doctor immediately:
red urine
unusual bruising or bleeding
black, tarry stools
fever
chills
dizziness or feeling of faintness
pain in your side or back
shortness of breath or wheezing
swelling of the feet or ankles
rash
hearing loss

Tell your doctor if either of these symptoms is severe or lasts for several hours:
mouth blistering
fatigue

If you experience any of the following symptoms, contact your doctor as soon as possible:
Thinned or brittle hair
loss of appetite or weight
stomach pain
reduction in blood cell production which may result in anaemia (you may feel tired, weak or fatigued), decreases platelets (you may have bruising, nosebleeds or bleeding gums) and decreased white blood cells (you may experience fever, sore throat or sores in your mouth)
bleeding
diarrhoea
constipation
nausea and vomiting
changes in taste
changes in vision
numbness or tingling in the fingertips

Not all side-effects reported for ASPEN CARBOPLATIN are included in this leaflet. Should your general health worsen while receiving ASPEN CARBOPLATIN, please consult your doctor, pharmacist or other health care professional for advice.
If you notice any side-effects not mentioned in this leaflet, please inform your doctor or pharmacist.

6. STORAGE AND DISPOSING OF ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg
Store at or below 25ºC. Protect from light. Keep in outer carton until required for use.
When reconstituted as directed, ASPEN CARBOPLATIN solutions are stable for 8 hours at room temperature at 25ºC. Since the formulation contains no antibacterial preservatives, it is recommended that any solution remaining after 8 hours be discarded.
KEEP OUT OF REACH OF CHILDREN.

7. PRESENTATION OF ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg
ASPEN CARBOPLATIN 50 mg: A single dose 8 mL Type I, clear, colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 50 mg of carboplatin as a 10 mg/mL solution in an outer carton.
ASPEN CARBOPLATIN 150 mg: A single dose 20 mL Type I, clear colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 150 mg of carboplatin as a 10 mg/mL solution in an outer carton.
ASPEN CARBOPLATIN 450 mg: A single dose 50 mL Type I, clear, colourless glass vial, with a bromobutyl rubber closure and an aluminium metal cap containing 450 mg of carboplatin as a 10 mg/mL solution in an outer carton.

8. IDENTIFICATION OF ASPEN CARBOPLATIN 50 mg, ASPEN CARBOPLATIN 150 mg AND ASPEN CARBOPLATIN 450 mg
A clear, colourless solution, free from visible particles.

9. REGISTRATION NUMBER
Aspen Carboplatin 50 mg: 41/26/0608
Aspen Carboplatin 150 mg: 41/26/0609
Aspen Carboplatin 450 mg: 41/26/0610

10. NAME AND ADDRESS OF REGISTRATION HOLDER
Pharmacare Limited
Building 12
Healthcare Park
Woodlands Drive
Woodmead
2191

11. DATE OF PUBLICATION
20 April 2012

New addition to this site: October 2014
Source: Pharmaceutical Industry

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