INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
P&U CARBOPLATIN CSV 150 mg/15 mL INJECTION
P&U CARBOPLATIN CSV 450 mg/45 mL INJECTION

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

P&U CARBOPLATIN CSV 150 mg/15 mL INJECTION
P&U CARBOPLATIN CSV 450 mg/45 mL INJECTION

COMPOSITION:
Each 1 mL contains 10 mg carboplatin

PHARMACOLOGICAL CLASSIFICATION:
A 26 Cytostatic agents

PHARMACOLOGICAL ACTION:
CARBOPLATIN is a platinum co-ordination compound with antitumour properties. It has biochemical properties similar to those of cisplatin, thus forming predominantly interstrand and intrastrand DNA cross links.
The effect is cell-cycle phase non-specific.
Pharmacokinetics:
Following IV administration, CARBOPLATIN exhibits a biphasic elimination. CARBOPLATIN is mainly excreted by the kidneys, about 70% of the dose being excreted within 24 hours. Platinum slowly becomes protein bound and is subsequently excreted with a half-life of 5 days or more. The terminal half-life of intact CARBOPLATIN is reported to be about 3 to 6 hours.

INDICATIONS:

•	Advanced ovarian carcinoma
•	Small cell carcinoma of the lung

CONTRA-INDICATIONS:
Hypersensitivity to CARBOPLATIN or any related platinum product.
CARBOPLATIN should be given at reduced doses to patients with impaired renal function and should be avoided in those with a creatinine clearance of 20 mL per minute or less.
CARBOPLATIN is contra-indicated in renal or hearing impairment or bone marrow depression.
Safety in pregnancy and lactation has not been established.

WARNINGS:
CARBOPLATIN should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.
Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Peripheral blood counts and renal function tests must be monitored closely. Blood counts at the beginning of therapy and weekly, to assess haematological nadir for dose adjustment are recommended. Neurological evaluations should also be performed on a regular basis.
The concomitant use of other nephrotoxic or ototoxic drugs should be avoided.
Because of the possibility of carcinogenicity and mutagenicity, patients of child bearing age or conceiving potential must exercise non-hormonal conception control.

DOSAGE AND DIRECTIONS FOR USE:
FOR INTRAVENOUS USE ONLY.
The physician should in all cases be familiar with the current literature before choosing a specific dosage.
CARBOPLATIN may be administered in combination with other anti-cancer drugs.
CARBOPLATIN is given by intravenous infusion over 15 to 60 minutes.
The dosage of CARBOPLATIN is based on the patient’s body surface area (m²).

•	Single agent therapy: an initial single dose of 360 to 400 mg/m² is recommended.
•	Combination therapy: in combination with other cytotoxic drugs CARBOPLATIN is recommended at the initial dosage of 300 mg/m².

Doses should be reduced in patients with renal impairment or at risk of myelosuppression. Subsequent doses should be adjusted according to the nadir of the white-blood cell and platelet counts, and should not be given more frequently than every 4 weeks. Lower doses may be required when CARBOPLATIN is given as part of a combination regimen.
No dosage regime for use in children is available due to limited clinical experience.
Dosage adjustments are needed in cases of impaired renal function, use in elderly patients or use in combination with other myelosuppressive agents.
The therapeutic dosage of CARBOPLATIN may have to be adjusted according to the bone marrow status and to renal function as follows.

•	Bone marrow: Administration of subsequent doses of CARBOPLATIN is not recommended before platelet levels return to at least 100 000 per cubic millimeter and leukocyte levels to at least 2 000 per cubic millimeter.
	A suggested dosage adjustment schedule for subsequent doses is:

Nadir after prior dose (cells per cubic millimeter)		% of prior dose to be given
Neutrophils	Platelets
>2 000 500-2 000 <500	>100 000 50 000-100 000 <50 000	125         100         75

•	Renal function: Patients with creatinine clearance values below 60 mL/min are at risk of CARBOPLATIN toxicity, therefore the dosage of CARBOPLATIN should be reduced in patients with impaired renal function as follows:

Creatinine clearance         (mL/min)	Recommended dose         (mg/m²)
41-59         16-40	250         200

Geriatric patients may require lower doses.

Dilution of the CARBOPLATIN injection can be made with dextrose 5% in water or 0,9% sodium chloride. Prior to administration, CARBOPLATIN solutions should be inspected visually for particulate matter and discolouration. Use the solution as soon as possible after preparation. Infusion should be completed within 24 hours of the preparation. Any solution not used must be discarded.
Note: CARBOPLATIN is incompatible with aluminium, do not use needles, intravenous sets or equipment containing aluminium for administration since an interaction may occur and a black precipitate will form.
Guidelines for handling of antineoplastic agents must be followed. Cautious and proper disposal of needles, syringes, containers and unused medication must be done.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Many of the adverse effects of CARBOPLATIN are an extension of their therapeutic action, which is not selective for malignant cells, but affects all rapidly-dividing cells.
In consequence, adverse effects may be expected where normal cell division is fairly rapid, e.g. the bone marrow, lymphoreticular tissue, gastro-intestinal mucosa, skin and gonads, as well as in the foetus. The effects may not manifest for days or weeks, depending both on the agents used and the rate of division in the tissue concerned, and may sometimes be cumulative. The most common serious effect, and one which frequently limits the doses that can be given is bone-marrow depression. It is suggested that use and administration be confined to experienced staff in specialised centres.
Bone marrow/Haematological toxicity:
Anaemia, leucopenia, neutropenia, thrombocytopenia is the result of dose related and reversible myelosuppression. Anaemia may be cumulative and transfusions are frequently necessary.
With leucopenia and thrombocytopenia, the leukocyte and platelet counts reach a nadir between 14 and 21 days after a dose, with recovery within 35 days, but recovery from leucopenia may be slower. Leucopenia and thrombocytopenia may result in symptomatic events such as infection or bleeding in a minority of the patients.
Nephrotoxicity:
Salt wasting nephropathy and decreased creatinine clearance and glomerular filtration rate have occurred. It has been suggested that renal toxicity may be more likely at cumulative CARBOPLATIN doses or in patients with renal damage.
Pre- and post-treatment hydration is not necessary with CARBOPLATIN. Previous therapy with cisplatin or concomitant administration of other nephrotoxic drugs (e.g. aminoglycosides) may increase the risk of nephrotoxicity.
Electrolyte disturbances, particularly hypomagnesemia and hypocalcemia may occur, possibly as a result of renal tubular damage. The destruction of large numbers of cells during therapy and the consequent release of breakdown products may also lead to problems with hyperuricaemia and acute renal failure due to uric acid nephropathy. The concomitant use of other nephrotoxic components should be avoided.
Gastro-intestinal toxicity:
The acute effects of CARBOPLATIN administration frequently include nausea and vomiting, often via a central mechanism, and are sometimes extremely severe. It may be treated or prevented by antiemetic medication.
Allergic reactions:
An allergic reaction can occur within minutes of administration and includes skin rash or itching and rarely, wheezing and should be treated with supportive therapy. Anaphylactic reactions can occur and supportive treatment should be available.
Ototoxicity:
It may be more severe in children and it can manifest as tinnitus, loss of hearing in the high frequency range and occasionally deafness or vestibular toxicity.
Routine neurological examination is advisable during CARBOPLATIN therapy, particularly in patients previously treated with cisplatin and in patients over 65 years of age.
CARBOPLATIN may produce cumulative ototoxicity
Neurotoxicity:
Neurological effects reported include peripheral neuropathies. In patients who had impaired renal function and were treated with high dose CARBOPLATIN, cortical blindness developed.
Other:
In addition, CARBOPLATIN is an irritant or vesicant, and produces local pain, irritation, and inflammation at the administration site; extravasation may lead to ulceration and necrosis.
Rarely, increases in liver enzymes, alopecia, flu-like symptoms, mucositis and stomatitis was reported.
Interactions:
Combinations of the following medications may also interact with CARBOPLATIN, the reaction is dose dependant. Blood dyscrasia causing medications, bone marrow depressants or radiotherapy, cisplatin, nephrotoxic medication, ototoxic medication, killed virus vaccines. The use of live vaccines is contra-indicated in these patients.
Concomitant administration with aminoglycosides results in an increased risk of nephrotoxicity and/or ototoxicity.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See "Side-effects and Special Precautions".
Treatment should be symptomatic and supportive.

IDENTIFICATION:
Clear, colourless to pale yellow solution, free from visible particles.

PRESENTATION:
P&U CARBOPLATIN CSV 150 mg/15 mL INJECTION

A single dose plastic vial containing 150 mg carboplatin as a 10 mg/mL solution.

P&U CARBOPLATIN CSV 450 mg/45 mL INJECTION

A single dose plastic vial containing 450 mg carboplatin as a 10 mg/mL solution.

STORAGE INSTRUCTIONS:
Store at room temperature below 25°C. Protect from light.
Any unused portion must be discarded.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:

P&U CARBOPLATIN CSV150 mg/15 mL INJECTION:	29/26/0501
P&U CARBOPLATIN CSV 450 mg/45 mL INJECTION:	30/26/0310

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pfizer Laboratories (Pty) Ltd
102 Rivonia Road
Sandton
2196

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
28 July 1999

New addition to this site: January 2005
Source: Pharmaceutical Industry
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2005