Carbosin 50 mg/5 ml/150 mg/15 ml/450 mg/45 ml/600 mg/60 ml

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.

CARBOSIN is contra-indicated in patients with a history of severe hypersensitivity reactions to carboplatin or other platinum-containing compounds. CARBOSIN should not be used in patients with severe pre-existing renal impairment (creatinine clearance at or below 20 ml/min). CARBOSIN should not be employed in severely myelosuppressed patients and/or in patients with localised tumoral bleeding. Pregnancy and lactation. (See PREGNANCY AND LACTATION)

Hypersensitivity reactions to CARBOSIN 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 u201cCONTRA-INDICATIONSu201d and u201cSIDE-EFFECTS: Hypersensitivity Reactionsu201d).

CARBOSIN should be used only by a medical practitioner experienced with 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 and 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 CARBOSIN and day 15 in patients receiving CARBOSIN in combination with other chemotherapeutic agents. Single intermittent courses of CARBOSIN should not be repeated until leucocyte, neutrophil and platelet counts have returned to normal. Transfusional support is frequently needed during treatment with CARBOSIN, 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 CARBOSIN dosages in these groups of patients should be appropriately reduced (see u201cDOSAGE AND DIRECTIONS FOR USEu201d) and the effects carefully monitored through frequent blood counts between courses.

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 CARBOSIN in doses higher than those recommended in patients with renal impairment. Other: Very high dosages of CARBOSIN (up to five times the single agent recommended dose or more) have resulted in severe abnormalities in hepatic and renal function. CARBOSIN carcinogenic potential has not been studied, but compounds with similar mechanisms of action and mutagenicity have been reported to be carcinogenic.

NOTE: CARBOSIN 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 CARBOSIN.

Paediatric Use: Safety and effectiveness in paediatric patients have not been systematically studied.

The use of CARBOSIN with nephrotoxic compounds is not recommended. Although CARBOSIN has limited nephrotoxic potential, 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 CARBOSIN was administered in combination with other ototoxic agents. CARBOSIN can induce nausea and vomiting, which can be more severe in previously treated patients (in particular in patients previously pre-treated with cisplatin).

Pregnancy: Pregnancy is a contra-indication. CARBOSIN has been shown to be an embryotoxin and mutagen. (See CONTRA-INDICATIONS)

Women of childbearing potential: It is recommended that patients with child-bearing or conceiving potential, who are receiving CARBOSIN, exercise adequate contraception control.

Lactation: Safety in lactation has not been established. It is not known whether this medicine is excreted in human milk. (See CONTRA-INDICATIONS)

Central Nervous System Disorders: Less frequent: Peripheral neuropathies have been observed, mild paraesthesiae occurring most frequently. The incidence and severity may be increased in patients previously treated with cisplatin. Clinical ototoxicity and other sensory disturbances (including visual disturbances and taste modifications) have been reported.

Gastro-intestinal disorders: Frequent: Nausea and vomiting are commonly seen. Nausea and vomiting usually cease within 24 hours after treatment. Emesis during carboplatin treatment can be effectively reduced by appropriate anti-emetic medication. Alternatively, emesis may be reduced by sustained administration schedules e.g. by dividing the total dose over 5 days, or over a 24 hour IV infusion. Pain, diarrhoea, constipation and anorexia have been reported.

Haematological System Disorders: Frequent: Myelosuppression is the major dose-limiting toxicity of carboplatin. Thrombocytopenia (platelets< 50,000/mm 3) is seen in most of the patients, with a nadir at about 3 weeks and full recovery at 4 u2013 5 weeks. Leucopenia (< 2,00/mm 3) is usually less pronounced, with a nadir at about 3 weeks and a somewhat slower recovery at 5 weeks. Neutropenia and anaemia (haemoglobin < 2 mg/dl) is commonly seen. Haemorrhagic complications, usually minor, have also been reported. Myelosuppression is more severe in patients with impaired renal function, patients with an inadequate bone marrow reserve, or patients with poor performance status.

Hepatic System Disorders: Less frequent: 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 may occur within minutes of administration and should be managed with appropriate supportive therapy.

Renal System Disorders: Frequent: Elevation of serum creatinine, elevation of blood urea, and of uric acid has been reported.

Other: Second malignancies have been reported in association with multi-drug therapy; however the relationship to CARBOSIN is unclear. Respiratory, cardiovascular, mucosal, genito-urinary, 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. Haemolytic-uremic syndrome has been reported less frequently. Malaise has also been reported. Serum electrolytes: Decreases in serum electrolytes (sodium, potassium, magnesium and calcium) have been reported after treatment with CARBOSIN. Several cases of hyponatremia have been reported.

There is no known antidote for CARBOSIN 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 CARBOSIN has been associated with loss of vision.