Kemocarb

Carboplatin.

Each mL contains Carboplatin BP 10 mg.
KEMOCARB (Carboplatin) is a platinum coordination compound that is used as a cancer chemotherapeutic agent.
The chemical name for carboplatin is platinum, diamine [1,1 - cyclobutane - dicarboxylate (2) - 0,0] [SP-4-2-] and the molecular formula is C₆H_t2N₂O₄pt and the molecular weight is 371.25.
Excipient/Inactive Ingredients: Water for injection.

Mechanism of Action: Carboplatin is a second generation platinum compound that may be classified as a non-classical alkylating agent and is cell-cycle nonspecific. It is a cytotoxic platinum complex that reacts with nucleophilic site of DNA. This causes interstrand and intrastrand cross links and DNA protein cross links, which inhibit DNA, RNA and protein synthesis.
Pharmacokinetics: Following administration of Carboplatin, the majority of the dose is rapidly cleared from the blood and largely excreted in urine within 6 hours. The remaining drug is eliminated in a biphasic manner, with mean half life of 2.5 hours and about 5 days. The rate of binding to plasma protein is significantly lower accounting for the greater proportion of free drug available for rapid excretion. The degree of urinary excretion indicates less organ retention of the drug. The major route of elimination of carboplatin is renal excretion. Patients with creatinine clearance of approximately 60 ml/min or greater excrete 65% of the dose in the urine within 12 hours and 71% of the dose within 24 hours. All of the platinum in the 24-hour urine is present as carboplatin. Only 3% to 5% of the administered platinum is excreted in the urine between 24 and 96 hours. In patients with creatinine clearance below 60 ml/min, the total body and renal clearances of carboplatin decrease as the creatinine clearance decreases and, therefore, reduced renal function increase the serum half life of carboplatin and results in increased myelotoxicity. Carboplatin dosages should, therefore, there is little concentration of carboplatin at the renal tubular level which may account for its diminished nephrotoxic potential as compared to cisplatin.

Carboplatin is used in the treatment of advanced ovarian cancer, and may be used in combination with other chemotherapeutic agents for treatment of small cell lung cancer, non-small cell lung cancer, head and neck cancer and in genitourinary cancer, particularly in testicular, bladder and cervical cancers.

KEMOCARB (Carboplatin) is given in doses of 360 mg/m² body surface area by intravenous infusion over 15 minutes to 1 hour. Doses should not be given more frequently than every 4 weeks and should be reduced in patients at risk of myelosup­pression. Lower doses may also be given as part of combination regimens.
Preparation of intravenous solution: Immediately before use each vial of KEMOCARB (Carboplatin) should be diluted to concentrations as low as 0.5 mg/ml with 5% Dextrose or 0.9% Sodium Chloride Injection.

There is no known antidote for Carboplatin overdosage. The anticipated complications of overdosage would be secondary to bone marrow suppression and/or hepatic toxicity.

Carboplatin is contraindicated in patients with a history of severe allergic reactions to Cisplatin or other platinum containing compounds.
Carboplatin should not be employed in patients with severe bone marrow depression or significant bleeding.

Carboplatin should be administered under the supervision of a qualified physician 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.
Bone marrow suppression is dose-related and may be severe, resulting in infection and/or bleeding.
Anemia may be cumulative and may require transfusion support.
Carboplatin can induce emesis. The incidence and intensity of emesis can be reduced by using premeditation with antiemetics.
Anaphylactic-like reactions to Carboplatin have been reported and may occur within minutes of carboplatin administration. Epinephrine, corticosteroids and antihistamines have been employed to alleviate symptoms.
Carboplatin has limited nephrotoxic potential but concomitant treatment with aminoglycosides has resulted in increased renal and/or audiologic toxicity and caution must be exercised when a patient receives both drugs.
Peripheral neurotoxicity is infrequent, its incidence increases in patients older than 65 years and in patients previously treated with cisplatin.
Loss of vision, which can be complete for light colors, may occur after the use of carboplatin with doses higher than those recommended. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.
Needles or intravenous administration sets containing aluminum part that may come in contact with Carboplatin should not be used for the preparation or the administration of the drug. Aluminum can react with carboplatin causing precipitate formation and loss of potency.
Carboplatin is mutagenic both in-vitro and in-vivo.
Use in Pregnancy: Carboplatin may cause foetal harm when administered to a pregnant woman and is embryotoxic and teratogenic in rats. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the foetus. Woman of child bearing potential should be advised to avoid becoming pregnant.

Use in Pregnancy: Carboplatin may cause fetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryotoxic and teratogenic in rats. If this drug is used during pregnancy or if the patient becomes pregnant while receiving carboplatin, the patient should be apprised of the potential hazard to the foetus. Women of child bearing potential should be advised to avoid becoming pregnant.
Use in Lactation: It is not known whether carboplatin is excreted in human milk. Because there is a possibility of toxicity in nursing infants secondary to carboplatin treatment of the mother, it is recommended that breast feeding be discontinued if the mother is being treated with Carboplatin.

Haematologic toxicity: Bone marrow suppression is the dose limiting toxicity of Carboplatin. Thrombocytopenia with platelet counts below 50,000/mm occurs in 25% of the patients, neutropenia with granulocyte counts, below 1,000/mm occurs in 16% of the patients, leucopenia with WBC counts below 2,000/mm occurs in 15% of the patients.
The nadir usually occurs about day 21 in patients receiving single agent therapy. By day 28, 90% of patients have platelet counts above 100,000/mm³ 74% have neutrophil counts above 2,000/mm, 67% have leukocyte counts above 4,000/mm³. Marrow suppres­sion is usually more severe in patients with impaired kidney function. Patients with poor performance status have also experienced a higher incidence of severe leucope­nia and thrombocytopenia. Anemia with hemoglobin less than 11 g/dl occurs in majority of the patients who start therapy with a baseline above the value. The inci­dence of anemia increases with increasing exposure to carboplatin. Transfusions may be required in some patients treated with carboplatin. Bone marrow depression may be more severe when carboplatin is combined with other bone marrow suppressing drugs or with radiotherapy.
Gastrointestinal toxicity: Vomiting occurs in about 65% of the patients and in about one third of these patients, it is severe. Nausea alone occurs in an additional 10-15% of patients. Both nausea and vomiting usually cease within 24 hours of treatment and are often responsive to antiemetic measures. Emesis was increased when carboplatin was used in combination with other emetogenic compounds. Other gastrointestinal effects observed frequently were pain, in 17% of the patients; diarrhea, in 6%; and constipation, also in 6%.
Neurologic toxicity: Peripheral neuropathies have been observed in small number of patients receiving carboplatin with mild paresthesias occurring most frequently. Patients older than 65 years have an increased risk for peripheral neuropathies. Clinical ototoxicity and other sensory abnormalities such as visual disturbances and change in taste occurs rarely. Central nervous system symptoms have been reported in fewer patients and appear to be most often related to the use of antiemetics. Although the overall induced of peripheral neurologic side effect induced by carboplatin is low, prolonged treatment may result in cumulative neurotoxicity.
Nephrotoxicity: Development of abnormal renal function test results is uncommon with carboplatin. Creatinine clearance has proven to be the most sensitive measure of kidney function in patients receiving carboplatin, and it appears to be the most useful test for correlating drug clearance and bone marrow suppression.
Hepatic toxicity: Abnormal liver function tests in patients may be found with normal baseline value. These abnormalities (e.g. SGOT, total bilirubin and alkaline phosphatase) have generally been mild and reversible in about one-half of the cases, although the role of metastatic tumour in the liver may complicate the assessment in many patients.
Electrolyte changes: The abnormally decreased serum electrolyte values may be found in some patients. Electrolyte supplementation is not routinely administered concomitantly with carboplatin, and these electrolyte abnormalities are rarely associat­ed with symptoms.
Allergic reactions: Hypersensitivity to Carboplatin develops only in a small number of patients and consists of rash, urticaria, erythema, pruritus and rarely bronchospasm and hypotension. These reactions are successfully managed with standard epinephrine, corticosteroid and antihistamine therapy.
Others: Pain and asthenia occurs most frequently. Alopecia, cardiovascular, respiratory genitourinary and mucosal side effects occur only in small number of patients.

Handling and Disposal: Caution should be exercised in handling and preparing carboplatin solutions. The use of gloves is recommended. If carboplatin solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious of water.
Unused portion and all material that have been utilized for dilution and administration should be disposed of according to standard procedures for anticancer drugs.

Store in a cool and dark place. Do not Freeze.
Store at 15-30°C. Protect from light.

Cytotoxic Chemotherapy

L01XA02 - carboplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.

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