Naproplat

Each mL contains: Carboplatin, BP 10 mg.

Antineoplastic.
Pharmacology: Mechanism of Action: Carboplatin is 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 sites of DNA. This causes intrastrand and interstrand 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 of plasma protein is significantly lower accounting for the 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 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 increases the serum half-life of Carboplatin and results in increased myelotoxicity. Carboplatin dosages should, therefore, be reduced in these patients since carboplatin is eliminated almost completely by glomerular filtration, 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, small cell lung cancer, head and neck cancer and in genito-urinary cancer, particularly in testicular, bladder and cervical cancers. Antitumor activity of Carboplatin has also been observed in pediatric brain tumor (medulloblastoma).

Carboplatin is given in doses of 400 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 or as prescribed by the physician.
Preparation of Intravenous Solution: Immediately before use, each vial of Carboplatin should be diluted to concentration 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 reaction 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 premedication 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 that recommended. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.
Carboplatin may cause fetal harm when administered to a pregnant women and is embryotoxic and teratogenic in rats. If this drug is used during pregnancy, the patient should be appraised of the potential hazard to the fetus. Woman of child-bearing potential should be advised to avoid becoming pregnant.
Needles or intravenous administration sets containing aluminum parts 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 vivo and in vitro.

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 appraised of the potential hazard to the fetus. 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 breastfeeding be discontinued if the mother is being treated with Carboplatin.

Hematologic toxicity: Bone marrow suppression is the dose-limiting toxicity of Carboplatin. Thrombocytopenia with platelet counts below 50,000/mm³ occurs in 25% of the patients; neutropenia with granulocyte counts below 1,000/mm³ occurs in 16% of patients; leucopenia with WBC counts below 2,000/mm³ occurs in 15% of patients. This 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/mm³; 67% have leucocyte 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 starts therapy with a baseline above value. The incidence of anemia increases with the 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 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 compound. 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 numbers 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 occur 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 incidence of peripheral neurologic side effects 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 measures of kidney functions in patients receiving carboplatin, and it appears to be 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 (eg. SGOT, total bilirubin and alkaline phosphatase) have generally been mild and reversible in about one-half of the cases, although the role of metastatic tumor 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 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, genito-urinary and mucosal side effects occur only in small number of patients.

Store at temperatures not exceeding 25°C.
Protect from light.
When prepared as directed, NAPROPLAT aqueous solution is stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that NAPROPLAT aqueous solution be discarded 8 hours after dilution.
Solution with precipitate to be discarded.
Discard unused portion.

Cytotoxic Chemotherapy

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

Rx