Carbotinol

Carbotinol

carboplatin

Manufacturer:

Korea United Pharma

Distributor:

Qualimed
Full Prescribing Info
Contents
Carboplatin.
Description
Each 15 mL vial contains Carboplatin, BP 150 mg.
Each 45 mL vial contains Carboplatin, BP 450 mg.
Action
Pharmacotherapeutic Group: Antineoplastic agent. ATC Code: LO1X A02.
Carboplatin, like Cisplatin, interferes with DNA intrastrand and interstrand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.
Paediatric patients: Safety and efficacy in children have not been established.
Pharmacokinetics: Following intravenous injection carboplatin exhibits a biphasic elimination and is excreted primarily in the urine, about 70% of a dose being excreted within 24 hours, almost all unchanged. 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/Uses
Advanced ovarian carcinoma of epithelial origin in: First line therapy; second line therapy, after other treatments have failed. Small cell carcinoma of the lung.
Dosage/Direction for Use
Carboplatin should be used by the intravenous route only. The recommended dosage of carboplatin in previously untreated adult patients with normal kidney function is 400 mg/m2 as a single I.V. dose administered by short-term (15-60 minutes) infusion. Therapy should not be repeated until 4 weeks after the previous carboplatin course.
Reduction of the initial dosage by 20-25% is recommended for those patients who present with risk factors such as prior myelosuppressive treatment and low performance status (ECOG-Zubrod 2-4 or Karnofsky below 80).
Dilution: The product may be diluted with 5% Glucose for injection or 0.9% Sodium Chloride for injection to concentrations as low as 0.5 mg/mL. When diluted as directed, carboplatin solutions are stable for 8 hours stored at room temperature or 24 hours stored under refrigeration. Since no antibacterial preservatives are contained in the formulation, it is recommended that any carboplatin solution be discarded after 8 hours from dilution if stored at room temperature or after 24 hours if stored under refrigeration.
Pharmaceutical Precautions: Since mixing with other drugs may cause crystal formation or apparent change, the mixture injection should be avoided.
The drug should not be diluted with aminoic acid (methionine, cysteine) containing sulfur.
When the drug is diluted with water solution containing NaCl, KCl, CaCl2, such as physiological saline solution, it is recommended that carboplatin solution be administered within 8 hours after dilution.
Equipment containing aluminum should not be used during preparation and administration of carboplatin.
Aluminum can react with carboplatin causing precipitate formation and loss of potency.
The drug should not be injected with other antitumor agents.
The drug should be protected from light or high temperature.
Induration, necrobiosis may occur due to extravasation of the solution in intravenous injection. Therefore, intravenous administration should be taken with caution to prevent the leakage of the solution.
Overdosage
There is no known antidote for carboplatin overdosage. No overdosage occurred during clinical trials. If necessary, however, the patient may need supportive treatment relating to myelosuppression, renal, hepatic and auditory function impairment. Reports of doses up to 1600 mg/m2 indicate patients feeling extremely ill with diarrhoea and alopecia developing. Use of higher than recommended doses of carboplatin has been associated with loss of vision.
Contraindications
Carboplatin should not be used in patients with severe pre-existing renal impairment.
Carboplatin should not be employed in severely myelosuppressed patients.
Carboplatin is also contraindicated in patients with a history of severe allergic reactions to carboplatin or other platinum containing compounds.
Special Precautions
Hematologic tests and renal function tests should be monitored closely. Blood counts should be performed prior to commencement of Carboplatin therapy, and at weekly intervals thereafter. Neurological evaluation and an assessment of hearing should also be performed on a regular basis. Long-term therapy may cause severe adverse reactions and become chronic, therefore it should be cautioned.
Carboplatin myelosuppression is closely related to its renal clearance: patients with abnormal kidney function or receiving concomitant therapy with other drugs with nephrotoxic potential are likely to experience more severe and prolonged myelotoxicity. Renal function parameters should, therefore, be carefully assessed before and during therapy. Carboplatin courses should not be repeated more frequently than monthly under normal circumstances. Thrombocytopenia, leucopenia and anemia occur after administration of carboplatin. Frequent monitoring of peripheral blood counts is recommended throughout and following therapy with carboplatin. Carboplatin combination therapy with other myelosuppressive compounds must be planned very carefully with respect to dosages and timing in order to minimize additive effects. Supportive transfusional therapy may be required in patients who suffer severe myelosuppression.
Carboplatin should only be administered under the supervision of a qualified physician who is experienced in the use of chemotherapeutic agents. Diagnostic and treatment facilities should be readily available for management of therapy and possible complications.
Carboplatin can cause nausea and vomiting. Premedication with antiemetics has been reported to be useful in reducing the incidence and intensity of these effects.
Renal function impairment may be encountered with carboplatin. Although no clinical evidence on compounding nephrotoxicity has been accumulated, it is recommended not to combine carboplatin with aminoglycosides or other nephrotoxic compounds.
As for other platinum coordination compounds, allergic reactions to carboplatin have been reported. These may occur within minutes of administration and should be managed with appropriate supportive therapy.
Manifestation or exacerbation of infections, bleeding tendency should be taken with caution.
Use in children or patients of childbearing potential should be taken with caution.
Others: In cases where the efficacy of cisplatin administration has not been acceptable, the efficacy of carboplatin may also be unacceptable.
Carboplatin has shown mutagenicity in bacteria and lymphocyte cell of human. It also has shown clastogenicity in hamsters.
In chronic toxicity (i.v.) tests in rats, adenocarcinoma of glandula parotis and glandula mammaria, premalignant lesion of prostate has been reported to occur.
Cardiac infarction, cerebral infarction have been reported to occur during concomitant administration with other antineoplastic agents.
Use in children: The recommended dosage for children has not been established.
Use in pregnancy & lactation: The safe use of carboplatin during pregnancy has not been established; carboplatin has been shown to be an embryotoxin and mutagen in several experimental systems. Carboplatin has been shown to be embryotoxic and teratogenic in rats.
Carboplatin has been reported to be distributed in human milk; therefore, the administration should be avoided in nursing mothers.
Use In Pregnancy & Lactation
The safe use of carboplatin during pregnancy has not been established; carboplatin has been shown to be an embryotoxin and mutagen in several experimental systems.
Carboplatin has been shown to be embryotoxic and teratogenic in rats.
Carboplatin has been reported to be distributed in human milk; therefore, the administration should be avoided in nursing mothers.
Adverse Reactions
Hematological: Bone marrow suppression is the dose-limiting toxicity of carboplatin. Thrombocytopenia with platelet counts below 50,000/mm3 occurs in 35% of pretreated ovarian cancer patients. The nadir usually occurs between 14-21 days, with recovery within 35 days from the start of therapy.
Leucopenia has also occurred in approximately 20% of patients but its recovery from the day of nadir (14-28 days) may be slower and usually occurs within 42 days from the start of therapy. A hemoglobin decrease may be observed in some patients.
Myelosuppression may be more severe and prolonged in patients with impaired renal function, extensive prior treatment, poor performance status and age above 65.
Myelosuppression is also worsened by therapy combining carboplatin with other compounds that are myelosuppressive.
Myelosuppression is usually reversible and not cumulative when carboplatin is used as a single agent and at the recommended dosage and frequencies of administration.
Infections as complications have occasionally been reported. Hemorrhagic complications, usually minor, have also been reported.
Nephrotoxicity: Renal toxicity is usually not dose-limiting in patients receiving carboplatin, nor does it require preventive measures such as high volume fluid hydration or forced diuresis. Nevertheless, increasing blood urea or serum creatinine levels can occur. Renal function impairment, as defined by a decrease in the creatinine clearance below 60 mol/min, may also be observed. The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function before carboplatin treatment. It is not clear whether an appropriate hydration program might overcome such an effect, but dosage reduction or discontinuation of therapy is required in the presence of severe alteration of renal function tests.
Decreases in serum electrolytes (magnesium, potassium and rarely, calcium) have been reported after treatment with carboplatin but have not been reported to be severe enough to cause the appearance of clinical signs or symptoms.
Gastrointestinal: Nausea without vomiting occurs in about ¼ of the patients receiving carboplatin; vomiting has been reported in half of the patients and 1/3 of these suffer severe emesis. Nausea and vomiting usually disappear within 24 hours after treatment and are usually responsive to (and may be prevented by) anti-emetic medication. ¼ of patients experience no nausea or vomiting.
Allergic Reactions: Hypersensitivity to carboplatin has been reported in 2% of the patients. These allergic reactions have been similar in nature and severity to those reported with other platinum-containing compounds, i.e., rash, urticaria, erythema, pruritus, and rarely, bronchospasm and hypotension.
Ototoxicity: Subclinical decrease in hearing acuity, consisting of high-frequency (4000-8000 Hz) hearing loss determined by audiogram, has been reported in 15% of the patients treated with carboplatin. However, only 1% of patients present with clinical symptoms, manifested in the majority of cases by tinnitus. In patients who have been previously treated with cisplatin and have developed hearing loss related to such treatment, the hearing impairment may persist, or worsen.
Neurotoxicity: The incidence of peripheral neuropathies after treatment with carboplatin is 6%. In the majority of the patients neurotoxicity is limited to paraesthesia and decreased deep tendon reflexes. The frequency and intensity of this side effect increases in patients previously treated with cisplatin.
Hepatic: Abnormalities of liver function tests (usually mild to moderate) have been reported with carboplatin in about 1/3 of the patients with normal baseline values. The alkaline phosphatase level is increased more frequently than SGOT, SGPT or total bilirubin. The majority of these abnormalities regress spontaneously during the course of treatment.
Others: Pain and asthenia were the most frequently reported miscellaneous adverse effects; their relationship to the tumor and to anemia was likely. Alopecia was reported (3%). Cardiovascular, respiratory, genitourinary and mucosal side effects have occurred in 6% or less of the patients. Cardiovascular events (cardiac failure, embolism, cerebrovascular accidents) were fatal in less than 1%of the patients and did not appear to be related to chemotherapy. Cancer-associated hemolytic uremic syndrome has been reported rarely.
Drug Interactions
Adverse effects including bone marrow depression may vary by concomitant administration with other antineoplastic agents or radiotherapy.
Concomitant administration of aminoglycoside antibiotics may result in increased nephrotoxicity.
Storage
Store at temperatures between 2-8°C. Refrigerate, do not freeze. Protect from light.
ATC Classification
L01XA02 - carboplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.
Presentation/Packing
Infusion 10 mg/mL (clear, colorless solution in vial) x 15 mL x 1's, 45 mL x 1's.
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