Biovinate

Biovinate

carboplatin

Manufacturer:

UNILAB, Inc

Distributor:

UNILAB, Inc
Full Prescribing Info
Contents
Carboplatin.
Indications/Uses
Initial treatment of advanced ovarian carcinoma of epithelial origin in established combinations with other approved chemotherapeutic agents.
For the palliative treatment of ovarian carcinoma of epithelial origin refractory to standard chemotherapy with or without cisplatin.
For the treatment of small cell lung carcinoma (SCLC).
Dosage/Direction for Use
General Dosing Information: Aluminum reacts with carboplatin. DO NOT use needles or IV sets containing aluminum parts that may come in contact with the drug in the preparation or administration of carboplatin. (see Interactions).
Carboplatin should be used by intravenous route only.
No pre- or post-treatment hydration or diuresis is necessary when carboplatin is administered.
Treatment should generally not be repeated until 4 weeks after the previous carboplatin course and/or until the neutrophil count is at least 2,000 cells/mm3 and the platelet count is at least 100,000 cells/mm3.
Initial dosage should be reduced by 20-25% in patients with risk factors such as previous myelosuppressive therapy and/or poor performance status (ECOG-Zubroid 2-4 or Karnofsky below 80).
Dosage must be based on the clinical, renal and hematologic response and tolerance of the patient in order to obtain optimum therapeutic outcome with minimum adverse effects.
As Monotherapy: The recommended initial dose of carboplatin for previously untreated patients with normal renal function is 400 mg/m2, given as a single IV infusion over 15 to 60 minutes every 4 weeks (see Formula Dosing).
An initial dose of 360 mg/m2 IV carboplatin once every 4 weeks (or longer if delayed for hematologic toxicity) can be used for the treatment of recurrent ovarian cancer.
Determination of the hematologic nadir by weekly blood counts during the initial courses of carboplatin treatment is recommended for subsequent courses of therapy (see Dosage Adjustment as follows).
In Combination with Cyclophosphamide: An initial dose of 300 mg/m2 IV carboplatin can be used in adults for the treatment of advanced ovarian cancer (stage III and IV) in combination with cyclophosphamide. The subsequent dosage of the drug should be adjusted according to the patient's hematologic tolerance of the previous dose. Do not administer the next dose until the patient's hematologic function is within acceptable limits (For cyclophosphamide dosage adjustments, see product's labeling information).
In Other Combination Regimens: Clinicians should consult published protocols for the dosage of each chemotherapeutic agent and the method and sequence of administration when carboplatin is used as a component of a multiple-drug regimen.
Formula Dosing: Carboplatin's initial dose may be calculated by using a mathematical formula based on the patient's renal function and desired platelet nadir. The use of Calvert's formula, as compared to empirical dose calculation based on body surface area allows adjustment for patient variation in pretreatment renal function.
The formula is based on glomerular filtration rate (GFR in mL/min) and carboplatin AUC (in mg/mL·min). The total dose is calculated in mg, not in mg/m2.
Total Dose (mg) = target AUC x (GFR + 25)
Target AUCs providing the most appropriate dosage range are based on the treatment status of the patient: See Table 1.

Click on icon to see table/diagram/image

Subsequent carboplatin dose should be adjusted according to hematologic tolerance to the previous dose (see Dosage Adjustments as follows).
The Calvert formula should not be used to determine carboplatin dosage for children or for adults with severe renal impairment (i.e., GFR <20 mL/min) since it is not sufficiently accurate.
Dosage Adjustments: Pretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
No specific dosage adjustment data for children has been calculated.
Subsequent doses of carboplatin in single or combination therapy should be based on the hematologic response of the patient. (See Table 2.)

Click on icon to see table/diagram/image

Geriatric Dosing: Because renal function is often reduced in geriatric patients, dosing formulas incorporating estimates of GFR should be used to provide predictable plasma carboplatin AUCs and minimize the risk of toxicity.
Dose in Patients with Renal Impairment: Patients with impaired renal function or creatinine clearances of <60 mL/min are at an increased risk of myelosuppression during carboplatin therapy that dosage in such patients should be adjusted according to the degree of renal impairment. The initial dose of carboplatin may be based on the following creatinine clearance: See Table 3.

Click on icon to see table/diagram/image

Subsequent dosage should be adjusted according to the patient's tolerance to the previous dose and acceptable level of myelosuppression.
Limited data are available for patients with creatinine clearance of <15 mL/min to permit dosage recommendations.
Contraindications
Carboplatin is contraindicated in the following conditions: Hypersensitivity to carboplatin, cisplatin or other platinum containing compounds.
Hypersensitivity to mannitol.
Pre-existing severe renal impairment (creatinine clearance <30 mL/min).
Severe myelosuppression.
Bleeding tumors.
Yellow fever vaccine.
Pregnant or breastfeeding women.
Special Precautions
General: Since carboplatin is a highly toxic drug with a narrow therapeutic index, therapeutic effect is unlikely to occur without some evidence of toxicity. Carboplatin should only be administered under the supervision of a qualified physician experienced in cancer chemotherapeutic drugs. Blood counts as well as renal and hepatic function tests must be monitored closely. Diagnostic and treatment facilities should be readily available for appropriate management of therapy and possible complications.
Generally, carboplatin courses should not be administered more frequently than every 4 weeks to ensure that the nadir in blood counts has occurred and that there has been recovery to a satisfactory level.
Discontinue carboplatin therapy if severe myelosuppression or abnormal renal or hepatic function is observed.
Myelosuppression: Myelosuppression, especially thrombocytopenia, may be more severe and prolonged in patients with abnormal renal function and who are receiving concomitant therapy with nephrotoxic drugs.
The occurrence, severity and protraction of myelosuppression is likely to be greater in older patients, those who have received extensive prior treatment with carboplatin for their disease or with cisplatin and have poor performance status. Renal function parameters of patients should be assessed prior, during and after carboplatin therapy. Dosage of carboplatin should be appropriately reduced in these groups and the effects carefully monitored through frequent blood counts between courses.
Combination therapy with other myelosuppressive drugs may require dosage and timing schedule modification in order to minimize additive effects. Peripheral blood counts (including platelets, white blood cells and hemoglobin) should be assessed during and after therapy.
Hypersensitivity/Allergic reactions: Observe patients carefully. Like with other platinum-based drugs, allergic reactions appear most often during administration that may necessitate discontinuation of infusion. In such cases, appropriate symptomatic treatment that includes antihistamine, adrenaline and/or glucocorticoids must also be initiated.
Hematologic Toxicity: Bone marrow suppression (leukopenia, neutropenia and thrombocytopenia) is dose-dependent and dose-limiting toxicity. Frequently monitor peripheral blood counts during carboplatin therapy, and when appropriate, until recovery is achieved because this will monitor toxicity and help determine the nadir and recovery of hematological parameters. This will also assist in subsequent adjustment of dosage of the drug. Median nadir occurs at day 21 in patients receiving single agent carboplatin and at day 15 in patients receiving combination therapy with other chemotherapeutic drugs. Do not repeat intermittent courses of carboplatin until leukocyte, neutrophil, and platelet counts have normalized that usually takes 5 to 6 weeks. Lowest levels of platelets and white cells are seen between days 14 to 21 and 14 to 28, respectively.
Since anemia is cumulative, transfusions may be needed during treatment with carboplatin, particularly in patients receiving prolonged therapy (i.e., more than 6 cycles).
Nephrotoxicity: Carboplatin is excreted mainly in the urine and renal function must be monitored in patients receiving the drug. The incidence and severity of nephrotoxicity may increase in patients with impaired renal function prior to carboplatin therapy. It is unclear if appropriate hydration programme might overcome such an effect but dosage reduction or discontinuation of therapy is required when there is severe alteration in renal function test. Impairment of renal function is more likely in patients who have experienced nephrotoxicity with cisplatin use.
Neurotoxicity: Patients older than 65 years and/or previously treated with cisplatin have an increased risk of peripheral neurologic toxicity (limited to paresthesia and decrease in osteotendinous reflexes). Monitoring and neurological examinations should be carried out at regular intervals.
There have been reports of visual disturbances, including loss of vision, in post-carboplatin use in doses higher than those recommended in patients with renal impairment. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.
Ototoxicity: Cases of auditory defects have been reported with carboplatin use. Ototoxicity may be more pronounced when used in children and more likely seen in patients previously treated with cisplatin. Since delayed onset hearing loss have also been reported in pediatric patients, long-term audiometric follow-up in this population is recommended.
Gastrointestinal: Carboplatin can induce emesis, which can be more severe in patients previously receiving emetogenic therapy. Nausea and/or vomiting, which are generally mild to moderate in severity may occur within 6 to 12 hours after carboplatin administration and may persist up to 24 hours or longer. Incidence and intensity of emesis have been reduced by using premedication with antiemetics. Although no conclusive efficacy data exist with carboplatin's schedules, lengthening the duration of single IV administration to 24 hours or dividing the total dose over 5 consecutives daily pulse doses has resulted in reduced emesis.
Immunosuppressant Effects/Increased Susceptibility to Infections: Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including carboplatin may result in serious or fatal infections (see Interactions).
Carcinogenicity, Mutagenicity, Impairment of Fertility: Carboplatin is mutagenic in both in vitro and in vivo experimental models. The carcinogenic potential of carboplatin has not been fully established. However, drugs with similar mechanisms of action and evidence of mutagenic effects have been reported to be carcinogenic.
Patients receiving antineoplastic therapy may experience gonadal suppression resulting in amenorrhea or azospermia depending on the dose and length of therapy and may be irreversible. Men are advised not to father a child during and six months post treatment with carboplatin. These patients should seek advice regarding sperm preservation prior to initiation of therapy because of the possibility of irreversible infertility due to carboplatin therapy.
Effects on ability to drive and use machines: Carboplatin may cause nausea, vomiting, vision abnormalities and ototoxicity; therefore, patients should be warned of the potential effect of the drug on the ability to drive and use machines.
Use in Children: The safety and efficacy of carboplatin in children have not been established.
Use in Elderly: The safety and efficacy of carboplatin when used in geriatric patients have not been established. Geriatric patients experienced severe thrombocytopenia more frequently than in younger patients. Also, carboplatin-induced peripheral neuropathy appears to be more common in adults older than 65 years of age than in younger patients. Among a total of 1942 patients (21% of whom were ≥65 years old) receiving carboplatin monotherapy in different tumor types, a similar incidence of adverse effects was observed in younger and older patients. Other reported clinical experience has not identified differences between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal function and decreased hematopoietic function should be considered when determining dosage.
Use In Pregnancy & Lactation
Use in Pregnancy: There is evidence that carboplatin can cause fetal toxicity when administered to pregnant women. It has been shown to be embryotoxic and teratogenic in rats receiving it during organogenesis. To date, there are no adequate or controlled studies using carboplatin to establish its safety in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant. If the patient becomes pregnant while taking carboplatin or if the drug is administered during pregnancy, the patient should be informed of the potential harm to the fetus.
Use in Lactation: It is not known whether carboplatin is excreted in human milk. Because there is a possibility of toxicity in nursing infants if the drug were distributed into milk, breastfeeding should be discontinued during carboplatin therapy.
Adverse Reactions
Neoplasms benign, malignant and unspecified (inc cysts and polyps): Secondary acute malignancies, myeloid leukemia, myelodysplastic syndrome.
Infections and infestations: Infection.
Blood and lymphatic system disorders: Myelosuppression, thrombocytopenia, neutropenia, leukopenia, anemia, bone marrow failure, febrile neutropenia.
Immune system disorders: Hypersensitivity, anaphylactoid type reaction, bronchospasm, urticaria, facial edema, exfoliative dermatitis.
Metabolism and nutrition disorders: Dehydration, anorexia, hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia.
Nervous system disorders: Peripheral neuropathy, paresthesia, decrease of osteotendinous reflexes, sensory disturbance, dysgeusia, cerebrovascular accident, perioral tingling.
Eye disorders: Visual disturbance (including rare cases of loss of vision).
Ear and labyrinth disorders: Hypoacusia, tinnitus, hearing loss.
Cardiac disorders: Cardiac failure, dyspnea, tachycardia, ischemic coronary artery disorders (myocardial infarction, cardiac arrest, angina, myocardial ischemia).
Vascular disorders: Hemorrhage, cardiovascular disorder, embolism, hypertension, hypotension, anaphylactic shock.
Respiratory, thoracic and mediastinal disorders: Respiratory disorder, interstitial lung disease, pulmonary fibrosis, hypoxia.
Gastrointestinal disorders: Vomiting, nausea, abdominal pain, diarrhea, constipation, stomatitis, cramps.
Skin and subcutaneous tissue disorders: Alopecia, skin disorder, rash, erythema, pruritus, erythematous rash.
Musculoskeletal and connective tissue disorders: Musculoskeletal disorder, chills, myalgia, arthralgia.
Renal and urinary disorders: Hemolytic-uremic syndrome, urogenital disorder, abnormal renal function, acute renal failure.
General disorders and administration site conditions: Mucous membrane disorder, asthenia, malaise, fever, mucositis, fatigue, pain, flu-like symptoms.
Investigations: Creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver function test abnormal, blood sodium decreased, blood potassium decreased, blood calcium decreased, blood magnesium decreased, blood bilirubin increased, blood creatinine increased, blood uric acid increased.
Injury, poisoning and procedural complications: Ototoxicity, injection site necrosis, injection site reaction (burning, pain, reddening, swelling, urticaria) injection site extravasation, injection site erythema.
Drug Interactions
Aluminum: Aluminum reacts with carboplatin causing a black precipitate to form. Do not use needles, syringes, catheters or IV administration sets that contain aluminum parts that may come in contact with carboplatin when used for the preparation or administration of the drug.
Oral anticoagulants: Treatment with anticoagulants is frequent due to the increased thrombotic risk in cases of tumoral diseases. International normalized ratio (INR) should be monitored frequently in patients treated with anticoagulants since intra-individual variability of the coagulability during diseases and the possibility of interaction between oral anticoagulants and antineoplastic drugs are likely to occur.
Myelosuppressive Therapy or Radiation Therapy: Concomitant use of carboplatin may potentiate the hematologic toxicity of the other agents and vice versa. Patients receiving concurrently or who have received myelosuppressive or radiation therapy should be carefully monitored. Dosage of the drug and time of administration should be managed to minimize additive toxic effects.
Phenytoin, Fosphenytoin: Phenytoin digestive absorption is reduced by carboplatin hence increasing the risk of exacerbation of convulsion. Also there is risk of toxicity enhancement or loss of efficacy of carboplatin due to increased hepatic metabolism of phenytoin.
Nephrotoxic or Ototoxic Agents (e.g., aminoglycosides, vancomycin, capreomycin and loop diuretics): Concurrent administration may increase carboplatin's nephrotoxicity and ototoxicity risks.
Emetogenic Agents: an increased incidence of emesis has been associated with concomitant use of carboplatin and other emetogenic drugs or when carboplatin is administered to patients who previously received emetogenic therapy.
Vaccines: Yellow fever vaccine is contraindicated with carboplatin. Concomitant use of live attenuated vaccines with carboplatin is not recommended because it may result in systemic and possible fatal disease. This risk is increased in patients who are already immunocompromised by their underlying disease.
ATC Classification
L01XA02 - carboplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.
Presentation/Packing
Soln for infusion (vial) 150 mg/15 mL x 25 mL x 1's. 450 mg/45 mL x 50 mL x 1's.
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