| Product Description: | CARBOplatin Injection 450 mg/45 mL (10 mg/mL), 45 mL packaged in a 100 mL Multi-Dose Vial, Rx only, Manufactured for: Mylan Institutional LLC, Rockford, IL 61103, Made in India, NDC 67457-493-46, UPC 3 67457 49346 6. |
|---|---|
| Status: | Ongoing |
| City: | Rockford |
| State: | IL |
| Country: | US |
| Voluntary/Mandated: | Voluntary: Firm Initiated |
| Initial Firm Notification: | Letter |
| Distribution Pattern: | Nationwide |
| Classification: | Class I |
| Product Quantity: | 4,445 vials |
| Reason For Recall: | Presence of Particulate Matter: visible foreign particulate matter observed during testing of retention samples. |
| Recall Initiation Date: | 20150318 |
| Report Date: | 20150826 |
Carboplatin
Loading...Carboplatin Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
Bone marrow suppression (leukopenia, neutropenia, and thrombocytopenia) is dose-dependent and is also the dose-limiting toxicity. Peripheral blood counts should be frequently monitored during carboplatin treatment and, when appropriate, until recovery is achieved. Median nadir occurs at day 21 in patients receiving single agent carboplatin. In general, single intermittent courses of carboplatin should not be repeated until leukocyte, neutrophil, and platelet counts have recovered.
Since anemia is cumulative, transfusions may be needed during treatment with carboplatin, particularly in patients receiving prolonged therapy.
Bone marrow suppression is increased in patients who have received prior therapy, especially regimens including cisplatin. Marrow suppression is also increased in patients with impaired kidney function. Initial carboplatin dosages in these patients should be appropriately reduced (see DOSAGE AND ADMINISTRATION) and blood counts should be carefully monitored between courses. The use of carboplatin in combination with other bone marrow suppressing therapies must be carefully managed with respect to dosage and timing in order to minimize additive effects.
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. Clinically significant hearing loss has been reported to occur in pediatric patients when carboplatin was administered at higher than recommended doses in combination with other ototoxic agents.
Carboplatin can induce emesis, which can be more severe in patients previously receiving emetogenic therapy. The incidence and intensity of emesis have been reduced by using premedication with antiemetics. Although no conclusive efficacy data exist with the following schedules of carboplatin, lengthening the duration of single intravenous administration to 24 hours or dividing the total dose over five consecutive daily pulse doses has resulted in reduced emesis.
Although peripheral neurotoxicity is infrequent, its incidence is increased in patients older than 65 years and in patients previously treated with cisplatin. Pre-existing cisplatin-induced neurotoxicity does not worsen in about 70% of the patients receiving carboplatin as secondary treatment.
Loss of vision, which can be complete for light and colors, has been reported after the use of carboplatin with doses higher than those recommended in the package insert. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.
As in the case of 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. There is increased risk of allergic reactions including anaphylaxis in patients previously exposed to platinum therapy. (See CONTRAINDICATIONS and ADVERSE REACTIONS: Allergic Reactions.)
High dosages of carboplatin (more than four times the recommended dose) have resulted in severe abnormalities of liver function tests.
Carboplatin may cause fetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryotoxic and teratogenic in rats. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Initial Treatment of Advanced Ovarian Carcinoma: Carboplatin Injection is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of Carboplatin Injection and cyclophosphamide. Two randomized controlled studies conducted by the NCIC and SWOG with carboplatin vs. cisplatin, both in combination with cyclophosphamide, have demonstrated equivalent overall survival between the two groups (see CLINICAL STUDIES).
There is limited statistical power to demonstrate equivalence in overall pathologic complete response rates and long-term survival (≥ 3 years) because of the small number of patients with these outcomes: the small number of patients with residual tumor <2 cm after initial surgery also limits the statistical power to demonstrate equivalence in this subgroup.
Secondary Treatment of Advanced Ovarian Carcinoma: Carboplatin Injection is indicated for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.
Within the group of patients previously treated with cisplatin, those who have developed progressive disease while receiving cisplatin therapy may have a decreased response rate.
History
There is currently no drug history available for this drug.
Other Information
Carboplatin Injection is supplied as a sterile, aqueous solution available in 50 mg/5 mL, 150 mg/15 mL or 450 mg/45 mL multi-dose vials containing 10 mg/mL of carboplatin for administration by intravenous infusion. Each mL contains 10 mg carboplatin and Water for Injection, USP.
Carboplatin is a platinum coordination compound that is used as a cancer chemotherapeutic agent. The chemical name for carboplatin is platinum, diammine [1,1-cyclobutane-dicarboxylato(2-)-0,0’]-,(SP-4-2), and has the following structural formula:
Carboplatin is a crystalline powder with the molecular formula of C6H12N204Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 14 mg/mL, and the pH of a 1% solution is 5-7. It is virtually insoluble in ethanol, acetone, and dimethylacetamide.
Sources
Carboplatin Manufacturers
-
Hospira Worldwide, Inc.
![Carboplatin Injection, Solution [Hospira Worldwide, Inc.]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Carboplatin | Hospira Worldwide, Inc.
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of Carboplatin Injection.
Single Agent Therapy: Carboplatin Injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of Carboplatin Injection should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
Combination Therapy with Cyclophosphamide: In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin Injection - 300 mg/m2 IV on day 1 every four weeks for six cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every four weeks for six cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of Carboplatin Injection in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
Dose Adjustment Recommendations: Pretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
* Percentages apply to Carboplatin Injection as a single agent or to both Carboplatin Injection and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.Platelets
Neutrophils
Adjusted Dose* (From Prior Course)
>100,000
>2000
125%
50-100,000
500-2000
No Adjustment
<50,000
<500
75%
Carboplatin Injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney Function: Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent Carboplatin Injection therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance
Recommended Dose on Day 1
41 - 59 mL/min
16 - 40 mL/min
250 mg/m2
250 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.
Formula Dosing: Another approach for determining the initial dose of Carboplatin Injection is the use of mathematical formulae, which are based on a patient’s preexisting renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY.) The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient’s glomerular filtration rate (GFR in mL/min) and Carboplatin Injection target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of Carboplatin Injection is calculated in mg,
not mg/m2.The target AUC of 4-6 mg/mL•min using single agent Carboplatin Injection appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single agent Carboplatin Injection administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously
Treated PatientsGr 3 or Gr 4
Gr 3 or Gr 4
AUC (mg/mL•min)
Thrombocytopenia
Leukopenia
4 to 5
16%
13%
6 to 7
33%
34%
Geriatric Dosing: Because renal function is often decreased in elderly patients, formula dosing of Carboplatin Injection based on estimates of GFR should be used in elderly patients to provide predictable plasma Carboplatin Injection AUCs and thereby minimize the risk of toxicity.
-
Teva Parenteral Medicines, Inc.
Carboplatin | Teva Parenteral Medicines, Inc.
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin injection.
Single Agent TherapyCarboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert (see CLINICAL STUDIES).
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets Neutrophils Adjusted Dose1
(From Prior Course)> 100,000
> 2,000
125%
50 to 100,000
500 to 2,000
No Adjustment
< 50,000
< 500
75%
Carboplatin injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance Recommended Dose on Day 141 to 59 mL/min
250 mg/m2
16 to 40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin injection is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin (see CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and carboplatin injection target area under the concentration versus time curve (AUC in mg/mL∙min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
_____________________________________________________________________________________
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
_____________________________________________________________________________________
The target AUC of 4 mg/mL∙min to 6 mg/mL∙min using single agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients AUC (mg/mL∙min) Gr 3 or Gr 4
Thrombocytopenia Gr 3 or Gr 4
Leukopenia4 to 5
16%
13%
6 to 7
33%
34%
Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin injection based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin injection AUCs and thereby minimize the risk of toxicity.
-
Mylan Institutional Llc
Carboplatin | Mylan Institutional Llc
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin.
Single-Agent TherapyCarboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin―300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide―600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
*Percentages apply to Carboplatin Injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.
Platelets
Neutrophils
Adjusted Dose*(From Prior Course)
>100,000
>2,000
125%
50 - 100,000
500 – 2,000
No Adjustment
<50,000
<500
75%
Carboplatin is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance
Recommended Dose on Day 1
41 - 59 mL/min
250 mg/m2
16 - 40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin is the use of mathematical formulae, which are based on a patient’s pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient’s glomerular filtration rate (GFR in mL/min) and carboplatin target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg)=(target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of Carboplatin Injection is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients
AUC (mg/mL•min)
Gr 3 or Gr 4 Thrombocytopenia
Gr 3 or Gr 4 Leukopenia
4 to 5
6 to 7
16%
33%
13%
34%
Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONSCarboplatin injection is a premixed aqueous solution of 10 mg/mL carboplatin.
Carboplatin aqueous solution can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.
When prepared as directed, carboplatin aqueous solutions are stable for 8 hours at room temperature (25° C). Since no antibacterial preservative is contained in the formulation, it is recommended that carboplatin aqueous solutions be discarded 8 hours after dilution.
-
Hospira Worldwide, Inc.
Carboplatin | Foshan Nanhai Jinxiong Toys C O., Ltd
Directions
rub a dime sized drop into hands. for children under 6 use under adult supervision. -
App Pharmaceuticals, Llc
Carboplatin | App Pharmaceuticals, Llc
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of Carboplatin Injection.
Single Agent TherapyCarboplatin Injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of Carboplatin Injection should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin Injection — 300 mg/m2 IV on day 1 every four weeks for six cycles (alternatively see Formula Dosing).
Cyclophosphamide — 600 mg/m2 IV on day 1 every four weeks for six cycles. For directions regarding the use and administration of cyclophosphamide, please refer to its package insert (see CLINICAL STUDIES).
Intermittent courses of Carboplatin Injection in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets
Neutrophils
Adjusted Dose *
(From Prior Course)
> 100,000
> 2000
125%
50 to 100,000
500 to 2000
No Adjustment
< 50,000
< 500
75%
* Percentages apply to Carboplatin Injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50 to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.
Carboplatin Injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single agent Carboplatin Injection therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine
Clearance
Recommended
Dose on Day 1
41 to 59 mL/min
250 mg/m2
16 to 40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of Carboplatin Injection is the use of mathematical formulae, which are based on a patient’s pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin (see CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient’s glomerular filtration rate (GFR in mL/min) and Carboplatin Injection target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) × (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
The target AUC of 4 to 6 mg/mL•min using single agent Carboplatin Injection appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single agent Carboplatin Injection administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients
AUC (mg/mL•min)
Gr 3 or Gr 4
Thrombocytopenia
Gr 3 or Gr 4
Leukopenia
4 to 5
16%
13%
6 to 7
33%
34%
Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.
-
Sandoz Inc
Carboplatin | Sandoz Inc
NOTE : Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of Carboplatin Injection.
Single-Agent TherapyCarboplatin Injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of Carboplatin Injection should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin Injection - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide-600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of Carboplatin Injection in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets Neutrophils Adjusted Dose*
(From Prior Course) * Percentages apply to carboplatin injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted to a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.> 100,000
> 2,000
125%
50–100,000
500–2,000
No Adjustment
< 50,000
< 500
75%
Carboplatin Injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renal-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance Recommended Dose on Day141–59 mL/min
250 mg/m2
16–40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of Carboplatin Injection is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (see CLINICAL PHARMACOLOGY.)
The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and Carboplatin Injection target area under the concentration versus time curve (AUC in mg/mL∙min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg)=(target AUC) × (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL∙min to 6 mg/mL∙min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients AUC (mg/mL∙min) Gr 3 or Gr 4
Thrombocytopenia Gr 3 or Gr 4
Leukopenia4 to 5
16%
13%
6 to 7
33%
34%
Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of Carboplatin Injection based on estimates of GFR should be used in elderly patients to provide predictable plasma Carboplatin Injection AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONSCarboplatin Injection is a premixed aqueous solution of 10 mg/mL carboplatin.
Carboplatin Injection, 10 mg/mL aqueous solution can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.
When prepared as directed, Carboplatin Injection aqueous solutions are stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that Carboplatin Injection aqueous solutions be discarded 8 hours after dilution.
-
Sagent Pharmaceuticals
Carboplatin | Sagent Pharmaceuticals
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin.
Single-Agent TherapyCarboplatin Injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
* Percentages apply to Carboplatin Injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.
Platelets Neutrophils Adjusted Dose*
(From Prior Course) >100,000 >2,000 125% 50-100,000 500-2,000 No Adjustment <50,000 <500 75%Carboplatin is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline
Creatinine Clearance Recommended
Dose on Day 1 41 mL/min - 59 mL/min 250 mg/m2 16 mL/min - 40 mL/min 200 mg/m2The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY.) The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and carboplatin target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of Carboplatin is calculated in mg, not mg/m2.The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients
AUC (mg/mL•min) Gr 3 or Gr 4
Thrombocytopenia Gr 3 or Gr 4
Leukopenia 4 to 5
6 to 7 16%
33% 13%
34% Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.
-
Mylan Institutional Llc
Carboplatin | Mylan Institutional Llc
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin.
Single-Agent TherapyCarboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin―300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide―600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
*Percentages apply to Carboplatin Injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.
Platelets
Neutrophils
Adjusted Dose*(From Prior Course)
>100,000
>2,000
125%
50 - 100,000
500 – 2,000
No Adjustment
<50,000
<500
75%
Carboplatin is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance
Recommended Dose on Day 1
41 - 59 mL/min
250 mg/m2
16 - 40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin is the use of mathematical formulae, which are based on a patient’s pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient’s glomerular filtration rate (GFR in mL/min) and carboplatin target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg)=(target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of Carboplatin Injection is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients
AUC (mg/mL•min)
Gr 3 or Gr 4 Thrombocytopenia
Gr 3 or Gr 4 Leukopenia
4 to 5
6 to 7
16%
33%
13%
34%
Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONSCarboplatin injection is a premixed aqueous solution of 10 mg/mL carboplatin.
Carboplatin aqueous solution can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.
When prepared as directed, carboplatin aqueous solutions are stable for 8 hours at room temperature (25° C). Since no antibacterial preservative is contained in the formulation, it is recommended that carboplatin aqueous solutions be discarded 8 hours after dilution.
-
Sun Pharma Global Fze
Carboplatin | Sun Pharma Global Fze
NOTE: Aluminum reacts with carboplatin injection causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin injection.
Single-Agent Therapy
Carboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin injection should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with Cyclophosphamide
In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin injection - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See CLINICAL STUDIES.)
Intermittent courses of carboplatin injection in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment Recommendations
Pretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets
Neutrophils
Adjusted Dose *
(From Prior Course)
>100,000
>2,000
125%
50 to 100,000
500 to 2,000
No Adjustment
<50,000
<500
75%
* Percentages apply to carboplatin injection as a single agent or to both carboplatin injection and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.
Carboplatin injection is usually administered by an infusion lasting 15 minutes or longer. No pre - or post -treatment hydration or forced diuresis is required.
Patients with Impaired Kidney Function
Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin injection therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance
Recommended Dose on Day 1
41 to 59 mL/min
250 mg/m2
16 to 40 mL/min
200 mg/m2
The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient’s tolerance based on the degree of bone marrow suppression.
Formula Dosing
Another approach for determining the initial dose of carboplatin injection is the use of mathematical formulae, which are based on a patient’s pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY.) The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and carboplatin target area under the concentration versus time curve (AUC in mg/mL·min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN INJECTION DOSING
Total Dose (mg) = (target AUC) x (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin injection is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin injectionappears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin injectionadministered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients
AUC (mg/mL·min)
Gr 3 or Gr 4 Thrombocytopenia
Gr 3 or Gr 4 Leukopenia
4 to 5
16%
13%
6 to 7
33%
34%
Geriatric Dosing
Because renal function is often decreased in elderly patients, formula dosing of carboplatin injectionbased on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONS
Carboplatin injectionis a premixed aqueous solution of 10 mg/mL carboplatin. Carboplatin injectioncan be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.
When prepared as directed, carboplatin injection
is stable for 8 hours at room temperature (25° C). Since no antibacterial preservative is contained in the formulation, it is recommended that carboplatin injection be discarded 8 hours after dilution.
-
Teva Parenteral Medicines, Inc.
Carboplatin | Teva Parenteral Medicines, Inc.
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin injection.
Single Agent TherapyCarboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert (see CLINICAL STUDIES).
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets Neutrophils Adjusted Dose*
(From Prior Course) * Percentages apply to carboplatin injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies. > 100,000 > 2,000 125% 50 to 100,000 500 to 2,000 No Adjustment < 50,000 < 500 75%Carboplatin injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance Recommended Dose on Day 1 41 to 59 mL/min 250 mg/m2 16 to 40 mL/min 200 mg/m2The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin injection is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin (see CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and carboplatin injection target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) × (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL•min to 6 mg/mL•min using single agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients AUC (mg/mL∙min) Gr 3 or Gr 4 Thrombocytopenia Gr 3 or Gr 4 Leukopenia 4 to 5 16% 13% 6 to 7 33% 34% Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin injection based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin injection AUCs and thereby minimize the risk of toxicity.
PREPARATION OF INTRAVENOUS SOLUTIONSCarboplatin injection is a premixed aqueous solution of 10 mg/mL carboplatin.
Carboplatin aqueous solution can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.
When prepared as directed, carboplatin aqueous solutions are stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that carboplatin aqueous solutions be discarded 8 hours after dilution.
-
Teva Parenteral Medicines, Inc.
Carboplatin | Teva Parenteral Medicines, Inc.
NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of carboplatin injection.
Single Agent TherapyCarboplatin injection, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of carboplatin should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Combination Therapy with CyclophosphamideIn the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:
Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide - 600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert (see CLINICAL STUDIES).
Intermittent courses of carboplatin in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.
Dose Adjustment RecommendationsPretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.
The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.
Platelets Neutrophils Adjusted Dose*
(From Prior Course) * Percentages apply to carboplatin injection as a single agent or to both carboplatin and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies. > 100,000 > 2,000 125% 50 to 100,000 500 to 2,000 No Adjustment < 50,000 < 500 75%Carboplatin injection is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.
Patients with Impaired Kidney FunctionPatients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.
Baseline Creatinine Clearance Recommended Dose on Day 1 41 to 59 mL/min 250 mg/m2 16 to 40 mL/min 200 mg/m2The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.
These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.
Formula DosingAnother approach for determining the initial dose of carboplatin injection is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin (see CLINICAL PHARMACOLOGY). The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).
A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and carboplatin injection target area under the concentration versus time curve (AUC in mg/mL∙min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN DOSING
Total Dose (mg) = (target AUC) × (GFR + 25)
Note: With the Calvert formula, the total dose of carboplatin is calculated in mg, not mg/m2.
The target AUC of 4 mg/mL∙min to 6 mg/mL∙min using single agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.
% Actual Toxicity in Previously Treated Patients AUC (mg/mL∙min) Gr 3 or Gr 4 Thrombocytopenia Gr 3 or Gr 4 Leukopenia 4 to 5 16% 13% 6 to 7 33% 34% Geriatric DosingBecause renal function is often decreased in elderly patients, formula dosing of carboplatin injection based on estimates of GFR should be used in elderly patients to provide predictable plasma carboplatin injection AUCs and thereby minimize the risk of toxicity.
![Carboplatin Injection, Solution [Teva Parenteral Medicines, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=b5603e69-0ff0-4db0-b788-78b83ecb00d6&name=image-02.jpg)
![Carboplatin Injection [Mylan Institutional Llc ]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=806736d3-215a-4df5-8187-97f2161e5a53&name=carbo-inj-novaplus-mylan-figure-02.jpg)
![Carboplatin Injection, Solution Carboplatin Injection, Solution [Hospira Worldwide, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=f330117b-e3fa-4c56-8397-9a0b2e02baab&name=pirate.jpg)
![Carboplatin Injection, Solution [App Pharmaceuticals, Llc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=b92dcedd-d358-e821-c478-6a469c30b26b&name=Carbo-150mg-Crtn-Lbl.jpg)
![Carboplatin Injection, Solution [Sandoz Inc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=7307d15b-4548-41e4-bf02-cc4c2927bbf9&name=4ab1835d-95a1-4864-9739-d26fee1e4d8b-02.jpg)
![Carboplatin Injection, Solution [Sagent Pharmaceuticals]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=a7f256b2-4705-4e26-8996-72ac367842ed&name=car05-0001-02.jpg)
![Carboplatin Injection [Mylan Institutional Llc ]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=91bc1221-4191-4970-88e3-a1659bc75392&name=carboinj91063-figure-02.jpg)
![Carboplatin Injection [Sun Pharma Global Fze]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=2ccca2f5-518d-438c-8e62-5b1bcf2005b7&name=carboplatin-carton-15mL.jpg)
![Carboplatin Injection [Teva Parenteral Medicines, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=bdb0b6dd-91d3-4896-be6e-313ea907d8bb&name=670b25ff-ff6d-4311-8750-ad462eae168d-02.jpg)
![Carboplatin Injection, Solution [Teva Parenteral Medicines, Inc.]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=f330f5a2-2cad-402f-bcbb-26245a753276&name=8a02dbf8-1ceb-4870-923b-4b925246fc95-02.jpg)
Login To Your Free Account