DOSAGE AND ADMINISTRATION
NOTE: Aluminum reacts with carboplatin, USP 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 injection300 mg/m² IV on day 1 every 4 weeks
for 6 cycles (alternatively see Formula Dosing).
Cyclophosphamide600 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
The suggested dose adjustments for single agent or
combination therapy shown in the table below is 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.
||Adjusted Dose* (From Prio r Course)
| > 100,000
|| > 2,000
| < 50,000
|| < 500
|*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
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, USP 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
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 patients
tolerance based on the degree of bone marrow suppression.
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, USP (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 Cr-EDTA clearance.
CALVERT FORMULA FOR CARBOPLATIN, USP DOSING
Total Dose (mg)= (target AUC) X (GFR + 25)
Note: With the Calvert formula, the total dos e of
carboplatin injection calculated in mg, not mg/m² .
The target AUC of 4 mg/mL•min to 6 mg/mL•min using
single-agent carboplatin, USP 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, USP administered to previously treated
patients and the likelihood of developing toxicity.
||% Actual Toxicity in Previously Treated Patients Gr 3 or Gr 4 Thrombocytopenia
||Gr 3 or Gr 4 Leukopenia
|4 to 5
|6 to 7
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.
Preparation Of Intravenous Solutions
Carboplatin 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.
Each mL of carboplatin injection contains 10 mg of
carboplatin, USP in water for injection and is available as follows:
NDC 57277-105-05 50 mg/5 mL vials (with blue flip-off
seals), individually cartoned.
NDC 57277-106-15 150 mg/15 mL vials (with royal blue
flip-off seals), individually cartoned.
NDC 57277-107-45 450 mg/45 mL vials (with yellow flip-off
seals), individually cartoned.
Unopened vials of carboplatin injection are stable to the
date indicated on the package when stored at 20°-25° C (68°t o 77° F); [see USP
Controlled Room Temperature].
PROTECT FROM LIGHT.
Carboplatin injection multidose vials maintain microbial,
chemical, and physical stability for up to 14 days at 25°C following multiple
Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration. Solutions for
infusion should be discarded 8 hours after preparation.
Handling And Disposal
Caution should be exercised in handling and preparing
carboplatin injection. Several guidelines on this subject have been published. 1-4
To minimize the risk of dermal exposure, always wear
impervious gloves when handling vials containing carboplatin injection. If
carboplatin injection contacts the skin, immediately wash the skin thoroughly
with soap and water. If carboplatin injection contacts mucous membranes, the
membranes should be flushed immediately and thoroughly with water. More
information is available in the references listed below.
1. NIOSH Alert: Preventing occupational exposures to
antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S.
Department of Health and Human Services, Public Health Service, Centers for
Disease Control and Prevention, National Institute for Occupational Safety and
Health, DHHS (NIOSH) Publication No. 2004-165.
2. OSHA Technical Manual, TED 1-0.15A, Section VI:
Chapter 2. Controlling occupational exposure to hazardous drugs. OSHA, 1999.
Am J Health-Syst Pharm. 2006;63:1172-1193.
4. Polovich M, White JM, Kelleher LO, eds. 2005.
Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd
ed. Pittsburgh, PA: Oncology Nursing Society.
Manufactured in India by: Alidac Pharmaceuticals Limited,
Ahmedabad, Gujurat. Manufactured for: Sanja
Pharmaceuticals Company, Peachtree Corners, GA 30092, USA. Revised: March 2016