ALERT: U.S.

Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a
concise summary of this information. For verbatim wording of the boxed warning, consult the
product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
CARBOplatin may be confused with CISplatin, oxaliplatin
Paraplatin may be confused with Platinol
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this
medication among its list of drugs which have a heightened risk of causing significant
patient harm when used in error.
Pronunciation
(KAR boe pla tin)

Canadian Brand Names
Paraplatin-AQ
Pharmacologic Category
Antineoplastic Agent, Alkylating Agent; Antineoplastic Agent, Platinum Analog
Use: Labeled Indications
Treatment of ovarian cancer
Use: Unlabeled/Investigational
Lung cancer, head and neck cancer, endometrial cancer, esophageal cancer, bladder cancer,
breast cancer, cervical cancer, CNS tumors, germ cell tumors, osteogenic sarcoma, and high-
dose therapy with stem cell/bone marrow support
Dosing: Adults
Refer to individual protocols: Note: Doses are usually determined by the AUC using the Calvert
formula.
IVPB, I.V. infusion:
Ovarian cancer: 300-360 mg/m
2
every 4 weeks
Autologous BMT (unlabeled use): 1600 mg/m
2
(total dose) divided over 4 days
In adults, dosing is commonly calculated using the Calvert formula:
Total dose (mg) = Target AUC x (GFR + 25)
Usual target AUCs:
Previously untreated patients: 6-8
Previously treated patients: 4-6
Intraperitoneal (unlabeled use): 200-650 mg/m
2
in 2 L of dialysis fluid have been administered
into the peritoneum of ovarian cancer patients or target AUC: 5-7
Dosing: Elderly
The Calvert formula should be used to calculate dosing for elderly patients.
Dosing: Pediatric
Refer to individual protocols:
IVPB, I.V. infusion:
Solid tumor (unlabeled use): 300-600 mg/m
2
once every 4 weeks
Brain tumor (unlabeled use): 175 mg/m
2
weekly for 4 weeks every 6 weeks, with a 2-
week recovery period between courses
Dosing: Renal Impairment
Note: Dose determination with Calvert formula uses GFR and, therefore, inherently adjusts for
renal dysfunction.
The FDA-approved labeling recommends the following dosage adjustment guidelines:
Baseline Cl
cr
41-59 mL/minute: Initiate at 250 mg/m
2
and adjust subsequent doses based on
bone marrow toxicity
Baseline Cl
cr
16-40 mL/minute: Initiate at 200 mg/m
2
and adjust subsequent doses based on
bone marrow toxicity
Baseline Cl
cr
15 mL/minute: No guidelines are available.
The following dosage adjustments have been used by some clinicians (Aronoff, 2007): Adults
(for dosing based on mg/m
2
):
Hemodialysis: Administer 50% of dose
Continuous ambulatory peritoneal dialysis (CAPD): Administer 25% of dose
Continuous renal replacement therapy (CRRT): 200 mg/m
2

Dosing: Hepatic Impairment
Minimal hepatic metabolism; dosage adjustment may not be needed. No specific dosage
adjustment guidelines are available.
Dosing: Adjustment for Toxicity
Platelets <50,000 cells/mm
3
or ANC <500 cells/mm
3
: Administer 75% of dose
Dosing: Combination Regimens
Adenocarcinoma, unknown primary:
Carbo-Tax (Adenocarcinoma)
Paclitaxel-Carboplatin-Etoposide
PCE
Bladder cancer:
Gemcitabine-Carboplatin (Bladder Cancer)
Paclitaxel-Carboplatin (Bladder Cancer)
Paclitaxel-Carboplatin-Gemcitabine
Breast cancer:
Docetaxel-Trastuzumab-Carboplatin
ICE-T
Trastuzumab-Paclitaxel-Carboplatin
Cervical cancer: Paclitaxel-Carboplatin (Cervical Cancer)
Head and neck cancer:
Carboplatin-Cetuximab
Cetuximab-Carboplatin-Fluorouracil
Fluorouracil + Carboplatin
Lung cancer (nonsmall cell):
Carbo-Tax (NSCLC)
CaT (NSCLC)
EC (NSCLC)
Gemcitabine-Carboplatin (NSCLC)
Paclitaxel-Carboplatin-Bevacizumab
PC (NSCLC)
Lung cancer (small cell): EC (Small Cell Lung Cancer)
Lymphoma, non-Hodgkin's:
ICE (Lymphoma, non-Hodgkin's)
RICE
Malignant pleural mesothelioma: Pemetrexed-Carboplatin
Neuroblastoma:
CE (Neuroblastoma)
CE-CAdO
CI (Neuroblastoma)
Osteosarcoma: ICE (Sarcoma)
Ovarian cancer:
Carbo-Tax (Ovarian Cancer)
CaT (Ovarian Cancer)
CC
Gemcitabine-Carboplatin (Ovarian Cancer)
Prostate cancer:
Estramustine + Docetaxel + Carboplatin
Paclitaxel + Estramustine + Carboplatin
Retinoblastoma: CE (Retinoblastoma)
Rhabdomyosarcoma: CEV
Sarcoma, soft tissue:
ICE (Sarcoma)
ICE-T
Oncology: Bone Marrow - High Dose
I.V.: 1.2-2.4 g/m
2
administered as 3-4 divided doses every 24-48 hours; generally infused over at
least 60 minutes; 400 mg/m
2
has been infused over 15-30 minutes; generally combined with
other high-dose chemotherapeutic drugs.
Calculations
Body Surface Area: Adults
Body Surface Area: Pediatrics
Calvert Formula
Administration: I.V.
Infuse over 15 minutes to 24 hours. May also be administered intraperitoneally. When
administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be
administered before platinum derivatives to limit myelosuppression and to enhance efficacy.
Administration: I.V. Detail
Observe serum creatinine. Carboplatin is nephrotoxic and drug accumulation occurs with
decreased creatinine clearance.
pH: 5-7
Storage
Store intact vials at room temperature of 15C to 30C (59F to 86F); protect from light.
Further dilution to a concentration as low as 0.5 mg/mL is stable at room temperature (25C)
for 8 hours in NS; stable at room temperature or under refrigeration for at least 9 days in D
5
W,
although the manufacturer states to use within 8 hours due to lack of preservative.
Powder for reconstitution: Reconstituted to a final concentration of 10 mg/mL is stable for 5
days at room temperature (25C).
Solution for injection: Multidose vials are stable for up to 14 days after opening when
stored at room temperature.
Reconstitution
Reconstitute powder to yield a final concentration of 10 mg/mL. Reconstituted carboplatin 10
mg/mL should be further diluted to a final concentration of 0.5-2 mg/mL with D
5
W or NS for
administration.
Compatibility
Stable in D
5
1
/
4
NS, D
5
1
/
2
NS, D
5
NS, D
5
W, NS.
Y-site administration: Compatible: Allopurinol, amifostine, aztreonam, cefepime, cladribine,
doxorubicin liposome, etoposide phosphate, filgrastim, fludarabine, gatifloxacin,
gemcitabine, granisetron, linezolid, melphalan, ondansetron, paclitaxel,
piperacillin/tazobactam, propofol, sargramostim, teniposide, thiotepa, topotecan,
vinorelbine. Incompatible: Amphotericin B cholesteryl sulfate complex.
Compatibility when admixed: Compatible: Cisplatin, etoposide, floxuridine, ifosfamide,
ifosfamide with etoposide, paclitaxel. Incompatible: Fluorouracil, mesna.
Contraindications
History of severe allergic reaction to cisplatin, carboplatin, other platinum-containing
formulations, or any component of the formulation; pregnancy; breast-feeding
Allergy Considerations
Platinum Derivative Allergy
Warnings/Precautions
Boxed warnings:
Allergic reactions: See Concerns related to adverse effects below.
Bone marrow suppression: See Concerns related to adverse effects below.
Experienced physician: See Other warnings/precautions below.
Vomiting: See Concerns related to adverse effects below.
Special handling:
Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
Allergic reactions: [U.S. Boxed Warning]: Increased risk of allergic reactionsin
patients previously exposed to platinum therapy.
Bone marrow suppression: [U.S. Boxed Warning]: Bone marrow suppression, which
may be severe, is dose related; reduce dosage in patients with bone marrow
suppression and impaired renal function. Anemia is cumulative.
Liver function abnormalities: High doses have resulted in severe abnormalities of liver
function tests.
Vision loss: Loss of vision (reversible) has been reported with higher than
recommended doses.
Vomiting: [U.S. Boxed Warning]: May occur and is dose related.
Disease-related concerns:
Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
Cisplatin: There is an increased incidence of peripheral neuropathy in patients who
have previously received cisplatin.
Taxane derivatives: When administered as sequential infusions, taxane derivatives
(docetaxel, paclitaxel) should be administered before the platinum derivatives
(carboplatin, cisplatin) to limit myelosuppression and to enhance efficacy.
Special populations:
Elderly: There is an increased incidence of peripheral neuropathy in patients >65 years
of age.
Pediatrics: Clinically significant hearing loss has been reported to occur in pediatric
patients when therapy was administered at higher than recommended doses in
combination with other ototoxic agents.
Other warnings/precautions:
Experienced physician: [U.S. Boxed Warning]: Should be administered under the
supervision of an experienced cancer chemotherapy physician.
Geriatric Considerations
Peripheral neuropathy is more frequent in patients >65 years of age.
Pregnancy Risk Factor
D
Lactation
Excretion in breast milk unknown/contraindicated
Breast-Feeding Considerations
Due to the potential for toxicity in nursing infants, breast-feeding is contraindicated.
Adverse Reactions
Percentages reported with single-agent therapy.
>10%:
Central nervous system: Pain (23%)
Endocrine & metabolic: Hyponatremia (29% to 47%), hypomagnesemia (29% to 43%),
hypocalcemia(22% to 31%), hypokalemia (20% to 28%)
Gastrointestinal: Vomiting (65% to 81%), abdominal pain (17%), nausea (10% to 15%)
Hematologic: Myelosuppression (dose related and dose limiting; nadir at ~21 days;
recovery by ~28 days), leukopenia (85%; grades 3/4: 15% to 26%), anemia (71% to
90%; grades 3/4: 21%), neutropenia (67%; grades 3/4: 16% to 21%),
thrombocytopenia (62%; grades 3/4: 25% to 35%)
Hepatic: Alkaline phosphatase increased (24% to 37%), AST increased (15% to 19%)
Neuromuscular & skeletal: Weakness (11%)
Renal: Creatinine clearance decreased (27%), BUN increased (14% to 22%)
1% to 10%:
Central nervous system: Neurotoxicity (5%)
Dermatologic: Alopecia (2% to 3%)
Gastrointestinal: Constipation (5%), diarrhea (6%), stomatitis/mucositis (1%), taste
dysgeusia (1%)
Hematologic: Hemorrhagic complications (5%)
Hepatic: Bilirubin increased (5%)
Local: Pain at injection site
Neuromuscular & skeletal: Peripheral neuropathy (4% to 6%; up to 10% in older and/or
previously-treated patients)
Ocular: Visual disturbance (1%)
Otic: Ototoxicity (1%)
Renal: Creatinine increased (6% to 10%)
Miscellaneous: Infection (5%), hypersensitivity (2%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Anaphylaxis,
anorexia, bronchospasm, cardiac failure, cerebrovascular accident, embolism, erythema,
fever, hemolytic uremic syndrome (HUS), hyper-/hypotension, malaise, necrosis (associated
with extravasation), nephrotoxicity, neurotoxicity, pruritus, rash, secondary malignancies,
urticaria, vision loss
Oncology: Vesicant
No
Oncology: Emetic Potential
Moderate (30% to 60%)
Oncology: Bone Marrow - Unique Toxicity
Dermatologic: Alopecia
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Nausea, vomiting, mucositis
Hepatic: Liver function tests elevated
Renal: Nephrotoxicity
Drug Interactions
Aminoglycosides: May enhance the ototoxic effect of CARBOplatin. Especially with higher
doses of carboplatin. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider
therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab.
Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect of Taxane
Derivatives. Administer Taxane derivative before Platinum derivative when given as
sequential infusions to limit toxicity. Risk D: Consider therapy modification
Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of Topotecan. Risk D:
Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor
therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines
(Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live).
Vaccinal infections may develop. Immunosuppressants may also decrease therapeutic
response to vaccines. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid black cohosh, dong quai in estrogen-dependent tumors.
Monitoring Parameters
CBC (with differential and platelet count), serum electrolytes, creatinine clearance, liver function
tests, BUN, creatinine
Nursing: Physical Assessment/Monitoring
Assess patient allergy history prior to therapy and note specific use cautions (eg, bone marrow
suppression and renal function). Assess other pharmacological or herbal products patient may be
taking for potential interactions (especially products that may be ototoxic or nephrotoxic and
need for sequencing with taxane derivatives). Assess results of laboratory tests (hematology,
electrolytes, renal and hepatic function), prior to treatment and on a regular basis during therapy.
Monitor patient response (eg, nausea and vomiting; pretreatment with antiemetic may be
required), ototoxicity (audiometry may be advisable), bone marrow depression, anemia,
bleeding, peripheral neuropathy frequently throughout therapy. Teach patient (or caregiver)
possible side effects/appropriate interventions and adverse symptoms to report.
Monitoring: Lab Tests
CBC with differential and platelet count, serum electrolytes, creatinine clearance, liver function,
BUN, creatinine
Patient Education
Do not take any new medication during therapy unless approved by healthcare provider. This
medicine can only be administered intravenously. Report immediately any redness, burning,
pain, or swelling at infusion site. It is important that you maintain adequate nutrition (small,
frequent meals may help) and adequate hydration (2-3 L/day of fluids) unless instructed to
restrict fluid intake. You will be susceptible to infection (avoid crowds and exposure to infection
and do not have any vaccinations without consulting prescriber). May cause nausea and vomiting
(small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help - if
unresolved, consult prescriber for antiemetic); mouth sores (use soft toothbrush or cotton swabs
for mouth care); or loss of hair (reversible). Report chest pain or palpitations; sore throat, fever,
chills, unusual fatigue; unusual bruising/bleeding; respiratory difficulty; numbness, pain, or
tingling in extremities; muscle cramps or twitching; change in hearing acuity; or other persistent
adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant.
Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to
become pregnant. Male/female: Consult prescriber for instruction on appropriate contraceptive
measures. This drug may cause severe fetal defects. Do not breast-feed.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult
specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution: 50 mg, 150 mg, 450 mg
Injection, solution: 10 mg/mL (5 mL, 15 mL, 45 mL, 60 mL)
Injection, solution [preservative free]: 10 mg/mL (5 mL, 15 mL, 45 mL)
Generic Available
Yes
Mechanism of Action
Carboplatin is an alkylating agent which covalently binds to DNA; possible cross-linking and
interference with the function of DNA
Pharmacodynamics/Kinetics
Distribution: V
d
: 16 L/kg; into liver, kidney, skin, and tumor tissue
Protein binding: 0%; platinum is 30% irreversibly bound
Metabolism: Minimally hepatic to aquated and hydroxylated compounds
Half-life elimination: Terminal: 22-40 hours; Cl
cr
>60 mL/minute: 2.5-5.9 hours
Excretion: Urine (~60% to 90%) within 24 hours