Dosing and uses of Carboplatin
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 150mg
injectable solution
- 10mg/mL (in vials of 50, 150, 450, and 600 mg)
Advanced Ovarian Carcinoma
Single agent: 360 mg/m² IV q4Weeks
Combination treatment: 300 mg/m² IV (plus cyclophosphamide 600 mg/m² IV) q4Weeks
Dose Modifications
For SI units: Count in US units x 10^6/L
Give full dose if
- Platelets 50-100,000
- Neutrophils 500-2000
Give 125% if
- Platelets >100000
- Neutrophils >2000
Give 75% if
- Platelets <50000
- Neutrophils <500
Renal Impairment
CrCl 41-59 mL/min: 250 mg/m² IV on day 1
CrCl 16-40 mL/min: 200 mg/m² IV on day 1
CrCl <15 mL/min: Not recommended
Hepatic Impairment
Dose adjustment may not be necessary; not studied
Administration
Do not repeat dose until ANC >2000 AND platelets >100000
Infuse over >15 minutes
Monitor: CBC weekly
Other Indications & Uses
Off-label: testicular cancer, head and neck cancer, cervix cancer, small cell lung cancer, progressive diffuse large B-cell lymphoma
Pediatric dosage forms and strengths
lyophilized powder for reconstitution
- 150mg
injectable solution
- 10mg/mL (in vials of 50, 150, 450, and 600 mg)
General Dosing Guidlines
Solid tumor
- 300-600 mg/m² IV q4Weeks
Sarcoma (bone/soft tissue)
- 400 mg/m²/day for 2 days every 21 days
Brain tumor
- 175 mg/m² qWeek x 4 weeks with a 2 weeks recovery period between courses
Bone marrow transplant preparative regimen
- 500 mg/m²/day x 3 days
Retinoblastoma
- 1-2 mL subconjunctival injection of 10 mg/mL solution per dose
Geriatric dosage forms and strengths
Calvert formula should be used to calculate dosing
Carboplatin adverse (side) effects
>10%
Leukopenia (26-97%)
Neutropenia (21-96%)
Nausea (81-93%)
Vomiting (81-93%)
Anemia (14-90%)
Magnesium loss (43-61%)
Thrombocytopenia (33-66%)
Alopecia (2-49%)
Asthenia (11-41%)
Elevated alkaline phosphatase (29-37%)
Central neurotoxicity (5-26%)
Elevated AST (19-20%)
Peripheral neuropathy (6-15%)
1-10%
Immune hypersensitivity reaction (2-9.2%)
Elevated bilirubin (5%)
Frequency not defined
Visual disturbance (rare)
Postmarketing Reports
Dehydration
Stomatitis
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician. Increased risk of allergic reactions in patients previously exposed to platinum. The allergic reaction may occur within minutes of carboplatin administration
Bone marrow suppression, which may be severe and may result in infection or bleeding, is dose related. Reduce dosage in patients with bone marrow suppression and impaired renal function. Anemia is cumulative
Vomiting is a frequent adverse effect and is dose related
Contraindications
Severe hypersensitivity to carboplatin, other platinum compounds, mannitoL
Severe myelosuppression, significant bleeding
Severe renal dysfunction
Pregnancy/lactation
Cautions
Pediatric patients, elderly, renal impairment, hearing impairment, neuropathy, neuromuscular disease, prior cisplatin treatment, concomitant neurotoxic agents, concomitant ototoxic agents
Avoid aluminum needles/intravenous sets for preparation/administration
Less nephrotoxic than cisplatin
Avoid pregnancy
Abnormal liver function tests reported with high doses
Risk of neuropathy increases in patients >65 years and patients treated previously with the drug
Ototoxicity may occur
Caution in patients with renal impairment; patients with renal failure are at increased risk for bone marrow suppression
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Carboplatin
Mechanism of action
Platinum coordination compound; covalently binds to DNA; cross-links strands of DNA
Not a true alkylating agent
Absorption
Peak plasma time: 2-4 hr
Distribution
Protein bound: 87% (platinum)
Vd: 16 L
Elimination
Clearance: 4.4 L/hr
Excretion: Urine (70% as carboplatin)
Half-life
- Carboplatin: 3-6 hr
- Free ultrafilterable platinum: 6 hr
- Total plasma platinum: 4-6 days
Administration
IV Incompatibilities
Solution: Na Bicarb 200 mm
Additive: fluorouracil, mesna
Y-site: amphotericin B cholesteryl-SO4
IV Compatibilities
Solution: D5W, D5W in NS, Ns
Additive: cisplatin, etoposide, floxuridine, ifosfamide, ifosfamide with etoposide, paclitaxeL
Y-site (partial list): allopurinol, etoposide PO4, filgrastim, gemcitabine, granisetron, linezolid, ondansetron, paclitaxel, piperacillin-tazobactam, propofoL
IV Preparation
Single-dose lyophilized powder (reconstitution require)
- Reconstitute powder with sterile water for injection, D5W, or 0.9% NaCl to yield a final concentration of 10 mg/mL
- Can be further diluted to concentrations as low as 0.5 mg/mL with D5W or 0.9% NaCl
Multidose premixed injectable solution
- Available as a 10 mg/mL aqueous solution
- Can be further diluted to concentrations as low as 0.5 mg/mL with D5W or 0.9% NaCl
IV Administration
Administer IV over 15 min or continuous IV infusion over 24 hr
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
Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can cause precipitate formation and loss of potency)
Storage
Single-dose lyophilized powder (reconstitution required)
- Unreconstituted vials: Stable at controlled room temperature (20-25°C [68-77°F]); protect from light
- Reconstituted vials and diluted solutions: Stable for 8 hr at room temperature (25°C [77°C]); since no antibacterial preservative is contained in the formulation, discard 8 hr after dilution
Multidose premixed injectable solution
- Unopened multidose vials: Stable to the date indicated on the package when stored at 20-25°C (68-77°F) and protected from light
- Multidose vials maintain microbial, chemical, and physical stability for up to 14 days at 25°C following multiple needle entries
