Carboplatin

L01X - Other antineoplastic agents ATC L01XA02 Small molecule approved 1989 Parenteral Black-box warning

JFDA label: Neoplatin Vial

⚠ Black-Box Warning

Experienced physician:
Bone marrow suppression:
Vomiting:
Hypersensitivity reactions:
Vomiting

Mechanism of Action

Inhibitor of DNA — DNA inhibitor

Target	Action	Gene / class
DNA efficacy	INHIBITOR

Indications

Approved

Ovarian cancer, advanced

Off-label

Anal cancer (advanced)
Bladder cancer
Breast cancer (metastatic)
CNS tumors (pediatric)
Cervical cancer (recurrent or metastatic)
Endometrial cancer
Esophageal cancer
Gastric cancer
Head and neck cancer
Hematopoietic stem cell transplant (adults)
Hematopoietic stem cell transplant (pediatric)
Hodgkin lymphoma (relapsed or refractory)
Malignant pleural mesothelioma
Melanoma (advanced or metastatic)
Merkel cell carcinoma
Neuroendocrine tumors, advanced, atypical or poorly differentiated (nonpulmonary)
Non-Hodgkin lymphomas (relapsed or refractory)
Non-small cell lung cancer
Retinoblastoma
Sarcomas (Ewing sarcoma and osteosarcoma)
Small cell lung cancer
Testicular cancer
Thymic malignancies
Thyroid cancer (anaplastic), advanced
Unknown primary adenocarcinoma
Wilms tumor (pediatric)

Class profile

mechanismClass	Platinum compound
targetMolecule	DNA (intrastrand cross-links)
targetPathway	DNA damage response/apoptosis
generation	2nd generation platinum
primaryTumors	Ovarian,Lung,Head and neck,Testicular
resistanceMechanisms	Cross-resistance with cisplatin (shared NER mechanism),ERCC1 overexpression
source	NCCN/OncoKB/Goodman&Gilman13ed

Contraindications

Source: Lexicomp

History of severe allergic reaction to carboplatin, cisplatin, other platinum-containing formulations, mannitol, or any component of the formulation Absolute
should not be used in patients with severe bone marrow depression or significant bleeding Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (3)

Very Common Pain

Common neurotoxicity · Peripheral neuropathy

Hepatobiliary disorders (3)

Very Common Increased serum alkaline phosphatase · increased serum AST

Common Increased serum bilirubin

Renal and urinary disorders (3)

Very Common Decreased creatinine clearance · increased blood urea nitrogen

Common Increased serum creatinine

Blood and lymphatic system disorders (7)

Very Common anemia · Bone marrow depression (dose related and dose limiting; nadir at ~21 days with single-agent therapy) · leukopenia · neutropenia · thrombocytopenia

Common Bleeding complications · hemorrhage

Immune system disorders (1)

Very Common Hypersensitivity

Metabolism and nutrition disorders (4)

Very Common hypocalcemia · hypokalemia · hypomagnesemia · Hyponatremia

Gastrointestinal disorders (7)

Very Common abdominal pain · nausea

Common Constipation · diarrhea · dysgeusia · mucositis · stomatitis

Skin and subcutaneous tissue disorders (1)

Common Alopecia

Musculoskeletal and connective tissue disorders (1)

Very Common Weakness

Eye disorders (1)

Common Visual disturbance

Ear and labyrinth disorders (1)

Common Ototoxicity

Infections and infestations (1)

Common Infection

Dosing

Source: Lexicomp

Note: Doses for adults are commonly calculated by the target AUC using the Calvert formula, where Total dose (mg) = Target AUC x (GFR + 25). If estimating GFR instead of a measured GFR, the FDA recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity. Carboplatin is associated with a moderate to high emetic potential in adult patients (dose/AUC dependent); antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016). Ovarian cancer, advanced: Manufacturer's labeling: IV: 360 mg/m2 every 4 weeks (as a single agent) or 300 mg/m2 every 4 weeks (in combination with cyclophosphamide) for 6 cycles or Target AUC 4 to 6 (single agent; in previously treated patients) Off-label dosing for advanced ovarian cancer: IV: Target AUC 5 to 7.5 every 3 weeks (in combination with paclitaxel) (Ozols 2003; Parmar 2003) or Target AUC 2 once weekly (in combination with weekly paclitaxel) for 18 consecutive weeks (Pignata 2014) or Target AUC 5 every 3 weeks (in combination with docetaxel) (Vasey 2004) Off-label dosing for malignant germ cell tumor: IV: 400 mg/m2 on day 1 (in combination with etoposide) every 4 weeks for 3 cycles (Williams 2004) Anal cancer, advanced (off-label use): IV: Target AUC 6 on days 1 and 22 every 6 weeks for up to 4 cycles (in combination with paclitaxel and fluorouracil) (Hainsworth 2001) or Target AUC 5 or 6 every 3 weeks (in combination with paclitaxel) (Kim 2014). Additional data may be necessary to further define the role of carboplatin in the treatment of this condition. Bladder cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with gemcitabine) (Bamias 2006) or Target AUC 6 every 3 weeks (in combination with paclitaxel) (Vaughn 2002) Breast cancer, metastatic (off-label use): IV: Target AUC 6 every 3 weeks (in combination with trastuzumab and paclitaxel) (Robert 2006) or Target AUC 6 every 3 weeks (in combination with trastuzumab and docetaxel) (Pegram 2004; Valero 2011) Cervical cancer, recurrent or metastatic (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Pectasides 2009) or Target AUC 5 to 6 every 4 weeks (in combination with paclitaxel) (Tinker 2005) or 400 mg/m2 every 28 days (as a single agent) (Weiss 1990) Endometrial cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Pectasides 2008) or Target AUC 2 on days 1, 8, and 15 every 28 days (in combination with paclitaxel) (Secord 2007) Esophageal cancer (off-label use): IV: Target AUC 2 once weekly for 5 weeks (in combination with paclitaxel and radiation therapy) prior to surgery (van Hagen 2012; van Meerten 2006) or Target AUC 5 every 3 weeks (in combination with paclitaxel) (El-Rayes 2004) Gastric cancer (off-label use): IV: Target AUC 2 once weekly for 5 weeks (in combination with paclitaxel and concurrent radiation) prior to surgery (van Hagen 2012) or Target AUC 5 to 6 every 3 weeks (in combination with p

(For additional information see "Carboplatin: Pediatric drug information") Carboplatin is associated with a high emetic potential in pediatric patients; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011). Central nervous system tumors (off-label use): Glioma: Infants ≥3 months, Children, and Adolescents: IV: Induction: 175 mg/m2 weekly for 4 weeks every 6 weeks for 2 cycles, with a 2-week recovery period between courses (in combination with vincristine) (Packer 1997) Maintenance: 175 mg/m2 weekly for 4 weeks (in combination with vincristine) for up to 12 cycles, with a 3-week recovery period between cycles (Packer 1997) Neuroblastoma, localized and unresectable: IV: Children ≥10 kg: 200 mg/m2/day days 1, 2, and 3 every 21 days for 2 cycles (in combination with etoposide for 2 cycles then followed by cyclophosphamide, doxorubicin and vincristine) (Rubie 1998) or Children Hematopoietic stem cell transplant (HSCT) (off-label use): IV: Infants ≥6 months and Children ≤3 years: Consolidation regimen: 17 mg/kg over 2 hours on days 0 and 1 of a 21-day cycle for 3 cycles (in combination with thiotepa), followed by stem cell infusion at least 48 hours after the last thiotepa dose (Cohen 2015) Children and Adolescents: Conditioning regimen: ~500 mg/m2/day for 3 consecutive days; dosing utilized pediatric Calvert formula with a target AUC 7 (in combination with thiotepa and topotecan) (Gilheeny 2010; Kushner 2001) Retinoblastoma (off-label use): Rodriguez-Galindo 2003: Infants and Children: IV: GFR ≥50 mL/minute/m2: 560 mg/m2 in combination with vincristine every 21 days for 8 cycles GFR 2: Dosing utilized modified Calvert formula with a target AUC 6.5 in combination with vincristine every 21 days for 8 cycles Friedman 2000: Infants and Children ≤3 years: IV: 18.6 mg/kg on day 0 every 28 days in combination with etoposide and vincristine for 6 cycles (VEC regimen) Children >3 years: IV: 560 mg/m2 on day 0 every 28 days in combination with etoposide and vincristine for 6 cycles (VEC regimen) Sarcomas: Ewing sarcoma, osteosarcoma (off-label uses): IV: 400 mg/m2/day for 2 days every 21 days (in combination with ifosfamide and etoposide) (van Winkle 2005) Wilms tumor (off-label use): Children and Adolescents: IV: 160 mg/m2/day for 5 consecutive days every 21 days (in combination with etoposide) for 2 cycles (Pein 1994) or 400 mg/m2/day for 2 days (in combination with ifosfamide and etoposide) every 21 days (ICE regimen) (Abu-Ghosh 2002) or modified Calvert formula with a target AUC 6 for 1 day (in combination with ifosfamide and etoposide) every 21 days (ICE regimen) for 2 cycles, followed by vincristine, dactinomycin and doxorubicin (VAD regimen), surgery, radiation therapy, the VAD regimen and one more cycle of ICE for a total of 36 weeks of treatment (Daw 2009). Additional data may be necessary to further define the role of carboplatin in the treatment of this condition.

The Calvert formula should be used to calculate dosing for elderly patients. Refer to adult dosing.

Note: Dose determination with Calvert formula uses GFR and, therefore, inherently adjusts for renal dysfunction. The manufacturer’s labeling recommends the following dosage adjustments for single-agent therapy: Adults: Baseline CrCl 41 to 59 mL/minute: Initiate at 250 mg/m2 and adjust subsequent doses based on bone marrow toxicity Baseline CrCl 16 to 40 mL/minute: Initiate at 200 mg/m2 and adjust subsequent doses based on bone marrow toxicity Baseline CrCl ≤15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling. The following dosage adjustments have also been recommended: Aronoff 2007: Adults (Note: For dosing based on mg/m2): GFR >50 mL/minute: No dosage adjustment is necessary GFR 10 to 50 mL/minute: Administer 50% of the usual dose GFR Hemodialysis: Administer 50% of the usual dose Continuous ambulatory peritoneal dialysis (CAPD): Administer 25% of the usual dose Continuous renal replacement therapy (CRRT): 200 mg/m2 Children: GFR Hemodialysis, peritoneal dialysis, continuous renal replacement therapy (CRRT): Use Calvert formula incorporating patient’s GFR Janus 2010: Hemodialysis: Carboplatin dose (mg) = Target AUC x 25; administer on a nondialysis day, hemodialysis should occur between 12 to 24 hours after carboplatin dose

There are no dosage adjustments provided in the manufacturer’s labeling; however, carboplatin undergoes minimal hepatic metabolism therefore dosage adjustment may not be needed.

Warnings & Precautions

Source: Lexicomp

Bone marrow suppression

Bone marrow suppression, which may be severe, is dose related; may result in infection (due to neutropenia) or bleeding (due to thrombocytopenia); anemia may require blood transfusion. Reduce dosage in patients with bone marrow suppression; cycles should be delayed until WBC and platelet counts have recovered. In patients receiving single agent carboplatin, the median nadir typically occurs at day 21. Patients who have received prior myelosuppressive therapy and patients with renal dysfunction are at increased risk for bone marrow suppression. Anemia is cumulative. Monitor blood counts closely.

GI toxicity

Vomiting may occur. Carboplatin is associated with a moderate to high emetic potential in adult patients (dose dependent) and a high emetic potential in pediatric patients; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016). Nausea and vomiting may be more severe in patients who have received prior emetogenic therapy.

Hypersensitivity/anaphylactoid reactions

Anaphylactic-like reactions have been reported with carboplatin; may occur within minutes of administration. Epinephrine, corticosteroids, and antihistamines have been used to treat symptoms. The risk of allergic reactions (including anaphylaxis) is increased in patients previously exposed to platinum therapy. Skin testing and desensitization protocols have been reported (Confina-Cohen 2005; Lee 2004; Markman 2003).

Liver function abnormalities

High doses (>4 times the recommended dose) have resulted in severe abnormalities of liver function tests.

Neurotoxicity

Although peripheral neuropathy occurs infrequently, the incidence of peripheral neuropathy is increased in patients >65 years of age and those who have previously received cisplatin treatment.

Ototoxicity

Ototoxicity may occur when administered concomitantly with aminoglycosides. 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 (eg, aminoglycosides). In a study of children receiving carboplatin for the treatment of retinoblastoma, those • Renal toxicity: Carboplatin has a limited potential for nephrotoxicity unless administered concomitantly with aminoglycosides. Use caution with concomitant administration with aminoglycosides or other nephrotoxic medications.

Vision loss

Loss of vision (usually reversible within weeks of discontinuing) has been reported with higher-than-recommended doses. Disease-related concerns:

Renal impairment

Use with caution in patients with renal impairment; patients with renal dysfunction are at increased risk for bone marrow suppression. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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

Patients >65 years of age are more likely to develop thrombocytopenia (severe) and peripheral neuropathy. Other warnings/precautions:

Dosing with Calvert formula

When calculating the carboplatin dose using the Calvert formula and an eGFR, the laboratory method used to measure serum creatinine may impact dosing. Compared to other methods, standardized isotope dilution mass spectrometry (IDMS) may underestimate serum creatinine values in patients with low creatinine values (eg, ≤0.7 mg/dL) and may overestimate GFR in patients with normal renal function. This may result in higher calculated carboplatin doses and increased toxicities. If using IDMS, the FDA recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity.

Experienced physician

Should be administered under the supervision of an experienced cancer chemotherapy physician.

Pregnancy & Lactation

Pregnancy

FDA category D

Adverse events have been observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant during treatment.

Lactation

It is not known if carboplatin is present in breast milk. Due to the potential for toxicity in the breasfed infant, the manufacturer recommends discontinuing breastfeeding during carboplatin treatment.

Monitoring

Efficacy	Tumour response (RECIST criteria, tumour markers, imaging); progression-free survival; performance status (ECOG/Karnofsky)
Toxicity	CBC with differential (nadir timing depends on agent); LFTs; renal function; ECG (QT for relevant agents); echocardiogram for cardiotoxic agents (anthracyclines, trastuzumab); cumulative dose tracking for dose-limited toxicities
Clinical pearl	Treatment response is assessed after 2–3 cycles. Grade 3–4 toxicities typically require dose reduction or interruption per protocol-defined criteria.
Counseling	Attend all scheduled blood tests and imaging appointments. Report fever > 38°C (risk of neutropaenic sepsis — medical emergency), unusual bleeding, or new pain immediately.

Chemistry & Properties

Formula	C6H12N2O4Pt
Molecular weight	371.25 g/mol
IUPAC name	azane;cyclobutane-1,1-dicarboxylate;platinum(2+)
CAS	41575-94-4
PubChem CID	10339178

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.489 h
Volume of distribution	0.638 L/kg
Protein binding	20.5%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Inhibitor	—
CYP2C9	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)BCRP (Substrate)MRP2 (Substrate)OATP1B3 (Substrate)OCT2 (Substrate)OCT3 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Certolizumab pegol	major
Cidofovir	major
Cladribine	major
Clozapine	major
Deferiprone	major
Etanercept	major
Fingolimod	major
Golimumab	major
Infliximab	major
Inotersen	major
Leflunomide	major
Measles virus vaccine live attenuated	major
Mumps virus strain B level jeryl lynn live antigen	major
Natalizumab	major
Ozanimod	major
Rotavirus vaccine	major
Rubella virus vaccine	major
Samarium (153Sm) lexidronam	major
Siponimod	major
Smallpox (Vaccinia) Vaccine, Live	major
Sorafenib	major
Talimogene laherparepvec	major
Teriflunomide	major
Thalidomide	major
Thiotepa	major
Tofacitinib	major
Topotecan	major
Typhoid vaccine (live)	major
Upadacitinib	major
Varicella Zoster Vaccine (Recombinant)	major
Yellow Fever Vaccine	major
Aldesleukin	moderate
Alefacept	moderate
Alemtuzumab	moderate
Amikacin	moderate
Amikacin (liposome)	moderate
Amiodarone	moderate

Showing 40 of 100+.

Registered Products (15)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
ADCARB	Vial 150 mg/15 ml	1 vial	Ibn Rushd Drug Store	—
Adcarb	Vial 450 mg/45 ml	1 vial	Beta Drugs Ltd	—
Carboplan Solution For Infusion	Infusion 450 mg/45 ml	1 vial	Manar Drug Store	—
Carboplan Solution For Infusion 150mg/15 Vial	Infusion 150 mg/15 ml	1 vial	Manar Drug Store	—
Carboplatin Vial	Vial 450 mg/45 ml	1 vial	Petra Drug Store	—
Carboplatin Vial	Vial 10 mg/ml	1 vial	Petra Drug Store	—
Carboplatin Vial	Vial 50 mg/5 ml	1 vial	Petra Drug Store	—
KARBOTEEN	Vial 450 mg/45 ml	1 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	—
Karboteen	Vial 150 mg/15 ml	1 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	—
Kemocarb Inj	Injection 10 mg/ml	15 ml pack varies	Sun Set Drug Store	—
Kemocarb Inj	Injection 10 mg/ml	45 ml pack varies	Sun Set Drug Store	—
Megaplatin Vial	Vial 150 mg/15 ml	1 vial	Orient Montreal Drug Store	—
Neoplatin Injection	Injection 150 mg/15 ml	15 ml	Ibn Rushd Drug Store	—
Neoplatin Injection	Injection 50 mg/5 ml	5 ml	Ibn Rushd Drug Store	—
Neoplatin Vial	Vial 450 mg/45 mg	45 ml	Ibn Rushd Drug Store	—