PARAPLATIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).

How it works

Carboplatin, a platinum-based alkylating agent, forms interstrand and intrastrand DNA cross-links by binding to DNA guanine bases, inhibiting DNA replication and transcription, leading to cell cycle arrest and apoptosis.

What the body does with it

Metabolism	Carboplatin is minimally metabolized in the liver; the majority of the drug is eliminated unchanged by renal excretion via glomerular filtration and tubular secretion. It is not extensively metabolized by cytochrome P450 enzymes.
Excretion	Renal excretion: ~70-90% of platinum is excreted in urine within 24 hours, primarily as unchanged drug. Fecal excretion: <6%. Biliary excretion: minimal.
Half-life	Terminal elimination half-life: 2.6-5.1 hours (initial phase), 22-52 hours (terminal phase) for total platinum; 1.3-2.1 hours for ultrafilterable platinum. Clinically, the terminal half-life reflects slow release of protein-bound platinum.
Protein binding	Protein binding: ~90% of circulating platinum is irreversibly bound to plasma proteins (primarily albumin) within 4 hours of infusion; only free drug is pharmacologically active.
Volume of Distribution	Volume of distribution: 10-16 L/kg (total platinum), 0.3-0.5 L/kg (ultrafilterable platinum). High Vd indicates extensive tissue distribution, including into tumors.
Bioavailability	IV administration only; oral bioavailability is negligible (<2%) due to poor absorption and rapid degradation in GI tract.
Onset of Action	IV administration: onset of antineoplastic effect occurs within hours to days, with maximal effect typically observed after multiple cycles; not immediately measurable.
Duration of Action	Duration of action is prolonged due to DNA adduct persistence; clinical effects persist for weeks, with myelosuppression nadir at 14-21 days post-dose.

Classification & Brands

Action Class	Platinum compounds-Anticancer
Brand Substitutes	Womaplat 450mg Injection, Naproplat 450mg Injection, Adcarb 450mg Injection, Celcarb 450mg Injection, Carboplatin 450mg Injection

Dosing & administration

360 mg/m2 IV every 3 weeks or area under the curve (AUC) 4-6 mg/mL/min IV every 3-4 weeks using Calvert formula.

Dosage form	INJECTABLE
Renal impairment	Creatinine clearance (CrCl) 41-59 mL/min: 250 mg/m2 IV every 3-4 weeks; CrCl 16-40 mL/min: 200 mg/m2 IV every 3-4 weeks; CrCl <15 mL/min: not recommended. Alternatively, AUC dosing: CrCl 41-59 mL/min: AUC 4; CrCl 16-40 mL/min: AUC 3; CrCl <15 mL/min: not recommended.
Liver impairment	No specific Child-Pugh based modifications established; use caution in severe hepatic impairment; baseline dose reduction to 200-250 mg/m2 recommended in patients with bilirubin >1.5 mg/dL or transaminases >2x upper limit of normal.
Pediatric use	300-600 mg/m2 IV every 3-4 weeks; alternatively, 90-150 mg/m2 IV weekly for 4 weeks then 2-week rest. Adjust for renal function using Calvert formula with pediatric GFR estimation.
Geriatric use	No specific dose adjustment solely for age; calculate dose based on GFR using Calvert formula; monitor for increased myelosuppression and neurotoxicity; consider starting at lower AUC (4-5) in patients with decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).

Breastfeeding	Excreted in human milk; no M/P ratio available. Risk of severe neonatal adverse effects; contraindicated during breastfeeding. Discontinue drug or nursing.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of teratogenicity; embryotoxicity, fetal malformations (neural tube, skeletal, cardiovascular). Second and third trimesters: Risk of fetal growth restriction, prematurity, low birth weight, neonatal myelosuppression, and long-term developmental effects.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Carboplatin should be administered under the supervision of a physician experienced in cancer chemotherapy. Myelosuppression is dose-dependent and may be severe, with bone marrow suppression requiring close monitoring. Anaphylactic reactions have been reported and may be fatal. Use caution in patients with prior hypersensitivity to platinum compounds.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of severe allergic reactions to carboplatin or other platinum-containing compounds; severe bone marrow suppression; significant bleeding disorders; severe renal impairment (creatinine clearance < 30 mL/min) unless benefit outweighs risk.

Clinical Precautions

Precautions

Bone marrow suppression (thrombocytopenia, neutropenia, anemia) is dose-limiting; monitor blood counts. Nephrotoxicity may occur, especially in patients with renal impairment; assess renal function before and during therapy. Neurotoxicity (peripheral neuropathy) is less common than with cisplatin but may occur. Ototoxicity risk increases with higher cumulative doses. Anaphylactic reactions can occur. Hemolytic uremic syndrome has been reported. Use caution in patients with prior platinum hypersensitivity.

Clinical Tips & Counseling

Drug interactions

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PARAPLATIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).

How it works

What the body does with it

Metabolism	Carboplatin is minimally metabolized in the liver; the majority of the drug is eliminated unchanged by renal excretion via glomerular filtration and tubular secretion. It is not extensively metabolized by cytochrome P450 enzymes.
Excretion	Renal excretion: ~70-90% of platinum is excreted in urine within 24 hours, primarily as unchanged drug. Fecal excretion: <6%. Biliary excretion: minimal.
Half-life	Terminal elimination half-life: 2.6-5.1 hours (initial phase), 22-52 hours (terminal phase) for total platinum; 1.3-2.1 hours for ultrafilterable platinum. Clinically, the terminal half-life reflects slow release of protein-bound platinum.
Protein binding	Protein binding: ~90% of circulating platinum is irreversibly bound to plasma proteins (primarily albumin) within 4 hours of infusion; only free drug is pharmacologically active.
Volume of Distribution	Volume of distribution: 10-16 L/kg (total platinum), 0.3-0.5 L/kg (ultrafilterable platinum). High Vd indicates extensive tissue distribution, including into tumors.
Bioavailability	IV administration only; oral bioavailability is negligible (<2%) due to poor absorption and rapid degradation in GI tract.
Onset of Action	IV administration: onset of antineoplastic effect occurs within hours to days, with maximal effect typically observed after multiple cycles; not immediately measurable.
Duration of Action	Duration of action is prolonged due to DNA adduct persistence; clinical effects persist for weeks, with myelosuppression nadir at 14-21 days post-dose.

Classification & Brands

Action Class	Platinum compounds-Anticancer
Brand Substitutes	Womaplat 450mg Injection, Naproplat 450mg Injection, Adcarb 450mg Injection, Celcarb 450mg Injection, Carboplatin 450mg Injection

Dosing & administration

360 mg/m2 IV every 3 weeks or area under the curve (AUC) 4-6 mg/mL/min IV every 3-4 weeks using Calvert formula.

Dosage form	INJECTABLE
Renal impairment	Creatinine clearance (CrCl) 41-59 mL/min: 250 mg/m2 IV every 3-4 weeks; CrCl 16-40 mL/min: 200 mg/m2 IV every 3-4 weeks; CrCl <15 mL/min: not recommended. Alternatively, AUC dosing: CrCl 41-59 mL/min: AUC 4; CrCl 16-40 mL/min: AUC 3; CrCl <15 mL/min: not recommended.
Liver impairment	No specific Child-Pugh based modifications established; use caution in severe hepatic impairment; baseline dose reduction to 200-250 mg/m2 recommended in patients with bilirubin >1.5 mg/dL or transaminases >2x upper limit of normal.
Pediatric use	300-600 mg/m2 IV every 3-4 weeks; alternatively, 90-150 mg/m2 IV weekly for 4 weeks then 2-week rest. Adjust for renal function using Calvert formula with pediatric GFR estimation.
Geriatric use	No specific dose adjustment solely for age; calculate dose based on GFR using Calvert formula; monitor for increased myelosuppression and neurotoxicity; consider starting at lower AUC (4-5) in patients with decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).

Breastfeeding	Excreted in human milk; no M/P ratio available. Risk of severe neonatal adverse effects; contraindicated during breastfeeding. Discontinue drug or nursing.
Teratogenic Risk	Pregnancy Category D. First trimester: High risk of teratogenicity; embryotoxicity, fetal malformations (neural tube, skeletal, cardiovascular). Second and third trimesters: Risk of fetal growth restriction, prematurity, low birth weight, neonatal myelosuppression, and long-term developmental effects.
Fetal Monitoring