CARBOPLATIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Carboplatin forms platinum-DNA adducts, causing intrastrand crosslinks and G2/M cell cycle arrest, leading to apoptosis.
| Metabolism | Carboplatin undergoes minimal hepatic metabolism; its elimination is primarily renal via glomerular filtration and tubular secretion, with an elimination half-life of 2.6-5.5 hours in patients with normal renal function. |
| Excretion | Renal: ~65% of platinum excreted in urine within 24 hours, primarily as unchanged carboplatin; ~32% as metabolites. Biliary/fecal excretion is minimal (<6%). |
| Half-life | Terminal elimination half-life: 2.6-5.9 hours in adults with normal renal function. In patients with creatinine clearance <60 mL/min, half-life is prolonged (up to 17-26 hours). Clinically, dosing adjustments are required based on Calvert formula using glomerular filtration rate. |
| Protein binding | Platinum from carboplatin is ~24% bound to albumin and other plasma proteins; binding is irreversible and increases with time. Free platinum fraction is >75% initially. |
| Volume of Distribution | Volume of distribution (Vd): 0.24-0.36 L/kg (total platinum); 0.15-0.25 L/kg (free platinum). Distributes into total body water; significant binding to tissues with higher concentrations in liver, kidney, skin, and tumors. |
| Bioavailability | Not available; carboplatin is administered only intravenously. Oral bioavailability is negligible due to instability in gastric acid and low permeability. |
| Onset of Action | Intravenous: Onset of myelosuppression typically occurs 7-14 days after administration; nadir at 14-21 days. Antineoplastic effect may take weeks to become clinically evident. |
| Duration of Action | Myelosuppression (thrombocytopenia, neutropenia) recovery usually within 3-4 weeks. Duration of antineoplastic effect varies with tumor type; typically, cycles every 3-4 weeks. |
| Action Class | Platinum compounds-Anticancer |
| Brand Substitutes | Womaplat 450mg Injection, Naproplat 450mg Injection, Adcarb 450mg Injection, Celcarb 450mg Injection, Karplat 450mg Injection, Stricarb 150mg Injection, Karplat 150mg Injection, Womaplat 150mg Injection, Adcarb 150mg Injection, Innocar 150 Injection |
IV infusion over 15-60 minutes, target AUC 4-6 using Calvert formula (dose = target AUC × (GFR + 25)). Adults: typical initial dose 400 mg/m² every 4 weeks or AUC 5-6 every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | Calvert formula required: CrCl (mL/min) measured or estimated. For CrCl 41-59: reduce dose 25%; CrCl 16-40: reduce dose 50%; CrCl ≤15: consider alternative. Hemodialysis: administer after dialysis at reduced dose (e.g., AUC 2-3). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: consider 25% dose reduction; Child-Pugh C: not recommended (insufficient data). Monitor toxicity. |
| Pediatric use | Solid tumors: 400-560 mg/m² IV every 4 weeks; or AUC 4-6. CNS tumors: 175 mg/m² weekly for 4 weeks. Adjust per Calvert formula using GFR measured by nuclear medicine or Schwartz formula. |
| Geriatric use | Use Calvert formula with estimated CrCl (Cockcroft-Gault). Consider lower target AUC (4-5) to reduce myelosuppression. Monitor renal function and blood counts closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Nephrotoxic drugs may enhance platinum-induced renal toxicity Myelosuppression is dose-related and is the dose-limiting toxicity.
| Breastfeeding | Carboplatin is excreted into human milk, but the milk-to-plasma (M/P) ratio is approximately 0.05. Due to potential for infant myelosuppression, ototoxicity, and carcinogenesis, breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Carboplatin is teratogenic in pregnancy. First trimester exposure is associated with major congenital malformations (neural tube defects, craniofacial anomalies, limb defects) and miscarriage. Second and third trimester exposure may cause intrauterine growth restriction, myelosuppression in the neonate, and potential long-term neurodevelopmental effects. Use is contraindicated unless no alternative. |
■ FDA Black Box Warning
Bone marrow suppression (primarily thrombocytopenia, leukopenia, and anemia) is dose-dependent and may be severe. Myelosuppression is exacerbated in patients with prior chemotherapy or renal impairment.
| Serious Effects |
Severe bone marrow depression. Known hypersensitivity to carboplatin or other platinum-containing compounds. Severe renal impairment (creatinine clearance <15 mL/min) unless dose adjusted. Nursing mothers (discontinue breastfeeding).
| Precautions | Bone marrow suppression (monitor CBCs). Nephrotoxicity (dose adjustment based on Calvert formula using GFR). Neurotoxicity (peripheral neuropathy, especially with prolonged use). Ototoxicity (high frequency hearing loss). Anaphylactic reactions. Nausea/vomiting (highly emetogenic). Secondary malignancies. Fetal harm if used in pregnancy. |
| Food/Dietary | No specific dietary restrictions or food interactions are established for carboplatin. However, patients should maintain adequate hydration. Avoid alcohol to prevent additional gastrointestinal irritation. Grapefruit and St. John's wort have no known interaction with carboplatin. |
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| Fetal Monitoring | Maternal monitoring: Complete blood count (CBC) with differential and platelets, renal function (serum creatinine, BUN), and liver function tests before each cycle. Fetal monitoring: Serial growth ultrasounds (every 4-6 weeks) for intrauterine growth restriction; consider antenatal fetal surveillance (non-stress test, biophysical profile) after viability. |
| Fertility Effects | Carboplatin is potentially gonadotoxic. In females, it can cause ovarian failure, amenorrhea, and reduced fertility, especially with cumulative dosing. In males, it may cause oligospermia or azoospermia. Fertility preservation counseling before treatment is recommended. |
| Clinical Pearls | Carboplatin dosing is based on Calvert formula using glomerular filtration rate (GFR) and target area under the curve (AUC). Monitor for thrombocytopenia, which is dose-limiting and more pronounced than with cisplatin. Do not use aluminum needles or IV sets as aluminum can react with carboplatin, causing precipitate. Administer over 15-60 minutes; avoid rapid infusion. Premedication for emesis is required (e.g., aprepitant, 5-HT3 antagonist). Ensure adequate hydration but less critical than with cisplatin due to lower nephrotoxicity. Myelosuppression is cumulative; nadir typically at day 14-21. |
| Patient Advice | Your dose is calculated based on your kidney function. · You may experience low blood counts; call if fever, unusual bleeding, or bruising. · Nausea and vomiting are common; take anti-nausea medication as prescribed. · Avoid aspirin, ibuprofen, or other NSAIDs unless approved by your doctor. · Fertility preservation options should be discussed before treatment. |