PARAPLATIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).
Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).
Ovarian carcinoma: treatment of advanced ovarian carcinoma in combination with other chemotherapy agentsNon-small cell lung cancer: treatment of advanced NSCLC in combination with other agentsOff-label: head and neck cancer, bladder cancer, endometrial cancer, testicular cancer, small cell lung cancer
Nausea, Vomiting, Anemia (low number of red blood cells), Fatigue, Low blood platelets, Increased liver enzymes, Decreased white blood cell count (neutrophils), Stomatitis (Inflammation of the mouth), Peripheral neuropathy (tingling and numbness of feet and hand), Diarrhea
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.
| 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. |
| Molecular Weight | 371.25 |
| Action Class | Platinum compounds-Anticancer |
| Brand Substitutes | Womaplat 450mg Injection, Naproplat 450mg Injection, Adcarb 450mg Injection, Celcarb 450mg Injection, Carboplatin 450mg Injection |
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. |
| 1st trimester | Avoid. Carboplatin is associated with teratogenicity and embryotoxicity in animal studies; human data limited but risk of fetal harm. |
| 2nd trimester | Use only if clearly needed. Risk of fetal growth restriction and malformations; consider delayed therapy. |
| 3rd trimester | Use only if clearly needed. Risk of neonatal myelosuppression, infection, and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for PARAPLATIN (PARAPLATIN).
| Placental transfer | Carboplatin crosses the placenta; fetal plasma concentrations are approximately 10-50% of maternal levels. |
| Breastfeeding | Carboplatin is excreted into human milk in low concentrations; due to potential for serious adverse effects in the nursing infant, breastfeeding is not recommended during therapy and for at least 2 weeks after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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 | Monitor complete blood count with differential (myelosuppression), renal function (serum creatinine, BUN), hepatic function (transaminases, bilirubin), audiometry (ototoxicity), and fetal ultrasound for growth and anomalies during pregnancy. |
| Fertility Effects | Carboplatin is gonadotoxic; causes irreversible ovarian failure in premenopausal women and azoospermia in men. Impairs fertility and may lead to premature menopause. |
■ 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.
| Serious Effects |
History of severe allergic reaction to carboplatin or other platinum compoundsSevere myelosuppression (unless benefits outweigh risks)Significant bleeding disorders
| 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. |
| Food/Dietary | No significant food interactions. Avoid grapefruit and grapefruit juice if patient is on concurrent CYP3A4-metabolized drugs (e.g., aprepitant). |
| Clinical Pearls | Paraplatin (carboplatin) dosing is based on renal function using Calvert formula to calculate AUC. Dose adjustments required for CrCl <60 mL/min. Administer IV infusion over 15-60 minutes. Hypersensitivity reactions may occur after multiple cycles; premedicate with antihistamines and corticosteroids if prior reaction. Monitor CBC weekly during treatment. Emetogenic potential: moderate-high; use antiemetic prophylaxis. Avoid concurrent nephrotoxic drugs. Myelosuppression (especially thrombocytopenia) is dose-limiting. |
| Patient Advice | This drug may lower your blood cell counts; report any signs of infection (fever, chills), easy bruising or bleeding, or unusual tiredness. · You may experience nausea or vomiting; take anti-nausea medications as prescribed. · Avoid live vaccines during treatment and for 6 months after. · Tell your doctor if you have had an allergic reaction to platinum-based drugs. · Use effective contraception during and for 6 months after treatment; do not breastfeed. · Drink plenty of fluids to stay hydrated unless otherwise instructed. · Report any hearing changes, ringing in ears, or numbness/tingling in hands or feet. |
Loading safety data…