ELOXATIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELOXATIN (ELOXATIN).
Oxaliplatin undergoes non-enzymatic biotransformation to form platinum-DNA adducts, leading to inhibition of DNA replication and transcription, and ultimately cell death. It is a third-generation platinum-based alkylating agent.
| Metabolism | Oxaliplatin undergoes rapid non-enzymatic biotransformation in plasma and tissues to form active platinum derivatives, primarily via displacement of the oxalate ligand. Minimal hepatic metabolism; elimination is predominantly renal. |
| Excretion | Renal: ~54% of platinum excreted in urine within 48 hours; fecal: small amount (<2%); biliary excretion is minimal. |
| Half-life | Terminal half-life of ultrafilterable platinum: ~10-27 hours (mean ~14 hours); total platinum: ~40-50 hours. Clinical context: prolonged exposure due to tissue binding. |
| Protein binding | Platinum binds >90% to plasma proteins, mainly albumin and gamma-globulins; irreversible binding. |
| Volume of Distribution | Vd of ultrafilterable platinum: ~0.4-0.6 L/kg; total platinum: ~4-6 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: Not bioavailable (unstable in GI tract); IV: 100%. |
| Onset of Action | IV: Clinical effect (antitumor) onset within hours to days, but radiologic response may take weeks. |
| Duration of Action | Duration of antitumor effect varies; platinum persists in tissues for weeks. Clinical monitoring for neuropathy continues post-infusion. |
85 mg/m2 IV over 2 hours on day 1, repeated every 2 weeks (adjuvant); 85 mg/m2 IV over 2 hours on day 1, repeated every 2 weeks or 130 mg/m2 IV over 2 hours on day 1, repeated every 3 weeks (advanced disease).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl ≥60 mL/min: No adjustment; CrCl 50-59 mL/min: No adjustment; CrCl 40-49 mL/min: Administer 85 mg/m2, but no data for 130 mg/m2; CrCl 30-39 mL/min: Administer 85 mg/m2 with caution, no data for 130 mg/m2; CrCl 20-29 mL/min: Administer 85 mg/m2 with extreme caution, no data for 130 mg/m2; CrCl <20 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment required; Child-Pugh B: No adjustment required; Child-Pugh C: Use with caution; no specific dose reduction defined. |
| Pediatric use | Not approved for pediatric use. No established dosing guidelines. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function and adjust according to calculated creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELOXATIN (ELOXATIN).
| Breastfeeding | It is unknown whether oxaliplatin or its metabolites are excreted in human milk. Due to potential serious adverse reactions in nursing infants, including myelosuppression and neurotoxicity, breastfeeding is not recommended during treatment and for at least 3 months after the last dose. No M/P ratio data available. |
| Teratogenic Risk | Eloxatin (oxaliplatin) is a platinum-based antineoplastic agent classified as FDA Pregnancy Category D. There is evidence of fetal harm based on animal studies and its mechanism of action (DNA cross-linking). Use during pregnancy is contraindicated unless maternal benefit outweighs risk. First trimester exposure carries highest risk of major malformations; second and third trimester exposure may cause fetal growth restriction, myelosuppression, and neurotoxicity. |
■ FDA Black Box Warning
Anaphylactic-like reactions to oxaliplatin have been reported, which may occur within minutes of administration and require immediate discontinuation and symptomatic treatment. Oxaliplatin should be discontinued if severe hypersensitivity occurs.
| Serious Effects |
["History of severe hypersensitivity to oxaliplatin or any components of the formulation","Severe renal impairment (creatinine clearance <30 mL/min)","Bone marrow suppression with baseline neutrophil count <1.5 × 10^9/L or platelet count <75 × 10^9/L","Pregnancy (can cause fetal harm)"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis) have been reported and may be life-threatening. Discontinue permanently if severe reaction occurs.","Peripheral neuropathy, which may be acute (reversible) or chronic (persistent), is dose-limiting and requires dose adjustment or discontinuation.","Hepatotoxicity, including hepatic sinusoidal obstruction syndrome, has been reported. Monitor liver function.","Pulmonary toxicity, including pulmonary fibrosis, has been observed. Discontinue if interstitial lung disease is suspected.","Bleeding risk due to thrombocytopenia; monitor platelet counts.","Rhabdomyolysis has been reported; monitor for muscle pain/weakness.","Post-marketing reports of reversible posterior leukoencephalopathy syndrome (RPLS); discontinue if symptoms occur."] |
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| Fetal Monitoring | Complete blood counts (CBC) with differential, liver function tests (LFTs), renal function tests, and serum electrolytes including calcium, magnesium, and potassium. Monitor for peripheral neuropathy, hypersensitivity reactions, and gastrointestinal toxicity. Fetal monitoring includes serial growth ultrasounds and assessment of amniotic fluid volume. If used during pregnancy, consider fetal echocardiography. |
| Fertility Effects | Oxaliplatin may cause irreversible gonadal suppression, including ovarian failure and azoospermia. Animal studies demonstrate reduced fertility and impaired spermatogenesis. Pre-treatment fertility counseling and options for gamete preservation should be offered to men and women of childbearing potential. |