OXALIPLATIN

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Oxaliplatin is a platinum-based alkylating agent that forms inter- and intrastrand DNA crosslinks, inhibiting DNA replication and transcription, leading to cell death.

What the body does with it

Metabolism	Oxaliplatin undergoes rapid non-enzymatic biotransformation to active metabolites. Primarily eliminated by renal excretion. Not extensively metabolized by cytochrome P450 enzymes.
Excretion	Renal excretion accounts for approximately 50% of the administered platinum, with the remainder eliminated via biliary/fecal routes. Platinum accumulates in erythrocytes and is slowly cleared.
Half-life	Terminal elimination half-life is approximately 40-50 hours for ultrafilterable platinum (active species) and 240-500 hours for total platinum (bound to plasma proteins and erythrocytes). The prolonged half-life reflects slow release from tissue binding.
Protein binding	Approximately 90% of ultrafilterable platinum is protein-bound, primarily to albumin and gamma-globulins. Irreversible binding to erythrocytes occurs.
Volume of Distribution	Volume of distribution is large, approximately 200-500 L/m² (or 3-6 L/kg), indicating extensive tissue distribution. Platinum accumulates in tissues, especially erythrocytes, kidney, and liver.
Bioavailability	Bioavailability: Not applicable (IV only). Oral bioavailability is negligible due to poor absorption and extensive first-pass metabolism.
Onset of Action	Intravenous: Clinical effect (antitumor activity) onset is delayed, typically observed after multiple cycles (weeks). No immediate therapeutic effect.
Duration of Action	Duration of action is prolonged due to DNA adduct persistence. Clinical effects (response or toxicity) may persist for weeks after administration. Cumulative sensory neurotoxicity is dose-limiting.

Classification & Brands

Dosing & administration

85 mg/m² intravenously over 2 hours every 2 weeks in combination with 5-fluorouracil and leucovorin (FOLFOX regimen).

Dosage form	INJECTABLE
Renal impairment	CrCl ≥30 mL/min: no adjustment needed. CrCl <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended.
Pediatric use	Not established; clinical trials used 130 mg/m² intravenously over 2 hours every 3 weeks, but not approved for routine use.
Geriatric use	No dose adjustment based solely on age, but monitor for increased neurotoxicity and myelosuppression.

Use during pregnancy

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

Clinical note

Other nephrotoxic drugs may enhance platinum-induced renal toxicity Can cause peripheral sensory neuropathy and pharyngolaryngeal dysesthesia.

Breastfeeding	Excretion in human milk unknown; due to high molecular weight (397 Da) and protein binding (>90%), M/P ratio not determined. Potential for severe adverse reactions in nursing infant; discontinue breastfeeding during therapy and for 3 months after last dose.
Teratogenic Risk	Oxaliplatin is platinum-based antineoplastic with teratogenic potential. First trimester: high risk of congenital malformations (neural tube, skeletal, cardiovascular). Second/third trimester: risk of fetal growth restriction, low birth weight, preterm delivery. Known to cause embryolethality in animal studies.

Warnings & precautions

■ FDA Black Box Warning

Permanent neurological deficit may occur. Persistent paresthesias or dysesthesias that do not resolve may require discontinuation. Acute laryngopharyngeal dysesthesia syndrome may occur with infusion.

Side Effect Profile

Common Effects	Neurotoxicity
Serious Effects

Absolute Contraindications

["History of severe hypersensitivity to oxaliplatin or other platinum compounds","Severe renal impairment (creatinine clearance < 30 mL/min)","Pre-existing peripheral sensory neuropathy with functional impairment"]

Clinical Precautions

Precautions

["Peripheral neuropathy: acute and cumulative, may be dose-limiting","Anaphylactic reactions: observe for signs of hypersensitivity during infusion","Hepatotoxicity: monitor liver function tests","Renal impairment: dose adjustment required for severe renal impairment","Neutropenia and thrombocytopenia: monitor blood counts regularly","QT interval prolongation: monitor ECG in patients with electrolyte abnormalities or other QT-prolonging drugs"]

Clinical Tips & Counseling

Drug interactions

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