OXALIPLATIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Oxaliplatin is a platinum-based alkylating agent that forms inter- and intrastrand DNA crosslinks, inhibiting DNA replication and transcription, leading to cell death.
| 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. |
| Molecular Weight | 397.29 |
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. |
| 1st trimester | Avoid. Oxaliplatin is a platinum-based antineoplastic agent with known teratogenicity in animal studies. Risk of fetal harm outweighs potential benefits; effective contraception is recommended during treatment. |
| 2nd trimester | Avoid. Limited human data, but animal studies show embryotoxicity and fetotoxicity. Use only if clearly needed and potential benefit justifies risk to the fetus. Consider alternative therapy if possible. |
| 3rd trimester | Avoid. Possible risk of fetal and neonatal toxicity (e.g., myelosuppression). Use only if life-threatening condition where no safer alternative exists. |
Clinical note
Other nephrotoxic drugs may enhance platinum-induced renal toxicity Can cause peripheral sensory neuropathy and pharyngolaryngeal dysesthesia.
| Placental transfer | Oxaliplatin crosses the placenta. Platinum-DNA adducts have been detected in fetal tissues in animal studies. Human data limited but expected to transfer based on molecular weight and pharmacokinetics. |
| Breastfeeding |
■ 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.
| Common Effects | Neurotoxicity |
| Serious Effects |
History of severe hypersensitivity to oxaliplatin or any platinum-containing compoundSevere renal impairment (CrCl <20 mL/min or on dialysis)Severe myelosuppression (ANC <1.5 x 10^9/L or platelet count <75 x 10^9/L) at start of therapyPeripheral sensory neuropathy with functional impairment (Grade ≥3)Concurrent administration of nephrotoxic agents (e.g., cisplatin, if possible) should be avoided
| 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 |
Loading safety data…
| Oxaliplatin is likely excreted into breast milk due to low molecular weight and long half-life. Potential for serious adverse reactions in nursing infants, including myelosuppression and gastrointestinal toxicity. Breastfeeding is not recommended during therapy and for at least 3 months after the last dose. Alternative feeding methods should be considered. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| Fetal Monitoring | Regular complete blood count, liver function tests, serum creatinine, electrolytes. Monitor for neurotoxicity (cumulative sensory). Fetal ultrasound for growth restriction, anomaly scan, and serial growth assessments. Cardiotocography in third trimester if indicated. |
| Fertility Effects | Reversible or permanent gonadal suppression in both sexes. In males: oligospermia, azoospermia; may impair fertility. In females: amenorrhea, premature ovarian failure, reduced ovarian reserve. Pre-treatment fertility preservation counseling recommended. |
| Food/Dietary | Avoid cold foods and beverages, including ice cream, frozen drinks, and refrigerated items, for at least 3-5 days after infusion to prevent cold-induced paresthesias. Also avoid alcohol, which can exacerbate neurotoxicity. Do not consume grapefruit or grapefruit juice, as it may alter drug metabolism. Maintain a balanced diet with soft, warm foods if oral mucositis occurs. |
| Clinical Pearls | Oxaliplatin is associated with two distinct types of neuropathy: acute, cold-induced paresthesias that occur during or shortly after infusion, and chronic, cumulative sensory neuropathy. Premedicate with antiemetics (e.g., dexamethasone and a 5-HT3 antagonist) and consider calcium and magnesium infusions before and after oxaliplatin to reduce neurotoxicity. Avoid cold exposure during and for several days after infusion. Administer over 2-6 hours as per protocol. Monitor for laryngopharyngeal dysesthesia, which can present as difficulty breathing or swallowing; treat immediately with warm compresses and reassurance. Oxaliplatin is incompatible with sodium chloride solutions; always dilute in dextrose 5% in water. Do not use aluminum-containing needles or IV sets due to degradation. |
| Patient Advice | Avoid cold drinks, ice, and cold liquids for 3-5 days after each treatment to prevent severe throat and mouth discomfort. · Wear warm clothing, gloves, and avoid touching cold objects (e.g., freezer handles, cold doorknobs) during and after infusion. · Report any numbness, tingling, or pain in hands or feet, especially with cold exposure, to your healthcare provider. · Use a scarf or warm mask to protect your throat from cold air when going outside. · Do not drink alcohol during treatment without consulting your doctor, as it may worsen side effects. · Take anti-nausea medications as prescribed before and after chemotherapy to prevent vomiting. · Drink plenty of warm or room temperature fluids to stay hydrated. · Contact your doctor immediately if you experience difficulty breathing, swallowing, or sudden facial swelling. |