PACLITAXEL

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Binds to microtubules, promoting their stabilization and inhibiting depolymerization, thereby disrupting mitotic spindle function and causing cell cycle arrest at G2/M phase.

What the body does with it

Metabolism	Primarily hepatic via CYP2C8 and CYP3A4; biliary excretion.
Excretion	Primarily hepatobiliary elimination: >90% in feces; renal excretion accounts for <10% (5-10% unchanged).
Half-life	Terminal half-life: 15-50 hours (mean ~20 h), highly dependent on dose and schedule; prolonged with hepatic impairment due to decreased clearance.
Protein binding	89-98% bound, primarily to albumin (AAG to a lesser extent).
Volume of Distribution	Vd: 2- 3 L/kg (227-683 L/m²), indicating extensive tissue distribution and binding to microtubules.
Bioavailability	IV only (100% bioavailable); oral bioavailability <10% due to first-pass metabolism and P-glycoprotein efflux; not administered orally.
Onset of Action	IV: Onset of antimitotic effect within 30-60 minutes of infusion (cell cycle phase-specific).
Duration of Action	Duration of cytotoxic effect: sustained for 2-3 weeks after a single dose due to prolonged intracellular retention and slow elimination from tissues.

Classification & Brands

Dosing & administration

175 mg/m2 IV over 3 hours every 3 weeks for metastatic breast cancer, or 135 mg/m2 IV over 24 hours every 3 weeks for metastatic ovarian cancer.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for GFR ≥20 mL/min. For GFR <20 mL/min, consider avoiding use or reducing dose by 25-50% based on tolerability; insufficient data for severe renal impairment.
Liver impairment	Child-Pugh A: 175 mg/m2. Child-Pugh B: Reduce dose by 25%, start at 130 mg/m2. Child-Pugh C: Contraindicated or reduce dose by 50-75% with close monitoring.
Pediatric use	Not established; clinical trials used 200-350 mg/m2 IV over 3-24 hours based on protocol, but efficacy and safety not determined.
Geriatric use	No specific dose adjustment recommended; monitor for increased myelosuppression and neuropathy, consider lower starting dose for patients >70 years.

Use during pregnancy

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

Clinical note

Strong CYP3A4 or CYP2C8 inhibitors may increase levels Can cause severe hypersensitivity reactions myelosuppression and peripheral neuropathy.

Breastfeeding	Paclitaxel is excreted into human breast milk. The milk-to-plasma (M/P) ratio is unknown. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during paclitaxel therapy and for at least 2 weeks after the last dose.
Teratogenic Risk	Paclitaxel is a pregnancy category D drug. First trimester exposure is associated with major congenital malformations, including neural tube defects, cardiac anomalies, and skeletal abnormalities. Second and third trimester exposure can cause fetal growth restriction, oligohydramnios, and preterm delivery. There is also an increased risk of spontaneous abortion and fetal death.

Warnings & precautions

■ FDA Black Box Warning

Paclitaxel should not be administered to patients with baseline neutrophil counts less than 1,500 cells/mm³. Severe hypersensitivity reactions can occur, and appropriate premedication is required.

Side Effect Profile

Common Effects	breast cancer
Serious Effects

Absolute Contraindications

["Hypersensitivity to paclitaxel or polyoxyl 35 castor oil (Cremophor EL)","Baseline neutrophil count <1,500 cells/mm³","Active serious infection"]

Clinical Precautions

Precautions

["Hematologic toxicity (neutropenia, thrombocytopenia)","Hypersensitivity reactions (premedicate with corticosteroids, antihistamines, H2 antagonists)","Cardiac conduction abnormalities (bradycardia, hypotension)","Peripheral neuropathy (dose-dependent)","Extravasation risk (local tissue injury)","Fetal harm (Pregnancy Category D)"]

Clinical Tips & Counseling

Drug interactions

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