ABRAXANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ABRAXANE (ABRAXANE).
Microtubule inhibitor that promotes assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization, resulting in inhibition of cell division and cell death.
| Metabolism | Paclitaxel is metabolized primarily by CYP2C8 to 6-alpha-hydroxypaclitaxel (inactive) and by CYP3A4 to minor metabolites. Phase I hydroxylation is the main route. No significant phase II metabolism. |
| Excretion | Primarily hepatobiliary; less than 10% excreted unchanged in urine. Fecal excretion accounts for approximately 70% of dose, with biliary excretion being the major route. |
| Half-life | Terminal elimination half-life is approximately 27 hours for paclitaxel when administered as Abraxane. This long half-life supports weekly dosing schedules due to prolonged exposure. |
| Protein binding | Approximately 94% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 230 L/m² (or 3.3 L/kg based on 70 kg), indicating extensive tissue binding and distribution beyond plasma volume. |
| Bioavailability | Only intravenous administration; oral bioavailability is negligible (<1%) due to first-pass metabolism and P-glycoprotein efflux. |
| Onset of Action | Onset of clinical antimitotic effect occurs within hours of infusion, with maximal effect observed after 24-48 hours corresponding to peak mitotic arrest. |
| Duration of Action | Duration of action is typically 2-3 weeks, corresponding to the dosing interval. Myelosuppression nadir occurs at 10-14 days, with recovery by day 21. |
| Action Class | Antimicrotubule agents- Taxanes |
| Brand Substitutes | Oncotaxel 100mg Injection, Altaxel 100mg Injection, Cytax 100mg Injection, Mitotax 100mg Injection, Paclitec 100 Injection |
260 mg/m2 intravenously over 30 minutes every 3 weeks
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for creatinine clearance ≥ 30 mL/min; insufficient data for severe renal impairment (CrCl < 30 mL/min). |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose to 200 mg/m2; Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity, particularly myelosuppression and neuropathy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ABRAXANE (ABRAXANE).
| Breastfeeding | Excretion into human milk unknown; paclitaxel is lipophilic and likely present. M/P ratio not established. Due to potential severe adverse effects on nursing infant, breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | Pregnancy category D. Abraxane (paclitaxel protein-bound) is embryo-fetal toxic. Administration during first trimester carries high risk of major congenital malformations (neural tube defects, cardiac anomalies, skeletal defects). Second and third trimester exposure associated with intrauterine growth restriction, oligohydramnios, and preterm birth. Contraindicated in pregnancy unless no alternative for life-threatening condition. |
■ FDA Black Box Warning
Neutropenia: Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm^3.
| Serious Effects |
["Hypersensitivity to paclitaxel or any component of the formulation","Neutrophil count less than 1500 cells/mm^3"]
| Precautions | ["Severe neutropenia and febrile neutropenia; monitor blood counts frequently","Hypersensitivity reactions, including severe reactions; premedicate and monitor","Cardiovascular effects including myocardial ischemia and infarction","Respiratory effects including pneumonitis and pulmonary fibrosis","Neurologic toxicity, including peripheral neuropathy","Pancreatitis in combination with gemcitabine","Hepatic impairment reduces clearance and increases toxicity","Fetal harm if used during pregnancy"] |
| Food/Dietary | Grapefruit and grapefruit juice may inhibit CYP2C8 and CYP3A4 metabolism of paclitaxel, potentially increasing exposure; advise avoidance or limitation. Alcohol should be avoided due to additive hepatic toxicity and exacerbation of neuropathy. No specific dietary restrictions otherwise; encourage adequate hydration and nutrition. |
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| Fetal Monitoring | During pregnancy: serial fetal ultrasound for growth, amniotic fluid volume, and anatomy; biophysical profile after 32 weeks. Monitor maternal blood counts (neutropenia, thrombocytopenia), liver function, and peripheral neuropathy. In non-pregnant: CBC with differential, hepatic function tests before and during each cycle. |
| Fertility Effects | Paclitaxel is gonadotoxic. In females: may cause ovarian failure (amenorrhea, elevated FSH), infertility, premature menopause, especially with cumulative doses. In males: potential for oligospermia or azoospermia; impact on fertility may be reversible or permanent. Pre-treatment fertility preservation counseling recommended. |
| Clinical Pearls | ABRAXANE (nab-paclitaxel) is a solvent-free albumin-bound formulation of paclitaxel, eliminating the need for premedication with corticosteroids and antihistamines required with cremophor-based paclitaxel. Monitor for peripheral neuropathy, bone marrow suppression, and hypersensitivity reactions (rare due to absence of Cremophor EL). Dose adjustment for hepatic impairment is necessary; use caution in patients with bilirubin > 1.5 mg/dL. ABRAXANE can cause ocular/visual disturbances; discontinue if severe. Administer over 30-40 minutes (shorter infusion time than paclitaxel). |
| Patient Advice | Report any numbness, tingling, or burning pain in hands/feet immediately (signs of peripheral neuropathy). · Notify your doctor if you experience shortness of breath, severe fatigue, easy bruising/bleeding, or fever (signs of low blood counts). · Avoid alcohol and limit grapefruit/grapefruit juice consumption during treatment. · Use effective contraception during treatment and for at least 3 months after the last dose. · Do not drive or operate heavy machinery if you experience vision changes, dizziness, or severe fatigue. |