BLACK BOX WARNING
- anaphylaxis and severe hypersensitivity reactions — premedicate with corticosteroids, antihistamines, H2 blockers
- myelosuppression — do not administer if neutrophils <1500/mm3
paclitaxel
Brand: Taxol, Abraxane (nab-paclitaxel)
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: taxane antineoplastic
Drug Family: antineoplastic
Subclass: microtubule-stabilizing agent
Organ Systems: hematology-oncology
Mechanism of Action
Binds and stabilizes polymerized microtubules, preventing depolymerization; unlike vinca alkaloids (which prevent polymerization), paclitaxel locks microtubules in the polymerized state; cells arrest in mitosis because chromosomes cannot be separated.
beta-tubulin (microtubule stabilization)
Indications
- ovarian cancer (first-line with carboplatin)
- breast cancer (adjuvant and metastatic)
- NSCLC (with carboplatin)
- Kaposi sarcoma
- pancreatic cancer (nab-paclitaxel + gemcitabine)
Contraindications
- paclitaxel hypersensitivity
- pre-existing significant peripheral neuropathy (relative)
- neutrophil count <1500/mm3
Adverse Effects
Common
- peripheral neuropathy (dose-limiting, sensory-predominant)
- myelosuppression (neutropenia)
- alopecia (complete)
- myalgia/arthralgia
Serious
- severe hypersensitivity reactions (from Cremophor EL vehicle — anaphylaxis, severe hypotension, bronchospasm)
- peripheral neuropathy (dose-limiting)
- myelosuppression
- bradycardia/heart block (during infusion)
- mucositis
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | widely distributed; large Vd; highly protein-bound; minimal CNS penetration |
| Metabolism | hepatic CYP2C8 (primarily) and CYP3A4 |
| Excretion | biliary/fecal (89%); renal (minor) |
| Half-life | 3–52 hours (dose and schedule dependent) |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | every 3 weeks or weekly |
| Protein Binding | 89–98% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| doxorubicin (when given after paclitaxel) | sequence-dependent cardiotoxicity and myelosuppression increase | major |
| CYP3A4 inhibitors (azoles, cyclosporine) | increase paclitaxel levels; greater toxicity | major |
| cisplatin | sequence matters — cisplatin before paclitaxel worsens myelosuppression | major |
Nursing Considerations
- Premedication protocol is mandatory: dexamethasone (given the evening before AND morning of), diphenhydramine, and ranitidine or famotidine — to prevent Cremophor EL vehicle-related hypersensitivity reactions.
- Use non-PVC tubing and non-DEHP containers (Cremophor EL leaches DEHP from PVC tubing — avoid standard IV tubing).
- Observe patient closely for hypersensitivity during the first 15 minutes of infusion; have epinephrine, IV diphenhydramine, and corticosteroids immediately available.
- Monitor peripheral neuropathy at each cycle; numbness and tingling in hands and feet is common — assess using standardized scales.
Clinical Pearls
- Paclitaxel's microtubule-stabilizing mechanism is the opposite of vinca alkaloids (which prevent polymerization) but achieves the same mitotic arrest; this unique mechanism means paclitaxel and vincristine can be combined without antagonism.
- Nab-paclitaxel (Abraxane) replaces Cremophor EL with albumin nanoparticles, eliminating the hypersensitivity reaction risk from the vehicle and allowing higher doses with equivalent or better efficacy.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.