Dosing and uses of Taxol (paclitaxel)
Adult dosage forms and strengths
injectable solution
- 6mg/mL
Ovarian Cancer
Premedicate to prevent hypersensitivity reactions (eg, dexamethasone, diphenhydramine, H2 blockers)
Previously untreated: 175 mg/m² IV over 3 hours q3Weeks (follow with cisplatin), Or
135 mg/m² IV over 24 hours q3Weeks (follow with cisplatin)
Previously treated: Various regimens exist: 135-175 mg/m² IV over 3 hours q3Weeks
Breast Cancer
Node positive (adjuvant chemotherapy): 175 mg/m² IV over 3 hours q3Weeks 4 times (with doxorubicin-containing regimen)
Metastatic Disease (failure of initial chemotherapy or relapse within 6 months following adjuvant chemotherapy): 175 mg/m² IV over 3 hours q3Weeks
Non-small Cell Lung Cancer
135 mg/m² IV over 24 hours q3Weeks (follow with cisplatin)
AIDS-related Kaposi's Sarcoma (2nd-line Treatment)
135 mg/m² IV over 3 hours q3Weeks; Or
100 mg/m² IV over 3 hours q2Weeks
Pancreatic Cancer (Off-label)
Investigational: 125 mg/m² IV with gemcitabine
Dosage modifications
If baseline PMN <1500/m³, do not re-treat until PMN >1500/m³ and platelet count >100,000/m³
If severe neutropenia occurs (PMN <500/m³ for 7 days), reduce subsequent doses by 20%
Renal impairment: No dosage adjustment required
Hepatic Impairment
With solid carcinomas and not Kaposi sarcoma
24-hr infusion
- AST/ALT <2 x ULN and bilirubin ≤1.5 mg/dL: 135 mg/m² over 24 hr
- AST/ALT 2-<10 x ULN and bilirubin ≤1.5 mg/dL: 100 mg/m² over 24 hr
- AST/ALT <10 x ULN and bilirubin 1.6-7.5 mg/dL: 50 mg/m² over 24 hr
- AST/ALT ≥10 x ULN OR bilirubin >7.5 mg/dL: Do not administer
3-hr infusion
- AST/ALT <10 x ULN and bilirubin <1.25 x ULN: 175 mg/m² over 3 hr
- AST/ALT <10 x ULN and bilirubin 1.26-2 x ULN: 135 mg/m² over 3 hr
- AST/ALT <10 x ULN and bilirubin 2.01-5 x ULN: 90 mg/m² over 3 hr
- AST/ALT ≥10 x ULN OR bilirubin >5 x ULN: Do not administer
Orphan Designations
Pancreatic cancer
- Sponsors
- MediGene AG; Lochhamer Strasse 11, D-82152 Planegg/Martinsried, Germany
- Abraxis BioScience, LLC; 11755 Wilshire Blvd; Los Angeles, CA 90025
- Luitpold Pharmaceuticals, Inc; Clinical Research and Development, 800 Adams Avenue; Valley Forge, PA 19403
Esophageal cancer
- Sponsor: Protherics, Inc; 5214 Maryland Way, Suite 405; Brentwood, TN 37027
Adenocarcinoma of the stomach or lower esophagus
- Sponsor: Luitpold Pharmaceuticals, Inc; Clinical Research and Development, 800 Adams Avenue; Valley Forge, PA 19403
Brain cancer
- Sponsor: Protherics, Inc; 5214 Maryland Way, Suite 405; Brentwood, TN 37027
Hormone-refractory prostate cancer
- Sponsor: Luitpold Pharmaceuticals, Inc; Clinical Research and Development, 800 Adams Avenue; Valley Forge, PA 19403
Non-Small Cell Lung Cancer
- Polymer surgical mesh delivering paclitaxel
- Sponsor: AcuityBio, Inc; 200 Upland Road; Newton, MA 02460
Ovarian Cancer
- Sponsor: NanOlogy, LLC; 231 Bonetti Drive; San Luis Obispo, California 93401
Other Indications & Uses
Off-label: head/neck cancer, small-cell lung cancer, upper GI adenocarcinoma, hormone-refractory prostate cancer, NHL, urothelium transitional cell carcinoma, stage IIB-IV melanoma
Pediatric dosage forms and strengths
Safety and efficacy not established
Taxol (paclitaxel) adverse (side) effects
>10%
Neutropenia (78-100%)
Alopecia (55-96%)
Anemia (47-96%)
Arthralgia/myalgia (93%)
Diarrhea (90%)
Leukopenia (90%)
Nausea/vomiting (9-88%)
Opportunistic infections (76%)
Peripheral neuropathy (42-79%)
Thrombocytopenia (4-68%)
Mucositis (5-45%)
Hypersensitivity (2-45%)
Renal impairment (34%)
Hypotension (17%)
1-10%
Bradycardia (3%)
<1%
Grand mal seizures
Cardiac conduction abnormalities
Frequency not defined
Pyrexia
Dehydration
Pancytopenia
Congestive heart failure
Left ventricular dysfunction
Stevens-Johnson syndrome, toxic epidermal necrolysis, and extravasation
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to diagnose and manage complications
The drug is contraindicated in patients with solid tumor who have baseline neutrophil counts <1500 cells/m³ and in patients with AIDS-related Kaposi sarcoma who have baseline neutrophil counts <1000 cells/m³; perform frequent peripheral blood counts to monitor for occurrence of bone marrow suppression, primarily neutropenia, which may result in infection
Fatal anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in patients despite premedication
Pretreat all patients with corticosteroids, diphenhydramine, and H2 antagonists
Do not rechallenge patients who experience severe hypersensitivity reactions to the drug
Contraindications
Hypersensitivity to paclitaxel or castor oiL
Pregnancy
Solid tumor w/baseline PMN <1500 cells/m³
AIDS-related Kaposi's sarcoma with baseline PMN <1000 cells/m³
Cautions
Irritant
Concomitant radiation therapy
Elderly
Avoid pregnancy
May increase the risk of cardiac dysfunction if received in conjunction with trastuzumab or anthracyclines
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Taxol (paclitaxel)
Mechanism of action
Natural taxane, prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition
Pharmacokinetics
Protein bound: 89-98%
Vd: 227-688 L/m²
Metabolism: Metabolized by CYP2C8, CYP3A4
Metabolites: 6-alpha-hydroxypaclitaxel (major)
Half-life elimination: 27hr terminaL
Excretion: Feces (20%); urine (4%)
Administration
IV Incompatibilities
Additive: cisplatin (comp at low paxlitaxel conc; incomp at high paclitaxel conc)
Y-site: amphotericin B, amphotericin B cholesteryl sulfate, chlorpromazine, doxorubicin liposomal, hydroxyzine, methylprednisolone sodium succinate, mitoxantrone
IV Compatibilities
Additive: carboplatin, doxorubicin
Y-site (partial list): acyclovir, ampicillin-sulbactam, bleomycin, carboplatin, cisplatin, cytarabine, diphenhydramine, famotidine, furosemide, granisetron, heparin, linezolid, lorazepam, MgSO4, morphine SO4, ondansetron, KCl, propofol, NaHCO3, vancomycin
IV Preparation
Further dilution in NS or D5W to a concentration of 0.3-1.2 mg/mL
Standard dilution (IVPB): dose/500-1000 mL D5W or Ns
IV Administration
Irritant
Mfr recommends administration over 1-24 hr
Administer taxane derivatives before platinum derivatives (cisplatin, carboplatin) in sequential infusions to limit myelosuppression and to enhance efficacy
Administer corticosteroids, H1-antagonists, H2 antagonists, prior to paclitaxel administration to minimize potential for anaphylaxis
Non-PVC tubing should be used to minimize leaching
Contact of undiluted concentrate with plasticized PVC equipment or devices is not recommended
Administer through IV tubing containing an in-line (0.22 micron) filter
Should be dispensed in either glass or Excel/PAB
