paclitaxel (Rx)

>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

Contraindications

Patients with solid tumors or patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of <1,500 cells/mm³

Documented hypersensitivity to drug or excipients

Cautions

All patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists; fatal reactions have occurred in patients despite premedication; patients who experience severe hypersensitivity reactions to paclitaxel should not be rechallenged with the drug

Bone marrow suppression (primarily neutropenia) is dose-dependent and is dose-limiting toxicity; should not be administered to patients with baseline neutrophil counts <1,500 cells/mm³ (<1,000 cells/mm3 for patients with KS); frequent monitoring of blood counts should be instituted during paclitaxel treatment; patients should not be re-treated with subsequent cycles of paclitaxel until neutrophils recover to a level >1,500 cells/mm³ (>1,000 cells/mm³ for patients with KS) and platelets recover to a level >100,000 cells/mm³

Severe conduction abnormalities have been documented in <1% of patients during paclitaxel therapy and in some cases requiring pacemaker placement; if patients develop significant conduction abnormalities during paclitaxel infusion, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel

Contact of the undiluted concentrate with plasticized polyvinyl chloride (PVC) equipment or devices used to prepare solutions for infusion is not recommended; in order to minimize patient exposure to the plasticizer DEHP [di-(2-ethylhexyl)phthalate], which may be leached from PVC infusion bags or sets, diluted paclitaxel solutions should preferably be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets

Paclitaxel should be administered through an in-line filter with a microporous membrane not greater than 0.22 microns; use of filter devices such as IVEX-2R filters which incorporate short inlet and outlet PVC-coated tubing has not resulted in significant leaching of DEHP

May increase the risk of cardiac dysfunction if received in conjunction with trastuzumab or anthracyclines

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.

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%)

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