Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of ABRAXANE has not been studied.

Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.

Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis (approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1 to 5% of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS).

Pregnancy

Teratogenic Effects

Pregnancy Category D
(See WARNINGS section).

Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Following intravenous administration of carbon-14 labeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than in plasma and declined in parallel with the plasma concentrations. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued when receiving ABRAXANE® therapy.

Pediatric Use
The safety and effectiveness of ABRAXANE in pediatric patients have not been eva luated.

Geriatric use
Of the 229 patients in the randomized study who received ABRAXANE, 11% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among elderly patients who received ABRAXANE.

Ability to Drive and Use Machines
Adverse events such as fatigue, lethargy, and malaise may affect the ability to drive and use machines.

Information for Patients
(See Patient Information Leaflet).

ADVERSE REACTIONS
The following table shows the frequency of important adverse events in the randomized comparative trial for the patients who received either single-agent ABRAXANE® or paclitaxel injection for the treatment of metastatic breast cancer.

Table 3: Frequency* of Important Treatment Emergent Adverse Events in the Randomized Study on an Every-3-Weeks Schedule  Percent of Patients
 ABRAXANE®
260/30min†
(n=229) Paclitaxel Injection
175/3h‡,§
(n=225)
*
Based on worst grade.
†
ABRAXANE dose in mg/m2/duration in minutes.
‡
paclitaxel injection dose in mg/m2/duration in hours.
§
paclitaxel injection pts received premedication.
¶
Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea, chest pain, hypotension) that began on a day of dosing.
#
Severe events are defined as at least