extremely remote. No cases of transmission of viral diseases or CJD have
ever been identified for albumin.
5.8 Use in Pregnancy
ABRAXANE can cause fetal harm when administered to a pregnant woman.
Administration of paclitaxel formulated as albumin-bound particles to rats
during pregnancy at doses lower than the maximum recommended human
dose, based on body surface area, caused embryo-fetal toxicities, including
intrauterine mortality, increased resorptions, reduced numbers of live
fetuses, and malformations.
There are no adequate and well-controlled studies in pregnant women
receiving ABRAXANE. If this drug is used during pregnancy, or if the
patient becomes pregnant while receiving this drug, the patient should
be apprised of the potential hazard to the fetus. Women of childbearing
potential should be advised to avoid becoming pregnant while receiving
ABRAXANE [see Use in Specific Populations (8.1)].
5.9 Use in Men
Men should be advised not to father a child while receiving ABRAXANE
[see Nonclinical Toxicology (13.1)].
6 ADVERSE REACTIONS
Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared to rates in the clinical trials of another drug and may
not reflect the rates observed in practice.
The most common adverse reactions (≥ 20%) of ABRAXANE in combination
with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia,
peripheral neuropathy, nausea, and fatigue [see Adverse Reactions (6.2)].
The most common serious adverse reactions of ABRAXANE in combination
with carboplatin are anemia (4%) and pneumonia (3%). The most common
adverse reactions resulting in permanent discontinuation of ABRAXANE
are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy
(1%). The most common adverse reactions resulting in dose reduction of
ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia
(6%). The most common adverse reactions leading to withholding or
delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia
(30%), and anemia (16%).
6.2 Clinical Trials Experience in Non-Small Cell Lung Cancer
Adverse reactions were assessed in 514 ABRAXANE/carboplatin-treated
patients and 524 paclitaxel injection/carboplatin-treated patients receiving
first-line systemic treatment for locally advanced (stage IIIB) or metastatic
(IV) non-small cell lung cancer (NSCLC) in a multicenter, randomized,
open-label trial. ABRAXANE was administered as an intravenous infusion
over 30 minutes at a dose of 100 mg/m2 on Days 1, 8, and 15 of each
21-day cycle. Paclitaxel injection was administered as an intravenous
infusion over 3 hours at a dose of 200 mg/m2, following premedication.
In both treatment arms carboplatin at a dose of AUC = 6 mg•min/mL was
administered intravenously on Day 1 of each 21-day cycle after completion
of ABRAXANE/paclitaxel infusion.
The differences in paclitaxel dose and schedule between the two arms limit
direct comparison of dose- and schedule-dependent adverse reactions.
Among patients evaluable for adverse reactions, the median age was
60 years, 75% were men, 81% were White, 49% had adenocarcinoma,
43% had squamous cell lung cancer, 76% were ECOG PS 1. Patients in
both treatment arms received a median of 6 cycles of treatment.
The following common (≥ 10% incidence) adverse reactions were
observed at a similar incidence in ABRAXANE plus carboplatin-treated and
paclitaxel injection plus carboplatin-treated patients: alopecia 56%, nausea
27%, fatigue 25%, decreased appetite 17%, asthenia 16%, constipation
16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10%
(incidence rates are for the ABRAXANE plus carboplatin treatment group).
Table 7 provides the frequency and severity of laboratory-detected
abnormalities which occurred with a difference of ≥ 5% for all grades (1-4)
or ≥ 2% for Grade 3-4 toxicity between ABRAXANE plus carboplatin-treated patients or paclitaxel injection plus carboplatin-treated patients.
Table 7: Selected Hematologic Laboratory-Detected Abnormalities
With a Difference of ≥ 5% for grades (1-4) or ≥ 2% for
Grade 3-4 Toxicity Between Treatment Groups
ABRAXANE Paclitaxel Injection
Grades Grade Grades Grade
1-4 (%) 3-4 (%) 1-4 (%) 3-4 (%)
Anemia1,2 98 28 91 7
Neutropenia1,3 85 47 83 58
Thrombocytopenia1,3 68 18 55 9
1 508 patients assessed in ABRAXANE/carboplatin-treated group
2 514 patients assessed in paclitaxel injection/carboplatin-treated group
3 513 patients assessed in paclitaxel injection/carboplatin-treated group
Table 8 provides the frequency and severity of adverse reactions, which
occurred with a difference of ≥ 5% for all grades (1-4) or ≥ 2% for
Grade 3-4 between either treatment group for the 514 ABRAXANE plus
carboplatin-treated patients compared with the 524 patients who received
paclitaxel injection plus carboplatin.
Table 8: Selected Adverse Reactions with a Difference of ≥5% for
All Grade Toxicity or ≥2% for Grade 3-4 Toxicity Between Treatment Groups
ABRAXANE Paclitaxel Injection
(100 mg/m2 (200 mg/m2
weekly) every 3 weeks)
+ carboplatin + carboplatin
Grade Grade Grades Grade
System MedDRA v 12.1 1-4 3-4 1-4 3-4
Organ Preferred Toxicity Toxicity Toxicity Toxicity
Class Term (%) (%) (%) (%)
Nervous system Peripheral 48 3 64 12
Generaldisorders Edema 10 0 4 <1
and administration peripheral
Respiratory Epistaxis 7 0 2 0
Musculoskeletal Arthralgia 13 <1 25 2
tissue disorders Myalgia 10 <1 19 2
a Peripheral neuropathy is defined by the MedDRA Version 14.0 SMQ
neuropathy (broad scope).
For the ABRAXANE plus carboplatin treated group, 17/514 (3%) patients
developed Grade 3 peripheral neuropathy and no patients developed
Grade 4 peripheral neuropathy. Grade 3 neuropathy improved to Grade 1
or resolved in 10/17 patients (59%) following interruption or discontinuation
6.4 Postmarketing Experience with ABRAXANE and other Paclitaxel
Unless otherwise noted, the following discussion refers to the adverse
reactions that have been identified during post-approval use of ABRAXANE.
Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency
or establish a causal relationship to drug exposure. In some instances,
severe events observed with paclitaxel injection may be expected to occur