Approved Drug Label (PDF)
8
Use in Specific Populations
8.3 Females and Males of Reproductive Potential
Additions and/or revisions underlined:
Based
on findings in animals, Docetaxel Injection can cause fetal harm when
administered to a pregnant woman [see Use
in Specific Populations (8.1)].
Pregnancy Testing
Verify pregnancy status in females of reproductive potential
prior to initiating Docetaxel Injection.
Contraception
Females
Based on genetic
toxicity findings, advise females of reproductive potential
to use effective contraception during treatment and for 2 months
after the last dose of Docetaxel Injection.
Males
Based on
genetic toxicity findings, advise male patients with female partners of
reproductive potential to use effective contraception during treatment and for 4
months after the last dose of Docetaxel Injection.
Infertility
Based on findings
in animal studies,
Docetaxel Injection may impair fertility
in males of reproductive potential [see Nonclinical Toxicology (13.1)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions
and/or revisions underlined:
…
Embryo-Fetal Toxicity
Docetaxel can cause fetal harm. Advise
patients to inform
their healthcare provider
of a known or suspected
pregnancy. Advise patients to avoid becoming pregnant while receiving this
drug. Advise female patients of reproductive potential to use effective
contraceptives during treatment and for 2 months after the last dose of
docetaxel. Advise male patients with female partners of reproductive potential
to use effective contraception during treatment and for 4 months after
the last dose of docetaxel [see Warnings
and Precautions (5.12),
and Use in Specific Populations (8.1, 8.3)].
…
PATIENT INFORMATION
Additions and/or revisions underlined:
…
Females who are able to become pregnant:
Your healthcare provider will check
to see if you are pregnant before you start treatment with Docetaxel
Injection.
You should use effective
birth control (contraception) during treatment with Docetaxel Injection and for 2 months
after the last dose.
Males with female partners who are able to become pregnant should use effective
birth control during
treatment with Docetaxel
Injection and for 4 months after the last dose.
…
What are the ingredients in Docetaxel Injection? Active ingredient: docetaxel
anhydrous USP
Inactive ingredients: anhydrous citric
acid for pH adjustment, polysorbate 80 and dehydrated alcohol solution
…
Approved Drug Label (PDF)
Boxed Warning
(Addition of the
word Injection throughout section; additions and/or revisions are underlined)
Docetaxel Injection should not be given to patients with bilirubin greater
than or equal to upper limit of normal (ULN), or to patients with AST and/or
ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. Patients
with elevations of bilirubin or abnormalities of transaminase concurrent with
alkaline phosphatase are at increased risk for the development of grade 4
neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe
stomatitis, severe skin toxicity, and toxic death. Patients with isolated
elevations of transaminase >1.5 × ULN also had a higher rate of febrile
neutropenia grade 4 but did not have an increased
incidence of toxic death. Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior
to each cycle of Docetaxel Injection therapy…
4
Contraindications
(Additions and/or
revisions underlined)
Docetaxel
Injection is contraindicated in patients with:
5
Warnings and Precautions
5.12 Embryo-Fetal Toxicity
(Newly added
subsection)
Based on findings from animal reproduction studies and its mechanism
of action, docetaxel
can cause fetal harm when administered to a pregnant
woman. Available data from case reports
in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform
the drug-associated risk of major birth defects,
miscarriage or adverse maternal or fetal outcomes.
In animal reproduction studies, administration of docetaxel
to pregnant rats and rabbits
during the period of organogenesis caused embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended
human dose based on body surface area, respectively.
Advise pregnant women and females
of reproductive potential
of the potential risk to a fetus.
Verify pregnancy status in females
of reproductive potential
prior to initiating docetaxel. Advise females of reproductive potential to use effective
contraception during
treatment and for 6 months
after the last dose of docetaxel. Advise male patients
with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of docetaxel.
5.4 Enterocolitis and Neutropenic Colitis
(Newly added
subsection)
Enterocolitis and neutropenic colitis (typhlitis) have occurred in patients treated with Docetaxel Injection alone and in combination with other chemotherapeutic agents, despite the coadministration of G-CSF.
Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis and neutropenic enterocolitis may develop
at any time, and could lead to death as early as the first day of symptom onset. Monitor patients closely
from onset of any symptoms of gastrointestinal toxicity. Inform patients to contact
their healthcare provider
with new, or worsening symptoms
of gastrointestinal toxicity.
5.5 Hypersensitivity Reactions
(Additions and/or
revisions underlined)
Patients should be observed
closely for hypersensitivity reactions, especially during the first and second
infusions. Severe hypersensitivity reactions characterized by generalized
rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported
in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate
discontinuation of the Docetaxel Injection
infusion and aggressive therapy. Patients with a history of severe hypersensitivity
reactions should not be rechallenged with Docetaxel Injection.
Patients who
have previously experienced a hypersensitivity reaction
to paclitaxel may develop a hypersensitivity reaction to docetaxel
that may include severe or fatal reactions such as anaphylaxis. Monitor
patients with a previous
history of hypersensitivity to paclitaxel closely
during initiation of docetaxel therapy. Hypersensitivity reactions may occur
within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized
skin reactions occur, interruption of therapy
is not required. All patients
should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel
Injection.
5.7 Second Primary Malignancies
(Additions and/or
revisions underlined)
Second primary malignancies, notably
acute myeloid leukemia (AML), myelodysplastic syndrome
(MDS), Non-Hodgkin’s Lymphoma (NHL), and renal cancer, have been reported
in patients treated
with docetaxel-containing regimens. These
adverse reactions
may occur several months
or years after
docetaxel-containing therapy.
Treatment-related AML or MDS has occurred in patients given anthracyclines and/or cyclophosphamide, including use in adjuvant therapy
for breast cancer. In the adjuvant
breast cancer trial (TAX316) AML occurred in 3 of 744 patients who received docetaxel, doxorubicin and cyclophosphamide (TAC) and in 1 of 736 patients
who received fluorouracil, doxorubicin and cyclophosphamide. In TAC-treated patients, the risk of delayed
myelodysplasia or myeloid leukemia requires hematological follow-up. Monitor patients for second
primary malignancies.
6
Adverse Reactions
(Additions and/or
revisions underlined)
The most serious
adverse reactions from docetaxel
are:
Hepatic Impairment
Hematologic Effects
Enterocolitis and Neutropenic
Colitis
Hypersensitivity Reactions
Second Primary Malignancies
Alcohol Content
6.1 Clinical Trials Experience
(Extensive newly
added information; please refer to label for complete information)
6.2 Postmarketing Experience
(Additions and/or
revisions underlined)
Body as a whole: diffuse pain, chest pain, radiation
recall phenomenon, injection
site recall reaction (recurrence
of skin reaction at
a site of previous extravasation following administration of docetaxel at a
different site) at the site of previous extravasation.
Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction. Ventricular arrhythmia including ventricular tachycardia has been reported in patients
treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide, and may be associated with fatal outcome.
Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, has
been reported with a potential fatal outcome. Abdominal pain, anorexia,
constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, intestinal obstruction, ileus, and dehydration as a consequence to gastrointestinal events have been reported.
Hypersensitivity: rare cases of anaphylactic shock have been reported.
Very rarely these cases resulted
in a fatal outcome
in patients who received
premedication. Hypersensitivity reactions with potential
fatal outcome have been reported with docetaxel in patients
who previously experienced hypersensitivity reactions to paclitaxel.
Metabolism and nutrition disorders: electrolyte imbalance, including cases of
hyponatremia, hypokalemia,
hypomagnesemia, and hypocalcemia
has been reported.
Second primary malignancies: second primary malignancies, including AML, MDS, NHL, and renal cancer, have been reported
in patients treated with docetaxel-containing regimens.
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and
Lactation Labeling Rule (PLLR); Additions and/or revisions underlined)
Risk Summary
Based on findings
in animal reproduction studies and its mechanism
of action, Docetaxel
Injection can cause fetal harm when administered to a pregnant
woman. Available data from case reports
in the literature and pharmacovigilance with docetaxel use
in pregnant women are not sufficient to inform
the drug-associated risk of major birth defects,
miscarriage, or adverse
maternal or fetal outcomes.
Docetaxel Injection contains
alcohol which can interfere
with neurobehavioral development. In animal
reproductive studies, administration of docetaxel
to pregnant rats and rabbits during
the period of organogenesis caused an increased incidence of embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively. Advise pregnant
women and females of reproductive potential of the
potential risk to a fetus.
The estimated
background risk of major birth defects
and miscarriage for the indicated
populations is unknown.
All pregnancies have a background risk of birth defect,
miscarriage, or other adverse
outcomes. In the U.S. general
population, the estimated
background risk of major birth defects
and miscarriage in clinically recognized
pregnancies is 2% to 4% and 15%
to 20%, respectively.
Clinical
Considerations
Docetaxel
Injection contains alcohol. Published studies
have demonstrated that alcohol is associated with fetal harm including
central nervous system abnormalities,
behavioral disorders, and impaired intellectual
development.
Data
Animal data
Intravenous administration of greater than or equal to 0.3 and 0.03 mg/kg/day docetaxel
to pregnant rats and rabbits,
respectively, during
the period of organogenesis caused an increased incidence of intrauterine mortality, resorptions, reduced
fetal weights, and fetal ossification delays. Maternal toxicity
was also observed at
these doses, which were approximately 0.02 and
0.003 times the daily maximum
recommended human dose based on body surface area, respectively.
8.2 Lactation
(Pregnancy and
Lactation Labeling Rule (PLLR); Additions and/or revisions underlined)
Risk Summary
There is no information regarding the presence
of docetaxel in human milk, or on its effects on milk production or the breastfed child. No lactation studies in animals
have been conducted. Because of the potential for serious adverse reactions
in a breastfed child, advise women not to breastfeed
during treatment with Docetaxel Injection
and for 1 week after the
last dose.
8.3 Females and Males of Reproductive Potential
(Newly added
subsection)
Pregnancy Testing
Verify pregnancy status in females
of reproductive potential
prior to initiating Docetaxel Injection.
Contraception
Females
Docetaxel
Injection can cause fetal harm when administered to a pregnant
woman. Advise females of reproductive potential to use effective contraception during treatment
and for 6 months after the last dose of Docetaxel Injection.
Males
Based on genetic toxicity
findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment
and for 3 months after the last dose of Docetaxel
Injection.
Infertility
Based on findings in animal studies, Docetaxel Injection may impair fertility
in males of reproductive
potential.
8.4 Pediatric Use
(Extensive revisions; please refer
to label for complete information)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
(Extensive revisions; please refer to label for
complete information)
PATIENT
INFORMATION
(Extensive revisions; please refer to label for complete information)
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