Approved Drug Label (PDF)
5
Warnings and Precautions
5.7
Embryo-Fetal Toxicity
Additions
and/or revisions underlined:
Based
on its mechanism of action, YONDELIS can cause fetal harm when administered to
a pregnant woman. Advise females of reproductive potential to use effective
contraception during therapy and for at least 8 months after the last
dose of YONDELIS. Advise males with female partners of reproductive potential
to use effective contraception during therapy and for at least 5 months after
the last dose of YONDELIS [see Use in
Specific Populations (8.1, 8.3)].
8
Use in Specific Populations
8.2
Lactation
Additions
and/or revisions underlined:
Risk
Summary
There
are no data on the presence of trabectedin in human milk, the effects on the
breastfed child, or the effects on milk production. Because of the
potential for serious adverse reactions from YONDELIS in a breastfed child,
advise a nursing woman to discontinue nursing during treatment with and for
3 months after the last dose of YONDELIS.
8.3
Females and Males of Reproductive Potential
Additions
and/or revisions underlined:
.
. .
Contraception
Females
Advise
female patients of reproductive potential to use effective contraception during
and for 8 months after the last dose of YONDELIS [see Use in Specific Populations (8.1)].
Males
YONDELIS
may damage spermatozoa, resulting in possible genetic and fetal abnormalities.
Advise males with a female sexual partner of reproductive potential to use
effective contraception during and for 5 months after the last dose of YONDELIS
[see Nonclinical Toxicology (13.1)].
.
. .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT
COUNSELING INFORMATION
Additions
and/or revisions underlined:
.
. .
Rhabdomyolysis: Advise patients to contact their
healthcare provider if they experience severe muscle pain or weakness, or if
they experience reddish-brown urine [see
Warnings and Precautions (5.2)].
.
. .
Cardiomyopathy: Advise patients to contact their
healthcare provider immediately for new onset chest pain, shortness of
breath, fatigue, lower extremity edema, or heart palpitations [see Warnings and Precautions (5.4)].
.
. .
Females
and males of reproductive potential:
Advise females of reproductive potential to use effective contraception during
treatment with YONDELIS and for at least 8 months after last dose.
Advise males with female partners of reproductive potential to use effective
contraception during treatment with YONDELIS and for at least 5 months after
the last dose [see Warnings and
Precautions (5.7) and Use in Specific Populations (8.3)].
Lactation: Advise females not to breastfeed
during treatment with and for 3 months after the last dose of YONDELIS [see Use in Specific Populations (8.2)].
PATIENT
INFORMATION
Extensive changes; please refer to label
for complete information.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Neutropenic Sepsis
(Additions
and/or revisions are underlined)
…
Assess neutrophil count prior to administration of each dose of YONDELIS
and periodically throughout the treatment cycle. Withhold or reduce dose of YONDELIS
based on severity of adverse reaction.
5.2 Rhabdomyolysis
(Additions
and/or revisions are underlined)
…
Assess CPK levels
prior to each administration of YONDELIS. Withhold,
reduce dose, or permanently discontinue based
on severity of adverse reaction.
5.4 Cardiomyopathy
(Additions
and/or revisions are underlined)
Cardiomyopathy including cardiac failure, congestive heart failure, ejection fraction decreased, diastolic dysfunction, or right ventricular dysfunction can occur with
YONDELIS. In Trial ET743-SAR-3007, a significant decrease in LVEF was defined as an absolute
decrease of greater than or equal to 15% or below the lower limit of normal with an absolute decrease
of greater than or equal to 5%. Patients with a history of New York Heart Association Class
II to IV heart failure or abnormal
left ventricular ejection fraction (LVEF) at baseline
were ineligible. In Trial ET743-SAR-3007, cardiomyopathy occurred in 23 patients (6%) receiving
YONDELIS and in four patients (2.3%) receiving dacarbazine. Grade
3 or
4 cardiomyopathy occurred
in 15 patients (4%) receiving YONDELIS and 2 patients (1.2%) receiving dacarbazine; cardiomyopathy leading to death
occurred in 1 patient (0.3%) receiving YONDELIS and in none of the patients
receiving dacarbazine. The median time to development of Grade 3 or 4 cardiomyopathy in patients
receiving YONDELIS was
5.3 months
(range: 26 days to 15.3 months).
Patients with LVEF <
lower limit of normal, prior cumulative anthracycline dose of ?300 mg/m2, age ?65 years, or a history
of cardiovascular disease
may be at increased risk of cardiac dysfunction. Assess LVEF by echocardiogram (ECHO) or multigated acquisition (MUGA) scan before
initiation of YONDELIS
and at 2- to 3-month intervals thereafter until YONDELIS is discontinued. Discontinue treatment with YONDELIS based on severity of adverse reaction.
Approved Drug Label (PDF)
8
Use in Specific Populations
8.3 Females and Males of Reproductive Potential
(addition
underlined)
Pregnancy Testing
Verify the pregnancy status of females of
reproductive potential prior to initiating YONDELIS
…
8.4 Pediatric Use
(additions
underlined)
Safety and effectiveness in pediatric patients have not
been established.
Safety (n=61) and efficacy (n=58) were
assessed across five open-label studies (NCT00006463, NCT01453283, NCT00005625,
NCT00070109, and ET-B-023-00) in pediatric patients (aged 2 to <17 years)
with pediatric histotypes of sarcoma (predominantly rhabdomyosarcoma,
osteosarcoma, Ewing sarcoma, and non-rhabdomyosarcoma soft tissue sarcoma). No
new safety signals were observed in pediatric patients across these studies.
Pharmacokinetic parameters in 17 pediatric
patients (aged 3 to 17 years) were within the range of values previously
observed in adults given the same dose per body surface area.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Capillary Leak Syndrome
(Newly added subsection)
Capillary leak syndrome (CLS)
characterized by hypotension, edema, and hypoalbuminemia has been reported with
YONDELIS, including serious CLS resulting in death. Monitor for signs and symptoms
of CLS. Discontinue YONDELIS and promptly
initiate standard management for patients with CLS, which may include a need for
intensive care.
6
Adverse Reactions
(Additions and/or revisions
are underlined)
The following adverse reactions
are discussed in more detail in other sections of the labeling:
• Capillary Leak Syndrome
6.2 Postmarketing Experience
(Newly added subsection)
The following adverse reactions
have been identified during post-approval use of YONDELIS. 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.
Vascular disorders: capillary
leak syndrome .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions
are underlined)
Advise the patient to read
the FDA-approved patient labeling (Patient Information).
Capillary leak syndrome: Advise
patients to report symptoms such as edema with or without hypotension.
PATIENT INFORMATION YONDELIS® (yon-DEL-ess) (trabectedin) for injection
(Additions and/or revisions are underlined)
What are the
possible side effects of YONDELIS?
• Heart muscle problems, including heart failure. Your healthcare provider will do a test to check your heart function
before you start YONDELIS, and during treatment. If you develop heart muscle problems
or heart failure during treatment with YONDELIS, your healthcare provider
may stop your treatment.
• Capillary leak syndrome. YONDELIS can cause fluid to
leak from the blood vessels into the body’s tissues. This condition is called “Capillary
Leak Syndrome” (CLS). CLS can cause you to have symptoms that may lead to death.
Tell your healthcare provider right away if you develop swelling, dizziness or lightheadedness
with or without a sudden drop in blood pressure.
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