Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Embryo-Fetal Toxicity
(Additions and/or revisions
underlined)
Based on animal data
and its mechanism of action ZEPZELCA can cause fetal harm when administered to
a pregnant woman. Intravenous administration of a single dose of lurbinectedin
(approximately 0.2 times the 3.2 mg/m^2 clinical dose) to pregnant
animals during the period of organogenesis caused 100% embryolethality in rats. Advise
pregnant women of the potential risk to a fetus. Advise female patients of reproductive
potential to use effective contraception during treatment with ZEPZELCA and for
6 months after the last dose. Advise male patients with female partners
of reproductive potential to use effective contraception during treatment with
ZEPZELCA and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)].
6
Adverse Reactions
(Additions and/or revisions
underlined)
The following clinically significant adverse reactions
are described elsewhere in the labeling:
7
Drug Interactions
7.1 Effect of Other Drugs on ZEPZELCA
Strong and Moderate CYP3A
Inhibitors
(Additions and/or revisions
underlined)
Coadministration of
ZEPZELCA with a strong or a moderate CYP3A inhibitor increases
lurbinectedin systemic exposure
[see Clinical Pharmacology (12.3)], which may increase the incidence and severity of adverse
reactions to ZEPZELCA.
Avoid grapefruit and Seville oranges
during ZEPZELCA treatment, as these contain
strong or moderate inhibitors
of CYP3A.
Strong CYP3A
Inhibitors
Avoid coadministration of ZEPZELCA with strong CYP3A
inhibitors. If coadministration cannot be avoided, reduce the dose of ZEPZELCA
[see Dosage and Administration (2.3)].
Moderate CYP3A Inhibitors
Avoid coadministration of ZEPZELCA with moderate CYP3A inhibitors. If coadministration
cannot be avoided, consider dose reduction of ZEPZELCA if clinically indicated [see Dosage and Administration (2.2)].
Strong CYP3A Inducers
Avoid coadministration
of ZEPZELCA with strong CYP3A inducers. Coadministration of ZEPZELCA with a strong CYP3A inducer
may decrease lurbinectedin systemic exposure, which may decrease the efficacy of
ZEPZELCA [see Clinical Pharmacology (12.3)].
8
Use in Specific Populations
8.2 Lactation
Risk Summary
(Additions and/or revisions
underlined)
There are no data on the presence
of lurbinectedin in human milk or its effects on the breastfed child or on milk production.
Because of the potential for serious adverse reactions from
ZEPZELCA in breastfed
children, advise women not to breastfeed during treatment with ZEPZELCA and for
2 weeks after the last dose.
8.3 Females and Males of Reproductive Potential
(Additions and/or revisions
underlined)
ZEPZELCA can cause embryolethality at doses lower than the human dose of 3.2 mg/m2
[see Use in Specific Populations (8.1)]. Pregnancy Testing
Verify the pregnancy status of females
of reproductive potential
prior to initiating ZEPZELCA. Contraception
Females
Advise female patients of reproductive potential
to use effective contraception during treatment
with ZEPZELCA and for 6 months after the last dose.
Males
Advise males with a
female sexual partner of reproductive potential to use effective contraception during
treatment with ZEPZELCA
and for 4 months after the last dose.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions
underlined)
Advise the patient to read the FDA-approved patient
labeling (Patient Information). Myelosuppression
Advise patients to
immediately contact their healthcare provider for fever, other signs of
infection, unusual bruising,
bleeding, tiredness or pallor [see
Warnings and Precautions (5.1)].
Hepatotoxicity
Advise patients
to contact their healthcare provider
immediately for signs and symptoms suggestive of hepatotoxicity [see
Warnings and Precautions (5.2)].
Extravasation Resulting in Tissue Necrosis
Advise patients to
contact their healthcare provider immediately for signs and symptoms of
extravasation. The time to onset
of necrosis after extravasation may vary [see
Warnings
and Precautions (5.3)].
Rhabdomyolysis
Advise patients
to contact their healthcare provider
immediately for signs and symptoms
of rhabdomyolysis [see Warnings and
Precautions (5.4)].
Embryo-Fetal Toxicity
· Advise pregnant women
and females of reproductive potential of the potential risk to a fetus. Advise
females to inform their healthcare provider of a known or suspected pregnancy [see
Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].
· Advise females
of reproductive potential
to use effective contraception during treatment
with ZEPZELCA and for 6 months after the last dose [see Use in Specific Populations (8.3)].
· Advise males with
female partners of reproductive potential to use effective contraception during
treatment with ZEPZELCA
and for 4 months after the last dose [see Use in Specific Populations (8.3)].
Lactation
Advise women
not to breastfeed during treatment with ZEPZELCA and for at least 2 weeks after the last dose [see Use in Specific Populations (8.2)].
Drug Interactions
Advise patients
to inform their
healthcare providers of all concomitant medications, herbal and dietary supplements. Advise patients
to avoid grapefruit products and Seville oranges during treatment with
ZEPZELCA [see Drug Interactions (7.1)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Extravasation Resulting in Tissue Necrosis
New subsection
added
Extravasation
of ZEPZELCA resulting in skin and soft tissue injury, including necrosis
requiring debridement, can occur. Consider use of a central venous catheter to
reduce the risk of extravasation, particularly in patients with limited venous
access. Monitor patients for signs and symptoms of extravasation during the
ZEPZELCA infusion. If extravasation occurs, immediately discontinue the
infusion, remove the infusion catheter, and monitor for signs and symptoms of
tissue necrosis. The time to onset of necrosis after extravasation may vary.
Administer
supportive care and consult with an appropriate medical specialist as needed
for signs and symptoms of extravasation. Administer subsequent infusions at a
site that was not affected by extravasation.
5.4 Rhabdomyolysis
New
subsection added
Rhabdomyolysis
has been reported in patients treated with ZEPZELCA. Monitor creatine
phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during
treatment as clinically indicated. Withhold or reduce the dose based on
severity [see Dosage and Administration
(2.2)].
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
Extravasation
Resulting in Tissue Necrosis [see Warnings and
Precautions (5.3)]
Rhabdomyolysis
[see Warnings and Precautions (5.4)]
6.2 Postmarketing
Experience
New
subsection added
The
following adverse reactions have been identified during post-approval use of
ZEPZELCA. 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.
General disorders
and administration site conditions: Extravasation including tissue necrosis
requiring debridement.
Musculoskeletal
and Connective Tissue Disorders: Rhabdomyolysis.
Metabolism and
nutrition disorders:
Tumor lysis syndrome.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
underlined…
Extravasation
Resulting in Tissue Necrosis
Advise
patients to contact their healthcare provider immediately for signs and
symptoms of extravasation. The time to onset of necrosis after extravasation
may vary [see Warnings and Precautions (5.3)].
Rhabdomyolysis
Advise
patients to contact their healthcare provider immediately for signs and
symptoms of rhabdomyolysis [see Warnings and
Precautions (5.4)].
…
PATIENT
INFORMATION
Additions underlined
…
What
are the possible side effects of ZEPZELCA?
…
Leakage of ZEPZELCA out of your vein during the
infusion. If ZEPZELCA leaks into the tissues around your
infusion site, it can cause damage and death of tissue cells around the
infusion site. You may need to have surgery to remove any dead tissue. Tell
your healthcare provider right away if you see any ZEPZELCA leaking out of your
vein or around the catheter during your infusion, or if you notice any redness,
swelling, itching or discomfort at the infusion site at any time.
Severe muscle problems (rhabdomyolysis). Tell your healthcare provider if you have severe muscle pain or weakness.
…
Get Email Alerts |
Guide
