Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Cytokine
Release Syndrome
Additions and/or
revisions underlined:
…
Administer
IMDELLTRA following the recommended step-up dosing and administer concomitant
medications before and after Cycle 1 Day 1 and Cycle 1 Day 8 IMDELLTRA infusions
as described in Table 3
to reduce the risk of CRS
[see Dosage
and Administration (2.3)]. Administer IMDELLTRA in an appropriate healthcare facility
equipped to monitor and manage CRS. Ensure patients are well hydrated prior to
administration of IMDELLTRA.
Closely monitor
patients for signs
and symptoms of CRS during and after treatment with IMDELLTRA. At the first sign of CRS during
treatment, immediately discontinue IMDELLTRA infusion. If CRS occurs
during or after treatment, evaluate the patient for hospitalization and manage
based on severity [see Dosage and
Administration (2.5)].
Withhold or permanently discontinue IMDELLTRA based on severity
[see Dosage and Administration (2.5)]. Counsel patients
and caregivers to seek immediate medical attention should signs or
symptoms of CRS occur after discharge.
6
Adverse Reactions
6.1 Clinical
Trials Experience
Additions and/or
revisions underlined:
…
Table 16 summarizes laboratory abnormalities in DeLLphi-300 and DeLLphi-301.
Table 16. Laboratory Abnormalities (greater than or equal to 20%) That Worsened from Baseline in Patients with ES - SCLC in DeLLphi-300 and DeLLphi-301
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or
revisions underlined:
…
What
is the most important information I should know about IMDELLTRA? IMDELLTRA can cause
serious side effects, including:
Cytokine Release Syndrome
(CRS). IMDELLTRA can cause CRS that can be severe, life-threatening, or
cause death. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS,
including:
…
Due to the risk of CRS and neurologic problems you will be monitored
as follows during IMDELLTRA treatment:
Cycle 1
Day 1 and Day 8 doses:
your healthcare provider will monitor
you for 6 to 8 hours from the start of your IMDELLTRA infusions in an appropriate healthcare setting that
can manage possible side effects.
you should remain
within 1 hour of an appropriate healthcare setting for a total of 48 hours
from
the start of your Day 1 and Day 8 IMDELLTRA infusions and be accompanied by a caregiver.
Day 2 and Day 9, your healthcare provider will check you for any signs
or symptoms, including
checking your temperature, breathing, heart rate, blood pressure, and
oxygen levels.
Day 15 dose, your healthcare provider will watch you for 6 to 8 hours after your infusion.
Cycle 2 doses, your healthcare provider
will watch you for 6 to 8 hours after your infusion.
Cycle 3 and Cycle 4 doses,
your healthcare provider
will watch you for 3 to 4 hours after your infusion.
Cycle 5 and later
doses, your healthcare provider
will watch you for 2 hours after your infusion.
If you develop
signs or symptoms of CRS or neurologic problems during treatment with IMDELLTRA,
your healthcare provider will treat you as needed, you may need to be hospitalized, and your IMDELLTRA treatment may be
temporarily or completely stopped.
…
How will I receive IMDELLTRA?
…
Your IMDELLTRA treatment schedule is divided
into cycles that are usually
28 days (4 weeks) long. In Cycle 1,
you will receive 3 doses of IMDELLTRA (Days 1, 8, and 15). After Cycle 1, you
will receive 2 doses of IMDELLTRA each cycle (Days 1 and 15).
…
The most common side effects of IMDELLTRA also include:
…
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
…
Advise patients that they should be monitored from the start of the IMDELLTRA infusion for 6 to 8
hours on Cycle 1
Day 1 and Cycle 1 Day 8 doses
in an appropriate healthcare
setting [see Warnings and Precautions
(5.1)].
Advise patients
that an assessment including vital signs check will be performed
on Cycle 1 Days 2 and 9.
…
Approved Drug Label (PDF)
Boxed Warning
Additions
and/or revisions underlined:
WARNING: CYTOKINE
RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR
CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release
syndrome (CRS), including life-threatening or fatal reactions, can occur
in patients receiving IMDELLTRA. Initiate IMDELLTRA using the step- up dosing
schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA until
CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and Warnings and Precautions
(5.1)].
Neurologic toxicity
and immune effector cell-associated neurotoxicity syndrome (ICANS), including
life-threatening or fatal reactions, can occur in patients receiving
IMDELLTRA. Monitor patients for signs and symptoms of neurologic toxicity,
including ICANS, during treatment and treat promptly. Withhold IMDELLTRA until
ICANS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and
Warnings and Precautions (5.2)].
5
Warnings and Precautions
Extensive
changes; please refer to label for complete information.
6
Adverse Reactions
6.1
Clinical Trials Experience
Additions
and/or revisions underlined:
.
. .
The
pooled safety population described in the WARNINGS AND PRECAUTIONS reflects
exposure to intravenous IMDELLTRA, as a single agent, at the recommended dosage
of IMDELLTRA 1 mg on Cycle 1 Day 1 followed by 10 mg on Days 8 and 15, and then
every 2 weeks until disease progression or intolerable toxicity in 473
patients with small cell lung cancer enrolled in three clinical trials:
DeLLphi-300, DeLLphi-301 and DeLLphi-304. Among 473 patients who
received IMDELLTRA, 40% were exposed for 6 months or longer and 19%
were exposed for greater than one year. The most common (greater than or
equal to 20%) adverse reactions were CRS (57%), fatigue (48%),
decreased appetite (38%), dysgeusia (34%), pyrexia (33%),
constipation (31%), musculoskeletal pain (31%), and nausea (25%).
The most common (greater than or equal to 5%) Grade 3 or 4 laboratory abnormalities
were decreased lymphocytes (43%), decreased sodium (12%),
decreased total neutrophils (9%), and increased uric acid (6%).
Extensive
Stage Small Cell Lung Cancer
The
safety of IMDELLTRA was evaluated in 252 patients in DeLLphi-304, a
multicenter, randomized, open label trial in patients with extensive stage
small cell lung cancer (ES- SCLC) with disease progression following treatment
with platinum-based chemotherapy with or without an anti-PD-(L)1 antibody [see Clinical Studies (14.1)]. Patients
received IMDELLTRA (n=252) or investigator’s choice or investigator’s choice of
topotecan [n=176], lurbinectedin [n=45] or amrubicin [n=23].
Among
patients who received IMDELLTRA, 41% were exposed for 6 months or longer and
18% were exposed for greater than one year.
The
demographic characteristics of patients who received IMDELLTRA were: median age
64 years (range: 20 to 86); 71% male; 60%
White, 38 % Asian, 0.8% Black or African American; and 4.8%
were of Hispanic or Latino ethnicity.
Serious
adverse reactions occurred in 52% of patients who received IMDELLTRA.
Serious adverse reactions in >3% of patients included CRS (17%),
pyrexia (6%), pneumonia (5%) and ICANS (3.6%). Fatal
adverse reactions occurred in 8% of patients who received IMDELLTRA,
including one fatal adverse reaction of ICANS (0.4%). Fatal adverse
reactions occurring in more than one patient included pneumonia (1.6%),
cardio-respiratory arrest (1.6%), and sepsis (0.8%).
Permanent
discontinuation of IMDELLTRA due to an adverse reaction occurred in 6%
of patients. Adverse reactions which resulted in permanent discontinuation of
IMDELLTRA in > 1% of patients included pneumonia (1.2%).
Dosage
interruptions of IMDELLTRA due to an adverse reaction occurred in 38% of
patients. Adverse reactions which required dosage interruption in greater than
or equal to 2% of patients included neutropenia (5%), fatigue (4.4%),
pneumonia (4%), decreased appetite (2.8%), COVID-19 (2%).
Table
13 summarizes adverse reactions observed in DeLLphi-304.
Table 13. Adverse Reactions (greater than or equal to 15%) in Patients with
SCLC Who Received IMDELLTRA in DeLLphi-304
Newly
added table; please refer to label for complete information.
Clinically
relevant adverse reactions occurring in < 15% of patients who received
IMDELLTRA were immune effector cell-associated neurotoxicity syndrome,
neurotoxicity, tremor, seizure, ataxia, confusional state, delirium, dyspnea,
encephalopathy and weight decreased.
Table
14 summarizes laboratory abnormalities in DeLLphi-304.
Table 14. Laboratory Abnormalities (greater than or equal to 20%) That
Worsened from Baseline in Patients with SCLC in DeLLphi-304
Newly
added table; please refer to label for complete information.
DeLLphi-300 and
DeLLphi-301
The
safety of IMDELLTRA, as a single agent, at the recommended dosage was evaluated
in patients with extensive stage small cell lung cancer enrolled in DeLLphi-
300 and DeLLphi-301 [see Clinical Studies
(14.1)]. Among 187 patients who received IMDELLTRA, 31% were exposed for 6
months or longer and 14% were exposed for greater than one year.
.
. .
8
Use in Specific Populations
8.5
Geriatric Use
Additions
and/or revisions underlined:
Of
the 473 patients with SCLC who received IMDELLTRA 10 mg as a single
agent, 51% were 65 years of age or older and 11% were 75 years of
age or older. No overall differences in IMDELLTRA pharmacokinetics, safety or efficacy
were observed between older patients (greater than or equal to 65 years of age) and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION
GUIDE
Additions
and/or revisions underlined:
What is the most
important information I should know about IMDELLTRA? IMDELLTRA can cause
serious side effects, including:
- Cytokine Release Syndrome (CRS). CRS is common during treatment with
IMDELLTRA and can also be severe, life-threatening, or cause death.
Tell your healthcare provider or get medical help right away if you develop any
signs or symptoms of CRS, including:
.
. .
- blood
clots or unusual
bleeding or bleeding that lasts a long time
Due to the risk of
CRS, you will receive IMDELLTRA on a “step-up dosing schedule”:
.
. .
- Before
receiving your Day 1 and Day 8 doses of Cycle 1 of IMDELLTRA, you will be given
a medicine to help reduce your risk of CRS. This will be given into your vein
by intravenous (IV) infusion. You will also receive IV fluids after each of
your Cycle 1 Day 1 and Day 8 doses. Your healthcare provider will decide
if you need to receive medicines to help reduce your risk of CRS with future
doses.
.
. .
- Neurologic Problems. IMDELLTRA can cause neurologic
problems that can be severe, life-threatening, or cause death.
Neurologic problems may happen days or weeks after you receive IMDELLTRA. Your
healthcare provider may refer you to a healthcare provider who specializes in
neurologic problems. Tell your healthcare provider right away if you develop
any signs or symptoms of neurologic problems, including:
.
. .
.
. .
- muscle weakness or numbness of arms or
legs
.
. .
.
. .
What are the possible
side effects of IMDELLTRA? IMDELLTRA can cause serious side effects,
including:
- See
“What is the most important information
I should know about IMDELLTRA?”
- Low blood cell counts (cytopenia). Decreased blood cell counts can be
severe and may include the following:
- low
white blood cell counts (neutropenia). Low white blood cells can increase your
risk for infection.
- low
red blood cell counts (anemia). Low red blood cells can cause tiredness and
shortness of breath.
- low
platelet counts (thrombocytopenia). Low platelet counts can cause bruising or
bleeding problems.
- Infections. IMDELLTRA can cause serious
infections that can be life-threatening and cause death. Your healthcare
provider will check you for signs and symptoms of infection before and during
treatment with IMDELLTRA. Tell your healthcare provider right away if you
develop any signs or symptoms of infection during treatment with IMDELLTRA, including:
.
. .
- sore
throat or runny nose
.
. .
- yeast
infections in the mouth or other areas
- Liver problems. IMDELLTRA can cause increased liver
enzymes and bilirubin in your blood. These increases can happen with or without
you also having CRS. Tell your healthcare provider right away if you
develop any signs or symptoms of liver problems, including:
- Tiredness
- dark
urine
- loss
of appetite
- yellowing
of your skin or the white part of your eyes
- pain
in your right upper stomach-area
.
. .
The most common
severe abnormal blood test results with IMDELLTRA include: decreased white blood cells,
decreased sodium, and increased uric acid.
PATIENT COUNSELING INFORMATION
Additions
and/or revisions underlined:
Advise
the patient to read the FDA-approved patient labeling (Patient Information).
Cytokine
Release Syndrome (CRS)
Inform patients and their caregivers
of the risk of CRS, and to immediately contact their healthcare provider for
signs and symptoms associated with CRS including pyrexia, hypotension, fatigue,
tachycardia, headache, hypoxia, nausea and vomiting [see Warnings and Precautions (5.1)].
Advise
patients that they should be monitored from the start of the IMDELLTRA infusion
for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 doses in an
appropriate healthcare setting [see
Warnings and Precautions (5.1)].
.
. .
Neurologic
Toxicity Including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)
Discuss
the signs and symptoms associated with ICANS with patients and their
caregivers. Advise patients to immediately contact their healthcare
provider if they experience any signs or symptoms of ICANS, such as
encephalopathy, confusion, delirium, seizure, ataxia, weakness or numbness of
arms and legs, tremor, and headache.
.
. .
Cytopenias
Discuss
the signs and symptoms associated with cytopenias, including neutropenia and
febrile neutropenia, anemia, and thrombocytopenia with patients and their
caregivers [see Warnings and
Precautions (5.3)]. Inform patients that they will need to undergo lab
tests to monitor blood counts. Advise patients to immediately contact their
healthcare provider if they experience any signs or symptoms of cytopenias.
Infections
Discuss
the signs and symptoms of infections with patients and their caregivers.
Advise patients of the risk of serious infections, and to immediately contact
their healthcare provider for signs or symptoms of infections [see Warnings and Precautions (5.4)].
Hepatotoxicity
Discuss
the signs and symptoms of hepatotoxicity and bilirubin with patients and
their caregivers. Inform patients that they will need to undergo lab tests
to monitor liver function. Advise patients to immediately contact their
healthcare provider for signs and symptoms of liver dysfunction [see Warnings and Precautions (5.5)].
Hypersensitivity
Discuss
the signs and symptoms of allergic reactions with patients and their
caregivers. Advise patients to immediately seek medical attention for any
signs and symptoms of severe reactions [see
Warnings and Precautions (5.6)].
.
. .
Get Email Alerts |
Guide
