Approved Drug Label (PDF)
4
Contraindications
Additions and/or
revisions underlined:
Lumason is contraindicated in patients with known or suspected:
5
Warnings and Precautions
5.2 Hypersensitivity Reactions
Additions and/or revisions underlined:
In postmarketing use, serious hypersensitivity
reactions were observed during or shortly following sulfur
hexafluoride lipid-containing microsphere administration including:
Anaphylaxis, with manifestations that may include death, shock,
bronchospasm, dyspnea, throat tightness, angioedema, edema (pharyngeal,
palatal, mouth, peripheral, localized), swelling (face, eye, lip, tongue, upper
airway), facial hypoesthesia, rash,
urticaria, pruritus, flushing, and erythema.
These reactions may occur in patients with no history of prior
exposure to sulfur hexafluoride lipid-containing microspheres. Lumason
contains PEG. There may be increased risk of serious reactions including death
in patients with prior hypersensitivity reaction(s) to PEG [see Adverse Reactions (6.2)]. Clinically assess patients for prior
hypersensitivity reactions to products containing PEG, such as certain
colonoscopy bowel preparations and laxatives. Always have cardiopulmonary
resuscitation personnel and equipment readily available prior to Lumason
administration and monitor all patients
for hypersensitivity reactions.
6
Adverse Reactions
6.2 Postmarketing Experience
Additions and/or revisions underlined:
… Other serious reactions included arrhythmias and hypertensive
episodes. These reactions typically occurred within 30 minutes of Lumason
administration. These serious reactions may be increased among patients with
pre-existing PEG hypersensitivity and/or unstable cardiopulmonary conditions
(acute myocardial infarction, acute coronary artery syndromes, worsening or
unstable congestive heart failure, or serious ventricular arrhythmias) [see Warnings and Precautions (5.1, 5.2)].
Hypersensitivity
Anaphylaxis, with manifestations that may include death, shock,
bronchospasm, dyspnea, throat tightness, angioedema, edema (pharyngeal,
palatal, mouth, peripheral, localized), swelling (face, eye, lip, tongue, upper
airway), facial hypoesthesia, rash, urticaria, pruritus, flushing, and
erythema.
Approved Drug Label (PDF)
5
Warnings and Precautions
Hypersensitivity Reactions
Change in subsection title, from “Anaphylactoid Reactions” to “Hypersensitivity
Reactions”
Additions and/or
revisions underlined:
Hypersensitivity reactions
such as skin erythema, rash, urticaria, flushing,
throat tightness, dyspnea, or anaphylactic shock have uncommonly been observed following the injection of Lumason. These reactions may occur
in patients with no history
of prior exposure to
sulfur hexafluoride lipid containing microspheres.
Always have cardiopulmonary resuscitation
personnel and equipment
readily available prior to Lumason administration and
monitor all patients for hypersensitivity reactions.
Serious Cardiopulmonary Reactions
Change in subsection title, from “Cardiopulmonary Reactions” to “Serious
Cardiopulmonary Reactions”
Systemic Embolization
Additions and/or
revisions underlined:
When administering Lumason to patients
with cardiac shunt, microspheres can bypass
filtering by the
lung and enter
the arterial circulation.
Assess patients
with shunts for embolic
phenomena following Lumason
administration. Lumason
is only for
intravenous and/or intravesical administration; do not administer Lumason by intra-arterial injection.
Ventricular Arrhythmia Related to High Mechanical Index
Change in subsection title, from “High Mechanical Index” to “Ventricular Arrhythmia Related to High Mechanical Index”
Additions and/or
revisions underlined:
High ultrasound mechanical index values
may
cause microsphere cavitation or rupture
and lead to ventricular arrhythmias. Additionally,
end-systolic triggering with high mechanical indices has been reported
to cause ventricular arrhythmias.
Lumason is
not recommended for use at mechanical indices greater than 0.8.
6
Adverse Reactions
Clinical Trials Experience
Additions and/or
revisions underlined:
Adults
In completed
clinical trials, a total of
6984 adult subjects
(128 healthy volunteers
and
6856 patients)
received Lumason at cumulative doses ranging
from 0.2 to 161 mL (mean 9.8 mL). Lumason
was administered mainly as
single or multiple injections; however, some
subjects received infusion dosing. The
majority (75%) of subjects received Lumason at cumulative doses of 10 mL or
less. There were 64% men and 36% women, with an average age of
59 years
(range 17 to 99 years).
A total of
79% subjects were White;
4% were Black; 16% were Asian; <1% were Hispanic;
and
<1% were in other racial
groups or race was not reported.
In the clinical
trials, serious adverse reactions were observed in 2 subjects;
one who experienced
a hypersensitivity-type rash and presyncope and another who experienced anaphylactic
shock shortly following Lumason administration.
Changes to Table 1, please see label for complete
information.
In completed clinical trials for echocardiography, a total
of 12 pediatric patients received
Lumason at a dose
of 0.03 mL/kg. No adverse
reactions were identified in pediatric patients.
8
Use in Specific Populations
Animal Data
Newly added subsection
Lumason was administered intravenously to rats at
doses of 0.2, 1, and 5 mL/kg (approximately 0.4,
2, and 10 times the recommended
maximum human dose of 4.8 mL, respectively, based on body surface
area); Lumason doses were administered daily for about 30 consecutive days,
from two weeks before pairing until the end of organogenesis. Lumason was
administered intravenously to rabbits
at doses of
0.2, 1, and 5 mL/kg (approximately 0.8,
4, and 20 times the recommended
maximum human dose, respectively, based on
body surface area); Lumason
doses were administered
daily from gestation
day 6 to day 19 inclusive.
No significant findings
on the fetus were observed.
Lactation
Newly added subsection
Risk Summary
There are no
data on the presence
of Lumason in human
milk, the effects on the breastfed infant,
or the effects on milk production. The developmental and health
benefits of breastfeeding
should be considered along with the
mother’s clinical need for
Lumason and any potential
adverse effects on the breastfed
infant from Lumason or from the underlying maternal condition.
Pediatric Use
Newly added
information
Echocardiography
Safety and effectiveness
have been established for use in pediatric
patients with suboptimal echocardiograms to opacify
the left ventricular
chamber and to
improve delineation of the left endocardial
border. Safety and
effectiveness in pediatric patients
are
based on adequate and well-controlled studies
in adults and are supported
by a clinical study in 12 pediatric
patients (mean age: 13.8 years) with extrapolation of
efficacy to younger pediatric patients. No new adverse reactions
were reported in the pediatric study. Safety of intravenous use of
Lumason was based on
evaluation of published
literature involving the use of
Lumason in over
1400 pediatric patients (0 to 17 years).
Ultrasonography of the Liver
Safety and effectiveness
in
pediatric patients
has been established for use in ultrasonography of the
liver for characterization of
focal liver lesions from adequate and well
controlled trials in adult
patients and a clinical
study of 44 pediatric patients. Safety of
intravenous use of
Lumason was based on evaluation of published literature involving
use of Lumason in over 1400
pediatric patients. Non-fatal anaphylaxis was reported
in one pediatric patient.
Ultrasonography of the Urinary Tract
Safety and effectiveness
in
pediatric patients
has been established for use in ultrasonography of the urinary tract
for the evaluation of suspected
or known vesicoureteral
reflux from two published studies
comprising a total of 411
pediatric patients.
Safety of
intravesical use of Lumason was
based on evaluation
of published literature involving use of Lumason in
over 6000 pediatric patients. No adverse
reactions were reported.
Pregnancy
Risk Summary
There are no data with Lumason use in
pregnant women to inform
any drug-associated risks. No adverse developmental
outcomes were observed
in animal reproduction studies with administration of sulfur
hexafluoride lipid-type A microspheres in pregnant rats and rabbits during
organogenesis at doses up to at
least 10 and 20 times, respectively,
the maximum human dose of 4.8 mL
based on body surface area.
In the U.S.
general population, the estimated background risk
of major
birth defects and miscarriage in clinically
recognized pregnancies is 2-4% and
15-20%, respectively.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
Advise patients to inform their healthcare provider if they develop any symptoms of hypersensitivity after
LUMASON administration including
rash, wheezing, or shortness of breath.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Cardiopulmonary Reactions
(Revised subsection title)
5.2 Hypersensitivity Reactions
(Additions and/or revisions are underlined)
Always have cardiopulmonary resuscitation personnel and equipment
readily available prior to Lumason administration and monitor all patients for
hypersensitivity reactions.
5.3 Systemic Embolization
(Additions and/or revisions are underlined)
When administering Lumason to patients with cardiac shunt,
microspheres can bypass filtering by the lung and enter the arterial
circulation. Assess patients with shunts for embolic phenomena following
Lumason administration. Lumason is only for intravenous and/or
intravesical administration;
do not administer Lumason by intra-arterial injection.
5.4 Ventricular Arrhythmia Related to High Mechanical Index
(Subsection title revised; Addition
and/or revisions are underlined)
Lumason is not recommended for use at mechanical indices greater
than 0.8.
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions
and/or revisions are underlined)
Risk Summary
There are no data with Lumason use in pregnant women to
inform any drug- associated risks. No adverse developmental outcomes were
observed in animal reproduction studies with administration of sulfur
hexafluoride lipid-type A microspheres in pregnant rats and rabbits during
organogenesis at doses up to at least 10 and 20 times,
respectively, the maximum human dose of 4.8 mL based on body
surface area.
In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
Lumason was administered
intravenously to rats at doses of 0.2, 1, and 5 mL/kg (approximately 0.4, 2,
and 10 times the recommended maximum human dose of 4.8 mL, respectively, based
on body surface area); Lumason doses were administered daily for about 30
consecutive days, from two weeks before pairing until the end of organogenesis.
Lumason was administered intravenously to rabbits at doses of 0.2, 1, and 5
mL/kg (approximately 0.8, 4, and 20 times the recommended maximum human dose,
respectively, based on body surface area); Lumason doses were administered
daily from gestation day 6 to day 19 inclusive. No significant findings on
the fetus were observed.
8.2 Lactation
(Pregnancy and Lactation
Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)
Risk Summary
There are no data on the
presence of Lumason in human milk, the effects on the breastfed infant, or the
effects on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for
Lumason and any potential adverse effects on the breastfed infant from Lumason
or from the underlying maternal condition.
8.4 Pediatric Use
(Additions and/or revisions are
underlined)
Ultrasonography of the Liver
Safety of intravenous use of
Lumason was based on…
Ultrasonography of the Urinary
Tract
Effectiveness in pediatric
patients has been established for use in ultrasonography of the urinary tract
for the evaluation of suspected or known vesicoureteral reflux from two
published studies comprising a total of 411 pediatric patients. Safety
of intravesical use of Lumason was based on evaluation of published literature
involving use of Lumason in over 6000 pediatric patients. No adverse
reactions were reported.
Echocardiography
Safety
and effectiveness in pediatric
patients…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Advise patients to inform their
healthcare provider if they develop any symptoms of hypersensitivity after
LUMASON administration including rash, wheezing, or shortness of breath.
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