Approved Drug Label (PDF)
5
Warnings and Precautions
5.8 Thyroid
Dysfunction in Pediatric Patients 0 to 3 Years of Age
Additions
and/or revisions underlined:
Thyroid dysfunction characterized by hypothyroidism
or transient thyroid suppression has been reported after both single exposure
and multiple exposures to iodinated contrast media (ICM) in pediatric
patients 0 to 3 years of age.
Younger age, very low birth weight, prematurity, underlying
medical conditions affecting thyroid function, admission to neonatal
or pediatric intensive care units, and congenital cardiac conditions are
associated with an increased risk of hypothyroidism after ICM exposure.
Pediatric patients with congenital cardiac conditions may be at the
greatest risk given that they often require high doses of contrast during
invasive cardiac procedures.
An underactive thyroid during early life may be
harmful for cognitive and neurological development and may require thyroid
hormone replacement therapy. After exposure to ICM, individualize
thyroid function monitoring based on underlying risk factors, especially
in term and preterm neonates.
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
…
After
exposure to iodinated contrast media, individualize thyroid function monitoring in pediatric
patients 0 to 3 years of age based on underlying risk factors, especially
in term and preterm neonates [see
Warnings and Precautions (5.8) and Adverse
Reactions (6.2)].
…
Approved Drug Label (PDF)
5
Warnings and Precautions
Newly
added subsection:
5.8
Thyroid Dysfunction in Pediatric Patients 0 to 3 Years of Age
Thyroid
dysfunction characterized by hypothyroidism or transient thyroid suppression
has been reported after both single exposure and multiple exposures to
iodinated contrast media. Among patients 0 to 3 years of age exposed to
iodinated contrast media, thyroid dysfunction has been reported in 1% to 15%
depending on the age of the patient and the dose of the iodinated contrast
agent.
Younger
age, very low birth weight, prematurity, and the presence of other conditions,
such as, admission to neonatal or pediatric intensive care units, and cardiac
conditions are associated with an increased risk. Pediatric patients with
cardiac conditions may be at the greatest risk given that they often require
high doses of contrast during invasive cardiac procedures, such as
catheterization and computed tomography (CT).
Pediatric
patients 0 to 3 years of age warrant closer monitoring because an underactive
thyroid during early life may be harmful for motor, hearing, and cognitive
development and may require transient T4 replacement therapy. Evaluate thyroid
function in all pediatric patients 0 to 3 years of age within 3 weeks following
exposure to iodinated contrast media, especially in term and preterm neonates.
If thyroid dysfunction is detected, treat and monitor thyroid function as
clinically needed.
6
Adverse Reactions
Newly
added to bulleted line listing:
Additions and/or revisions underlined:
6.2 Post-marketing Experience
Additions
and/or revisions underlined:
Endocrine
Disorders: Hyperthyroidism,
hypothyroidism
8
Use in Specific Populations
8.4 Pediatric Use
Additions
and/or revisions underlined:
… Thyroid function tests indicative of thyroid
dysfunction, characterized by hypothyroidism or transient thyroid
suppression have been reported following iodinated contrast media
administration in pediatric patients, including term and preterm neonates.
Some patients were treated for hypothyroidism. Monitor pediatric patients 0
to 3 years of age closely, particularly those with one or more potential risk
factors, for thyroid dysfunction [see Warnings and Precautions (5.8)
and Adverse Reactions (6.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Newly added information:
Thyroid Dysfunction
Advise parents/caregivers about the risk of
developing thyroid dysfunction after VISIPAQUE administration. Advise
parents/caregivers about when to seek medical care for their child to monitor
for thyroid dysfunction [see Warnings and Precautions (5.8)].
Approved Drug Label (PDF)
5
Warnings and Precautions
5.10 Severe Cutaneous Adverse Reactions
(new subsection added)
Severe cutaneous adverse reactions (SCAR) may
develop from 1 hour to several weeks after intravascular contrast agent
administration. These reactions include Stevens-Johnson syndrome and toxic
epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis
(AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).
Reaction severity may increase and time to onset may decrease with repeat
administration of contrast agents;
prophylactic medications may not prevent or mitigate
severe cutaneous adverse reactions. Avoid administering
VISIPAQUE to patients with a history of a severe
cutaneous adverse reaction to VISIPAQUE.
6
Adverse Reactions
6.2 Post-marketing Experience
(additions underlined)
The following additional adverse reactions have been
identified during post approval use of VISIPAQUE. 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 exposure
Cardiovascular
Disorders: Cardiac arrest,
palpitations, spasms of coronary arteries, hypertension, and flushing.
Endocrine
Disorders: Thyroid
function tests indicative of hypothyroidism or transient thyroid suppression
have been uncommonly reported following iodinated contrast media administration
to adult and pediatric patients, including infants. Some patients were treated
for hypothyroidism. Hypoglycemia, hyperthyroidism.
Eye Disorders:
Transient visual impairment
including cortical blindness, diplopia, and blurred vision.
Gastrointestinal
Disorders: Abdominal pain,
pancreatitis, salivary gland enlargement.
General
Disorders and Administration Site Conditions:
Chills, pyrexia,
pain and discomfort, administration site reactions including extravasation.
Immune System
Disorders: Hypersensitivity
reactions, anaphylactic shock including, life-threatening or fatal anaphylaxis.
Nervous System
Disorders: Tremor (transient), coma, disturbance in
consciousness, transient contrast-induced encephalopathy caused by
extravasation of contrast media (including amnesia, hallucination, paralysis,
paresis, transient speech disorder, aphasia, dysarthria).
Psychiatric Disorders: Anxiety, agitation.
Respiratory,
Thoracic, and Mediastinal Disorders: Cough, sneezing, throat irritation or tightness,
laryngeal edema, pharyngeal edema, bronchospasm.
Skin and
subcutaneous tissue disorders: Reactions range from mild (e.g. rash,
erythema, pruritus, urticaria, and skin discoloration)to severe: [e.g. Stevens-Johnson syndrome and toxic
epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis
(AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)].
6.3 Pediatric Adverse Reactions
(subsection added)
The overall character, quality, and severity of
adverse reactions in pediatric patients is similar to that reported in adult
patients from post marketing surveillance and other information.
Additional safety data was obtained in studies of
VISIPAQUE in 459 pediatric patients. A total of 26 patients ranged in age from
birth to <29 days, 148 ranged from 29 days to 2 years, 263 from 2 to <12
years, and 22 from 12 to 18 years. A total of 252 (55%) of the patients were
male. The racial distribution was: Caucasian-81%, Black-14%, Oriental-2%, and
other or unknown-4%. The proportion of patients undergoing an intra-arterial
procedure by age was: 92 % (<29 days), 55% (29 days – 6 months), and 29 %
(>6 months). In these studies, adverse events were numerically higher in
pediatric patients less than one year of age compared to older pediatric
patients.
In pediatric patients who received intravenous
injections of VISIPAQUE for computerized tomography or excretory urography, a
concentration of 270 mg Iodine/mL was used in 144 patients, and a concentration
of 320 mg Iodine/mL in 154 patients. All patients received one intravenous
injection of 1-2 mL/kg.
In pediatric patients who received intra-arterial
and intracardiac studies, a concentration of 320 mg Iodine/mL was used in161
patients. Twenty-two patients were < 29 days of age; 78 were 29 days to 2
years of age; and 61 were over 2 years. Most of these pediatric patients
received initial volumes of 1-2 mL/kg and most patients received a maximum of 3
injections.
(addition
underlined)
The following clinically significant adverse
reactions are described elsewhere in the labeling:
Risks Associated
with Inadvertent Intrathecal Administration
Hypersensitivity
Reactions
Contrast Induced
Kidney Injury
Cardiovascular
Adverse Reactions
Thromboembolic
Events
Severe
Cutaneous Reactions
8
Use in Specific Populations
8.1 Pregnancy
(PLLR conversion)
Risk Summary
There are no data with iodixanol use in pregnant
women to inform any drug-associated risks. In animal reproduction studies, no
developmental toxicity occurred with intravenous iodixanol administration to
rats and rabbits at doses up to
0.24 (rat) or 0.48 (rabbit) times the maximum
recommended human intravenous dose (see
Data).
All pregnancies have a background risk of birth
defect, loss 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 2-4% and 15-
20%, respectively.
Data
Animal Data
Reproduction studies were performed in rats and
rabbits with intravenous administration of iodixanol at doses up to 2 g
Iodine/kg, daily, from implantation of the embryo (gestation day 7 in rat; 6 in
rabbit) through closure of the hard palate (gestation day 17 in rats; 18 in
rabbits). No maternal toxicity occurred, and no adverse effects occurred on
fetal survival, embryo-fetal development, or the ability of dams to rear a
litter.
8.2 Lactation
(PLLR conversion)
Risk Summary
There are no data on the presence of iodixanol in
human milk, the effects on the breastfed infant or the effects on milk
production. Iodinated contrast agents are poorly excreted into human milk and
are poorly absorbed by the gastrointestinal tract of a breastfed infant. The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for VISIPAQUE and any potential adverse effects
on the breastfed infant from VISIPAQUE or from the underlying maternal
condition.
Clinical Considerations
Interruption of breastfeeding after exposure to
iodinated contrast agents is not necessary because the potential exposure of
the breastfed infant to iodine is small. However, a lactating woman may
consider interrupting breastfeeding and pumping and discarding breast milk for
10 hours (approximately 5 elimination half-lives) after VISIPAQUE
administration in order to minimize drug exposure to a breast fed infant.
8.4 Pediatric Use
(additions underlined)
The safety and efficacy of VISIPAQUE have been
established in pediatric patients down to birth for angiocardiography, cerebral
arteriography, visceral arteriography, CT imaging of the head and body, and
excretory urography. The safety and efficacy of VISIPAQUE have also been
established in pediatric patients 12 years and older for intra-arterial digital
subtraction angiography, peripheral arteriography, CT imaging peripheral
venography and CCTA. Use of VISIPAQUE is supported by evidence from
adequate and well controlled studies of VISIPAQUE in adults and additional
safety data obtained in 459 pediatric patients. In general, the types of
adverse reactions reported are similar to those of adults.
A higher
number of adverse events in patients less than 1 year of age compared
to older patients were observed in a study of VISIPAQUE. The elimination
of VISIPAQUE is slower in this age group.
Thyroid function tests indicative of hypothyroidism
or transient thyroid suppression have been uncommonly reported following
iodinated contrast media administration to pediatric patients, including
infants. Some patients were treated for hypothyroidism.
Pediatric patients at higher risk of experiencing an
adverse reaction during and after administration of any contrast agent may
include those with asthma, hypersensitivity to other medication and/or
allergens, cyanotic and acyanotic heart disease, congestive heart failure, or a
serum creatinine greater than 1.5 mg/dL. Pediatric patients with immature renal
function or dehydration may be at increased risk for adverse events due to
slower elimination of iodinated contrast agents.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(subsection revised, additions
underlined)
Hypersensitivity Reactions
Advise the patient concerning the risk of
hypersensitivity reactions that can occur both during and after VISIPAQUE
administration. Advise the patient to report any
signs or symptoms of hypersensitivity reactions during the procedure and to
seek immediate medical attention for any signs or symptoms experienced after
discharge.
Advise patients to inform their physician if they
develop a rash after receiving VISIPAQUE [see
Warnings and Precautions
Contrast Induced Acute Kidney Injury
Advise the patient concerning appropriate hydration
to decrease the risk of contrast induced acute kidney injury.
Extravasation
If extravasation occurs during injection, advise
patients to seek medical care for progression of symptoms.
Other
Physician labeling Rule (PLR)
conversion.
Get Email Alerts |
Guide
