FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.
Product Label Table of Contents
ISOVUE (lopamidol Injection) formulations
are stable, aqueous, sterile, and nonpyrogenic solutions for intravascular
Each mL of ISOVUE-200
(lopamidol Injection 41%) provides 408 mg iopamidol with 1 mg tromethamine
and 0.26 mg edetate calcium disodium. The solution contains approximately
0.029 mg (0.001 mEq) sodium and 200 mg organically bound iodine per
Each mL of ISOVUE-250 (lopamidol
Injection 51%) provides 510 mg iopamidol with 1 mg tromethamine and
0. 33 mg edetate calcium disodium. The solution contains approximately
0.036 mg (0.002 mEq) sodium and 250 mg organically bound iodine per
Each mL of ISOVUE-300 (lopamidol
Injection 61%) provides 612 mg iopamidol with 1 mg tromethamine and
0.39 mg edetate calcium disodium. The solution contains approximately
0.043 mg (0.002 mEq) sodium and 300 mg organically bound iodine per
Each mL of ISOVUE-370 (lopamidol
Injection 76%) provides 755 mg iopamidol with 1 mg tromethamine and
0.48 mg edetate calcium disodium. The solution contains approximately
0.053 mg (0.002 mEq) sodium and 370 mg organically bound iodine per
The pH of ISOVUE contrast
media has been adjusted to 6.5-7.5 with hydrochloric acid and/or sodium
hydroxide. Pertinent physicochemical data are noted below. ISOVUE
(lopamidol Injection) is hypertonic as compared to plasma and cerebrospinal
fluid (approximately 285 and 301 mOsm/kg water, respectively).
|Osmolality @ 37° C|
|Viscosity (cP) @ 37° C||2.0||3.0||4.7|| 9.4|
|@ 20° C||3.3||5.1||8.8||20.9|
|Specific Gravity @ 37° C ||1.227||1.281||1.339|| 1.405|
lopamidol is designated chemically
Organically Bound Iodine: 49%
Intravascular injection of a radiopaque diagnostic agent opacifies
those vessels in the path of flow of the contrast medium, permitting
radiographic visualization of the internal structures of the human
body until significant hemodilution occurs.
Following intravascular injection, radiopaque diagnostic
agents are immediately diluted in the circulating plasma. Calculations
of apparent volume of distribution at steady-state indicate that iopamidol
is distributed between the circulating blood volume and other extracellular
fluid; there appears to be no significant deposition of iopamidol
in tissues. Uniform distribution of iopamidol in extracellular fluid
is reflected by its demonstrated utility in contrast enhancement of
computed tomographic imaging of the head and body following intravenous
of intravenously administered iopamidol in normal subjects conform
to an open two-compartment model with first order elimination (a rapid
alpha phase for drug distribution and a slow beta phase for drug elimination).
The elimination serum or plasma half-life is approximately two hours;
the half-life is not dose dependent. No significant metabolism, deiodination,
or biotransformation occurs.
is excreted mainly through the kidneys following intravascular administration.
In patients with impaired renal function, the elimination half-life
is prolonged dependent upon the degree of impairment. In the absence
of renal dysfunction, the cumulative urinary excretion for Iopamidol,
expressed as a percentage of administered intravenous dose is approximately
35 to 40 percent at 60 minutes, 80 to 90 percent at 8 hours, and 90
percent or more in the 72- to 96-hour period after administration.
In normal subjects, approximately one percent or less of the administered
dose appears in cumulative 72- to 96-hour fecal specimens.
ISOVUE may be visualized in the renal parenchyma
within 30-60 seconds following rapid intravenous administration. Opacification
of the calyces and pelves in patients with normal renal function becomes
apparent within 1 to 3 minutes, with optimum contrast occurring between
5 and 15 minutes. In patients with renal impairment, contrast visualization
may be delayed.
little tendency to bind to serum or plasma proteins.
No evidence of in vivo complement activation has been found
in normal subjects.
indicate that iopamidol does not cross the blood-brain barrier to
any significant extent following intravascular administration.
ISOVUE (lopamidol Injection) enhances
computed tomographic brain imaging through augmentation of radiographic
efficiency. The degree of enhancement of visualization of tissue density
is directly related to the iodine content in an administered dose;
peak iodine blood levels occur immediately following rapid injection
of the dose. These levels fall rapidly within five to ten minutes.
This can be accounted for by the dilution in the vascular and extracellular
fluid compartments which causes an initial sharp fall in plasma concentration.
Equilibration with the extracellular compartments is reached in about
ten minutes, thereafter the fall becomes exponential. Maximum contrast
enhancement frequently occurs after peak blood iodine levels are reached.
The delay in maximum contrast enhancement can range from five to forty
minutes depending on the peak iodine levels achieved and the cell
type of the lesion. This lag suggests that radiographic contrast enhancement
is at least in part dependent on the accumulation of iodine within
the lesion and outside the blood pool, although the mechanism by which
this occurs is not clear. The radiographic enhancement of nontumoral
lesions, such as arteriovenous malformations and aneurysms, is probably
dependent on the iodine content of the circulating blood pool.
In CECT head imaging, ISOVUE (lopamidol
Injection) does not accumulate in normal brain tissue due to the presence
of the blood-brain barrier. The increase in x-ray absorption in normal
brain is due to the presence of contrast agent within the blood pool.
A break in the blood-brain barrier such as occurs in malignant tumors
of the brain allows the accumulation of the contrast medium within
the interstitial tissue of the tumor. Adjacent normal brain tissue
does not contain the contrast medium.
In nonneural tissues (during computed tomography of
the body), iopamidol diffuses rapidly from the vascular into the extravascular
space. Increase in x-ray absorption is related to blood flow, concentration
of the contrast medium, and extraction of the contrast medium by interstitial
tissue of tumors since no barrier exists. Contrast enhancement is
thus due to the relative differences in extravascular diffusion between
normal and abnormal tissue, quite different from that in the brain.
The pharmacokinetics of iopamidol in both
normal and abnormal tissue have been shown to be variable. Contrast
enhancement appears to be greatest soon after administration of the
contrast medium, and following intraarterial rather than intravenous
administration. Thus, greatest enhancement can be detected by a series
of consecutive two- to three-second scans performed just after injection
(within 30 to 90 seconds), i.e., dynamic computed tomographic imaging.
Indications And Usage
ISOVUE (lopamidol Injection) is indicated
for angiography throughout the cardiovascular system, including cerebral
and peripheral arteriography, coronary arteriography and ventriculography,
pediatric angiocardiography, selective visceral arteriography and
aortography, peripheral venography (phlebography), and adult and pediatric
intravenous excretory urography and intravenous adult and pediatric
contrast enhancement of computed tomographic (CECT) head and body
imaging (see below).
Cect Head Imaging
ISOVUE may be used to refine diagnostic
precision in areas of the brain which may not otherwise have been
ISOVUE may be useful to investigate the
presence and extent of certain malignancies such as: gliomas including
malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas
and gangliomas, ependymomas, medulloblastomas, meningiomas, neuromas,
pinealomas, pituitary adenomas, craniopharyngiomas, germinomas, and
metastatic lesions. The usefulness of contrast enhancement for the
investigation of the retrobulbar space and in cases of low grade or
infiltrative glioma has not been demonstrated.
In calcified lesions, there is less likelihood of enhancement.
Following therapy, tumors may show decreased or no enhancement.
The opacification of the inferior vermis
following contrast media administration has resulted in false-positive
diagnosis in a number of otherwise normal studies.
ISOVUE may be beneficial in the image enhancement
of nonneoplastic lesions. Cerebral infarctions of recent onset may
be better visualized with contrast enhancement, while some infarctions
are obscured if contrast media are used. The use of iodinated contrast
media results in contrast enhancement in about 60 percent of cerebral
infarctions studied from one to four weeks from the onset of symptoms.
Sites of active infection may also
be enhanced following contrast media administration.
Arteriovenous malformations and aneurysms will show
contrast enhancement. For these vascular lesions, the enhancement
is probably dependent on the iodine content of the circulating blood
Hematomas and intraparenchymal
bleeders seldom demonstrate any contrast enhancement. However, in
cases of intraparenchymal clot, for which there is no obvious clinical
explanation, contrast media administration may be helpful in ruling
out the possibility of associated arteriovenous malformation.
Cect Body Imaging
ISOVUE (lopamidol Injection) may be used
for enhancement of computed tomographic images for detection and evaluation
of lesions in the liver, pancreas, kidneys, aorta, mediastinum, abdominal
cavity, pelvis and retroperitoneal space.
Enhancement of computed tomography with ISOVUE may be
of benefit in establishing diagnoses of certain lesions in these sites
with greater assurance than is possible with CT alone, and in supplying
additional features of the lesions (e.g., hepatic abscess delineation
prior to percutaneous drainage). In other cases, the contrast agent
may allow visualization of lesions not seen with CT alone (e.g., tumor
extension), or may help to define suspicious lesions seen with unenhanced
CT (e.g., pancreatic cyst).
Contrast enhancement appears to be greatest within 60 to 90 seconds
after bolus administration of contrast agent. Therefore, utilization
of a continuous scanning technique (“dynamic CT scanning”) may improve
enhancement and diagnostic assessment of tumor and other lesions such
as an abscess, occasionally revealing unsuspected or more extensive
disease. For example, a cyst may be distinguished from a vascularized
solid lesion when precontrast and enhanced scans are compared; the
nonperfused mass shows unchanged x-ray absorption (CT number). A vascularized
lesion is characterized by an increase in CT number in the few minutes
after a bolus of intravascular contrast agent; it may be malignant,
benign, or normal tissue, but would probably not be a cyst, hematoma,
or other nonvascular lesion.
Because unenhanced scanning may provide adequate diagnostic information
in the individual patient, the decision to employ contrast enhancement,
which may be associated with risk and increased radiation exposure,
should be based upon a careful evaluation of clinical, other radiological,
and unenhanced CT findings.
Severe Adverse Events-lnadvertent
Serious adverse reactions have been reported due to the inadvertent
intrathecal administration of iodinated contrast media that are not
indicated for intrathecal use.
These serious adverse reactions include: death,
convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis,
acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia,
and brain edema. Special attention must be given to insure that this
drug product is not inadvertently administered intrathecally.
Nonionic iodinated contrast media inhibit
blood coagulation, in vitro, less than ionic contrast
media. Clotting has been reported when blood remains in contact with
syringes containing nonionic contrast media.
Serious, rarely fatal, thromboembolic events causing
myocardial infarction and stroke have been reported during angiographic
procedures with both ionic and nonionic contrast media. Therefore,
meticulous intravascular administration technique is necessary, particularly
during angiographic procedures, to minimize thromboembolic events.
Numerous factors, including length of procedure, catheter and syringe
material, underlying disease state, and concomitant medications may
contribute to the development of thromboembolic events. For these
reasons, meticulous angiographic techniques are recommended including
close attention to guidewire and catheter manipulation, use of manifold
systems and/or three way stopcocks, frequent catheter flushing with
heparinized saline solutions, and minimizing the length of the procedure.
The use of plastic syringes in place of glass syringes has been reported
to decrease but not eliminate the likelihood of in vitro clotting.
Caution must be exercised
in patients with severely impaired renal function, those with combined
renal and hepatic disease, or anuria, particularly when larger or
repeat doses are administered.
Radiopaque diagnostic contrast agents are potentially hazardous in
patients with multiple myeloma or other paraproteinemia, particularly
in those with therapeutically resistant anuria. Myeloma occurs most
commonly in persons over age 40. Although neither the contrast agent
nor dehydration has been proved separately to be the cause of anuria
in myelomatous patients, it has been speculated that the combination
of both may be causative. The risk in myelomatous patients is not
a contraindication; however, special precautions are required.
Contrast media may promote sickling in
individuals who are homozygous for sickle cell disease when injected
intravenously or intraarterially.
Administration of radiopaque materials to patients known or suspected
of having pheochromocytoma should be performed with extreme caution.
If, in the opinion of the physician, the possible benefits of such
procedures outweigh the considered risks, the procedures may be performed;
however, the amount of radiopaque medium injected should be kept to
an absolute minimum. The blood pressure should be assessed throughout
the procedure and measures for treatment of a hypertensive crisis
should be available. These patients should be monitored very closely
during contrast enhanced procedures.
Reports of thyroid storm following the use of iodinated
radiopaque diagnostic agents in patients with hyperthyroidism or with
an autonomously functioning thyroid nodule suggest that this additional
risk be evaluated in such patients before use of any contrast medium.
Severe Cutaneous Adverse
Reactions: 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 agent; prophylactic medications
may not prevent or mitigate severe cutaneous adverse reactions. Avoid
administering Isovue to patients with a history of a severe cutaneous
adverse reaction to Isovue.
which involve the use of any radiopaque agent should be carried out
under the direction of personnel with the prerequisite training and
with a thorough knowledge of the particular procedure to be performed.
Appropriate facilities should be available for coping with any complication
of the procedure, as well as for emergency treatment of severe reaction
to the contrast agent itself. After parenteral administration of a
radiopaque agent, competent personnel and emergency facilities should
be available for at least 30 to 60 minutes since severe delayed reactions
may occur. Caution should be exercised in hydrating patients with
underlying conditions that may be worsened by fluid overload, such
as congestive heart failure.
Diabetic nephropathy may predispose to acute renal impairment following
intravascular contrast media administration. Acute renal impairment
following contrast media administration may precipitate lactic acidosis
in patients who are taking biguanides.
The administration of iodinated contrast media may
aggravate the symptoms of myasthenia gravis.
Preparatory dehydration is dangerous and may contribute
to acute renal failure in patients with advanced vascular disease,
diabetic patients, and in susceptible nondiabetic patients (often
elderly with preexisting renal disease). Patients should be
well hydrated prior to and following iopamidol administration. The possibility of a reaction, including serious, life-threatening,
fatal, anaphylactoid or cardiovascular reactions, should always be
considered (see ADVERSE REACTIONS). Patients at increased risk include those with a history of a previous
reaction to a contrast medium, patients with a known sensitivity to
iodine per se, and patients with a known clinical hypersensitivity
(bronchial asthma, hay fever, and food allergies). The occurrence
of severe idiosyncratic reactions has prompted the use of several
pretesting methods. However, pretesting cannot be relied upon to predict
severe reactions and may itself be hazardous for the patient. It is
suggested that a thorough medical history with emphasis on allergy
and hypersensitivity, prior to the injection of any contrast medium,
may be more accurate than pretesting in predicting potential adverse
reactions. A positive history of allergies or hypersensitivity does
not arbitrarily contraindicate the use of a contrast agent where a
diagnostic procedure is thought essential, but caution should be exercised.
Premedication with antihistamines or corticosteroids to avoid or minimize
possible allergic reactions in such patients should be considered.
Recent reports indicate that such pretreatment does not prevent serious
life-threatening reactions but may reduce both their incidence and
such as pacemakers or cardiac medications, specifically beta-blockers,
may mask or alter the signs or symptoms of an anaphylactoid reaction,
as well as masking or altering the response to particular medications
used for treatment. For example, beta-blockers inhibit a tachycardiac
response, and can lead to the incorrect diagnosis of a vasovagal rather
than an anaphylactoid reaction. Special attention to this possibility
is particularly critical in patients suffering from serious, life-threatening
may be indicated in the performance of some procedures in selected
patients; however, a higher incidence of adverse reactions has been
reported with radiopaque media in anesthetized patients, which may
be attributable to the inability of the patient to identify untoward
symptoms, or to the hypotensive effect of anesthesia which can reduce
cardiac output and increase the duration of exposure to the contrast
Even though the osmolality
of iopamidol is low compared to diatrizoate or iothalamate based ionic
agents of comparable iodine concentration, the potential transitory
increase in the circulatory osmotic load in patients with congestive
heart failure requires caution during injection. These patients should
be observed for several hours following the procedure to detect delayed
hemodynamic disturbances. Injection site pain and swelling may occur.
In the majority of cases it is due to extravasation of contrast medium.
Reactions are usually transient and recover without sequelae. However,
inflammation and even skin necrosis have been seen on very rare occasions.
In angiographic procedures, the possibility
of dislodging plaques or damaging or perforating the vessel wall,
or inducing vasospasm, and or subsequent ischemic events, should be
borne in mind during catheter manipulations and contrast medium injection.
Test injections to ensure proper catheter placement are suggested.
Selective coronary arteriography should
be performed only in selected patients and those in whom the expected
benefits outweigh the procedural risk. The inherent risks of angiocardiography
in patients with pulmonary hypertension must be weighed against the
necessity for performing this procedure. Angiography should be avoided
whenever possible in patients with homocystinuria, because of the
risk of inducing thrombosis and embolism. See also Pediatric Use.
In addition to the general precautions previously described,
special care is required when venography is performed in patients
with suspected thrombosis, phlebitis, severe ischemic disease, local
infection or a totally obstructed venous system. Extreme caution during
injection of contrast media is necessary to avoid extravasation and
fluoroscopy is recommended. This is especially important in patients
with severe arterial or venous disease.
Parenteral drug products should be inspected
visually for particulate matter and discoloration prior to administration,
whenever solution and container permit. Iopamidol solutions should
be used only if clear and within the normal colorless to pale yellow
range. Discard any product which shows signs of crystallization or
damage to the container-closure system, which includes the glass container,
stopper and/or crimp.
desirable that solutions of radiopaque diagnostic agents for intravascular
use be at body temperature when injected. Withdrawal of contrast agents
from their containers should be accomplished under aseptic conditions
with sterile syringes. Sterile techniques must be used with any intravascular
injection, and with catheters and guidewires.
Patients should be well hydrated prior
to and following ISOVUE (lopamidol Injection) administration.
As with all radiopaque
contrast agents, only the lowest dose of ISOVUE necessary to obtain
adequate visualization should be used. A lower dose reduces the possibility
of an adverse reaction. Most procedures do not require use of either
a maximum dose or the highest available concentration of ISOVUE; the
combination of dose and ISOVUE concentration to be used should be
carefully individualized, and factors such as age, body size, size
of the vessel and its blood flow rate, anticipated pathology and degree
and extent of opacification required, structure(s) or area to be examined,
disease processes affecting the patient, and equipment and technique
to be employed should be considered.
Information For Patients
Patients receiving injectable radiopaque diagnostic
agents should be instructed to:
- Inform your physician if you are pregnant.
- Inform your physician if you are diabetic or if you have
multiple myeloma, pheochromocytoma, homozygous sickle cell disease,
or known thyroid disorder (see WARNINGS).
- Inform your physician if you are allergic to any drugs,
food, or if you had any reactions to previous injections of substances
used for x-ray procedures (see PRECAUTIONS-General).
- Inform your physician about any other medications you are
currently taking, including nonprescription drugs, before you have
- Advise patients to inform their physician if they develop
a rash after receiving Isovue.
Renal toxicity has been reported in a
few patients with liver dysfunction who were given oral cholecystographic
agents followed by intravascular contrast agents. Administration of
intravascular agents should therefore be postponed in any patient
with a known or suspected hepatic or biliary disorder who has recently
received a cholecystographic contrast agent.
Other drugs should not be admixed with iopamidol.
Drug/Laboratory Test Interactions
The results of PBI and radioactive iodine uptake
studies, which depend on iodine estimations, will not accurately reflect
thyroid function for up to 16 days following administration of iodinated
contrast media. However, thyroid function tests not depending on iodine
estimations, e.g., T3 resin uptake and total or free thyroxine (T4)
assays are not affected.
Any test which might be affected by contrast media should be performed
prior to administration of the contrast medium.
Laboratory Test Findings
In vitro studies with
animal blood showed that many radiopaque contrast agents, including
iopamidol, produced a slight depression of plasma coagulation factors
including prothrombin time, partial thromboplastin time, and fibrinogen,
as well as a slight tendency to cause platelet and/or red blood cell
aggregation (see PRECAUTIONS-General).
may occur in red cell and leucocyte counts, serum calcium, serum creatinine,
serum glutamic oxaloacetic transaminase (SGOT), and uric acid in urine;
transient albuminuria may occur.
These findings have not been associated with clinical manifestations.
Impairment Of Fertility
Long-term studies in animals have not been performed to evaluate
carcinogenic potential. No evidence of genetic toxicity was obtained
in in vitro tests.
Reproduction studies have been performed in rats and
rabbits at doses up to 2.7 and 1.4 times the maximum recommended human
dose (1.48 gl/kg in a 50 kg individual), respectively, and have revealed
no evidence of impaired fertility or harm to the fetus due to iopamidol.
There are, however, no adequate and well-controlled studies in pregnant
women. Because animal reproduction studies are not always predictive
of human response, this drug should be used during pregnancy only
if clearly needed.
It is not known whether this drug is excreted
in human milk. Because many drugs are excreted in human milk, caution
should be exercised when iopamidol is administered to a nursing woman.
Safety and effectiveness in children
has been established in pediatric angiocardiography, computed tomography
(head and body) and excretory urography. Pediatric patients at higher
risk of experiencing adverse events during contrast medium administration
may include those having asthma, a sensitivity to medication and/or
allergens, cyanotic heart disease, congestive heart failure, a serum
creatinine greater than 1.5 mg/dL or those less than 12 months of
Adverse reactions following the use
of iopamidol are usually mild to moderate, self-limited, and transient.
In angiocardiography (597 patients),
the adverse reactions with an estimated incidence of one percent or
higher are: hot flashes 3.4%; angina pectoris 3.0%; flushing 1.8%;
bradycardia 1.3%; hypotension 1.0%; hives 1.0%.
In a clinical trial with 76 pediatric patients undergoing
angiocardiography, 2 adverse reactions (2.6%) both remotely attributed
to the contrast media were reported. Both patients were less than
2 years of age, both had cyanotic heart disease with underlying right
ventricular abnormalities and abnormal pulmonary circulation. In one
patient preexisting cyanosis was transiently intensified following
contrast media administration. In the second patient preexisting decreased
peripheral perfusion was intensified for 24 hours following the examination.
(See “PRECAUTIONS” Section for
information on high risk nature of these patients.)
Intravascular injection of contrast media is frequently
associated with the sensation of warmth and pain especially in peripheral
arteriography and venography; pain and warmth are less frequent and
less severe with ISOVUE (lopamidol Injection) than with diatrizoate
meglumine and diatrizoate sodium injection.
The following table of incidence of reactions is based
on clinical studies with ISOVUE in about 2246 patients.
|Estimated Overall Incidence|
|System||> 1%||≤ 1%|
transient ischemic attack
burning sensation (1.4%)
tingling in arms
|Skin and Appendages||none||rash|
|Body as a Whole||hot flashes (1.5%)||headache|
|Special Senses||warmth (1.1%)||taste alterations|
Regardless of the contrast agent
employed, the overall estimated incidence of serious adverse reactions
is higher with coronary arteriography than with other
procedures. Cardiac decompensation, serious arrhythmias, or myocardial
ischemia or infarction have been reported with Isovue and may occur
during coronary arteriography and left ventriculography.
Following coronary and
ventricular injections, certain electrocardiographic changes (increased
QTc, increased R-R, T-wave amplitude) and certain hemodynamic changes
(decreased systolic pressure) occurred less frequently with ISOVUE
(lopamidol Injection) than with diatrizoate meglumine and diatrizoate
sodium injection; increased LVEDP occurred less frequently after ventricular
In aortography, the risks of procedures also include injury
to the aorta and neighboring organs, pleural puncture, renal damage
including infarction and acute tabular necrosis with oliguria and
anuria, accidental selective filling of the right renal artery during
the translumbar procedure in the presence of preexisting renal disease,
retroperitoneal hemorrhage from the translumbar approach, and spinal
cord injury and pathology associated with the syndrome of transverse
The following adverse
reactions have been reported for lopamidol: Cardiovascular: arrhythmia, arterial spasms, flushing, vasodilation, chest pain,
cardiopulmonary arrest; Nervous: confusion,
paresthesia, dizziness, temporary cortical blindness, temporary amnesia,
convulsions, paralysis, coma; Respiratory:
increased cough, sneezing, asthma, apnea, laryngeal edema, chest tightness,
rhinitis; Skin and Appendages: injection site
pain usually due to extravasation and/or erythematous swelling, pallor,
periorbital edema, facial edema; Urogenital: pain, hematuria; Special Senses: watery
itchy eyes, lacrimation, conjunctivitis; Musculoskeletal: muscle spasm, involuntary leg movement; Body as a whole: tremors, malaise, anaphylactoid reaction (characterized by cardiovascular,
respiratory and cutaneous symptoms), pain; Digestive: severe retching and choking, abdominal cramps. Some of these may
occur as a consequence of the procedure. Other reactions may also
occur with the use of any contrast agent as a consequence of the procedural
hazard; these include hemorrhage or pseudoaneurysms at the puncture
site, brachial plexus palsy following axillary artery injections,
chest pain, myocardial infarction, and transient changes in hepatorenal
chemistry tests. Arterial thrombosis, displacement of arterial plaques,
venous thrombosis, dissection of the coronary vessels and transient
sinus arrest are rare complications.
General Adverse Reactions
To Contrast Media
known to occur with parenteral administration of iodinated ionic contrast
agents (see the listing below) are possible with any nonionic agent.
Approximately 95 percent of adverse reactions accompanying the use
of other water-soluble intravascularly administered contrast agents
are mild to moderate in degree. However, life-threatening reactions
and fatalities, mostly of cardiovascular origin, have occurred. Reported
incidences of death from the administration of other iodinated contrast
media range from 6.6 per 1 million (0.00066 percent) to 1 in 10,000
patients (0.01 percent). Most deaths occur during injection or 5 to
10 minutes later, the main feature being cardiac arrest with cardiovascular
disease as the main aggravating factor. Isolated reports of hypotensive
collapse and shock are found in the literature. The incidence of shock
is estimated to be 1 out of 20,000 (0.005 percent) patients.
Adverse reactions to injectable contrast
media fall into two categories: chemotoxic reactions and idiosyncratic
reactions. Chemotoxic reactions result from the physicochemical properties
of the contrast medium, the dose, and the speed of injection. All
hemodynamic disturbances and injuries to organs or vessels perfused
by the contrast medium are included in this category.
Experience with iopamidol suggests there is much less
discomfort (e.g. pain and/or warmth) with peripheral arteriography.
Fewer changes are noted in ventricular function after ventriculography
and coronary arteriography.
reactions include all other reactions. They occur more frequently
in patients 20 to 40 years old. Idiosyncratic reactions may or may
not be dependent on the amount of drug injected, the speed of injection,
the mode of injection, and the radiographic procedure.
Idiosyncratic reactions are subdivided into
minor, intermediate, and severe. The minor reactions are self-limited
and of short duration; the severe reactions are life-threatening and
treatment is urgent and mandatory.
The reported incidence of adverse reactions to contrast media in
patients with a history of allergy is twice that for the general population.
Patients with a history of previous reactions to a contrast medium
are three times more susceptible than other patients. However, sensitivity
to contrast media does not appear to increase with repeated examinations.
Most adverse reactions to intravascular contrast agents appear within
one to three minutes after the start of injection, but delayed reactions
may occur. Delayed reactions, usually involving the skin, may uncommonly
occur within 2-3 days (range 1-7 days) after the administration of
contrast (see PRECAUTIONS-General). Delayed allergic reactions are more frequent in patients treated
with immunostimulants, such as interleukin-2.
In addition to the adverse drug reactions reported for
iopamidol, the following additional adverse reactions have been reported
with the use of other intravascular contrast agents and are possible
with the use of any water-soluble iodinated contrast agent:
hematomas, petechiae; Hematologic: neutropenia; Urogenital: osmotic nephrosis of proximal tubular cells,
renal failure; Special Senses: conjunctival
chemosis with infection; Endocrine: 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. Skin and Subcutaneous
Tissue Disorders: Skin necrosis; 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)].
Treatment of an overdose of an injectable
radiopaque contrast medium is directed toward the support of all vital
functions, and prompt institution of symptomatic therapy.
ISOVUE-300 (lopamidol Injection, 300 mgl/mL)
should be used. The usual individual injection by carotid puncture
or transfemoral catheterization is 8 to 12 mL, with total multiple
doses ranging to 90 mL.
ISOVUE-300 usually provides adequate visualization.
For injection into the femoral artery or subclavian artery, 5 to 40
mL may be used; for injection into the aorta for a distal runoff,
25 to 50 mL may be used. Doses up to a total of 250 mL of ISOVUE-300
have been administered during peripheral arteriography.
(lopamidol Injection, 200 mgl/mL) should be used. The usual dose is
25 to 150 mL per lower extremity. The combined total dose for multiple
injections has not exceeded 350 mL.
Selective Visceral Arteriography
(lopamidol Injection, 370 mgl/mL) should be used. Doses up to 50 mL
may be required for injection into the larger vessels such as the
aorta or celiac artery; doses up to 10 mL may be required for injection
into the renal arteries. Often, lower doses will be sufficient. The
combined total dose for multiple injections has not exceeded 225 mL.
ISOVUE-370 should be used. Pediatric
angiocardiography may be performed by injection into a large peripheral
vein or by direct catheterization of the heart.
The usual dose range for single injections is
provided in the following table:
|Usual Dose Range|
|< 2 years||10-15|
The usual recommended dose for
cumulative injections is provided in the following table:
|Cumulative Injection |
|Usual Recommended Dose|
|< 2 years||40|
ISOVUE-370 should be used. The usual dose for
selective coronary artery injections is 2 to 10 mL. The usual dose
for ventriculography, or for nonselective opacification of multiple
coronary arteries following injection at the aortic root is 25 to
50 mL. The total dose for combined procedures has not exceeded 200
mL. EKG monitoring is essential.
ISOVUE-250 ISOVUE-300 or ISOVUE-370
may be used. The usual adult dose for ISOVUE-250 is 50 to 100 mL,
for ISOVUE-300 is 50 mL and for ISOVUE-370 is 40 mL administered by
rapid intravenous injection.
Pediatric Excretory Urography
ISOVUE-250 or ISOVUE-300 may be used. The
dosage recommended for use in children for excretory urography is
1.2 mL/kg to 3.6 mL/kg for ISOVUE-250 and 1.0 mL/kg to 3.0 mL/kg for
ISOVUE-300. It should not be necessary to exceed a total dose of 30
grams of iodine.
ISOVUE-250 or ISOVUE-300 may be used.
CECT OF THE HEAD: The suggested dose for
ISOVUE-250 is 130 to 240 mL and for ISOVUE-300 is 100 to 200 mL by
intravenous administration. Imaging may be performed immediately after
completion of administration.
CECT OF THE BODY: The usual adult dose range for ISOVUE-250 is 130
to 240 mL and for ISOVUE-300 is 100 to 200 mL administered by rapid
intravenous infusion or bolus injection. Equivalent doses of ISOVUE-370
based on organically bound iodine content may also be used. The total
dose for either CECT procedure should not exceed 60 grams of iodine.
Pediatric Computed Tomography
ISOVUE-250 or ISOVUE-300 may be used.
The dosage recommended for use in children for contrast enhanced computed
tomography is 1.2 mL/kg to 3.6 mL/kg for ISOVUE-250 and 1.0 mL/kg
to 3.0 mL/kg for ISOVUE-300. It should not be necessary to exceed
a total dose of 30 grams of iodine.
Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many other drugs;
therefore, no other pharmaceuticals should be admixed with contrast
ISOVUE-200 (lopamidol Injection 41%)
Ten 50 mL single dose vials (NDC 0270-1314-30)
200 mL single dose bottles (NDC 0270-1314-15)
ISOVUE-250 (lopamidol Injection 51%)
Ten 50 mL single dose vials (NDC 0270-1317-05)
100 mL single dose bottles (NDC 0270-1317-02)
mL single dose bottles (NDC 0270-1317-09)
ISOVUE-300 (lopamidol Injection 61%)
30 mL single dose vials (NDC 0270-1315-25)
Ten 50 mL
single dose vials (NDC 0270-1315-30)
Ten 75 mL single
dose bottles (NDC 0270-1315-47)
Ten 100 mL single dose
bottles (NDC 0270-1315-35)
Ten 150 mL single dose bottles
(lopamidol Injection 76%)
Ten 50 mL single dose vials
Ten 75 mL single
dose bottles (NDC 0270-1316-52)
Ten 100 mL single dose
bottles (NDC 0270-1316-35)
Ten 125 mL single dose bottles
Ten 150 mL single dose bottles (NDC
Store at 20-25° C (68-77° F). [See
USP]. Protect from light.
lopamidol Injection is also available
as ISOVUE-M® for intrathecal administration.
Bracco Diagnostics Inc. - Monroe Township, NJ 08831
by BIPSO GmbH
78224 Singen (Germany)
Revised October 2019
Package Label.Principal Display Panel
200mL vial label
Isovue 250: 10x 100mL Box label
Isovue 300: 100mL Vial label
Isovue 370: 75mL Bottle label
* Please review the disclaimer below.