Isovue
(Iopamidol)Isovue Prescribing Information
ISOVUE (Iopamidol Injection) is indicated
for angiography throughout the cardiovascular system in adults, including
cerebral and peripheral arteriography, coronary arteriography and
ventriculography, selective visceral arteriography and aortography,
peripheral venography (phlebography), and in pediatric patients for
angiocardiography; or for intravenous use in adult and pediatric for
computed tomographic (CT) imaging of the head and body (see below).
ISOVUE
may be used to refine diagnostic precision in areas of the brain which
may not otherwise have been satisfactorily visualized.
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 pool.
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.
ISOVUE (Iopamidol 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.
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.
It
is desirable that solutions of radiopaque diagnostic agents for intravascular
use be at body temperature when injected. Sterile techniques must
be used with any intravascular injection.
The transferring
of ISOVUE from the ISOVUE Imaging Bulk Package container should be
performed utilizing aseptic technique. The Imaging Bulk Package closure
may be penetrated only one time, with a suitable sterile component
of the automated contrast injection system, contrast management system,
or contrast media transfer set approved or cleared for use with this
Imaging Bulk Package.
hydrated prior to and following ISOVUE (Iopamidol Injection) administration.
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.
None.
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 pre-existing cyanosis was transiently
intensified following contrast media administration. In the second
patient pre-existing decreased peripheral perfusion was intensified
for 24 hours following the examination. (See “
Diagnostic procedures
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.
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).
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
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
severity.
Pre-existing conditions, 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 reactions.
General anesthesia 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 agent.
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.
in selected patients and those in whom the expected benefits outweigh
the procedural risk. The inherent risks of
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
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.
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 (seeWARNINGS).
- 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 (seePRECAUTIONS-General).
- Inform your physician about any other medications you are currently taking, including nonprescription drugs, before you have this procedure.
- Advise patients to inform their physician if they develop a rash after receiving Isovue.
- Advise parents/caregivers about the risk of developing thyroid dysfunction after ISOVUE administration. Advise parents/caregivers about when to seek medical care for their child to monitor for thyroid function (seeWARNINGS).
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.
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.
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
Transitory changes 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
Effects
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 gI/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 and computed tomography (head and body). 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 age.
Thyroid function tests indicative of thyroid dysfunction, characterized by hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration in pediatric patients, including term and preterm neonates; some patients were treated for hypothyroidism. 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
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 (Iopamidol 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.
Adverse Reactions | ||
| Estimated Overall Incidence | ||
| System | > 1% | ≤ 1% |
| Cardiovascular | none | tachycardia hypotension hypertension myocardial ischemia circulatory collapse S-T segment depression bigeminy extrasystoles ventricular fibrillation angina pectoris bradycardia transient ischemic attack thrombophlebitis |
| Nervous | pain (2.8%) burning sensation (1.4%) | vasovagal reaction tingling in arms grimace faintness |
| Digestive | nausea (1.2%) | vomiting anorexia |
| Respiratory | none | throat constriction dyspnea pulmonary edema |
| Skin and Appendages | none | rash urticaria pruritus flushing |
| Body as a Whole | hot flashes (1.5%) | headache fever chills excessive sweating back spasm |
| Special Senses | warmth (1.1%) | taste alterations nasal congestion visual disturbances |
| Urogenital | none | urinary retention |
Regardless of the contrast agent
employed, the overall estimated incidence of serious adverse reactions
is higher with
procedures. Cardiac decompensation, serious arrhythmias, or myocardial
ischemia or infarction have been reported with ISOVUE and may occur
during
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 (Iopamidol Injection) than with
diatrizoate meglumine and diatrizoate sodium injection; increased
LVEDP occurred less frequently after ventricular iopamidol injections.
In
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 pre-existing renal
disease, retroperitoneal hemorrhage from the translumbar approach,
and spinal cord injury and pathology associated with the syndrome
of transverse myelitis.
The following adverse reactions
have been reported for Iopamidol:
cardiopulmonary arrest;
paresthesia, dizziness, temporary cortical blindness, temporary amnesia,
convulsions, paralysis, coma;
increased cough, sneezing, asthma, apnea, laryngeal edema, chest tightness,
rhinitis;
pain usually due to extravasation and/or erythematous swelling, pallor,
periorbital edema, facial edema;
itchy eyes, lacrimation, conjunctivitis;
respiratory and cutaneous symptoms), pain;
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.
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.
ISOVUE (Iopamidol Injection) is a stable,
aqueous, sterile, and nonpyrogenic solution for intravascular administration.
Each bottle is to be used as an Imaging Bulk Package for dispensing
multiple single doses of iopamidol injection for multiple patients,
using an automated contrast injection system, contrast management
system, or contrast media transfer set approved or cleared for use
with this contrast agent in this Imaging Bulk Package.
Each
mL of ISOVUE-300 (Iopamidol 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 mL.
Each mL of ISOVUE-370 (Iopamidol
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
mL.
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 (Iopamidol Injection) is hypertonic as compared to plasma
and cerebrospinal fluid (approximately 285 and 301 mOsm/kg water,
respectively).
Iopamidol | ||
| Parameter | 61% | 76% |
| Concentration (mg iodine/mL) | 300 | 370 |
| Osmolality @ 37° C (mOsm/kg water) | 616 | 796 |
| Viscosity (cP) @ 37° C | 4.7 | 9.4 |
| @ 20° C | 8.8 | 20.9 |
| Specific Gravity @ 37° C | 1.339 | 1.405 |
Iopamidol is designated chemically
as (S)-N,N’-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]-2,4,6-triiodo-5-lactamidoisophthalamide.
Structural formula:
 |
| MW 777.09 C17H22I3N3O8 CAS-60166-93-0 Organically Bound Iodine: 49% |