Isovue-m
(Iopamidol)Isovue-M Prescribing Information
ISOVUE-M (lopamidol Injection)
is indicated for intrathecal administration in adult neuroradiology
including myelography (lumbar, thoracic, cervical, total columnar),
and for contrast enhancement of computed tomographic (CECT) cisternography
and ventriculography. ISOVUE-M 200 (lopamidol Injection) is indicated
for thoraco-lumbar myelography in children over the age of two years.
In
approximately isotonic (ISOVUE-M 200) is recommended for examination
of the lumbar region. For movement of the contrast medium to distant
target areas the more concentrated ISOVUE-M 300 preparation should
be used to compensate for dilution of ISOVUE-M (lopamidol Injection)
with cerebrospinal fluid.
The usual recommended adult dose range for iopamidol is 2000-3000
mg iodine. Iopamidol formulated to contain more than 300 mgl/mL should
not be used intrathecally in adults. The minimum dose needed to perform
a procedure should always be used.
In
that is approximately isotonic (ISOVUE-M 200) is recommended for all
intrathecal procedures. In children, loss of contrast due to mixing
on movement of the medium is less apt to occur because of their shorter
spinal cord.
The usual
recommended pediatric dose range for iopamidol is 1400-2400 mg iodine.
Iopamidol formulated to contain more than 200 mgl/mL should not be
used intrathecally in children. The minimum dose needed to perform
a procedure should always be used. See pediatric
dosage table for recommended dosage.
Anesthesia is not necessary. However, young
children may require general anesthesia for technical reasons. Premedication
with sedatives or tranquillizers is usually not needed. In patients
with a history of seizure activity who are not on anticonvulsant therapy,
premedication with barbiturates or phenytoin should be considered.
Lumbar puncture is usually made
between L3 and L4; if pathology is suspected at this level, the interspace
immediately above or below may be selected. A lateral cervical puncture
may also be used.
fluid and consequent loss of contrast as well as premature cephalad
dispersion, injection must be made slowly over one to two minutes;
the needle may then be removed.
An interval of at least 48 hours should be
allowed before repeat examination; however, whenever possible five
to seven days is recommended.
only the lowest dose of ISOVUE-M 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-M; the combination
of dose and ISOVUE-M concentration to be used should be carefully
individualized, and factors such as age, body size, 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.
ISOVUE-M.
The
pediatric doses listed below, intended as a guideline, are based on
age rather than weight because the brain and CSF capacity is independent
of weight. Variations will depend on such factors as height, suspected
pathology, the patient’s condition, technique used, etc. (e.g. CT
or standard radiology or movement of the contrast media directed distal
to the site of injection).
Pediatric Dosage Table | ||
|---|---|---|
ISOVUE-M 200 (200 mgl/mL) | ||
Procedure | Age Years | Usual Recommended Dose (mL) |
| Lumbar, thoracic myelogram | 2-7 | 7-9 |
| 8-12 | 8-11 | |
| 13-18 | 10-12 | |
Concentration of Solution (mgI/mL) | Usual Recommended Dose (mL) | |
|---|---|---|
| Lumbar myelogram | 200 | 10 to 15 |
| Thoracic myelogram | 200 | 10 to 15 |
| Cervical myelogram | 200 | 10 to 15 |
| (via lumbar injection) | 300 | 10 |
| Cervical myelogram | 200 | 10 |
| (via lateral cervical injection) | ||
| Total columnar myelography | 300 | 10 |
| CT cisternography | 200 | 4 to 6 |
| (via lumbar injection) |
Following subarachnoid
injection, conventional radiography will continue to provide good
diagnostic contrast for at least 30 minutes. At about one hour, diagnostic
degree of contrast will not usually be available. However, sufficient
contrast for CT myelography will be available for several hours. CT
myelography following conventional myelography should be deferred
for at least four hours to reduce the degree of contrast.
Aspiration of iopamidol is unnecessary
following intrathecal administration (see
The pharmacokinetics 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.
Iopamidol is
rapidly absorbed into the bloodstream from cerebrospinal fluid (CSF);
following intrathecal administration, iopamidol appears in plasma
within one hour and virtually all of the drug reaches the systemic
circulation within 24 hours. Iopamidol is excreted mainly through
the kidneys following intrathecal administration, and the drug is
essentially undetectable in the plasma 48 hours later. 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 1 percent or less of the administered dose appears in
cumulative 72- to 96-hour fecal specimens.
Iopamidol displays little tendency to bind
to serum or plasma proteins.
No evidence of
activation has been found in normal subjects.
Animal studies indicate that iopamidol does
not cross the blood-brain barrier to any significant extent following
intravascular administration.
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 intrathecal use be at body temperature
when injected. Withdrawal of contrast agents from their containers
should be accomplished under aseptic conditions with sterile syringes.
Spinal puncture must always be performed under sterile conditions.
hydrated prior to and following ISOVUE-M (Iopamidol Injection) administration.
Intrathecal administration of
corticosteroids with iopamidol is contraindicated. Because of overdosage
considerations, immediate repeat myelography in the event of technical
failure is contraindicated (see interval recommendation under
In
approximately isotonic (ISOVUE-M 200) is recommended for examination
of the lumbar region. For movement of the contrast medium to distant
target areas the more concentrated ISOVUE-M 300 preparation should
be used to compensate for dilution of ISOVUE-M (lopamidol Injection)
with cerebrospinal fluid.
The usual recommended adult dose range for iopamidol is 2000-3000
mg iodine. Iopamidol formulated to contain more than 300 mgl/mL should
not be used intrathecally in adults. The minimum dose needed to perform
a procedure should always be used.
In
that is approximately isotonic (ISOVUE-M 200) is recommended for all
intrathecal procedures. In children, loss of contrast due to mixing
on movement of the medium is less apt to occur because of their shorter
spinal cord.
The usual
recommended pediatric dose range for iopamidol is 1400-2400 mg iodine.
Iopamidol formulated to contain more than 200 mgl/mL should not be
used intrathecally in children. The minimum dose needed to perform
a procedure should always be used. See pediatric
dosage table for recommended dosage.
Anesthesia is not necessary. However, young
children may require general anesthesia for technical reasons. Premedication
with sedatives or tranquillizers is usually not needed. In patients
with a history of seizure activity who are not on anticonvulsant therapy,
premedication with barbiturates or phenytoin should be considered.
Lumbar puncture is usually made
between L3 and L4; if pathology is suspected at this level, the interspace
immediately above or below may be selected. A lateral cervical puncture
may also be used.
fluid and consequent loss of contrast as well as premature cephalad
dispersion, injection must be made slowly over one to two minutes;
the needle may then be removed.
An interval of at least 48 hours should be
allowed before repeat examination; however, whenever possible five
to seven days is recommended.
only the lowest dose of ISOVUE-M 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-M; the combination
of dose and ISOVUE-M concentration to be used should be carefully
individualized, and factors such as age, body size, 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.
ISOVUE-M.
The
pediatric doses listed below, intended as a guideline, are based on
age rather than weight because the brain and CSF capacity is independent
of weight. Variations will depend on such factors as height, suspected
pathology, the patient’s condition, technique used, etc. (e.g. CT
or standard radiology or movement of the contrast media directed distal
to the site of injection).
Pediatric Dosage Table | ||
|---|---|---|
ISOVUE-M 200 (200 mgl/mL) | ||
Procedure | Age Years | Usual Recommended Dose (mL) |
| Lumbar, thoracic myelogram | 2-7 | 7-9 |
| 8-12 | 8-11 | |
| 13-18 | 10-12 | |
Concentration of Solution (mgI/mL) | Usual Recommended Dose (mL) | |
|---|---|---|
| Lumbar myelogram | 200 | 10 to 15 |
| Thoracic myelogram | 200 | 10 to 15 |
| Cervical myelogram | 200 | 10 to 15 |
| (via lumbar injection) | 300 | 10 |
| Cervical myelogram | 200 | 10 |
| (via lateral cervical injection) | ||
| Total columnar myelography | 300 | 10 |
| CT cisternography | 200 | 4 to 6 |
| (via lumbar injection) |
Following subarachnoid
injection, conventional radiography will continue to provide good
diagnostic contrast for at least 30 minutes. At about one hour, diagnostic
degree of contrast will not usually be available. However, sufficient
contrast for CT myelography will be available for several hours. CT
myelography following conventional myelography should be deferred
for at least four hours to reduce the degree of contrast.
Aspiration of iopamidol is unnecessary
following intrathecal administration (see
PHARMACOLOGY
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 intrathecal use be at body temperature
when injected. Withdrawal of contrast agents from their containers
should be accomplished under aseptic conditions with sterile syringes.
Spinal puncture must always be performed under sterile conditions.
hydrated prior to and following ISOVUE-M (Iopamidol Injection) administration.
Patient Management
- See WARNINGSregarding
discontinuation of neuroleptic agents. - Maintain normal diet up to 2 hours before procedure.
- Ensure hydration-fluids up to time of procedure.
- Use minimum dose and concentration required for satisfactory
contrast. - Inject slowly over 1 to 2 minutes to avoid excessive mixing.
- Abrupt or active patient movement causes excessive mixing
with CSF. - Instruct patient to remainpassive. Move
patientslowlyand only as necessary. - To maintain as a bolus, move medium to distal areavery slowlyunder fluoroscopic control.
- In all positioning techniques keep the patient’s head elevated
above highest level of spine. - Do not lower head of table more than 15° during thoraco-cervical
procedures. - In patients with excessive lordosis, consider lateral position
for injection and movement of the medium cephalad. - Avoid intracranial entry of a bolus.
- Avoid early and high cephalad dispersion of the medium.
- At completion of direct cervical or lumbo-cervical procedures,
raise head of table steeply (45°) for about 2 minutes to restore medium
to lower levels.
- Raise head of stretcher to at least 30° before moving patient
onto it. - Movement onto stretcher, and off the stretcher to bed, should
be done slowly with patient completely passive, maintaininghead upposition. - Before moving patient onto bed, raise head of bed 30° to
45° and maintain the patient in this position under close observation
for 12 to 24 hours. - Advise patient to remain still in bed, inhead upposition for the first 24 hours.
- Obtain visitors cooperation in keeping the patient quiet
and inhead upposition, especially in first few
hours. - Encourage oral fluids and diet as tolerated.
- Antinauseants of the phenothiazine class should not be administered
to the treat postprocedural nausea or vomiting (seeWARNINGS). Since persistent nausea and vomiting
may result in dehydration, prompt consideration of volume replacement
by intravenous fluids is recommended.
Many radiopaque contrast agents
are incompatible
and many other drugs; therefore, no other pharmaceuticals should be
admixed with contrast agents.
should not be performed in the presence of significant local or systemic
infection where bacteremia is likely.
The most frequently reported adverse
reactions following intrathecal administration of iopamidol are headache,
nausea, vomiting, and musculoskeletal pain. These reactions usually
occur 1 to 10 hours after injection, almost all occurring within 24
hours. They are usually mild to moderate in degree, lasting for a
few hours and usually disappearing within 24 hours. Rarely, headaches
may be severe or persist for days. Headache is often accompanied by
nausea and vomiting, and tends to be more frequent and persistent
in patients not optimally hydrated. Backache, neck stiffness, numbness
and paresthesias, leg or sciatic-type pain occurred less frequently,
often in the form of a transient exacerbation of preexisting symptomatology.
Transient alterations in vital signs may occur and their significance
must be assessed on an individual basis.
The following table of incidence of reactions
is based on clinical studies with ISOVUE-M (lopamidol Injection) in
about 686 patients.
| Estimated Overall Incidence | ||
|---|---|---|
| System | > 1% | ≤ 1% |
| Body as a Whole | headache (16.4%) | pyrexia muscle weakness hot flashes malaise fatigue weakness |
| Digestive | nausea (7.3%) vomiting (3.6%) | diarrhea heartburn |
| Musculoskeletal | back pain (2.2%) leg pain (1.4%) neck pain (1.1%) | leg cramps sciatica cervicobrachial irritation meningeal irritation radicular irritation lumbosacral other musculoskeletal pain involuntary movement burning sensation |
| Cardiovascular | hypotension (1.1%) | tachycardia hypertension chest pain |
| Nervous | none | emotional stress dizziness paresthesia confusion hallucinations lightheadedness syncope numbness cold extremities ataxia irritability |
| Urogenital | none | urinary retention |
| Respiratory | none | dyspnea |
| Skin and Appendages | none | rash |
| Miscellaneous | none | injection site pain |
Other adverse effects reported
in clinical literature for iopamidol include facial neuralgia, tinnitus,
and sweating.
Major
motor seizures have been reported in the clinical literature and since
market introduction in the United States. Early onset of seizures
(less than two hours) is indicative of early substantial intracranial
entry. Transitory EEG changes occur and usually take the form of slow
wave activity.
While
not observed in controlled clinical studies with ISOVUE-M (lopamidol
Injection), the following adverse reactions may occur because they
have been reported with ISOVUE-M and other nonionic water soluble
contrast agents: cardiovascular (arrhythmias); pulmonary (apnea);
bacterial meningitis, and aseptic meningitis syndrome; allergy or
idiosyncrasy (chills, pruritus, nasal congestion, Guillain-Barre syndrome);
CNS irritation (psycho-organic syndrome: mild and transitory perceptual
aberrations such as depersonalization, anxiety, depression, hyperesthesia,
disturbances in speech, sight, or hearing, and disorientation; in
addition, hyperreflexia or areflexia, hypertonia or flaccidity, restlessness,
tremor, echoacousia, echolalia, asterixis or dysphasia have occurred).
Profound mental disturbances have rarely been reported (various forms
and degrees of aphasia, mental confusion or disorientation); the onset
is usually at 8 to 10 hours and lasts for about 24 hours without aftereffects.
However, occasionally they have been manifest as apprehension, agitation
or progressive withdrawal to the point of stupor or coma. In a few
cases, these have been accompanied by transitory hearing loss or other
auditory symptoms and visual disturbances (believed subjective or
delusional). Persistent cortical loss of vision in association with
convulsions, and ventricular block have been reported. Rarely, persistent
though transitory weakness in the leg or ocular muscles has been reported.
include sensory and/or motor or nerve root disturbances, myelitis,
persistent leg muscle pain or weakness, or sixth nerve palsy, or cauda
equina syndrome. Muscle cramps, fasciculation or myoclonia, spinal
convulsion, paralysis, or spasticity are unusual.
Other drugs should not be admixed
with iopamidol (see
Intrathecal administration of
corticosteroids with iopamidol is contraindicated. Because of overdosage
considerations, immediate repeat myelography in the event of technical
failure is contraindicated (see interval recommendation under
should not be performed in the presence of significant local or systemic
infection where bacteremia is likely.
Many radiopaque contrast agents
are incompatible
and many other drugs; therefore, no other pharmaceuticals should be
admixed with contrast agents.
ISOVUE-M (lopamidol Injection) formulations
are stable, aqueous, sterile, and nonpyrogenic solutions for intrathecal
administration.
Each
mL of ISOVUE-M 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 mL.
Each mL of ISOVUE-M 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 mL.
The pH of ISOVUE-M contrast media has bean
adjusted to 6.5-7.5 with hydrochloric acid and/or sodium hydroxide.
Pertinent physicochemical data are noted below. ISOVUE-M (lopamidol
Injection) is hypertonic as compared to plasma and cerebrospinal fluid
(approximately 285 and 301 mOsm/kg water, respectively).
| Iopamidol | ||||
|---|---|---|---|---|
| Parameter | 41% | 61% | ||
| Concentration (mgl/mL) | 200 | 300 | ||
| Osmolality @ 37° C (mOsm/kg water) | 413 | 616 | ||
| Viscosity (cP) @ 37° C | 2.0 | 4.7 | ||
| @ 20° C | 3.3 | 8.8 | ||
| Specific Gravity @ 37° C | 1.216 | 1.328 |
lopamidol is designated
chemically as (S)-N,N’-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]- 2,4,6-triiodo-5-lactamidoisophthalamide.
Structural formula:
