a href=javascript:defwindow('water')>water soluble, tricarbocyanine dye with a peak spectral absorption at 800-810 nm in blood plasma or blood.
IC-GREEN™ contains not more than 5.0% sodium iodide. IC-GREEN™ is to be administered
intravenously.
The Aqueous Solvent provided, (pH of 5.5 to 6.5) is a prepared Sterile Water
for Injection used to dissolve IC-GREEN™.
CLINICAL PHARMACOLOGY
Following intravenous injection, IC-GREEN™ is rapidly bound to plasma protein, of which albumin is the principle
carrier (95%). IC-GREEN™ undergoes no significant extrahepatic or enterohepatic
circulation; simultaneous arterial and venous blood estimations have shown negligible
renal, peripheral, lung or cerebro-spinal uptake of the dye. IC-GREEN™ is taken
up from the plasma almost exclusively by the hepatic parenchymal cells and is
secreted entirely into the bile. After biliary obstruction, the dye appears
in the hepatic lymph, independently of the bile, suggesting that the biliary
mucosa is sufficiently intact to prevent diffusion of the dye, though allowing
diffusion of bilirubin. These characteristics make IC-GREEN™ a helpful index
of hepatic function.
INDICATIONS
AND USES
For determining cardiac output, hepatic function and liver blood flow, and for ophthalmic angiography.
DOSAGE AND ADMINISTRATION
INDICATOR-DILUTION STUDIES: IC-GREEN™ permits recording of the indicator-dilution curves for both diagnostic
and research purpose independently of fluctuations in oxygen saturation. In
the performance of dye dilution curves, a known amount of dye is usually injected
as a single bolus as rapidly as possible via a cardiac catheter into selected
sites in the vascular system. A recording instrument (oximeter or densitometer)
is attached to a needle or catheter for sampling of the dye-blood mixture from
a systemic arterial sampling site.
Under sterile conditions, the IC-GREEN™ powder should be dissolved with the
Aqueous Solvent provided for this product, and the solution used within 10 hours
after it is prepared. If a precipitate is present, discard the solution. The
amount of solvent to be used can be calculated from the dosage form which follows.
It is recommended that the syringe used for injection of the dye be rinsed with
this diluent. Isotonic saline should be used to flush the residual dye from
the cardiac catheter into the circulation so as to avoid hemolysis. With the
exception of the rinsing of the dye injection syringe, saline is used in all
other parts of the catheterization procedure.
This matter of rinsing the dye syringe with distilled water may not be critical,
since it is known that an amount of sodium chloride sufficient to make an isotonic
solution may be added to dye that has first been dissolved in distilled water.
This procedure has been used for constant-rate injection techniques without
precipitation of the dye.
The usual doses of IC-GREEN™ which have been used for dilution curves are as
follows:
Adults - 5.0 mg
Children - 2.5 mg
Infants - 1.25 mg
These doses of the dye are usually injected in a ml volume. An average of five
dilution curves are required in the performance of a diagnostic cardiac catheterization.
The total dose of dye injected should be kept below 2 mg/kg.
Calibrating Dye Curves: To quantitate the dilution curves,
standard dilutions of IC-GREEN™ in whole blood are made as follows. It is strongly
recommended that the same dye that was used for the injections be used in the
preparation of these standard dilutions. The most concentrated dye solution
is made by accurately diluting 1 ml of the 5 mg/ml dye with 7 ml of distilled
water. This concentration is then successively halved by diluting 4 ml of the
previous concentration with 4 ml of distilled water. (If a 2.5 mg/ml concentration
was used for the dilution curves, 1 ml of the 2.5 mg/ml dye is added to 3 ml
of distilled water to make the most concentrated "standard" solution. This concentration
is then successively halved by diluting 2 ml of the previous concentration with
2 ml of distilled water.) Then 0.2 ml portions (accurately measured from a calibrated
syringe) of these dye solutions are added to 5 ml aliquots of the subject's
blood, giving final concentrations of the dye in blood beginning with 24.0 mg/liter,
approximately (actual concentration depends on the exact volume of dye added).
This concentration is, of course, successively halved in the succeeding aliquots
of the subject's blood. These aliquots of blood containing known amounts of
dye, as well as a blank sample of which 0.2 ml of saline containing no dye has
been added, are then passed through the detecting instrument and a calibration
curve is constructed from the deflections recorded.
HEPATIC FUNCTION STUDIES: Due to its absorption spectrum,
changing concentrations of IC-GREEN™ (sterile indocyanine green) in the blood
can be monitored by ear densitometry or by obtaining blood specimens at timed
intervals. The technique for both methods is as follows.
The patient should be studied in a fasting, basal state. The patient should
be weighed and the dosage calculated on the basis of 0.5 mg/kg of body weight.
Under sterile conditions, the IC-GREEN™ powder should be dissolved with the
Aqueous Solvent provided. Exactly 5 ml of aqueous solvent should be added to
the 25 mg vial or exactly 10 ml of aqueous solvent should be added to the 50
mg vial, giving 5 mg of dye per ml of solution.
Inject the correct amount of dye into the lumen of an arm vein as rapidly as
possible, without allowing the dye to escape outside the vein. ( If the photometric
method is used, prior to injecting IC-GREEN™, withdraw 6 ml of venous blood
from the patient's arm for serum blank and standard curve construction, and
through the same needle, inject the correct amount of dye. )
Ear Densitometry: Ear oximetry has also been used and makes
it possible to monitor the appearance and disappearance of IC-GREEN™ without
the necessity of withdrawal and spectrophotometric analysis of blood samples
for calibration. An ear densitometer which has a compensatory photo-electric
cell to correct for changes in blood volume and hematocrit, and a detection
photocell which registers levels has been described. This device permits simultaneous
measurement of cardiac output, blood volume and hepatic clearance of IC-GREEN™
* and was found to provide a reliable index of plasma removal kinetice after
single injections or continuous intrusions of IC-GREEN™. This technique was
employed in newborn infants, healthy adults and in children and adults with
liver disease. The normal subject has a removal rate of 18-24% per minute. Due
to the absence of extra-hepatic removal, IC-GREEN™ was found to be ideally suited
for serial study of severe chronic liver disease and to provide a stable measurement
of hepatic blood flow. In larger doses, IC-GREEN™ has proven to be particularly
valuable in detecting drug-induced alterations of hepatic function and in the
detection of mild liver injury.
*Dichromatic earpiece densitometer supplied by The Waters Company, Rochester,
Minnesota.
A curve using the patient's blood and the vial of IC-GREEN™ being used in the
determination can be constructed as follows:
- Take 6 ml of non-dye-containing venous blood from the patient's arm. Place
in a test tube and allow the blood to clot. The serum is separated by centrifugation.
- Pipette 1 ml of the serum into a microcuvette.
- Add 1 lambda ((lambda)) of the 5 mg/ml aqueous IC-GREEN™ (sterile indocyanine
green) solution to the serum, giving a dilution of 5 mg/liter, the standard
for 50% retention. (The addition of 2 lambda ((lambda)) of the 5 mg/ml IC-GREEN™
solution would give 100% retention; however, this concentration cannot be
read on the spectrophotometer.)
- The optical density of this solution is read at 805 nm, using normal serum
as the blank.
- Using graph paper similar to that used in the illustration, plot the 50%
figure obtained in Step 4, and draw a line connecting this point with the
zero coordinates.
Percentage Retention: A single 20-minute sample (withdrawn
from a vein in the opposite arm to that injected) is allowed to clot, centrifuged
and its optical density is determined at 805 nm using the patient's normal serum
as the blank. Dye concentration is read from the curve above. A single 20-minute
sample of serum in healthy subjects should contain no more than 4% of the initial
concentration of the dye. The use of percentage retention is less accurate than
percentage disappearance rate, but provides reproducible results. Hemolysis
does not interfere with a reading.
Determination Using Disappearance Rate of Dye: To calculate
the percentage disappearance rate, obtain samples at 5, 10, 15 and 20 minutes
after injecting the dye. Prepare the sample as in the previous section and measure
the optical densities at 805 nm, using the patient's normal serum as the blank.
The IC-GREEN™ concentration in each timed specimen can be determined by using
the concentration curve illustrated. Plot values on semilogarithmic paper.
Specimens containing IC-GREEN™ should be read at the same temperature since
its optical density is influenced by temperature variations.
Normal Values: Percentage disappearance rate in healthy subjects is 18-24%
per minute. Normal biological half-time is 2.5-3.0 minutes.
OPHTHALMIC ANGIOGRAPHY STUDIES: The excitation and emission spectra
and the absorption spectra of IC-GREEN™ make it useful in ophthalmic angiography.
The peak absorption and emission of IC-GREEN™ lie in a region (800-850 nm) where
transmission of energy by the pigment epithelium is more efficient than in the
region of visible light energy. IC-GREEN™ also has the property of being nearly
98% bound to blood protein, and therefore, excessive dye extravasation does
not take place in the highly fenestrated choroidal vasculature It is, therefore,
useful in both absorption and fluorescence infrared angiography of the choroidal
vasculature when using appropriate filters and film in a fundus camera.
Dosages up to 40 mg IC-GREEN™ dye in 2 ml of aqueous solvent have been found
to give optimal angiograms, depending on the imaging equipment and technique
used. The antecubital vein injected IC-GREEN™ dye bolus should immediately be
followed by a 5 ml bolus of normal saline.
Clinically, angiograms of uniformly good quality can be assured only after
taking care to optimize the contributions of all possible factors such as, patient
cooperation and dye injection. The foregoing injection regimen is designed to
provide delivery of a spatially limited dye bolus of optimal concentration to
the choroidal vasculature following intravenous injection.
HOW SUPPLIED
AVAILABILITY
IC-GREEN™, Six each 25 mg vials and 10 ml ampules Aqueous solvent, NDC 17478-701-2.
Manufactured for:
Akorn, Inc
Buffalo Grove, IL 60089
SIDE EFFECTS
Anaphylactic or urticarial reactions have been reported in patients with or without history of allergy to iodides.
If such reactions occur, treatment with the appropriate agents, e.g., epinephrine,
antihistamines, and corticosteroids should be administered.
Drug Abuse and Dependence: IC-GREEN™ is not a controlled substance listed
in any of the Drug Enforcement Administration schedules. Its use is not known
to lead to dependence or abuse.
DRUG INTERACTIONS
No Information Provided.
WARNINGS
Two anaphylactic deaths have been reported following IC-GREEN™ administration during cardiac catheterization. One of these was in
a patient with a history of sensitivity to penicillin and sulfa drugs.
The Aqueous Solvent provided for this proiduct, pH 5.5 to 6.5, which is especially
prepared Sterile Water for Injection, should be used to dissolve IC-GREEN™ because
there have been reports of incompatibility with some commercially available
Water for Injection.
PRECAUTIONS
General: IC-GREEN™ Powder and Solution: IC-GREEN™ is unstable in aqueous solution and must be used within 10 hours.
However, the dye is stable in plasma and whole blood so that samples obtained
in discontinuous sampling techniques may be read hours later. Sterile techniques
should be used in handling the dye solution as well as in the performance of
the dilution curves.
IC-GREEN™ (sterile indocyanine green) powder may cling to the vial or lump
together because it is freeze-dried in the vials. This is not due to the
presence of water the moisture content is carefully controlled.
Heparin preparations containing sodium bisulfate reduce the absorption peak
of IC-GREEN™ in blood and, therefore, should not be used as an anticoagulant
for the collection of samples for analysis.
The plasma fractional disappearance rate at the recommended 0.5 mg/kg dose
has been reported to be significantly greater in women than in men, although
there was no significant difference in the calculated value for clearance.
Radioactive iodine uptake studies should not be performed for at least a week
following the use of IC-GREEN™.
Pregnancy Category C: Animal Reproduction studies have not
been conducted with IC-GREEN™. It is also not known whether IC-GREEN™ can cause
fetal harm when administered to a pregnant woman or can affect reproduction
capacity. IC-GREEN™ should be given to a pregnant woman only if clearly indicated.
Nursing Mothers: 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 IC-GREEN™ is administered to a nursing woman.
