Label: INDOCYANINE GREEN kit
INDOCYANINE GREEN injection, powder, lyophilized, for solution

General:

Indocyanine Green Powder and Solution: Indocyanine Green is unstable in aqueous solution and must be used within 6 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.

Indocyanine Green powder may cling to the vial or lump together because it is freeze-dried in the vials.

Drug Interactions:

Heparin preparations containing sodium bisulfite reduce the absorption peak of Indocyanine Green in blood and, therefore, should not be used as an anticoagulant or the collection of samples for analysis.

Drug/Laboratory Test interactions:

Radioactive iodine uptake studies should not be performed for at least a week following the use of Indocyanine Green.

Carcinogenesis, Mutagenesis, Impairment or Fertility:

No studies have been performed to evaluate the carcinogenicity, mutagenicity, or impairment of feritility

Pregnancy: Teratogenic Effects: Pregnancy Category C:

Animal Reproduction studies have not been conducted with Indocyanine Green. It is also not known whether Indocyanine Green can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Indocyanine Green should be given to a pregnant woman only if clearly indicated.

Nursing Mothers:

lt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Indocyanine Green is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness in pediatric patients have been established.

Indicator-Dilution Studies:

Indocyanine Green permits recording of the indicator-dilution curves for both diagnostic and research purposes 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 systematic arterial sampling site.

Under sterile conditions, the Indocyanine Green for Injection USP powder should be dissolved with Sterile Water for Injection, USP, and the solution used within 6 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. 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 Indocyanine Green which have been used for dilution curves are as follows:

 

- Adults-5 mg

 

- Children-2.5 mg

 

- Infants-1.25 mg

These doses of the dye are usually injected in a 1-mL volume. An average of five dilution curves is required in the performance of a diagnostic cardiac catheterization. The total dose of dye injected should be kept below 2 mg/kg.

Hepatic Function Studies:

Due to its absorption spectrum, changing concentrations of 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 Indocyanine Green for Injection USP powder should be dissolved with Sterile Water for Injection, USP. Exactly 5 mL of Sterile Water for Injection, USP, should be added to the 25-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 Indocyanine 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 Indocyanine 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 Indocyanine Green' and was found to provide a reliable index of plasma removal kinetics after single injections or continuous infusions of Indocyanine 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, Indocyanine 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, Indocyanine Green has proven to be particularly valuable in detecting drug-induced alterations of hepatic function and in the detection of mild liver injury.

Using the ear densitometer, a dosage of 0.5 mg/kg in normal subjects gives the following clearance pattern.

*Dichromatic earpiece densitometer supplied by The Waters Company, Rochester, Minnesota.

Photometric Method

Determination Using Percentage Retention of Dye:

A typical curve obtained by plotting dye concentration versus optical density is shown opposite. Percent retention can be read from this plot.

If more accurate results are desired, a curve using the patient's blood and the vial of Indocyanine Green being used in the determination can be constructed as follows:

1. Take 6 mL of non-dye-containing venous blood from the patients arm. Place in a test tube and allow the blood to clot. The serum is separated by centrifugation.
2. Pipette 1 ml. of the serum into a microcuvette.
3. Add 1 lambda (λ) of the 5-mg/mL aqueous Indocyanine Green solution to the serum, giving a dilution of 5 mg/liter, the standard for 50% retention. (The addition of 2 lambda (λ) of the 5-mg/mL Indocyanine Green solution would give 100% retention; however, this concentration cannot be read on the spectrophotometer.)
4. The optical density of this solution is read at 805 nm, using normal serum as the blank.
5. Plot the 50% figure obtained in Step 4, and draw a line connecting this point with the zero coordinates.

Ophthalmic Angiography Studies:

The excitation and emission spectra (Figure 1) and the absorption spectra (Figure 2) of Indocyanine Green make it useful in ophthalmic angiography. The peak. absorption and emission of Indocyanine 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. Indocyanine 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 Indocyanine Green dye in 2 mL of Sterile Water for Injection, USP, have been found to give optimal angiograms, depending on the imaging equipment and technique used. The antecubital vein injected Indocyanine 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.

Storage:

Store at 20° to 25° C [68 to 77 °F). [See USP Controlled Room Temperature.]

Rx only

Manufactured by:

Patheon Italia S.p.A.
Viale G.B. Stucchi 110
20900 Monza (MB)
ITALY

and

Pulsion Medical Systems SE
Hans-Riedl-Straβe 17
D-85622 Feldkirchen,
Germany

Manufactured for

Novadaq Technologies Inc.
Richmond, BC V6V 2A2
Canada

Distributed by:

LifeCell Corporation
Brachburg, NJ 08876

Sterile Water for Injection USP is Manufactured by:

Abraxis Pharmaceutical Products
Schaumburg, IL 60173
Oct 2011/Rev.00

Cod. 251316