001531 Indocyanine Green

DESCRIPTION

Indocyanine Green is a sterile, water soluble, tricarbocyanine dye with a peak spectral absorption at 800 - 810 nm in blood plasma or blood. Indocyanine Green contains not more than 5.0% sodium iodide.

The aqueous solvent provided with this product, pH of 5.5 to 6.5, is a prepared sterile water for injection used to dissolve Indocyanine Green.

CLINICAL PHARMACOLOGY

Following intravenous injection, Indocyanine Green is rapidly bound to plasma protein, of which albumin is the principle carrier (95%). Indocyanine Green undergoes no significant extrahepatic or enterohepatic circulation; simultaneous arterial and venous blood estimations have shown negligible renal, peripheral, lung or cerebrospinal uptake of the dye. Indocyanine 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 Indocyanine Green a helpful index of hepatic function.

INDICATIONS AND USAGE

For determining cardiac output, hepatic function and liver blood flow, and for ophthalmic angiography.

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 systemic arterial sampling site.

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.

CONTRAINDICATIONS

Indocyanine Green contains sodium iodide and should be used with caution in patients who have a history of allergy to iodides.

WARNINGS

Two anaphylactic deaths have been reported following Indocyanine 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 with this product, pH 5.5 to 6.5, which is especially prepared sterile water for injection, should be used to dissolve Indocyanine Green because there have been reports of incompatibility with some commercially available water for injection.

PRECAUTIONS

General

Indocyanine Green POWDER and SOLUTION: Indocyanine 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.

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 bisulfite reduce the absorption peak of Indocyanine 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.

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

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

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 Indocyanine Green is administered to a nursing woman.

ADVERSE REACTIONS

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

Indocyanine 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.

OVERDOSAGE

There are no data available describing the signs, symptoms, or laboratory findings accompanying overdosage. The LD50 after I.V. administration ranges between 60 and 80 mg/kg in mice, 50 and 70 mg/kg in rats and 50 and 80 mg/kg in rabbits.

DOSAGE AND ADMINISTRATION

INDICATOR-DILUTION STUDIES: Under sterile conditions, the Indocyanine Green powder should be dissolved with the Aqueous Solvent furnished, and the solution used within 10 hours after it is prepared. 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 Indocyanine Green which have been used for dilution curves are as follows:

Adults:

Children:

Infants:

CALIBRATING DYE CURVES: To quantitate the dilution curves, standard dilutions of Indocyanine 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 successfully 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, successfully 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.