AK-FLUOR® (Fluorescein Injection, USP) is a sterile solution in Water for Injection, of Fluorescein prepared with the aid of Sodium Hydroxide. Hydrochloric Acid and/or Sodium Hydroxide may be used to adjust pH (8.0-9.8). AK-FLUOR® is used intravenously as a diagnostic aid. The active ingredient exists as a sodium salt of fluorescein and is represented by the chemical structure:

MW= 376.28

ESTABLISHED NAME

Fluorescein Sodium

CHEMICAL NAME

Spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one,3'6'-dihydroxy, disodium salt

Indicated in diagnostic fluorescein angiography or angioscopy of the fundus and of the iris vasculature.

Inject the contents of the ampule or vial rapidly into the antecubital vein, after taking precautions to avoid extravasation. A scalp (butterfly) needle attached to a small syringe is ideal for administration. A syringe, filled with fluorescein, is attached to transparent tubing and a 25 gauge scalp vein needle for injection.

Insert the needle and draw the patient's blood to the hub of the syringe so that a small air bubble separates the patient's blood in the tubing from the fluorescein. With the room lights on, slowly inject the blood back into the vein while watching the skin over the needle tip. If the needle has extravasated, the patient's blood will be seen to bulge the skin and the injection should be stopped before any fluorescein is injected. When assured that extravasation has not occurred, the room light may be turned off and the fluorescein injection completed. Luminescence appears in the retina and choroidal vessels in 9 to 14 seconds and can be observed by standard viewing equipment. If potential allergy is suspected, an intradermal skin test may be performed prior to intravenous administration, i.e., 0.05 mL injection intradermally to be evaluated 30 to 60 minutes following injection. For pediatric patients, the dose is calculated on the basis of 35 mg for each ten pounds of body weight. Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

AK-FLUOR®, 10% (Fluorescein Injection, USP - Sterile) 100 mg/mL

NDC 17478-253-10 5 mL single dose vials in packs of 12
NDC 17478-254-10 5 mL ampules in packs of 25

AK-FLUOR®, 25% (Fluorescein Injection, USP - Sterile) 250 mg/Ml

NDC 17478-250-20 2 mL single dose vials in packs of 12
NDC 17478-251-20 2 mL ampules in packs of 12

Storage

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]; protect from freezing.

FL00N Rev. 08/05. Akorn Inc., Buffalo Grove, IL 60089. For product inquiry: 1 800 93AKORN (1-800-932-5676) www.akorn.com. FDA revision date: 8/8/2008

Nausea and headache, gastrointestinal distress, syncope, vomiting, hypotension, and other symptoms and signs of hypersensitivity have occurred. Cardiac arrest, basilar artery ischemia, severe shock, convulsions, and thrombophlebitis at the injection site and rare cases of death have been reported. Extravasation of the solution at the injection site causes intense pain at the site and a dull aching pain in the injected arm. (SEE WARNINGS.) Generalized hives and itching, bronchospasm and anaphylaxis have been reported. A strong taste may develop after injection.

The most common reaction is nausea.

No information provided.

Care must be taken to avoid extravasation during injection as the high pH of fluorescein solution can result in severe local tissue damage. The following complications resulting from extravasation of fluorescein have been noted to occur: sloughing of the skin, superficial phlebitis, subcutaneous granuloma, and toxic neuritis along the median curve in the antecubital area. Complications resulting from extravasation can cause severe pain in the arm for up to several hours. When significant extravasation occurs, the injection should be discontinued and conservative measures to treat damaged tissues and to relieve pain should be implemented. Do not mix or dilute with other solutions or drugs in syringe. Flush intravenous cannulas before and after drugs are injected to avoid physical incompatibility reactions. Rare cases of death due to anaphylaxis have been reported (See PRECAUTIONS).

Caution is to be exercised in patients with a history of allergy or bronchial asthma. An emergency tray including such items as 0.1% epinephrine for intravenous or intramuscular use; an antihistamine, soluble steroid, and aminophylline for intravenous use; oxygen should always be available in the event of possible reaction to fluorescein injection.¹ Use only if container is undamaged. If serious intolerance reactions occurred during a first angiography or if a history of severe allergic reactions has been revealed, any further indication of fluores-cein angiography should be considered with caution: the usefulness of the diagnosis should be weighed against the risk of a serious hypersensitivity accident.

Sodium fluorescein may cause serious intolerance reactions: these are always unpredictable but are more common amongst patients who have experienced a poorly tolerated injection of the product (except for symptoms of nausea and vomiting) or who present with a history of allergy: food or drug-induced urticaria, asthma, eczema, hay fever; those intolerance reactions may not be detected by a fluorescein test, which is of no value and may even be dangerous. A visit with a specialist in allergy may clarify the diagnosis.

Under different circumstances, which should be clarified by questioning the patient, the physician may need to administer premedication (although this may not prevent serious accidents):

• this comprises principally anti-H1 antihistamines via the oral route, the corticosteroids prior to the fluorescein injection.
• at present, it is not deemed useful to perform this premedication in all patients, given the very small percentage of accidents.

However, because of the risk of hypersensitivity reactions, the following measure should be taken throughout the procedure:

• the patient must be monitored by the ophthalmologist performing the procedure, throughout the procedure and for 30 minutes after its completion;
• venous access should be kept open for at least 5 minutes, so that any accident can be immediately treated;
• the resources necessary for emergency resuscitation must be available, based on the insertion of a second venous line to allow vascular filling (polyionic solution or colloidal plasma substitute), and the intravenous injection of adrenaline at an appropriate dose (cf. Interactions with other medicinal products and other forms of interaction).

Furthermore, in subjects identified as being at risk, but in whom the procedure is shown to be essential, it must be carried out in the presence of a specialist in resuscitation, particularly when the patient is under beta-blocker therapy, including in the form of eye drops such as adrenaline.

Finally, because of the alkaline pH of the solution, the fluorescein solution must not be injected outside the vein; it is important to ensure that the needle is correctly inserted in the vein before starting the fluorescein injection. If the product leaks into surrounding tissues, the injection should be stopped immediately.

Special precautions for use

A higher risk of adverse reactions in any patient receiving beta-blockers or ACE inhibitors.

In dialyzed patients, use half a 5-mL ampule (10%).

To prevent nausea in predisposed subjects, inject the product very slowly.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

There have been no long-term studies done using fluorescein in animals to evaluate carcinogenic potential.

Use In Pregnancy

Avoid angiography on patients who are pregnant, especially those in first trimester. There have been no reports of fetal complications for fluorescein injection during pregnancy.

Nursing Mothers

Fluorescein has been demonstrated to be excreted in human milk. Caution should be exercised when AK-FLUOR®(Fluorescein Injection, USP) is administered to a nursing woman.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Patient Warning

Skin will attain a temporary yellowish discoloration. Urine attains a bright yellow color. Discoloration of the skin fades in 6 to 12 hours; urine fluorescence in 24 to 36 hours.

REFERENCE

1. Schatz, Burton, Yannuzzi, Rabb. Interpretation of Fundus Fluorescein Angiography, p. 38, C.V. Mosby Co., St. Louis, MO, 1978

No information provided.

Contraindicated in those persons who have shown hypersensitivity to any component of this preparation. Do not use via the intrathecal or arterial routes. Use of this product is generally inadvisable if the patient has history of severe allergy to products containing fluorescein.

The yellowish-green fluorescence of the product demarcates the vascular area under observation, distinguishing it from adjacent areas.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.