FLUORESCITE

1 INDICATIONS AND USAGE FLUORESCITE ® Injection 10% is indicated in diagnostic fluorescein angiography or angioscopy of the retina and iris vasculature. FLUORESCITE ® Injection 10% is indicated in diagnostic fluorescein angiography or angioscopy of the retina and iris vasculature. (1)

6 ADVERSE REACTIONS Skin and Urine Discoloration The most common reaction is temporary yellowish discoloration of the skin and urine. Urine may attain a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine in 24 to 36 hours. Gastrointestinal Reactions Nausea, vomiting, and gastrointestinal distress are common adverse events. A strong taste may develop after injection. Hypersensitivity Reactions Symptoms and signs of hypersensitivity have occurred. Generalized hives and itching, bronchospasm and anaphylaxis have been reported. Rare cases of death have been reported. [see Contraindications (4.1) and Warnings and Precautions (5.1) ]. Cardiopulmonary Reactions Cardiac arrest, basilar artery ischemia, severe shock and death may occur rarely. Neurologic Reactions Headache may occur. Convulsions and syncope may rarely occur following injection. Thrombophlebitis Thrombophlebitis at the injection site has 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 Administration (2.3) and Warnings and Precautions (5.2) ]. The most common adverse reactions include skin discoloration, urine discoloration, nausea, vomiting, and gastrointestinal distress. (6) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories,Inc. at 1-800-757-9195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

4 CONTRAINDICATIONS FLUORESCITE ® Injection 10% is contraindicated in patients with known hypersensitivity to fluorescein sodium or any other ingredients in this product. Rare cases of death due to anaphylaxis have been reported. [see Warnings and Precautions (5.1) and Adverse Reactions (6) ]. Fluorescein sodium can induce serious intolerance reactions. These reactions of intolerance are always unpredictable but they are more frequent in patients who have previously experienced an adverse reaction after fluorescein injection (symptoms other than nausea and vomiting) or in patients with history of allergy such as food or drug induced urticaria, asthma, eczema, allergic rhinitis. Detailed questioning of each patient is recommended before the angiography to evaluate any prior history of allergy. FLUORESCITE ® Injection 10% is contraindicated in patients with known hypersensitivity to fluorescein sodium or any other ingredients in this product (4.1)

11 DESCRIPTION FLUORESCITE ® (fluorescein injection, USP) 10% contains fluorescein sodium (equivalent to fluorescein 10% w/v). It is a sterile solution for use intravenously as a diagnostic aid. Its chemical name is spiro[isobenzofuran-1(3H ),9'-[9H]xanthene]-3-one, 3'6'-dihydroxy, disodium salt. The active ingredient is represented by the chemical structure: FLUORESCITE ® (fluorescein injection, USP) 10% is supplied as a sterile, unpreserved, unit dose aqueous solution, that has a pH of 8.0 – 9.8 and an osmolality of 572-858 mOsm/kg. Active ingredient: fluorescein sodium Inactive Ingredients: Sodium hydroxide and/or hydrochloric acid (to adjust pH), and water for injection. chemical

2 DOSAGE AND ADMINISTRATION The normal adult dose of FLUORESCITE ® Injection 10% (100 mg/mL) is 500 mg via intravenous administration. (2.1) For children, the dose should be calculated on the basis of 7.7 mg for each kg of actual body weight (or 35 mg for each 10 pounds of body weight) up to a maximum of 500 mg via intravenous administration. (2.1) 2.1 Dosing Adult Dose- The normal adult dose of FLUORESCITE ® Injection 10% (100 mg/mL) is 500 mg via intravenous administration. For children, the dose should be calculated on the basis of 7.7 mg for each kg of actual body weight (or 35 mg for each 10 pounds of body weight) up to a maximum of 500 mg via intravenous administration. 2.2 Preparation for Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not mix or dilute with other solutions or drugs. Flush intravenous cannulas before and after drugs are injected to avoid physical incompatibility reactions. 2.3 Administration Inject the dose rapidly (1 mL per second is normally recommended) intravenously into the antecubital vein, after taking precautions to avoid extravasation. A syringe, filled with FLUORESCITE ® , may be attached to transparent tubing and a 23 gauge butterfly 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 usually appears in the retina and choroidal vessels in 7 to 14 seconds and can be observed by standard viewing equipment. Reduction in dose from 5 mL to 2 mL of FLUORESCITE ® Injection 10% may be appropriate in cases when a highly sensitive imaging system e.g., scanning laser ophthalmoscope is used.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fluorescein sodium responds to electromagnetic radiation and light between the wavelengths of 465-490 nm and fluoresces, i.e., emits light at wavelengths of 520-530 nm. Thus, the hydrocarbon is excited by blue light and emits light that appears yellowish-green. Following intravenous injection of fluorescein sodium in an aqueous solution, the unbound fraction of the fluorescein can be excited with a blue light flash from a fundus camera as it circulates through the ocular vasculature, and the yellowish green fluorescence of the dye is captured by the camera. In the fundus, the fluorescence of the dye demarcates the retinal and/or choroidal vasculature under observation, distinguishing it from adjacent areas/structures. 12.3 Pharmacokinetics Distribution: Within 7 to 14 seconds after intravenous (IV) administration into antecubital vein, fluorescein usually appears in the central artery of the eye. Within a few minutes of IV administration of fluorescein sodium, a yellowish discoloration of the skin occurs, which begins to fade after 6 to 12 hours of dosing. Various estimates of volume of distribution indicate that fluorescein distributes well into interstitial space (0.5 L/kg). Metabolism: Fluorescein undergoes rapid metabolism to fluorescein monoglucuronide. After IV administration of fluorescein sodium (14 mg/kg) to 7 healthy subjects, approximately 80% of fluorescein in plasma was converted to glucuronide conjugate after a period of 1 hour post dose, indicating relatively rapid conjugation. Excretion: Fluorescein and its metabolites are mainly eliminated via renal excretion. After IV administration, the urine remains slightly fluorescent for 24 to 36 hours. A renal clearance of 1.75 mL/min/kg and a hepatic clearance (due to conjugation) of 1.50 mL/min/kg have been estimated. The systemic clearance of fluorescein was essentially complete by 48 to 72 hours after administration of 500 mg fluorescein.

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3 DOSAGE FORMS AND STRENGTHS Single use 5 mL vial containing 100 mg/mL fluorescein. Single use 5 mL vial containing 100 mg/mL fluorescein. (3)

FLUORESCITE fluorescein sodium FLUORESCEIN SODIUM FLUORESCEIN SODIUM HYDROXIDE HYDROCHLORIC ACID WATER carton

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility There have been no long-term studies done using fluorescein in animals to evaluate carcinogenic potential.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility There have been no long-term studies done using fluorescein in animals to evaluate carcinogenic potential.

NDA021980

FLUORESCITE

fluorescein sodium

0065-0092

HUMAN PRESCRIPTION DRUG

OPHTHALMIC

PRINCIPAL DISPLAY PANEL NDC 0065-0092-65 1 Dozen 5 mL Vials Florescite ® 10% (fluorescein injection, USP) 10% STERILE 100 mg/mL Fluorescein Rx Only FOR INTRAVENOUS USE Store at 2° - 25° C (36° - 77° F) Do Not Freeze Alcon ® ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA ©2000-2009 Alcon, Inc. H11427-1009 LOT: EXP.: MFD.: NDC 0065-0092-65 1 Dozen 5 mL Vials Florescite * 10% (fluorescein injection, USP) 10% STERILE 100 mg/mL Fluorescein Rx Only FOR INTRAVENOUS USE Store at 2° - 25° C (36° - 77° F) Do Not Freeze Alcon ® a Novartis company Alcon Laboratories, Inc . Fort Worth, Texas 76134 USA * a trademark of Norvatis ©2000, 2009, 2015 Novartis GTIN: 10300650092651 S/N: LOT: EXP.: 9010833-0615 NDC 0065-0092-65 Fluorescite ® 10% (fluorescein injection, USP) 10% 100 mg/mL FLUORESCEIN 5 mL STERILE ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA ©2000-2009 Alcon, Inc. Rx Only H11426-0209 LOT: EXP.: carton label

17 PATIENT COUNSELING INFORMATION After administration of fluorescein sodium, skin will attain a temporary yellowish discoloration. Urine attains a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine in 24 to 36 hours. [ see Adverse Reactions (6) ] Distributed By: ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA © 2006, 2016 Novartis Revised: 2/2016 9014068-0117

8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

8.3 Nursing Mothers Fluorescein sodium injection has been demonstrated to be excreted in human milk for up to 4 days. Following fluorescein angiography, breast-feeding should therefore be discontinued for at least 4 days and the milk should be pumped off and discarded during this period.

8.4 Pediatric Use Pediatric patients have been included in clinical studies. No overall differences in safety or effectiveness have been observed between pediatric and adult patients.

8.1 Pregnancy Adequate animal reproduction studies have not been conducted with fluorescein sodium. It is also not known whether fluorescein sodium can cause fetal harm when administered to a pregnant woman. Fluorescein sodium should be given to a pregnant woman only if clearly needed.

8 USE IN SPECIFIC POPULATIONS Caution should be exercised when fluorescein sodium is administered to a nursing woman. (8.3) 8.1 Pregnancy Adequate animal reproduction studies have not been conducted with fluorescein sodium. It is also not known whether fluorescein sodium can cause fetal harm when administered to a pregnant woman. Fluorescein sodium should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers Fluorescein sodium injection has been demonstrated to be excreted in human milk for up to 4 days. Following fluorescein angiography, breast-feeding should therefore be discontinued for at least 4 days and the milk should be pumped off and discarded during this period. 8.4 Pediatric Use Pediatric patients have been included in clinical studies. No overall differences in safety or effectiveness have been observed between pediatric and adult patients. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied FLUORESCITE ® (fluorescein injection, USP) 10% is supplied in a single use 5 mL glass vial with a gray FluroTec coated chlorobutyl stopper and purple flip-off aluminum seal. The vial stopper is not made with natural rubber latex. The vial contains a sterile, red-orange solution of fluorescein sodium. NDC 0065-0092-65 16.2 Storage Store at 2°- 25°C (36°- 77°F). Do Not Freeze