Fluorescein

6. ADVERSE REACTIONS The most common adverse reactions include skin discoloration, urine discoloration, nausea, vomiting, and gastrointestinal distress. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Lambda Therapeutics Limited at 1-855-642-2594or email: safety.nexuspharma@lambda-cro.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ( 6 ) 6.1 Skin and urine discoloration The most common reaction is discoloration of the skin and urine. Skin will attain a temporary ye lowish discoloration. Urine attains a bright ye llow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine in 24 to 36 hours. 6.2 Gastrointestinal Reaction The next most common adverse reaction is nausea. Vomiting, and gastrointestinal distress have also occurred. A strong taste may develop after injection. 6.3 Hypersensitivity Reactions Symptoms and signs of hypersensitivity have occurred. Generalized hives and itching, bronchospasm and anaphylaxis have been reported. [see CONTRAINDICATIONS ( 4.1 ) and WARNINGS AND PRECAUTIONS ( 5.1 )] . 6.4 Cardiopulmonary Reactions Syncope and hypotension may occur. Cardiac arrest, basilar artery ischemia, severe shock and death may occur rarely [see WARNINGS AND PRECAUTIONS ( 5.1 )] . 6.5 Neurologic Reactions Headache may occur. Convulsions may rarely occur following injection. 6.6 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 )] .

4. CONTRAINDICATIONS Hypersensitivity to any component of this product. ( 4.1 ) 4.1 Hypersensitivity Fluorescein Injection, USP 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 ( 6.2 )] .

11. DESCRIPTION Fluorescein Injection, is a sterile solution for use intravenously as a diagnostic aid. It is a dark reddish orange solution with a pH of 8.3 to 9.8 and an osmolality of 572 to 858 mOsm/kg for the 10% and 1800 to 2200 mOsm/kg for the 25%. 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: MW = 376.27 Fluorescein Injection 10% contains: Active: fluorescein sodium (equivalent to fluorescein 10 % w/v, 100 mg/mL) Inactives: Sodium Hydroxide and/or Hydrochloric Acid may be used to adjust pH (8.3 to 9.8), and Water for Injection. Fluorescein Injection 25% contains: Active: fluorescein sodium (equivalent to fluorescein 25% w/v, 250 mg/mL) Inactives: Sodium Hydroxide and/or Hydrochloric Acid may be used to adjust pH (8.3 to 9.8), and Water for Injection. Chemical Structure

2. DOSAGE & ADMINISTRATION The normal adult dose of Fluorescein Injection 10%, is 5 mL (500 mg) and of Fluorescein Injection 25%, is 2 mL (500 mg) via intravenous administration. ( 2.1 ) For children, the dose should be calculated on the basis of 35 mg for each ten pounds of body weight (7.7 mg/kg body weight). ( 2.2 ) Do not mix or dilute with other solutions or drugs. ( 2.2 ) 2.1 Dosing Adult Dose The recommended dosage of Fluorescein Injection 10% (100 mg/mL) and of Fluorescein Injection 25% (250 mg/mL) is 500 mg via intravenous administration. Pediatric Dose For children, the dose is 7.7 mg/kg (actual body weight) up to a maximum of 500 mg, via intravenous infusion calculated on the basis of 35 mg for each 10 lbs. (4.54 kg) of body weight. 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. Discard unused portion. 2.3 Administration Inject the dose (over 5-10 seconds is normally recommended) into the antecubital vein, after taking precautions to avoid extravasation. A syringe, fi led with Fluorescein, 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 500 mg to 200 mg Fluorescein Injection, 10% may be appropriate in cases when a highly sensitive imaging system e.g., scanning laser ophthalmoscope is used.

1. INDICATIONS & USAGE Fluoresecin Injection 10%, , (100 mg/mL) and Fluorescein Injection 25% (250 mg/mL) is indicated in diagnostic fluorescein angiography or angioscopy of the retina and iris vasculature. Fluorescein Injection, USP is indicated in diagnostic fluorescein angiography or angioscopy of the retina and iris vasculature. ( 1 )

12. CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fluorescein sodium responds to electromagnetic radiation and light between the wavelengths of 465 to 490 nm and fluoresces, i.e., emits light at wavelengths of 520 to530 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 ye lowish 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 IV administration into the antecubital vein, fluorescein usually appears in the central retinal artery of the eye. Within a few minutes of IV administration of fluorescein sodium, a ye lowish discoloration of the skin occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume of distribution indicate that fluorescein distributes into interstitial space (0.5 L/kg). Metabolism. Fluorescein is metabolized 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. Excretion. Fluorescein and its metabolite 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 essentia ly complete by 48 to 72 hours after administration of 500 mg fluorescein.

12.1 Mechanism of Action Fluorescein sodium responds to electromagnetic radiation and light between the wavelengths of 465 to 490 nm and fluoresces, i.e., emits light at wavelengths of 520 to530 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 ye lowish 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 IV administration into the antecubital vein, fluorescein usually appears in the central retinal artery of the eye. Within a few minutes of IV administration of fluorescein sodium, a ye lowish discoloration of the skin occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume of distribution indicate that fluorescein distributes into interstitial space (0.5 L/kg). Metabolism. Fluorescein is metabolized 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. Excretion. Fluorescein and its metabolite 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 essentia ly complete by 48 to 72 hours after administration of 500 mg fluorescein.

20231025

5

3. DOSAGE FORMS & STRENGTHS Fluorescein Injection 10%, 100 mg/mL in a 5 mL single-dose vial. Fluorescein Injection 25%, 250 mg/mL in a 2 mL single-dose vial. Fluorescein Injection 10%, 100 mg/mL in a 5 mL single dose vial ( 3 ) Fluorescein Injection 25%, 250 mg/mL in a 2 mL single dose vial ( 3 )

Fluorescein Fluorescein Fluorescein Fluorescein Hydrochloric Acid Water Sodium Hydroxide Fluorescein Fluorescein Fluorescein Fluorescein Hydrochloric Acid Water Sodium Hydroxide

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.

ANDA215709

Fluorescein

Fluorescein

14789-123

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

Principal Display Panel – 5 mL Carton Label Rx Only NDC 14789-122-05 Fluorescein Injection, USP 10% 500 mg / 5 mL (100 mg/mL) 10 x 5 mL Sterile Single-dose Vials NEXUS PHARMACEUTICALS Principal Display Panel – 5 mL 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 WARNINGS AND PRECAUTIONS AND ADVERSE REACTIONS ( 6.1 )] . Rx only Manufactured in Italy for: Nexus Pharmaceuticals LLC. 400 Knightsbridge Parkway Lincolnshire, IL 60069 FLRPI01ITR01 Rev. 05/2023

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 has been demonstrated to be excreted in human milk. Caution should be exercised when fluorescein sodium is administered to a nursing woman.

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 Pregnancy Category C. 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 Pregnancy Category C. 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 has been demonstrated to be excreted in human milk. Caution should be exercised when fluorescein sodium is administered to a nursing woman. 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 Fluorescein Injection 10%, is supplied in a single-dose 5 mL glass vial with a gray bromobutyl serum siliconized stopper and orange flip-off cap. It contains a sterile dark reddish orange solution of fluorescein sodium. (NDC 14789-122-05) 5 mL, single dose vials in a package of 10. Fluorescein Injection 25%, is supplied in a single-dose 2 mL glass vial with a gray bromobutyl serum siliconized stopper and orange flip-off cap. It contains a sterile dark reddish orange solution of fluorescein sodium. (NDC 14789-123-05) 2 mL, single dose vials in a package of 10. Fluorescein Injection, USP should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from freezing.