FLUORESCEIN: 588 Adverse Event Reports & Safety Profile

DESCRIPTION: Fluorescein Sodium and Proparacaine Hydrochloride Ophthalmic Solution, USP (Sterile) is a sterile ophthalmic solution combining the disclosing action of Fluorescein with the anesthetic action of Proparacaine Hydrochloride. The active ingredient, Fluorescein Sodium , has the chemical name Spiro [isobenzofuran-1 (3H), 9'-[9H]xanthene]-3-one, 3' ,6' dihydroxy-,disodium salt. It is represented by the following structural formula: The active ingredient, Proparacaine Hydrochloride , has the chemical name Benzoic acid, 3-amino-4-propoxy-, 2-[diethylamino]ethyl ester monohydrochloride. It is represented by the following structural formula: EACH mL CONTAINS : ACTIVES: Fluorescein Sodium, USP, 0.25% [2.5 mg].

Proparacaine

Hydrochloride, USP, 0.5% [5mg]; INACTIVES: Povidone, Boric Acid, Water for Injection, Sodium Hydroxide, or/and Hydrochloric Acid may be added to adjust pH. PRESERVATIVE: Methylparaben 0.1%. structural formula structural formula

INDICATIONS: Intended for use when fitting contact lenses.

DIRECTIONS FOR USE: To insure full fluorescence and patient comfort, the impregnated tip should be moistened before application. One or two drops of sterile irrigating or saline solution should be used for this purpose. Touch conjunctiva or fornix as required with moistened tip. It is recommended that the patient blink several times after application. Grasp tabs between thumbs & index fingers Gently pull tabs apart Remove strip taking care to touch only the white portion of the strip 83851-100: Vista Fluroescein Sodium

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.

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)

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: [email protected] 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. <span class="opacity-50 text-xs">[see CONTRAINDICATIONS ( 4.1 ) and WARNINGS AND PRECAUTIONS ( 5.1 )]</span> .

6.4 Cardiopulmonary Reactions Syncope and hypotension may occur. Cardiac arrest, basilar artery ischemia, severe shock and death may occur rarely <span class="opacity-50 text-xs">[see WARNINGS AND PRECAUTIONS ( 5.1 )]</span> .

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. <span class="opacity-50 text-xs">[see ADMINISTRATION ( 2.3 ) and WARNINGS AND PRECAUTIONS ( 5.2 )]</span> .

AND PRECAUTIONS Respiratory reactions may require intervention. (5.1) Severe local tissue damage can occur with extravasation during injection. (5.2) Nausea and/or vomiting may occur within minutes following injection. (5.3)

5.1 Respiratory Reactions Caution is to be exercised in patients with a history of allergy or bronchial asthma. An emergency tray should be available in the event of possible reaction to FLUORESCITE ® Injection 10%. If a potential allergy is suspected, an intradermal skin test may be performed prior to intravenous administration, i.e., 0.05 mL injected intradermally to be evaluated 30 to 60 minutes following injection. Given the sensitivity and specificity of skin testing, a negative skin test is not proof that a patient is not allergic to fluorescein.

5.2 Severe Local Tissue Damage 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: severe pain in the arm for several hours, sloughing of the skin, superficial phlebitis, subcutaneous granuloma, and toxic neuritis along the median curve in the antecubital area. When significant extravasation occurs, the injection should be discontinued and conservative measures to treat damaged tissue and to relieve pain should be implemented. <span class="opacity-50 text-xs">[see Administration (2.3) and Adverse Reactions(6) ]</span>.

5.3 Nausea and/or Vomiting Nausea and/or vomiting and gastrointestinal distress occur commonly within the first few minutes following injection. These reactions usually subside within 10 minutes.

PRECAUTIONS: This product should be used cautiously and sparingly in patients with known allergies, cardiac disease, or hyperthyroidism. The long-term toxicity is unknown; prolonged use may possibly delay wound healing. Although exceedingly rare with ophthalmic application of local anesthetics, it should be borne in mind that systemic toxicity manifested by central nervous system stimulation followed by depression may occur. Protection of the eye from irritating chemicals, foreign bodies and rubbing during the period of anesthesia is very important. Tonometers soaked in sterilizing or detergent solutions should be thoroughly rinsed with sterile distilled water prior to use. Patients should be advised to avoid touching the eye until the anesthesia has worn off.