Product Monograph - Fluorescite
CLINICAL PHARMACOLOGY
The yellowish-green fluorescence of fluorescein demarcates the vascular area under observation distinguishing it from adjacent areas.
INDICATIONS AND CLINICAL USE
FLUORESCITE is indicated in:
- Diagnostic fluorescein angiography
- Angioscopy of the fundus and of the iris vasculature
CONTRAINDICATIONS
FLUORESCITE is contraindicated in patients who have shown hypersensitivity to fluorescein or to any other component of the preparation.
FLUORESCITE should not be injected intrathecally or intra-arterial.
WARNINGS AND PRECAUTIONS
General
NOT FOR INTRATHECAL USE – INTRAVENOUS INJECTION FOR OPHTHALMIC USE ONLY.
Fluorescein sodium can induce serious intolerance reactions. These intolerance reactions 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), in patients with a history of allergy (such as food or drug induced urticarial, asthma, eczema, allergic rhinitis) or in patients with a history of bronchial asthma.
Intradermal skin tests have limited predicted value with serious intolerance reactions to fluorescein. Fluorescein intolerance reactions can occur following a negative intradermal skin test.
Detailed questioning of each patient must be carried before the angiography to evaluate any prior history of cardiopulmonary disease or allergy or concomitant medications (see DRUG INTERACTIONS).
The risk of hypersensitivity reactions with fluorescein sodium requires:
- To have at one’s disposal appropriate material for emergency resuscitation (including the appropriate facilities and trained personnel), which is based at first on the installation of a 2nd intravenous line, allowing the restoration of the plasma volume (aqueous solution polyionic or colloidal substitute of plasma) and the intravenous injection of adrenaline and other standard resuscitation drugs at the recommended dosage (see DRUG INTERACTIONS);
- Close monitoring of the patient by the ophthalmologist performing the examination, throughout the examination and for at least 30 minutes thereafter;
- Maintaining the infusion line for at least 5 minutes, to treat a possible severe adverse reaction without delay;
- In addition, in patients identified as being at risk of hypersensitivity reactions, but in whom a fluorescein angiography is considered to be essential, it is recommended to carry out the procedures with the equipment and personnel trained in emergency resuscitation in the treatment room.
Serious Warnings and Precautions
The benefit of a fluorescein angiography should be balanced with the risk of severe hypersensitivity reactions (with fatal outcome in some cases).
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 the arm for up to several hours. The correct intravenous position of the needle tip must be ascertained. When significant extravasation occurs, the injection should be discontinued and conservative measures to treat the damaged tissue 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.
The benefit to risk of the angiography procedure should be considered in patients with pre- existing conditions, such as cardiovascular disease, diabetes mellitus, and multiple concomitant drug therapies, in particular beta-blockers (see INTERACTIONS). Literature suggests Fluorescein Angiography (FA) may cause contrast-induced Nephropathy (CIN) based on increased serum creatinine. CIN is a possible risk factor for end-stage renal disease progression.
FLUORESCITE contains up to 3.15 mmol (72.45 mg) sodium per dose. This should be taken into consideration by patients on a controlled sodium diet.
Discolouration: The patient must be made aware that after application, skin will attain a temporary yellowish discolouration and urine will attains a bright yellow colour. Discolouration of the skin fades in 6 to 12 hours; urine fluorescein fades in 24 to 36 hours.
Effects on Ability to Drive and Use Machines: The patient must be made aware that after application and until visual acuity returns to normal, driving a vehicle or operating dangerous machinery is not recommended.
Carcinogenesis and Mutagenesis
There have been no long-term studies done using fluorescein in animals to evaluate carcinogenic potential.
Sexual Function/Reproduction
Studies have not been performed to evaluate the effect of intravenous administration of fluorescein on fertility.
Special Populations
Pregnant Women: There are insufficient data available concerning the use of FLUORESCITE in pregnancy. Animal studies do not indicate teratogenic effects. However, due to limited experience, caution should be exercised when considering the use of FLUORESCITE during pregnancy.
Nursing Women: Fluorescein sodium is excreted in human milk for up to 7 days following systemic administration. A risk to the suckling child cannot be excluded. Following fluorescein angiography, breast-feeding should therefore be temporarily discontinued for at least 7 days and the milk should be pumped off and discarded during this period.
Pediatrics (< 18 years of age): FLUORESCITE may be used in pediatric patients less than 18 years of age.
Geriatrics (> 65 years of age): No overall differences in safety or effectiveness have been observed between elderly and other adult patients.
ADVERSE REACTIONS
The following adverse reactions have been reported with the use of FLUORESCITE. Frequencies cannot be estimated from the available data.
Cardiac disorders: angina pectoris, bradycardia, cardiac arrest, tachycardia Gastrointestinal disorders: abdominal discomfort, abdominal pain, gastrointestinal distress, diarrhea, nausea, retching, vomiting
General disorders and administration site conditions: asthenia, chest pain, chills, edema, extravasation, feeling hot, hot flush, malaise, pain
Immune system disorders: anaphylactic reaction, anaphylactic shock, hypersensitivity Nervous system disorders: cerebrovascular accident, convulsion, dizziness, dysgeusia, headache, hypoesthesia, loss of consciousness, paresthesia, syncope, tremor
Renal and urinary disorders: urine fluorescein
Respiratory, thoracic and mediastinal disorders: asthma, bronchospasm, cough, dyspnea, laryngeal edema, pulmonary edema, respiratory arrest, sneezing, throat irritation, throat tightness Skin and subcutaneous tissue disorders: cold sweat, eczema, erythema, hyperhidrosis, pruritis, rash, skin discolouration, urticarial
Vascular disorders: basilar artery ischemia, hypertension, hypotension, pallor, shock, thrombophlebitis, vasodilatation, vasospasm, vertebrobasilar insufficiency
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.
DRUG INTERACTIONS
Fluorescein is a relatively inert dye and specific drug interactions have not been reported. There are a few case reports of potential interactions with organic anion transporters and interference with certain laboratory tests. The fluorescence may interfere with the analysis of blood and urinary parameters for a period of 3 to 4 days. Caution is advised when performing therapeutic drug monitoring to drugs with a narrow therapeutic window, e.g. digoxin, quinidine. Compounds that inhibit or compete with the active transport of organic anions (e.g., probenecid) may affect the systemic profile of fluorescein.
The concomitant use of FLUORESCITE with beta-blocking agents (including eye drops) may rarely provoke severe anaphylactic reactions. Beta-blocking agents could reduce the vascular compensation reactions to anaphylactic shock and also reduce the effectiveness of adrenaline in the presence of cardiovascular collapse.
Concomitant intravenous injection of other solutions or the mixing of FLUORESCITE with other solutions should be avoided as the possibility of interactions cannot be excluded.
DOSAGE AND ADMINISTRATION
Use only if the container is undamaged.
Parental drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. 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.
Inject the contents of the vial or pre-filled syringe rapidly into the antecubital vein, after taking precautions to avoid extravasation. 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 injected intradermally to be evaluated 30 to 60 minutes following injection.
For children, the dose is calculated on the basis of 35 mg for each ten pounds of body weight.
OVERDOSAGE
No case of overdose has been reported. No toxic effects are expected given the minimal risk of overdose with FLUORESCITE.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
STORAGE AND STABILITY
Store at 2º - 30ºC (36º - 86ºF).
DOSAGE FORMS, COMPOSITION AND PACKAGING
FLUORESCITE contains:
Medicinal ingredient: fluorescein 10% w/v (as fluorescein sodium)
Non-medicinal ingredients: sodium hydroxide and/or hydrochloric acid (to adjust pH), water for injection.
FLUORESCITE is supplied as a 10% solution for injection in 5 mL vials.