FLUBORD

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLUBORD (FLUBORD)

Composition:

Active substance: flurbiprofen;

1 ml of solution contains flurbiprofen sodium (in the form of flurbiprofen sodium dihydrate) 0.3 mg;

Excipients: polyvinyl alcohol; sodium chloride; sodium citrate, dihydrate; potassium chloride; citric acid, monohydrate; disodium edetate; thiomersal; concentrated hydrochloric acid and/or sodium hydroxide; water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, colorless, slightly viscous solution.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory agents. ATC code S01BC04.

Pharmacological Properties.

Pharmacodynamics.

The active substance of the medicinal product, flurbiprofen, is a non-steroidal anti-inflammatory drug (NSAID) that inhibits the synthesis of prostaglandins by suppressing the enzyme cyclooxygenase.

Ophthalmic surgical procedures are associated with the release of prostaglandins, which may lead to prostaglandin-mediated miosis.

It has been established that administration of flurbiprofen in the form of eye drops prior to surgery inhibits the development of intraoperative miosis, presumably due to inhibition of prostaglandin synthesis in ocular tissues.

The aforementioned mechanism of action is not related to effects on sympathetic nervous system activity. In clinical studies, inhibition of acetylcholine-induced miosis was not observed.

It has also been established that prostaglandins are mediators in certain inflammatory processes in the eye. Animal studies have shown that prostaglandins damage the blood-aqueous barrier, cause vasodilation and increase vascular permeability, induce leukocytosis, and elevate intraocular pressure.

Pharmacokinetics.

The concentration of flurbiprofen in the intraocular fluid reaches 213 ng/mL after instillation every 30 minutes for 2 hours prior to surgery.

Clinical Characteristics.

Indications.

To inhibit miosis during surgery (flurbiprofen has no mydriatic effect; its use does not replace the need for mydriatic agents);

• For the treatment of inflammatory conditions of the anterior segment of the eye following surgical procedures and laser trabeculoplasty in patients in whom corticosteroids are contraindicated.

Contraindications.

• Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.
• Epithelial keratitis caused by Herpes simplex (dendritic keratitis).
• Hypersensitivity to acetylsalicylic acid (ASA) or other nonsteroidal anti-inflammatory drugs (NSAIDs) in medical history (risk of cross-reactivity hypersensitivity reactions exists).
• Disorders of hemostasis or concomitant use of medicinal products that prolong bleeding time (when using NSAIDs, there is a risk of prolonged bleeding due to impaired platelet aggregation).
• Third trimester of pregnancy.
• Intravitreal administration during surgical procedures.

Interaction with other medicinal products and other forms of interaction.

Although clinical studies with acetylcholine chloride and animal studies with acetylcholine chloride and carbachol did not reveal any interactions, and there are no theoretical grounds for pharmacological interaction, there have been reports of reduced efficacy of acetylcholine chloride and carbachol when used concomitantly with flurbiprofen.

Special precautions for use.

The use of flurbiprofen may impair the wound healing process.

There have been reports that flurbiprofen use increases the risk of bleeding from ocular tissues during surgical procedures.

Patients with a history of keratitis caused by Herpes simplex require monitoring during treatment with this medicinal product.

The medicinal product contains thiomersal, which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy.

Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and cardiac malformations with gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. In animal studies, administration of prostaglandin synthesis inhibitors resulted in increased pre- and post-implantation loss and embryolethality. Furthermore, an increased incidence of various developmental abnormalities, including cardiovascular defects, has been observed in animals treated with prostaglandin synthesis inhibitors during organogenesis.

During the first and second trimesters of pregnancy, the medicinal product should not be used except when clearly necessary.

When administering the medicinal product to women who are planning pregnancy or during the first and second trimesters of pregnancy, the lowest effective dose should be used for the shortest possible duration.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors pose risks to the fetus:

• cardiopulmonary toxicity (with closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction, which may progress to renal failure with subsequent oligohydramnios.

For the mother and child at the end of pregnancy:

• prolonged bleeding time (due to inhibition of platelet aggregation), which may occur even with low-dose administration;
• delayed uterine contractions, leading to delayed or prolonged labor.

The medicinal product is contraindicated during the third trimester of pregnancy.

Breastfeeding period.

According to available clinical data, NSAIDs may pass into breast milk in small amounts. The medicinal product should be avoided during breastfeeding if possible.

It is unknown whether flurbiprofen or its metabolites are excreted in human breast milk.

The decision regarding continuation or discontinuation of breastfeeding or continuation or discontinuation of treatment should be made after weighing the benefits of breastfeeding for the child against the benefits of treatment for the mother.

Ability to affect reaction speed when driving or operating machinery.

Transient blurred vision may occur after administration of flurbiprofen eye drops. In such cases, patients should refrain from driving or operating machinery until vision is fully restored.

Method of Administration and Dosage

The medicinal product is intended for ophthalmic use (into the conjunctival sac).

Adults.

Inhibition of miosis during surgery.

1 drop should be administered into the eye every 30 minutes, starting 2 hours before surgery. The last instillation should be performed 30 minutes before surgery.

Treatment of inflammatory conditions of the anterior segment of the eye following surgical intervention and laser trabeculoplasty.

24 hours after surgery, the medicinal product should be administered 1 drop 4 times daily for at least 7 days following laser trabeculoplasty or for 2–3 weeks following other surgical interventions.

To prevent contamination of the dropper tip and the contents of the bottle, care must be taken not to touch the eyelids, adjacent areas, or other surfaces with the tip of the dropper bottle.

If more than one ophthalmic agent is used locally, the interval between their administration should be at least 5 minutes. Ophthalmic ointments should be applied last.

Special patient categories.

Elderly patients.

No special recommendations for these patients are required.

Children.

The efficacy and safety of ophthalmic use of flurbiprofen in children have not been established.

Overdose.

Overdose with ophthalmic flurbiprofen is generally not associated with the development of severe adverse reactions.

In case of accidental ingestion of the solution from the bottle, symptomatic treatment should be administered.

Adverse Reactions

During clinical trials with flurbiprofen, the following adverse reactions have been reported.

Eye-related:

Very common (≥ 1/10) — eye irritation, eye pain, hyphema (see section "Special Warnings and Precautions for Use").

In the post-marketing period of flurbiprofen use, the following adverse reactions have been reported.

Eye-related:

Frequency unknown (cannot be estimated from available data) — intraocular hemorrhage (see section "Special Warnings and Precautions for Use"), mydriasis (persistent mydriasis), ocular hyperemia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine registration is highly important. It allows continuous monitoring of the benefit-risk ratio of the medicine. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life

3 years.

After opening the bottle, the medicinal product should be used within 15 days.

Storage conditions

Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging

2.5 ml in a dropper bottle; 1 dropper bottle per cardboard box.

Prescription status

Prescription only.

Manufacturer

UORLД MEDICIN ILAC SAN. VE TIDJ. A.Ш. /
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of business operations

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey /
15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing Authorization Holder

WORLD MEDICINE, LLC, Ukraine /
WORLD MEDICINE, LLC, Ukraine.