Clodifen

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

Composition:

Active substance: diclofenac;

1 ml of solution contains sodium diclofenac 1 mg;

Excipients: trometamol, polyethoxylated castor oil, disodium edetate, mannitol (E 421), benzalkonium chloride, diluted hydrochloric acid, purified water.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, colorless or slightly yellow solution.

Pharmacotherapeutic group.
Medicinal products used in ophthalmology. Anti-inflammatory agents. Diclofenac. ATC code S01B C03.

Pharmacological Properties.

Pharmacodynamics.

The active ingredient of the medicinal product, diclofenac, is a non-steroidal anti-inflammatory drug (NSAID) possessing analgesic and anti-inflammatory properties.

Inhibition of prostaglandin biosynthesis, which has been experimentally demonstrated, is considered a key factor in the mechanism of action of diclofenac. Prostaglandins play an important role in the etiology of inflammation and pain.

It has been established that the medicinal product:

• inhibits pupillary constriction during cataract surgery;
• reduces inflammation following surgical intervention;
• decreases the severity of pain and discomfort in ophthalmology associated with corneal epithelial damage after photorefractive keratectomy (PRK) or minor trauma;
• reduces the incidence of angiographically diagnosed cystoid macular edema following cataract surgery, although the clinical significance of this observation requires further investigation;
• reduces the intensity of postoperative inflammation and discomfort more effectively than topical steroids, without causing the adverse reactions typical of steroid agents, such as delayed healing of conjunctival wounds and increased intraocular pressure;
• reduces the intensity of ocular inflammation, pain, and discomfort (photophobia, burning/stinging, foreign body sensation, severe headache-like eye pain, and itching) more effectively than placebo following corneal surgery, such as radial keratotomy.

The effective daily dose of the medicinal product (approximately 0.25–0.5 mg of sodium diclofenac) corresponds to less than 1% of the recommended daily dose of diclofenac for rheumatic symptoms.

Pharmacokinetics.

Following instillation into the conjunctival sac, maximum concentrations of diclofenac in the cornea and conjunctiva are maintained for 30 minutes. Diclofenac is distributed predominantly in these two tissues as well as in the uvea of the eye. It is rapidly eliminated from the body, with complete elimination observed within 6 hours.

Penetration of diclofenac into the anterior chamber of the eye in humans has been demonstrated. However, the concentration of the active substance achieved in the blood is significantly below the detection limit and lacks clinical significance.

Clinical characteristics.

Indications.

• Inhibition of intraoperative miosis during cataract surgery.
• Treatment of postoperative inflammation following cataract removal.
• Management of pain and discomfort in ophthalmology associated with corneal epithelial damage after excimer photorefractive keratectomy (PRK) or minor non-penetrating trauma.
• Control of inflammation following argon laser trabeculoplasty (ALT).
• Reduction of signs and symptoms of seasonal allergic conjunctivitis (SAC) in ophthalmology.
• Treatment of inflammation and discomfort following strabismus surgery.
• Management of pain and discomfort in ophthalmology following radial keratotomy.

Contraindications.

• Hypersensitivity to diclofenac and/or to any excipients of the medicinal product.
• Use in patients with a history of bronchial asthma attacks, urticaria, or acute rhinitis associated with the use of acetylsalicylic acid or other medicinal products that inhibit prostaglandin synthetase activity (cross-sensitivity between acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs may occur).
• Intravitreal administration during surgical procedures.

Interaction with other medicinal products and other forms of interaction.

Ophthalmic solutions containing 0.1% diclofenac have been successfully used in clinical studies in combination with topical antibiotics and beta-blockers.

Concomitant use of topically applied NSAIDs, such as diclofenac, and topical corticosteroids in patients with severe pre-existing corneal inflammation may increase the risk of corneal complications; therefore, the medicinal product should be used with caution in such patients.

Concomitant use of topical diclofenac with medicinal products that prolong bleeding time may increase the risk of hemorrhage.

An interval of at least 5 minutes should be maintained between the administration of different ophthalmic medicinal products.

Special precautions for use.

The anti-inflammatory action of ophthalmic NSAIDs, including diclofenac, may mask the onset and/or progression of ocular infections. If infection is present or if there is a risk of developing infection, appropriate therapy (e.g., antibiotic treatment) should be used concomitantly with the medicinal product.

There is a theoretical possibility that patients receiving other medicinal products which prolong bleeding time or have haemostatic disorders may experience exacerbation of their condition during treatment with diclofenac, although reports of adverse reactions are lacking.

It is known that topically applied NSAIDs, including diclofenac, may slow or delay healing. Topically applied corticosteroids may also delay corneal healing. Caution should be exercised when using topical NSAIDs such as diclofenac concomitantly with topical corticosteroids. The medicinal product should be discontinued immediately in patients who develop symptoms of corneal integrity disruption (see section "Interaction with other medicinal products and other forms of interaction").

Patients who have undergone complex eye surgery, corneal denervation, or who have corneal epithelial defects, diabetes mellitus, non-infectious ocular diseases (e.g., dry eye syndrome), rheumatoid arthritis, or who have undergone repeated eye surgeries within a short period of time, are at increased risk of developing adverse effects of diclofenac on the cornea, which may threaten vision.

The use of NSAIDs, including diclofenac, within 24 hours before surgery or for more than 14 days after surgery may increase the risk/severity of corneal adverse events in patients.

Ophthalmic diclofenac is generally not known to have a significant effect on intraocular pressure. However, the medicinal product should be used with caution after cataract surgery, as in this case, an increase in intraocular pressure may occur.

After instillation of eye drops, nasolacrimal occlusion or closing the eyes for 3 minutes may reduce systemic absorption. This, in turn, may reduce systemic adverse reactions and increase the local activity of diclofenac.

The medicinal product contains benzalkonium chloride. Benzalkonium chloride has been reported to cause eye irritation, dry eye syndrome, and may affect the tear film and corneal surface. Therefore, the medicinal product should be used with caution in patients with dry eye syndrome and in patients with corneal disorders. Patients should be monitored in case of prolonged treatment.

Benzalkonium chloride may be absorbed by contact lenses and may alter their color. Contact lenses should be removed before instillation of eye drops and reinserted 15 minutes after instillation.

The medicinal product also contains polyoxylated castor oil, which may cause skin reactions.

Use during pregnancy or breastfeeding.

Pregnancy.

There are no data on the use of ophthalmic diclofenac during pregnancy. Animal studies have demonstrated reproductive toxicity.

First and second trimesters of pregnancy.

Animal studies conducted to date have not shown fetal risk, but controlled studies in pregnant women have not been performed.

Third trimester of pregnancy.

The medicinal product should not be used during the third trimester of pregnancy due to the potential risk of premature closure of the ductus arteriosus and possible inhibition of uterine contractions.

Breastfeeding period.

Diclofenac is excreted in breast milk; however, no effect on the breastfed infant is expected when therapeutic doses are used. Use of the medicinal product during breastfeeding is not recommended, except when the expected benefit outweighs the potential risk.

Ability to affect reaction speed when driving vehicles or operating machinery.

Patients who experience blurred vision should refrain from driving vehicles or operating machinery.

Method of administration and dosage.

The medicinal product is intended only for instillation into the conjunctival sac of the eye.

It must never be administered subconjunctivally, nor should it be directly injected into the anterior chamber of the eye.

Adults

Children.

The medicinal product should not be used in children. Experience with the use of ophthalmic diclofenac in this age group is limited to a few published clinical studies conducted in the field of strabismus surgery.

Overdose.

The risk of developing adverse reactions due to accidental oral intake of ophthalmic diclofenac is almost negligible, as the 5 mL bottle of eye drops contains only 5 mg of diclofenac sodium, corresponding to approximately 3% of the recommended maximum daily dose of diclofenac for oral administration. For comparison, the maximum daily dose of diclofenac recommended for oral use in children is 2 mg/kg body weight.

Side effects

Adverse reactions are classified by frequency of occurrence into the following categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

Eye disorders:

Common – punctate keratitis, eye pain, ocular mucosal irritation, itching, conjunctival hyperemia; uncommon – keratitis, increased intraocular pressure, corneal edema, conjunctival edema, corneal deposits, conjunctival follicles, eye discomfort, eye discharge, crusting on eyelid margins, increased lacrimation, eyelid irritation, eye redness; frequency not known – corneal perforation, ulcerative keratitis, corneal epithelial defects, corneal clouding, corneal thinning, allergic conjunctivitis and other allergic eye disorders, eyelid erythema, eyelid swelling and itching, blurred vision.

Infections and infestations:

Frequency not known – rhinitis.

Immune system disorders:

Uncommon – hypersensitivity reactions.

Respiratory, thoracic and mediastinal disorders:

Frequency not known – exacerbation of bronchial asthma, dyspnea, cough.

Skin and subcutaneous tissue disorders:

Frequency not known – urticaria, rash, eczema, erythema, pruritus.

General disorders and administration site conditions:

Uncommon – impaired healing.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life.

3 years. After opening the bottle, the product may be used for up to 4 weeks.

Storage conditions.

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

Packaging.

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

Prescription status.

Prescription only.

Manufacturer.

C.O. Rompharm Company S.R.L., Romania /
S.C. Rompharm Company S.R.L., Romania.

Manufacturer's address and location of operations.

Otopeni city, Eroilor str. № 1A, 075100, jud. Ilfov, Romania.

Marketing authorization holder.

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