Diftal®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIPHTALE® (DIPHTALE®)

Composition:

Active substance: diclofenac;

1 ml of the preparation contains 1 mg of sodium diclofenac, recalculated to 100 % substance;

Excipients: benzalkonium chloride, boric acid, sodium tetraborate, polysorbate 80, water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Agents used in ophthalmology. Anti-inflammatory agents. Diclofenac. ATC code S01BC03.

Pharmacological Properties

Pharmacodynamics

Diftal® contains sodium diclofenac—a nonsteroidal compound with pronounced anti-inflammatory and analgesic effects. Inhibition of prostaglandin biosynthesis, which has been experimentally demonstrated, is considered a key factor in the drug's mechanism of action. Prostaglandins play an important role in the etiology of inflammation and pain.

It has been established that Diftal®:

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

The effective daily dose following administration of Diftal® (approximately 0.25–0.5 mg of sodium diclofenac) corresponds to less than 1% of the recommended daily dose of the drug for rheumatic symptoms.

Pharmacokinetics

Penetration of diclofenac into the anterior chamber of the eye has been confirmed in humans. After instillation of sodium diclofenac as eye drops, no detectable levels of diclofenac were found in the human systemic circulation.

Clinical characteristics.

Indications.

• Inhibition of intraoperative miosis during cataract surgery (Diftal® does not have typical mydriatic properties and does not replace standard pharmacological agents causing pupil dilation).
• Treatment of postoperative inflammation following cataract extraction and other surgical procedures.
• Management of pain and discomfort in ophthalmology associated with corneal epithelial injury after excimer photorefractive keratectomy (PRK) or minor non-penetrating trauma.
• Control of inflammatory response 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 after radial keratotomy.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• As with other nonsteroidal anti-inflammatory drugs (NSAIDs), Diftal® is contraindicated in patients who have experienced asthma attacks, urticaria, or acute rhinitis associated with the administration of acetylsalicylic acid or other agents inhibiting prostaglandin synthetase activity. Cross-sensitivity between acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs may occur.
• Intraocular administration of the drug during surgical procedures.

Interaction with other medicinal products and other forms of interaction.

If more than one type of eye drops is prescribed, they should be administered at intervals of at least 5 minutes.

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

Concomitant use of Diftal® eye drops with medicinal products that prolong bleeding time may increase the risk of hemorrhage.

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

Special precautions for use.

This medicinal product contains benzalkonium chloride as a preservative, which may cause eye irritation. Contact with soft contact lenses should be avoided (remove contact lenses before administration of the product and reinsert them 15 minutes after administration). The product may discolor soft contact lenses.

It is recommended to refrain from wearing contact lenses during treatment of inflammatory eye diseases.

The anti-inflammatory effect 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 administered concomitantly with the use of this medicinal product.

There is a theoretical possibility that patients receiving other medicinal products that prolong bleeding time or who have hemostatic disorders may experience exacerbation of their condition during treatment with this product, although reports of adverse effects are lacking.

It is known that topically applied NSAIDs 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 steroid agents (see section "Interaction with other medicinal products and other forms of interaction").

Do not use for subconjunctival injections; do not inject into the anterior chamber of the eye.

Treatment with Diftal® should be discontinued immediately in patients who develop symptoms indicating corneal integrity impairment.

After instillation of eye drops, performing nasolacrimal occlusion for 3 minutes may reduce systemic absorption. This, in turn, may lead to reduced systemic side effects and increased local activity of the drug.

Use during pregnancy or breastfeeding.

Pregnancy.

There are no clinical data on the use of Diftal® 0.1% eye drops during pregnancy. Even though systemic exposure is lower than with oral administration, it is unknown whether the systemic effect of Diftal® 0.1% eye drops achieved after topical administration could be harmful to the embryo/fetus. Diftal® 0.1% eye drops should not be used during the first and second trimesters of pregnancy unless clearly necessary. If used, the dose should be as low as possible and the duration of treatment as short as possible.

During the third trimester of pregnancy, systemic use of prostaglandin synthesis inhibitors, including Diftal® 0.1% eye drops, may cause cardiovascular and renal toxicity in the fetus. At late stages of pregnancy, prolonged bleeding may occur in both mother and child, and labor may be delayed. Therefore, Diftal® 0.1% eye drops are not recommended during the last trimester of pregnancy.

Breastfeeding period.

Diclofenac passes into breast milk; however, effects of Diftal® 0.1% at therapeutic doses on the breastfed infant are not expected. The use of diclofenac in ophthalmology is not recommended during breastfeeding, except when the expected benefit of treatment outweighs the potential risk.

Ability to affect reaction speed when driving or operating machinery.

Patients experiencing blurred vision should refrain from driving or operating machinery.

Method of administration and dosage.

Diftal®, eye drops, is intended only for instillation into the conjunctival sac of the eye. It must never be administered subconjunctivally, nor should it be injected directly into the anterior chamber of the eye.

Opening the bottle is performed by puncturing the top part of the neck with a twisting cap until it stops.

For adults

Children.

The drug is not intended for use in children. Experience with the use of diclofenac in this age group is limited to several published clinical studies conducted in the field of surgical treatment of strabismus.

Overdose.

The risk of developing adverse effects due to accidental oral intake of the drug is almost negligible, since a 5 ml bottle of eye drops contains only 5 mg of sodium diclofenac, corresponding to approximately 3% of the recommended maximum daily dose of diclofenac for oral administration.

Adverse Reactions

Adverse reactions observed during clinical trials of the active substance can be categorized by frequency of occurrence: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known – cannot be estimated from 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, ocular discomfort, eye discharge, crust formation 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.

Immune system disorders

Uncommon: hypersensitivity reactions.

General disorders and administration site conditions

Uncommon: impaired healing.

Infections

Frequency not known: rhinitis.

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.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

The shelf life of the product after opening the vial is 28 days.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging

5 ml or 10 ml in a vial. 1 vial per carton.

Prescription status

Prescription only.

Manufacturer

JSC "Farmak".

Manufacturer's name and address of the place of business

74, Kyrylivska Street, Kyiv, 04080, Ukraine.