Farmadex

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FARM ADEX (FARM ADEH)

Composition:

Active substance: dexamethasone;

1 ml of solution contains: dexamethasone sodium phosphate, calculated as 100% dry substance – 1 mg;

Excipients: boric acid, sodium tetraborate, disodium edetate, benzalkonium chloride, water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group.

Anti-inflammatory agents used in ophthalmology. Corticosteroids, simple preparations. Dexamethasone. ATC code S01BA01.

Pharmacological properties.

Pharmacodynamics.

Corticosteroids exert anti-inflammatory effects by inhibiting endothelial cell vascular adhesion molecules, cyclooxygenase I or II, and cytokine release. As a result, the production of inflammatory mediators is reduced and leukocyte adhesion to vascular endothelium is suppressed, thereby preventing their penetration into inflamed ocular tissues. Dexamethasone exerts a pronounced anti-inflammatory effect with reduced mineralocorticoid effects compared to some other steroids and is one of the most potent anti-inflammatory agents available.

Pharmacokinetics.

Ophthalmic bioavailability of dexamethasone after topical ocular administration was studied in patients who underwent cataract surgery. Maximum dexamethasone concentration in the aqueous humor, approximately 30 ng/mL, was reached within 2 hours. Subsequently, the concentration declined with a half-life of 3 hours.

Dexamethasone is eliminated from the body via metabolism. Approximately 60 % of the dose is excreted in urine as 6-β-hydroxydexamethasone. Unchanged dexamethasone was not detected in urine. The plasma elimination half-life is relatively short – 3–4 hours. Dexamethasone is bound to serum albumin by approximately 77–84 %. Clearance ranges from 0.111 to 0.225 L/h/kg, and volume of distribution ranges from 0.576 to 1.15 L/kg. Bioavailability of dexamethasone following oral administration is approximately 70 %.

Clinical characteristics.

Indications.

Treatment of steroid-sensitive non-infectious inflammatory and allergic conditions of the conjunctiva, cornea, and anterior segment of the eye, including inflammatory reactions in the postoperative period.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Acute untreated bacterial infections.

Cowpox and smallpox, as well as other viral infections of the cornea and conjunctiva.

Fungal diseases of ocular structures.

Mycobacterial infections of the eye. Keratitis caused by herpes simplex.

Interaction with other medicinal products and other forms of interaction.

Interaction studies with other medicinal products have not been conducted.

Concomitant use of locally applied steroids and non-steroidal anti-inflammatory drugs (NSAIDs) for local application increases the risk of corneal wound healing complications.

CYP3A4 inhibitors (including ritonavir and cobicistat) may reduce the clearance of dexamethasone, leading to more severe adverse effects and adrenal cortex suppression / Cushing's syndrome. Such combination should be avoided unless the benefit outweighs the increased risk of systemic adverse effects of corticosteroids; in such cases, systemic corticosteroid side effects should be monitored in patients.

The use of mydriatic eye drops (e.g., atropine and other anticholinergic agents) that may cause elevated intraocular pressure, concomitantly with dexamethasone eye drops, may lead to additional increase in intraocular pressure.

If several medicinal products for local ocular application are used simultaneously, the interval between their administration should be at least 5 minutes.

Special precautions for use

For ophthalmic use only. This medication is not intended for injection or oral administration.

Do not use without medical examination. The medication should be prescribed only after biomicroscopic examination using a slit lamp and fluorescein staining test.

This medication is not effective in the treatment of Sjögren's keratoconjunctivitis.

Excessive and/or prolonged use of ophthalmic corticosteroids increases the risk of ocular complications and may lead to systemic adverse effects. If inflammation does not subside within a reasonable period during the course of therapy, alternative treatment approaches should be considered to reduce these risks.

Prolonged treatment with locally applied ophthalmic corticosteroids may lead to ocular hypertension and/or glaucoma, resulting in optic nerve damage, decreased visual acuity, visual field defects, and the development of posterior subcapsular cataract. Patients receiving long-term topical corticosteroid therapy should have regular and frequent monitoring of intraocular pressure. This is particularly important in children, as the risk of corticosteroid-induced ocular hypertension is higher and may occur earlier than in adults. The medication is not indicated for use in children. Patients with a personal or family history of glaucoma are at increased risk of corticosteroid-induced elevation of intraocular pressure. Such patients should be monitored weekly.

In acute purulent ocular infections, corticosteroids may mask or exacerbate existing infections. If treatment lasts longer than 10 days, intraocular pressure should be monitored.

The risk of corticosteroid-induced elevation of intraocular pressure and/or corticosteroid-induced cataract formation is increased in predisposed patients (e.g., patients with diabetes mellitus).

Visual disturbances may occur with both systemic and topical corticosteroid use. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist to evaluate possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy (CSCR), reported after systemic and topical corticosteroid use.

Cushing’s syndrome and/or adrenal suppression due to systemic absorption of ophthalmic formulations of dexamethasone may occur after intensive or long-term continuous therapy in susceptible patients, including children and patients receiving CYP3A4 inhibitors (including ritonavir and cobicistat). In such cases, treatment should be tapered gradually.

Corticosteroids may reduce resistance to bacterial, viral, or fungal infections and may mask clinical signs of infection, thereby interfering with the recognition of antibiotic inefficacy. Fungal infection should be considered in patients with persistent corneal ulceration who are receiving or have received these medications. Corticosteroid therapy should be discontinued if fungal infection develops.

Ophthalmic corticosteroids may delay corneal wound healing. It is also known that topically applied NSAIDs may slow or delay wound healing. Concomitant use of topical NSAIDs and topical corticosteroids increases the risk of wound healing complications (see section "Interaction with other medicinal products and other forms of interaction").

In patients with conditions causing thinning of the cornea or sclera, topical corticosteroid use may lead to perforation.

Treatment should not be discontinued prematurely due to the risk of inflammatory relapse following abrupt discontinuation of high-dose corticosteroids.

The medication should be used with particular caution and only in combination with antiviral therapy in the treatment of stromal keratitis or uveitis caused by herpes simplex; periodic slit-lamp microscopy is required.

Wearing contact lenses is not recommended during treatment of ocular inflammation.

The medication contains benzalkonium chloride, which may cause eye irritation and may discolor soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before instilling Pharmadex eye drops and to wait 15 minutes after instillation before reinserting contact lenses. Benzalkonium chloride may cause eye irritation, particularly in patients with dry eye symptoms or corneal disorders (diseases of the cornea, the transparent front layer of the eye).

After instillation of eye drops, the following measures are recommended to reduce systemic absorption:

• Keep eyelids closed for 2 minutes.
• Apply digital pressure to the tear duct (lacrimal sac) for 2 minutes.

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of Pharmadex eye drops during pregnancy are limited. Reproductive toxicity has been demonstrated in animal studies. Pharmadex is not recommended during pregnancy.

Breastfeeding

Systemic administration of corticosteroids results in their presence in human breast milk in concentrations that may affect the nursing infant. However, with topical administration of Pharmadex, systemic exposure is low.

It is unknown whether Pharmadex passes into breast milk. A risk to the nursing infant cannot be excluded. The possibility of temporarily discontinuing breastfeeding during treatment or discontinuing/withholding the medication should be considered, taking into account the potential benefit of the medication for the mother and the benefits of breastfeeding for the infant.

Effect on ability to drive and use machines

Pharmadex has no or negligible effect on the ability to drive or operate machinery. As with other eye drops, transient blurred vision or other visual disturbances may affect the ability to drive or operate machinery. If blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Administration and Dosage

Use in adults, including elderly patients

In cases of severe or acute inflammation, instill 1–2 drops into the conjunctival sac of the affected eye(s) every 30–60 minutes as initial therapy.

If a favorable response is observed, the dosage should be reduced to 1–2 drops into the conjunctival sac of the affected eye(s) every 2–4 hours.

Subsequently, the dosage may be further reduced to 1 drop 3–4 times daily, if this dose is sufficient to control inflammation.

If the desired therapeutic effect is not achieved within 3–4 days, additional systemic or subconjunctival therapy may be prescribed.

For chronic inflammation, the dosage is 1 or 2 drops into the conjunctival sac of the affected eye(s) every 3–6 hours, or more frequently if necessary.

For allergy or mild inflammation, the dosage is 1–2 drops into the conjunctival sac of the affected eye(s) every 3–4 hours until the desired effect is achieved.

Treatment should not be discontinued prematurely (see section "Special Precautions").

Regular monitoring of intraocular pressure is recommended.

After instillation, gentle closure of the eyelids or nasolacrimal occlusion is advised. This reduces systemic absorption of ophthalmic medications and decreases the likelihood of systemic adverse effects.

If multiple ophthalmic agents are prescribed, at least a 5-minute interval should be maintained between administrations. Ophthalmic ointments should be applied last.

Use in hepatic or renal impairment

Pharmadex has not been studied in patients with hepatic or renal disease. However, due to the low systemic absorption of dexamethasone following topical ocular administration, dosage adjustment is not required.

Administration method

Shake the bottle well before use.

To prevent contamination of the dropper tip and suspension, care must be taken not to touch the eyelids, surrounding areas, or any other surfaces with the dropper tip.

Caution! Do not tightly close the cap before first use! Before the initial use, screw the cap on the bottle completely. The spike located on the inner side of the cap will puncture the seal. Immediately before administration, hold the bottle in the palm of the hand to warm it to body temperature. Unscrew and remove the cap, then instill the solution into the eye by gently squeezing the bottle. After instillation, tightly screw the cap back on and store the medication according to the instructions provided.

Children. The efficacy and safety of this medicinal product in children have not been established.

Overdose

No cases of overdose have been reported.

In case of overdose with Pharmadex during topical ocular administration, wash the excess medication from the eye(s) with warm water.

Adverse reactions.

The most frequently observed adverse effect reported during clinical studies was eye discomfort.

Adverse effects were classified according to frequency: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10000 to <1/1000), very rare (<1/10000), or not known (frequency cannot be estimated from the available data). Within each frequency group, adverse effects are listed in order of decreasing severity. Data on adverse effects were obtained from clinical trials and from the post-marketing period of dexamethasone ophthalmic drops and/or ointment use.

The following adverse reactions have been identified based on post-marketing experience. Based on the available data, it is not possible to estimate their frequency.

Description of some adverse reactions.

Prolonged treatment with corticosteroids for local ophthalmic use may lead to ocular hypertension and/or glaucoma with subsequent optic nerve damage, decreased visual acuity and visual field changes, as well as formation of posterior subcapsular cataract (see section "Special precautions").

Since the drug contains corticosteroids, in the presence of diseases causing thinning of the cornea or sclera, the risk of perforation increases, especially after prolonged use.

Corticosteroids may reduce resistance to infections (see section "Special precautions").

Reporting of adverse reactions

Reporting of adverse reactions following drug registration is of great importance. It enables continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions.

Shelf life.

3 years.

After opening the bottle, the product is suitable for 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 of 2°C to 8°C. Keep out of reach of children.

Packaging. 5 ml or 10 ml in a bottle. 1 bottle in a pack.

Prescription status.

Prescription only.

Manufacturer. JSC "Farmak".

Address of manufacturer and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.