Dexamethasone efg

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXAMETHASONE WFZ (DEXAMETHASONE WFZ)

Composition:

Active substance: dexamethasone;

1 ml of suspension contains 1 mg of dexamethasone;

Excipients: sodium chloride, sodium hydrogen phosphate dodecahydrate, sodium dihydrogen phosphate monohydrate, disodium edetate, benzalkonium chloride solution, polysorbate 80, ethanol 96%, sodium hydroxide 10% solution, purified water.

Pharmaceutical form. Eye drops, suspension.

Main physicochemical properties: white-colored suspension; after shaking for 15 seconds, a uniform distribution of the solid phase is observed, which remains stable for at least 2 minutes.

Pharmacotherapeutic group. Anti-inflammatory agents used in ophthalmology. Simple corticosteroid preparations. ATC code S01BA01.

Pharmacological properties.

Pharmacodynamics.

Dexamethasone is a synthetic glucocorticosteroid with anti-inflammatory, anti-allergic, and antipruritic effects. It affects all phases of the inflammatory process. It reduces vascular permeability, inhibits leukocyte migration, phagocytosis, release of kinins, and antibody production.

Pharmacokinetics.

Dexamethasone administered into the conjunctival sac is absorbed into the aqueous humor, cornea, iris and choroid, ciliary body, and retina.

Absorption of dexamethasone from the conjunctival sac into the systemic circulation is minimal; therefore, systemic effects are not clinically significant.

Data on systemic toxicity of the active substance are well established. Systemic manifestations of dexamethasone may be related to effects associated with glucocorticosteroid imbalance. Repeated-dose toxicity studies of Dexamethasone VFZ eye drops in rabbits revealed systemic effects related to corticosteroids; however, even at doses significantly exceeding the human dose, these manifestations have minimal clinical significance. When Dexamethasone VFZ is used at recommended doses, the occurrence of such effects is unlikely.

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 components of the medicinal product.
• Acute untreated bacterial infections of the eye.
• Acute superficial keratitis caused by herpes simplex.
• Cowpox and smallpox, and other viral infections of the cornea and conjunctiva (except keratitis caused by herpes zoster).
• Fungal diseases of ocular structures and untreated parasitic infections.
• Mycobacterial infections of the eye.
• Perforations, ulcers, and corneal injuries with incomplete epithelialization (see also section "Special precautions").
• Ocular hypertension induced by glucocorticoids.

Interaction with other medicinal products and other forms of interaction.

Dexamethasone should not be combined with drugs used in glaucoma treatment; particularly, such combination should not be used for prolonged periods and in high doses, as this may lead to an increase in intraocular pressure.

Prolonged use of dexamethasone with anticholinergic agents (especially atropine and chemically related compounds) may cause elevated intraocular pressure.

Concomitant use of dexamethasone with agents affecting accommodation or causing pupillary dilation increases the risk of elevated intraocular pressure (especially in patients predisposed to closed-angle glaucoma).

Simultaneous administration of locally applied corticosteroids and locally applied non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of complications in corneal wound healing.

Therapeutic efficacy of dexamethasone may be reduced by phenytoin, phenobarbital, ephedrine, and rifampicin. Glucocorticoids may increase the requirement for salicylates due to increased plasma clearance of salicylate.

Inhibitors of CYP3A4 (including ritonavir and cobicistat) may decrease dexamethasone clearance and/or enhance the effect of adrenal suppression/Cushing's syndrome. Such combinations should be avoided except when the benefit outweighs the risk of increased systemic corticosteroid side effects; in such cases, careful monitoring of systemic corticosteroid effects is required.

Use of contact lenses increases the risk of infections.

When used concomitantly with ophthalmic medicinal products containing phosphates, there is an increased risk of corneal deposit accumulation or corneal clouding, especially in patients with compromised corneas.

Special precautions for use.

• For ophthalmic use only.
• To prevent possible systemic absorption after instillation of the medicinal product, the patient should press with a finger on the tear ducts for 2–3 minutes.
• Prolonged local ocular use of corticosteroids may lead to ocular hypertension and/or glaucoma with subsequent optic nerve damage, decreased visual acuity and visual field defects, as well as the development of posterior subcapsular cataract. During prolonged local ocular corticosteroid therapy, intraocular pressure should be monitored regularly (especially in patients who previously experienced increased intraocular pressure due to steroid use, patients with elevated intraocular pressure before starting steroid therapy, and patients with glaucoma). This is particularly important in children, as the risk of corticosteroid-induced ocular hypertension is higher in this population.

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

• Local corticosteroid therapy should not exceed one week, except under careful monitoring and regular measurement of intraocular pressure.
• Due to the potential for systemic absorption of dexamethasone, Cushing's syndrome and/or adrenal suppression may occur, particularly after prolonged continuous use of dexamethasone eye drops in susceptible patients, including children and patients taking 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 or delay the detection of such infections, interfering with the recognition of antibiotic inefficacy. In patients receiving or having received corticosteroid therapy, fungal corneal infection should be considered in cases of persistent corneal ulceration. Treatment should be discontinued if fungal infection occurs.
• Topically applied corticosteroids may delay corneal wound healing. Concomitant use of topical NSAIDs and corticosteroids may increase the risk of healing complications (see section "Interaction with other medicinal products and other forms of interaction").
• It is known that in patients with conditions causing thinning of the cornea or sclera, local use of corticosteroids may lead to perforation.
• Visual disturbances may occur with both systemic and local use of corticosteroids. If blurred vision or other visual disturbances occur, an ophthalmologist should be consulted to determine possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic corticosteroid use.
• The medicinal product should be used with particular caution and only in combination with antiviral therapy when treating stromal keratitis or uveitis caused by Herpes simplex. Cases of ocular Herpes simplex have been reported in patients undergoing systemic or local corticosteroid therapy for other conditions. The use of corticosteroids in the treatment of Herpes simplex, except for epithelial keratitis caused by Herpes simplex (in which corticosteroids are contraindicated), requires special caution; periodic biomicroscopy using a slit lamp is necessary.
• Wearing contact lenses is not recommended during treatment of ocular inflammation.
• Additionally, the product contains benzalkonium chloride, which may cause eye irritation and is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before instilling Dexamethasone VZF 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 epithelial disorders (the transparent front layer of the eye).
• Treatment should not be discontinued prematurely, as abrupt cessation of high-dose local steroid therapy may lead to rebound ocular inflammation.
• In acute purulent ocular infections, corticosteroids may mask infections or promote the spread of existing infection. If treatment lasts longer than 10 days, intraocular pressure should be monitored.
• During prolonged dexamethasone therapy, corneal status should be evaluated by fluorescein testing and intraocular pressure should be monitored. If fluorescein test is positive or intraocular pressure is elevated, treatment with the product should be discontinued.
• Cases of corneal calcification have been reported in patients receiving ophthalmic products containing phosphates, such as Dexamethasone VZF, requiring corneal transplantation to restore vision. At the first signs of corneal calcification, the product should be discontinued and further treatment should be continued with non-phosphate-containing ophthalmic preparations.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of Dexamethasone VZF eye drops during pregnancy are limited. Reports exist of effects on the fetus/newborn following systemic corticosteroid use at higher doses (intrauterine growth retardation, adrenal suppression). There are no reports of such effects with topical ocular use of this product. Reproductive toxicity has been demonstrated in animal studies.

The use of this medicinal product during pregnancy is not recommended.

Breastfeeding

Systemic administration of corticosteroids results in their presence in human breast milk in amounts that may affect the breastfed infant. However, systemic exposure following topical ocular administration is low. It is not known whether this medicinal product passes into breast milk. A risk to the breastfed infant cannot be excluded. The possibility of temporarily discontinuing breastfeeding during treatment or discontinuing/withholding therapy should be considered, taking into account the potential benefit of the drug for the mother and the benefit of breastfeeding for the infant.

Fertility.

Studies on the effect of dexamethasone instilled into the conjunctival sac on fertility have not been conducted. Clinical data on the effect of dexamethasone on male or female fertility are limited.

Ability to influence reaction speed when driving or operating machinery.

Dexamethasone has no effect or only a 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, the patient should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

For ophthalmic use only. Shake the bottle before use. To prevent contamination of the dropper tip and suspension, care must be taken not to touch the eyelids, adjacent areas, or other surfaces with the tip of the dropper bottle.

The frequency of instillation and duration of treatment depend on the severity of the underlying condition and the response to therapy.

Adults, including elderly patients.

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

When improvement is observed, reduce the dosage to 1–2 drops into the conjunctival sac of the affected eye(s) every 2–4 hours.

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

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

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

In 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.

Do not discontinue therapy prematurely.

After instillation, gentle closure of the eyelids or nasolacrimal occlusion is recommended. This reduces systemic absorption of the drug administered into the eye, thereby decreasing the likelihood of systemic adverse effects.

If several ophthalmic medicinal products are used simultaneously, an interval of at least 5 minutes should be maintained between their administration. Ophthalmic ointments should be applied last.

Use in hepatic and renal impairment.

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

Children.

The efficacy and safety of the drug for use in pediatric patients have not been established.

Overdose.

Prolonged local use of the medicinal product may result in systemic effects. Cases of overdose have not been reported.

In case of overdose following topical administration, wash out the excess drug from the eye(s) with warm water.

Accidental ingestion of the drug is not expected to cause serious adverse effects; however, it is recommended to drink sufficient fluids.

Adverse reactions

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

Adverse reactions 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 frequency not known (cannot be estimated from the available data). Within each frequency group, adverse reactions are listed in order of decreasing severity. Data on adverse reactions were obtained from clinical trials and from the post-marketing period of use of dexamethasone ophthalmic drops and/or ophthalmic ointment.

Description of some adverse reactions.

Increased intraocular pressure, glaucoma, and cataract may occur. Prolonged use of corticosteroids may lead to ocular hypertension/glaucoma (especially in patients who previously experienced elevated intraocular pressure after steroid administration, in patients with already high intraocular pressure prior to steroid use, and in patients with glaucoma), as well as the development of cataracts. Children and elderly patients are particularly sensitive to steroid-induced increases in intraocular pressure.

Elevated intraocular pressure due to local corticosteroid treatment is usually observed within 2 weeks of therapy.

Patients with diabetes mellitus are prone to develop subcapsular cataracts with local steroid use.

Immediately after instillation of the medication, discomfort, irritation, burning, stinging, itching, and blurred vision may occur. These effects are usually mild, transient, and without consequences.

In diseases causing corneal thinning, local steroid use may in some cases lead to perforation.

With frequent instillation, systemic absorption may occur, leading to associated suppression of adrenal cortex function. Isolated cases of corneal calcification have been reported with the use of ophthalmic solutions containing phosphates in certain patients with significant corneal damage.

Shelf life. 2 years.

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

Shelf life after first opening – 4 weeks.

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 of suspension in a polyethylene dropper bottle with a tamper-evident closure №1 in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

ROMFARM COMPANY SRL

ROMPHARM COMPANY SRL

Manufacturer's address and place of business.

Str. Eroilor, nr.1A, cladiri Rompharm 1 si Rompharm 2, Oras Otopeni, Judetul Ilfov, cod postal 075100, Romania