Dexanova

INSTRUCTIONS for medical use of the medicinal product DEXANOVA (DEXANOVA)

Composition:

Active substance: dexamethasone;

1 ml of solution contains dexamethasone phosphate 1 mg (as dexamethasone sodium phosphate);

Excipients: disodium phosphate, dodecahydrate; sodium chloride; disodium edetate; 1N solution of sodium hydroxide and/or 1N solution of hydrochloric acid (for pH adjustment); water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, colorless aqueous solution, free from visible particles, in a white opaque plastic ophthalmic dispenser.

Pharmacotherapeutic group. Ophthalmological anti-inflammatory agents, corticosteroids, single-component preparations. ATC code S01B A01.

Pharmacological properties.

Pharmacodynamics.

Dexamethasone sodium phosphate is a water-soluble inorganic ester of dexamethasone. It is a synthetic corticosteroid with anti-inflammatory, anti-allergic, and anti-pruritic effects. The anti-inflammatory effect of dexamethasone is approximately 25 times stronger than that of hydrocortisone and 5 times stronger than that of prednisolone. It affects all phases of the inflammatory process, reduces vascular permeability, inhibits leukocyte migration, phagocytosis, release of kinins, and antibody production.

Pharmacokinetics.

Due to its hydrophilic properties, dexamethasone sodium phosphate is poorly absorbed when applied onto intact corneal epithelium. After topical administration, dexamethasone sodium phosphate penetrates into the eye (into the aqueous humor, cornea, iris and choroid, ciliary body, and retina), nasal mucosa, and is hydrolyzed in the body to dexamethasone. Subsequently, dexamethasone and its metabolites are primarily excreted via the kidneys. Systemic absorption of dexamethasone from the conjunctival sac into the bloodstream is minimal; therefore, systemic effects are not clinically significant. Systemic toxicity data for the active substance are well established. Systemic manifestations of dexamethasone may be related to effects caused by glucocorticosteroid imbalance. Repeated-dose toxicity studies of dexamethasone sodium phosphate ophthalmic drops in rabbits revealed systemic corticosteroid-related effects; however, even at doses significantly exceeding the human dose, these effects were not clinically relevant. The occurrence of such effects is unlikely when dexamethasone is used at recommended doses.

Clinical characteristics.

Indications.

Treatment of non-infectious inflammatory diseases of the anterior segment of the eye.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients.
• Infectious eye diseases, unless concomitant antimicrobial therapy is administered, such as:
  • acute bacterial purulent infections, including those caused by Pseudomonas or mycobacteria;
  • fungal infections;
  • epithelial herpetic keratitis (dendritic keratitis), cowpox, varicella, and most other viral infections of the cornea and conjunctiva;
  • amebic keratitis.
• Corneal perforations, ulcers, and injuries with incomplete epithelialization (see also section "Special precautions").
• Glucocorticoid-induced ocular hypertension.

Interaction with other medicinal products and other forms of interaction.

If concomitant treatment with other ophthalmic drops is required, they should be administered no sooner than 15 minutes after instillation of the drug. Superficial stromal precipitates of calcium phosphates on the cornea have been observed when corticosteroids and beta-blockers are used concomitantly.

Dexamethasone should not be used simultaneously with medications used in glaucoma treatment, as such use, especially over prolonged periods and at high doses, may lead to an increase in intraocular pressure (IOP).

It is also known that concomitant use of topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) and topical steroids increases the risk of complications in corneal wound healing.

Concomitant use of dexamethasone with agents affecting ocular accommodation or causing pupillary dilation increases the risk of elevated intraocular pressure (particularly in patients with anatomical eye features predisposing to narrow-angle glaucoma).

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

CYP3A4 inhibitors (including ritonavir and cobicistat) may reduce dexamethasone clearance, leading to enhanced effects and adrenal suppression/Cushing's syndrome.

Concomitant use of corticosteroids should be avoided, except when the benefit outweighs the risk of systemic adverse effects. In such cases, patients should be informed about systemic effects of corticosteroids and should monitor their condition.

Special precautions for use.

Dexanova is a sterile solution that does not contain preservatives and is intended for ophthalmic instillation only!

Local corticosteroids should not be used in cases of eye redness without proper diagnosis.

Regular monitoring of patients is required during treatment with dexamethasone ophthalmic drops. Prolonged use of corticosteroids may lead to ocular hypertension/glaucoma (especially in patients who have previously experienced elevated intraocular pressure due to steroid use, patients with pre-existing high intraocular pressure before starting steroid therapy, or patients with glaucoma), as well as the development of cataracts, particularly in children and elderly patients. Dexamethasone ophthalmic drops should be prescribed with caution in children who have received prolonged systemic steroid therapy.

Corticosteroid therapy may reduce the patient's resistance to bacterial, viral, and fungal infections, potentially prolonging the course of ocular disease. In addition, topical application of corticosteroids may cause, exacerbate, or mask symptoms of opportunistic ocular infections.

When ocular infection is present, dexamethasone drops should be used in combination with appropriate and effective antimicrobial therapy. Such patients must undergo regular thorough ophthalmological examinations.

The drug should be used with particular caution and only in conjunction with antiviral therapy when treating stromal keratitis or uveitis caused by herpes simplex; periodic biomicroscopy using a slit lamp is required.

In certain specific inflammatory conditions, such as episcleritis, nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line agents. Dexamethasone should be used only if there are contraindications to the use of NSAIDs.

Corticosteroids applied topically to the eye may delay healing of corneal wounds.

Patients with corneal ulcers generally should not receive topical dexamethasone, except when inflammation is the primary cause of delayed healing and appropriate etiological treatment is administered. Such patients must undergo regular thorough ophthalmological examinations.

Thinning of the cornea and sclera increases the risk of perforation with local corticosteroid use.

Posterior subcapsular cataract may develop following cumulative doses of dexamethasone.

Patients with diabetes mellitus are also more prone to developing subcapsular cataracts after topical corticosteroid use.

The use of topical corticosteroids in the treatment of allergic conjunctivitis is recommended only in severe cases unresponsive to standard therapy and only for short periods.

Systemic absorption during intensive or prolonged continuous therapy with ophthalmic drops containing dexamethasone may lead to Cushing's syndrome and/or adrenal suppression in susceptible patients, children, and patients receiving CYP3A4 inhibitors (including ritonavir and cobicistat). In such cases, treatment should be tapered gradually.

This medicinal product contains 2.177 mg/mL of phosphates (see also section "Adverse reactions"). Cases of corneal calcification have been reported, requiring corneal transplantation to restore vision in patients receiving ophthalmic preparations containing phosphates. At the first signs of corneal calcification, the use of this product must be discontinued and further treatment should be continued with phosphate-free preparations.

Visual disturbances may occur with both systemic and topical use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should consult an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy.

Wearing contact lenses during treatment increases the risk of developing infections. The use of contact lenses should be avoided during therapy with ophthalmic drops containing corticosteroids.

Patients with a history of contact hypersensitivity to silver should not use this product, as the drops may contain trace amounts of silver.

Use during pregnancy or breastfeeding.

Pregnancy

There are insufficient data to assess the potential risks of using Dexanova during pregnancy. Corticosteroids cross the placental barrier. There are no data on teratogenic effects of the drug in humans following topical administration.

There have been reports of effects on the fetus/newborn following systemic administration of corticosteroids at higher doses (intrauterine growth retardation, adrenal insufficiency). There are no reports of such effects with topical ophthalmic use. The use of this drug during pregnancy is not recommended.

Breastfeeding

There are no data on the passage of the drug into breast milk, but a risk to the breastfed infant cannot be excluded. Therefore, the potential benefit of the therapy for the mother and the benefit of breastfeeding for the infant should be weighed, and either breastfeeding should be temporarily discontinued during treatment, or therapy with the drug should be stopped.

Fertility

There are insufficient data on the effect of dexamethasone on fertility.

Ability to affect reaction speed when driving or operating machinery.

As with other ophthalmic drops, instillation may cause transient blurred vision.

Until this effect subsides, patients should not drive or operate machinery.

Method of Administration and Dosage

The medicinal product is intended for ophthalmic use only.

This medicinal product should be used only under strict supervision of an ophthalmologist.

The usual dosage is 1 drop into the affected eye 4–6 times daily.

In severe cases, treatment may be initiated with 1 drop hourly. Subsequently, if a favorable therapeutic response is observed, the dosage should be reduced to 1 drop every 4 hours. A gradual reduction of the dosage is recommended to prevent disease recurrence. The duration of treatment may range from several days up to a maximum of 14 days.

Elderly Patients

There is extensive experience with the use of dexamethasone ophthalmic drops in elderly patients. The dosage recommendations provided above reflect the clinical data obtained from this experience.

Dexanova is a sterile solution that does not contain preservatives.

Patients must follow these instructions:

• wash hands thoroughly before instillation;
• instill one drop into the affected eye while looking upward and gently pulling down the lower eyelid with a finger. Avoid contact between the dropper tip and the eye or eyelids;
• immediately after instillation, gently press with a finger on the inner corner of the treated eye for several minutes to reduce the risk of systemic reactions and to enhance penetration of the active substance into the eye;
• after use and before re-instillation, the multidose bottle should be tapped once downward without touching the dropper tip to remove any residual liquid from the tip. This is necessary to ensure proper drop delivery in subsequent use;
• patients should be aware that ophthalmic solutions, if handled improperly, may become contaminated with common bacteria known to cause ocular infections.

Nasolacrimal occlusion by pressing on the tear ducts may reduce systemic absorption.

If several locally acting ophthalmic agents are used, they should be administered with an interval of at least 15 minutes.

Children

The safety and efficacy of the product in children have not been established.

Overdose

In case of overdose with topical administration, treatment should be discontinued and the eye(s) should be irrigated with sterile water.

Symptoms following accidental ingestion are unknown. However, as with ingestion of other corticosteroids, it may be advisable to drink plenty of fluids, perform gastric lavage, or induce vomiting.

Adverse Reactions

Adverse effects are classified according to their frequency of occurrence: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Endocrine system disorders: frequency not known – Cushing's syndrome, adrenal suppression (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions for use").

Eye disorders: very common – increased intraocular pressure*; common – discomfort*, irritation*, burning*, stinging*, itching*, and blurred vision (see section "Special precautions for use"); uncommon – allergic reactions and hypersensitivity reactions, delayed wound healing, posterior subcapsular cataract*, opportunistic infections, glaucoma*; very rare – conjunctivitis, mydriasis, facial swelling, ptosis; steroid-induced uveitis, corneal calcification, crystalline keratopathy, changes in corneal thickness*, corneal edema, corneal ulcer, and corneal perforation.

* See section "Description of selected adverse reactions"

Description of selected adverse reactions.

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

Increased intraocular pressure associated with local corticosteroid therapy usually occurs within 2 weeks of treatment.

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

Immediately after instillation, discomfort, irritation, burning, stinging, itching, and blurred vision may occur. These symptoms are generally mild and transient and do not have consequences.

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

With frequent instillations, systemic absorption may occur, leading to associated suppression of adrenal cortex function. There have been isolated reports of corneal calcification with the use of ophthalmic drops containing phosphates in some patients who had significant corneal damage.

Reporting of adverse reactions

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

Shelf life. 3 years.

After first opening of the bottle, the shelf life is 28 days.

Storage conditions.

No special storage conditions required.

Keep out of reach and sight of children.

Packaging.

6 ml in a polyethylene bottle with a multi-dose dropper applicator Novelia® and a tamper-evident screw cap; 1 or 3 bottles per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Manufacturer responsible for batch release:

Pharmaselect International Betriebsgesellschaft GmbH.

Address of manufacturer and site of operations.

Ernst-Melichar-Gasse 20, 1020 Vienna, Austria.

Phone/fax: +43 178603860 / +43 1786038620

Email: [email protected]