Summary of Product Characteristics (SmPC) - Dexamethasone Phosphate 1 mg/ml eye drops, solution

1 NAME OF THE MEDICINAL PRODUCT

Dexamethasone Phosphate 1mg/ml eye drops, solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml solution contains 1 mg of dexamethasone phosphate as dexamethasone sodium phosphate.

Excipient(s) with known effect.

1 ml solution contains 1.485 mg of phosphates equivalent to 5.600mg of Disodium phosphate dodecahydrate

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Eye drops, solution.

Clear, colourless solution, without visible particles

Osmolarity: 230-290 mosmol/kg

pH: 7.5-7.7

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

For treatment of non-infectious inflammatory conditions affecting the anterior segment of the eye.

4.2 Posology and method of administration

Dexamethasone Phosphate 1mg/ml eye drops, solution is for ocular use only. This product should be used only under close ophthalmic supervision.

Posology

The usual posology is of 1 drop 4 to 6 times daily in the affected eye. In severe cases, treatment may be started with 1 drop every hour but dosage should be reduced to one drop every 4 hours when favourable response is observed. Gradual tapering off is recommended in order to avoid a relapse.

The duration of treatment will generally vary from a few days to a maximum of 14 days.

Elderly patients

There has been wide experience with the use of dexamethasone eye drops in Formatted: Left: 3.17 cm, Right: 3.17 cm, Top: 2.54 cm, Bottom: 2.54 cm, Width: 21 cm, Height: 29.7 cm elderly patients. The dosage recommendations given above reflect the clinical data derived from this experience.

Paediatric population

Efficacy and safety has not been established in the paediatric population. In children, longterm continuous corticosteroid therapy should be avoided due to possible adrenal suppression (see section 4.4).

Method of administration

For ocular use only.

Dexamethasone Phosphate 1mg/ml eye drops, solution is a sterile solution that does not contain a preservative.

To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip of the bottle. Keep the bottle tightly closed when not in use.

Patients should be instructed:

To inspect the nozzle for any residual liquid after administering the dose.
To remove excess liquid, hold the bottle upright and gently shake it downward. Immediately replace and tighten the cap to prevent contamination. Ensuring the nozzle remains dry helps prevent microbial growth, maintaining the safety and effectiveness of the eye drops.
Nasolacrimal occlusion by compression of lacrimal ducts may reduce systemic absorption

4.3 Contraindications

Eye infections not controlled by anti-infectious treatment, such as:
Acute purulent bacterial infections including Pseudomonas and mycobacterial infections,
Fungal infections,
Epithelial Herpes simplex keratitis (dendritic keratitis), vaccinia, varicella zoster and most other viral infections of the cornea and conjunctiva, Amoebic Keratitis,
Perforation, ulceration and injury of cornea with uncompleted epithelialisation
(see also section 4.4),
Known glucocorticosteroid-induced ocular hypertension,
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Topical steroids should never be given for an undiagnosed red eye.

Patients should be monitored at frequent intervals during treatment with dexamethasone Phosphate eye drops. Prolonged use of corticosteroid treatment may result in ocular hypertension/glaucoma (especially for patients with previous IOP induced by steroids or with pre-existing high IOP or Glaucoma) and also cataract formation, especially in children and elderly population.

The use of corticosteroids may also result in opportunistic ocular infections due to the suppression of host response or to the delay of their healing. In addition, topical ocular corticosteroids may promote, aggravate or mask signs and symptoms of opportunistic eye infections.

Patients with an eye infection should only receive local steroid treatment when the infection has been controlled by an effective anti-infectious treatment. Such patients should be carefully and regularly monitored by an ophthalmologist.

In some particular inflammatory conditions such as episcleritis, NSAIDS are the first line treatment, Dexamethasone should be used only if NSAIDS are contraindicated.

Patients with a corneal ulcer should generally not receive topical dexamethasone except when inflammation is the main cause of healing delay and when the appropriate aetiological treatment has already been prescribed. Such patients should be carefully and regularly monitored by an ophthalmologist.

Thinning of the cornea and sclera may increase the risk of perforations with the use of topical corticosteroids.

This medicine contains 1.485 mg phosphates in 1ml. Corneal calcification requiring corneal graft surgery for visual rehabilitation has been reported for patients treated with ophthalmic preparations containing phosphates such as Dexamethasone Phosphate 1mg/ml eye drops, solution. At the first sign of corneal calcification the drug should be withdrawn and the patient should be switched to a phosphatefree preparation.

Posterior subcapsular cataract might occur at cumulative doses of dexamethasone.

Diabetics are also more prone to develop subcapsular cataracts following topical steroid administration.

The use of topical steroids in allergic conjunctivitis is only recommended for severe forms of allergic conjunctivitis not responding to standard therapy and only for a short period.

Cushing’s syndrome and/or adrenal suppression associated with systemic absorption of ocular dexamethasone may occur after intensive or long-term continuous therapy in predisposed patients, including children and patients treated with CYP3A4 inhibitors (including ritonavir and cobicistat). In these cases, treatment should be progressively discontinued.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Wearing of contact lenses during treatment with corticosteroid eye drops should be avoided.

Silver

This product can contain silver. Hypersensitivity to silver can occur.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

In case of concomitant treatment with other eye drops, solution, instillations should be spaced out by 15 minutes.

Superficial stromal corneal precipitations of calcium phosphate have been reported under combined use of corticosteroids and topical beta-blockers.

CYP3A4 inhibitors (including ritonavir and cobicistat): may decrease dexamethasone clearance resulting in increased effects and adrenal suppression/Cushing’s syndrome.

The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid effects.

4.6 Fertility, pregnancy and lactation

Pregnancy

Insufficient data are available on the use of Dexamethasone Phosphate 1mg/ml eye drops, solution in human pregnancy to assess possible harmful effects. Corticosteroids cross the placenta. Teratogenic effects have been observed in animals (see section 5.3). However, there is no evidence to date that teratogenic effects are induced in humans. After systemic use of corticosteroids, at higher doses, effects on the unborn/neonate (intrauterine growth inhibition, inhibition of the function of the adrenal cortex) have been reported. However, these effects have not been reported for ocular use.

As a precautionary measure, it is preferable to avoid the use of Dexamethasone Phosphate 1mg/ml eye drops, solution during pregnancy.

Breastfeeding

It is not known whether this medicine is excreted in breast milk. However the total dose of dexamethasone is low.

Dexamethasone 1mg/ml eye drops, solution can be used during lactation.

Fertility

There are no data on potential effects of Dexamethasone Phosphate 1 mg/ml on fertility.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

As with any eye drops, temporarily blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs, the patient must wait until the vision is clear before driving or using machines

4.8 Undesirable effects

Endocrine disorders:

Not known (cannot be estimated from the available data): Cushing’s syndrome, adrenal suppression* (see section 4.4)

Eye disorders:

Very common (≥1/10):

Increase of the intra-ocular pressure*.

Common (≥1/100 to <1/10):

Discomfort*, irritation*, burning*, stinging*, itching* and blurred vision (see also section 4.4)*.

-Uncommon (≥1/1,000 to <1/100):

Allergic and hypersensitivity reactions, delayed wound healing, posterior capsular cataract*, opportunistic infections, glaucoma*.

Very rare (<1/10,000, including isolated reports):

Conjunctivitis, mydriasis, facial oedema, ptosis, corticosteroid-induced uveitis, corneal calcifications, crystalline keratopathy, changes in corneal thickness*, corneal oedema, corneal

ulceration and corneal perforation.

* see section Description of selected adverse reactions

Description of selected adverse reactions

Increase of the intra-ocular pressure, glaucoma and cataract may occur. Prolonged use of corticosteroid treatment may result in ocular hypertension/glaucoma (especially for patients with previous IOP induced by steroids or with pre-existing high IOP or Glaucoma) and also cataract formation, Children and elderly patients may be particularly susceptible to steroid-induced IOP rise (see section, 4.4).

Increase of the intra-ocular pressure induced by corticosteroid topical treatment has been generally observed within 2 weeks of treatment (see section 4.4.).

Diabetics are also more prone to develop subcapsular cataracts following topical steroid administration.

Discomfort, irritation, burning, stinging, itching and blurred vision frequently may occur immediately after instillation. These events are usually mild and transient and have no consequences.

In diseases causing thinning of the cornea, topical use of steroids could lead to perforation in some cases (see section 4.4).

Depression of adrenal function associated with systemic absorption of the product may occur when the instillations are administered with a frequent dosing schedule (see also sections 4.2 and 4.4).

Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the

medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website:

www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

In the case of topical overdosage, the treatment should be stopped. In case of prolonged irritation, the eye(s) should be rinsed with sterile water.

The symptomatology due to accidental ingestion is not known. As with other corticosteroids however, the physician may consider gastric lavage or emesis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: OPHTHALMOLOGICALS, ANTIINFLAMMATORY AGENTS,

Corticosteroids, plain, ATC code: S01B A01

Dexamethasone sodium phosphate is a hydrosoluble inorganic ester of dexamethasone. It is a synthetic corticosteroid with an anti-inflammatory and antiallergic action. Dexamethasone has more potent antiinflammatory action compared to hydrocortisone (approximately 25:1) and prednisolone (approximately

5:1).

5.2 Pharmacokinetic properties

Due to its hydrophilic properties, dexamethasone sodium phosphate is barely absorbed by the intact epithelium of the cornea.

Following absorption via the eye and the nasal mucosa, dexamethasone sodium phosphate is hydrolyzed in the system to dexamethasone.

Afterwards, dexamethasone and its metabolites are mainly eliminated via the kidneys

5.3 Preclinical safety data

Mutagenic and tumorigenic potential

Present findings yield no indications of clinically relevant genotoxic properties of glucocorticoids.

Reproductive toxicity

In animal experiments, corticosteroids have been shown to produce foetal resorptions and cleft palate. In the rabbit corticosteroids have produced foetal resorptions and multiple abnormalities involving the head, ears, limbs and palate.

In addition, intrauterine growth inhibition and changes of functional development of the central nervous system have been reported.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium edetate

Disodium phosphate dodecahydrate

Sodium chloride

Sodium hydroxide or Hydrochloric acid (For pH

adjustment) Water for injections

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

24 months.

After first opening of the bottle: use after 28 days. Do not store above 30°C.

6.4 Special precautions for storage

Do not store above 30°C

Do not refrigerate or freeze

For storage after first opening, see section 6.3

6.5 Nature and contents of container

Clear and colorless aqueous solution in an LDPE (low density polyethylene) bottle, fitted with Novelia® HDPE (high density polyethylene) and silicone nozzle and with HDPE tamperevident cap.

Pack Size: 1 bottle of 5ml.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Kent Pharmaceuticals Limited,

2nd Floor, Connect 38,

1 Dover Place

Ashford,

Kent,

United

Kingdom,

TN23 1FB.

8 MARKETING AUTHORISATION NUMBER(S)

PL 08215/0199

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

15/06/2026

10 DATE OF REVISION OF THE TEXT