DEXAMETHASONE PHOSPHATE 1 MG / ML (AS SODIUM PHOSPHATE) EYE DROPS SOLUTION IN A SINGLE-DOSE CONTAINER - summary of medicine characteristics

Dexamethasone phosphate 1 mg/mL (as sodium phosphate) Eye drops, Solution in a single-dose container

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of eye drop solution contains 1 mg of dexamethasone phosphate (as dexamethasone sodium phosphate), equal to 40 ^g of dexamethasone phosphate (with theoretical drop volume of approximately 40 jiL).

This medicine contains 0.4461 mg phosphates in 0.3 mL which is equivalent to 1.487 mg/mL.

For the full list of excipients, see section 6.1.

Eye drops, solution in single-dose container (eye drops).

Clear and colourless solution in single-dose container, with a pH of 7.4–7.8 and osmolality of 230–290 mOsm/kg.

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 1 mg/mL (as sodium phosphate) Eye drops, Solution in a single-dose container is for ocular use only. This product should be used only under close ophthalmic supervision.

Posology

The usual dose is of 1 drop 4 to 6 times daily 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 elderly patients. The dosage recommendations given above reflect the clinical data derived from this experience.

Paediatric population

Efficacy and safety have not been established in the paediatric population.

In children, long-term continuous corticosteroid therapy should be avoided due to possible adrenal suppression (see section 4.4).

Method of administration

Dexamethasone phosphate 1 mg/ml, eye drops, solution is a sterile solution that does not contain a preservative. The solution from one individual single dose container is to be used immediately after opening for administration to the affected eye(s). The container (pipette) surface is non-sterile therefore NOT suitable for use during sterile ophthalmic surgery. Since sterility cannot be maintained after the individual single dose container is opened, any remaining contents must be discarded after administration.

Patients should be instructed:

– to wash their hands carefully prior to instillation,

– to avoid contact between the tip of the dispenser and the eye or eyelids,

– to throw away the single-dose container after use.

Nasolacrimal occlusion by compression of lacrimal ducts may reduce systemic absorption.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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 epithelisation (see also section 4.4),

Known glucocorticosteroid-induced ocular hypertension

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 receive local steroid treatment only 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 contra-indicated.

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.

Corneal calcification requiring corneal graft surgery for visual rehabilitation has been reported very rarely for patients treated with ophthalmic preparations containing phosphates, such as Dexamethasone phosphate, in presence of significative corneal damages or diseases. At the first sign of corneal calcification the drug should be withdrawn and the patient should be switched to a phosphate-free preparation.

In children, long-term continuous corticosteroid therapy should be avoided due to possible adrenal suppression.

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 recommended only for severe forms of allergic conjunctivitis not responding to standard therapy and only for a short period.

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

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.

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

Fertility

There are no data on potential effects of Dexamethasone phosphate 1 mg/ml, eye drops, solution 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

The list below mentions the adverse reactions reported with Dexamethasone, ranked under the following frequency classification: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100; very rare (<1/10,000).

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.

see section 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).

Very rarely cases of corneal calcification have been reported 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 at the 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 overdose, 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 induction.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Ophthalmologicals, anti-inflammatory agents, corticosteroid­s, plain

ATC code: S01BA01

Dexamethasone sodium phosphate is a hydro soluble inorganic ester of dexamethasone. It is a synthetic corticosteroid with an anti-inflammatory and antiallergic action. Dexamethasone has more powerful anti-inflammatory 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 fetal resorptions and cleft palate. In the rabbit corticosteroids have produced fetal 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,

Hydrochloric acid for pH adjustment

Sodium hydroxide for pH adjustment

Water for injections

6.2

Not applicable.

6.3

2 years.

After first opening of the sachet, use the single-dose containers within 60 days.

After opening of the single-dose container: any residual solution remained in the single dose container after instillation must be discarded.

6.4 Special precautions for storage

Keep the single-dose containers in their sachet in order to protect from light and use them within 60 days.

Store below 25°C.

For storage conditions after first opening of the single-dose container, see section 6.3.

6.5 Nature and contents of container

Dexamethasone phosphate eye drops solution is available in low density polyethylene single-dose units, containing 0.3 ml solution each.

Each strip of 5 single dose containers is packed in a PET/Alu/PE sachet.

The box contains 20 or 30 single dose containers.