SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Dropodex 0.1% w/v eye drops, solution.

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Dexamethasone sodium phosphate Ph Eur equivalent to 0.1% w/v dexamethasone.

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

Each individual single-dose unit contains 0.4mg dexamethasone phosphate (as dexamethasone sodium phosphate) in 0.4 ml of solution.

For full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Eye drops, solution

Single use eye drops which are sterile and preservative free.

A colourless solution when examined under suitable conditions of visibility, clear and free from particles.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Inflammatory conditions of the anterior segment of the eye, such as marginal keratitis, stromal oedema in keratitis, anterior uveitis, episcleritis (if NSAIDs are contraindicated or insufficient), scleritis, acute phase of severe allergic conjunctivitis not responding to standard therapy.

4.2    Posology and method of administration

Topical ophthalmic use.

Posology

Adults (including the elderly):

The usual dose in adults including the elderly is 1 drop, 4 to 6 times daily.

In severe conditions, the treatment can be used more frequently at first (1 drop every hour) and then reduced to 1 drop every 4 hours as the eye inflammation subsides. Dexamethasone sodium phosphate dosage should be progressively reduced.

Use in children and adolescents:

Use of Dropodex 0.1% w/v eye drops solution in children and adolescents must be restricted.

No data on safety and efficacy is available for children aged under 2 years. Currently available data are described in section 4.8, 5.1, and 5.2 but no recommendation on a posology can be made.

4.3 Contraindications

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

Use is contra-indicated in herpes simplex and other viral diseases of the cornea and conjunctiva, fungal disease, ocular tuberculosis, untreated purulent infections, patients with a history of acute epithelial herpes simplex keratitis or hypersensitivity to any component of the preparation.

4.4 Special warnings and precautions for use

For topical ophthalmic use only. Not for injection into the eye.

Care should be taken to ensure that the eye is not infected before Dropodex 0.1% w/v eye drops are used.

In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical corticosteroids.

Caution is also necessary when used in conjunction with antiviral therapy in the treatment of stromal keratitis or uvetis and use of periodic slit-lamp microscopy.

Corticosteroids may reduce resistance to and aid in the establishment of bacterial, viral and fungal infections and mask the clinical signs of infections, preventing recognition of ineffectiveness of the antibiotic. In such cases antibiotic therapy is mandatory. Fungal infection should be suspected in patients with persistent corneal ulceration who have been or are receiving these drugs, and corticosteroids therapy should be discontinued if fungal infection occurs.

This medicinal product contains phosphates which may lead to corneal deposits or corneal opacity when topically administered. It should be used with caution in patients presenting with compromised cornea and in instances where the patient is receiving polypharmacy with other phosphate containing eye medications (see section 4.5).

Topical corticosteroids should not be used for longer than one week except under ophthalmic supervision. Prolonged use of topical ophthalmic corticosteroids may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, reduced visual acuity, visual field defects and posterior subcapsular cataract formation. In patients receiving prolonged ophthalmic corticosteroid therapy, intraocular pressure and the lens should be checked routinely and frequently, particularly in patients with a history or presence of glaucoma. The dose of antiglaucoma medication may need to be adjusted in these patients. Prolonged use may also increase the hazard of secondary ocular infections. Topical ophthalmic corticosteroids may slow corneal wound healing.

Contact lenses should not be worn during treatment with corticosteroid eye drops due to increased risk of infection.

Systemic absorption may be reduced by compressing the lacrimal sac at the medial canthus for a minute during and following the instillation of the drops. (This blocks the passage of drops via the naso-lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.)

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

4.5 Interaction with other medicinal products and other forms of interaction

The risk of increased intraocular pressure associated with prolonged corticosteroid therapy may be more likely to occur with concomitant use of anticholinergics, especially atropine and related compounds, in patients predisposed to acute angle closure.

The risk of corneal deposits or corneal opacity may be more likely to occur in patients presenting with compromised cornea and receiving polypharmacy with other phosphate containing eye medications.

The following drug interactions are possible, but are unlikely to be of clinical significance, following the use of Dropodex 0.1% w/v eye drops in the eye:

The therapeutic efficacy of dexamethasone may be reduced by phenytoin, phenobarbitone, ephedrine and rifampicin.

Glucocorticoids may increase the need for salicylates as plasma salicylate clearance is increased.

If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of dexamethasone eye drops in pregnant women. Studies in animals have shown that topically applied steroids can be absorbed systemically and can cause abnormalities of foetal development in pregnant animals (see Section 5.3). Although the relevance of these findings to human beings has not been established, the use of Dropodex 0.1% w/v eye drops during pregnancy should be avoided.

Breast-feeding mothers

Systemically administered corticosteroids appear in human milk in quantities that could affect the child being breastfed. However, when instilled topically, systemic exposure is low. It is unknown whether dexamethasone is excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from dexamethasone therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects on ability to drive and use machines

Dropodex 0.1% w/v eye drops has no or negligible influence on the ability to drive and use machines however instillation of eye drops may cause transient blurring of vision. Warn patients not to drive or operate hazardous machinery until vision is clear.

4.8    Undesirable effects

The following undesirable effects are classified according to the following convention: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1000), very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness

Ocular disorders:

-    Very common (>1/10): intraocular pressure increased (after 2 weeks of treatment).

-    Common (>1/100, <1/10): Ocular discomfort after instillation, irritation, burning, eye pruritus and blurred vision. These symptoms are mild and transient with no consequences.

-    Uncommon (>1/1,000, <1/100): signs and symptoms of allergic or hypersensitive reactions can occur. The following corticoid specific undesirable effects can occur: delay in healing, risk of posterior subcapsular cataract formation, opportunist infections and glaucoma.

-    Very rare (<1/10,000, including isolated reports): conjunctivitis, eyelid oedema, corticoids induced uveitis, keratitis, corneal thinning, corneal oedema and ulcerations. Due to the steroid component, in diseases causing thinning of the cornea or sclera there is a higher risk for perforation especially after topical long treatments. General disorders and administration site conditions:

-    Uncommon (>1/1,000, <1/100): after long treatment posology, systemic absorption can occur with an inhibition of the adrenal function.

4.9    Overdose

Overdose is unlikely to occur as Dropodex 0.1% w/v eye drops are single-dose units. Excess Dropodex 0.1% w/v eye drops may be wiped away with a clean tissue.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic Group: Corticosteroids, plain. ATC code: S01 BA01

Dexamethasone is a highly potent and long-acting glucocorticoid. It has an approximately 7 times greater anti-inflammatory potency than prednisolone, another commonly prescribed corticosteroid.

The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.

Corticosteroids will inhibit phospholipase A2 thereby preventing the generation of substances which mediate inflammation, for example, prostaglandins. Corticosteroids also produce a marked, though transient, lymphocytopenia. This depletion is due to redistribution of the cells, the T lymphocytes being affected to a greater degree than the B lymphocytes. Lymphokine production is reduced, as is the sensitivity of macrophages to activation by lymphokines. Corticosteroids also retard epithelial regeneration, diminish post-inflammatory neo-vascularisation and reduce towards normal levels the excessive permeability of inflamed capillaries.

The actions of corticosteroids described above are exhibited by dexamethasone and they all contribute to its anti-inflammatory effect.

5.2 Pharmacokinetic properties

Absorption

When given topically to the eye, dexamethasone is absorbed into the aqueous humour, cornea, iris, choroid, ciliary body and retina. Systemic absorption occurs but may be significant only at higher dosages or in extended paediatric therapy. Up to 90% of dexamethasone is absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide individual variations.

Distribution

Tissue distribution studies in animals show a high uptake of dexamethasone by the liver, kidney and adrenal glands; a volume of distribution has been quoted as 0.58 l/kg. In man, over 60% of circulating steroids are excreted in the urine within 24 hours, largely as unconjugated steroid.

Biotransformation

Dexamethasone sodium phosphate is rapidly converted to dexamethasone within the circulation. Up to 77% of dexamethasone is bound to plasma proteins, mainly albumin. This percentage, unlike cortisol, remains practically unchanged with increasing steroid concentrations. The mean plasma half-life of dexamethasone is 3.6 ± 0.9h.

Elimination

Dexamethasone also appears to be cleared more rapidly from the circulation of the foetus and neonate than in the mother; plasma dexamethasone levels in the foetus and the mother have been found in the ratio of 0.32:1.

5.3 Preclinical safety data

Repeat dose topical ocular safety studies with dexamethasone in rabbits have shown systemic corticosteroid effects. Such effects are considered to be unlikely when dexamethasone eye drops are used as recommended.

Dexamethasone was clastogenic in the in vitro human lymphocyte assay and in vivo in the mouse micronucleus assay at doses in excess of those obtained following topical application. Conventional carcinogenicity studies with dexamethasone have not been performed.

Dexamethasone has been found to be teratogenic in animal models. Dexamethasone induced abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development.

There are no other preclinical data of relevance to the prescriber which are additional to that included in other sections of the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium chloride

Disodium edetate

Disodium phosphate dodecahydrate (E339)

Water, purified

6.2    Incompatibilities

None known. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3    Shelf life

Unopened: 30 months.

After opening the sachet: use contents within 28 days.

After opening the single-dose unit: Use immediately after opening the single-dose unit. Discard any unused content.

6.4    Special precautions for storage

Keep out of sight and reach of children.

Do not store above 25°C. Do not refrigerate or freeze. Store in original package. Discard any remaining single-dose units 28 days after opening the sachet.

6.5    Nature and contents of container

Dropodex 0.1% w/v eye drops is available in 0.4 ml transparent low density polyethylene single-dose units. Each pre-formable PET metal/PE transparent and PET metal/PE peelable sachet contains 5 single-dose units. 20 single-dose units are packed into one carton.

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

Moorfields Eye Hospital NHS Foundation Trust trading as Moorfields Pharmaceuticals 34 Nile Street

London N1 7TP

United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 11412/0145

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/01/2013

10    DATE OF REVISION OF THE TEXT

30/01/2013