In the Eye: For the short-term treatment of steroid responsive conditions of the eye when prophylactic antibiotic treatment is also required, after excluding the presence of fungal and viral disease.

In the Ear: Otitis Externa.

Posology

Adults (including elderly) and paediatric population:

In the Eye: One or two drops applied to each affected eye up to six times daily or more frequently if required.

In the Ear: Two or three drops instilled into the ear three or four times daily.

Method of administration

Auricular and Ocular use. Treatment duration should be short (not to exceed 7 days) (see section 4.4).

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

• Viral or fungal infections of the eye and ear.

• Untreated purulent infections of the eye and ear, which, like other diseases caused by micro-organisms, may be masked or enhanced by the presence of the steroid.

Use in the eye:

• Tuberculosis

• Glaucoma

• Herpes simplex and other viral diseases of the cornea and conjunctiva, including where herpetic keratitis (e.g. dendritic ulcer) is considered a possibility. Use of topical steroids in the latter condition can lead to extension of the ulcer and marked visual deterioration.

Use in the ear:

• Eardrum perforation because of the risk of ototoxicity.

Treatment should be discontinued if there are signs of sensitivity to any of its ingredients.

Treatment with corticosteroid/antibiotic combinations should not be continued for more than 7 days in the absence of any clinical improvement, since prolonged use may lead to occult extension of infections due to the masking effect of the steroid. Prolonged use may also lead to skin sensitisation and the emergence of resistant organisms.

Corticosteroids

Topical corticosteroids should never be given for an undiagnosed red eye as inappropriate use is potentially blinding (see section 4.3).

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.

Treatment with corticosteroid preparations should not be repeated or prolonged without regular review to exclude raised intraocular pressure, cataract formation or unsuspected infections.

Antibiotics

Ototoxicity

Aminoglycoside antibiotics may cause irreversible, partial, or total deafness when given systemically or when applied topically to open wounds or damaged skin. This effect is dose related and is enhanced by renal or hepatic impairment. Although this effect has not been reported following ocular use, the possibility should be considered when high dose topical is given to small children or infants.

Mitochondrial disorders

There have been reported cases of ototoxicity with aminoglycosides administered to patients with mitochondrial mutations, particularly the m.1555A>G mutation, which suggests an increased risk of ototoxicity in these patients, including cases where the patient's aminoglycoside serum levels were within the recommended range. Some cases were associated with a maternal history of deafness and/or mitochondrial mutation. Mitochondrial mutations are rare, and the penetrance of this observed effect is unknown.

Although no cases were identified with topical preparations of neomycin, framycetin or gentamicin, the potential for a similar effect with neomycin and other aminoglycosides administered topically cannot be ruled out.

Paediatric population

Although it is unlikely that infants will be treated with Sofradex for prolonged periods, there is a risk of adrenal suppression, even without occlusive dressings, after prolonged treatment of these patients with topical steroids.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. 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 side effects.

Pregnancy

There is inadequate evidence of safety in human pregnancy. Sofradex should be used during pregnancy only if the potential benefits to the mother outweigh the potential risks, including those to the fetus.

Topical administration of corticosteroids to pregnant animals can cause abnormalities of fetal development including cleft palate and intrauterine growth retardation. There may therefore be a very small risk of such effects in the human fetus.

There is a risk of fetal ototoxicity if aminoglycoside antibiotics preparations are administrated during pregnancy.

Breast-feeding

The product should be used during breast-feeding only if the potential benefits to the mother outweigh the potential risks, including those to the breast-fed child.

Sofradex Ear/Eye drops solution may cause transient blurring of vision on instillation. Patients must not drive or operate hazardous machinery unless vision is clear.

The following CIOMS frequency rating is used: Very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); rare (≥ 1/10 000 to <1/1000); very rare (<1/10 000), not known (cannot be estimated from the available data).

Eye disorders

Not known: blurred vision, glaucoma (see section 4.4)

Topical steroid use may result in increased intraocular pressure leading to optic nerve damage, reduced visual acuity and visual field defects.

Intensive or prolonged use of topical corticosteroids may lead to formation of posterior subcapsular cataracts.

In those diseases causing thinning of the cornea or sclera, corticosteroid therapy may result in the thinning of the globe leading to perforation.

Immune system disorders:

Not known: Hypersensitivity reactions, usually of the delayed type, may occur leading to irritation, burning, stinging, itching and dermatitis.

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

Long-term intensive topical use may lead to systemic effects.

Oral ingestion of the contents of one bottle (up to 10 ml) is unlikely to lead to any serious adverse effects.

Pharmacotherapeutic group: ophthalmological and otological preparations, corticosteroids and anti-infectives in combination, ATC Code: S03CA01.

Mechanism of action

Framycetin sulphate is an aminoglycoside antibiotic with a spectrum of activity similar to that of neomycin, this includes Staph. aureus and most clinically significant gram-negative organisms.

Gramicidin is an antimicrobial cyclic polypeptide active in vitro against many gram-positive bacteria. It is used for the local treatment of susceptible infections, sometimes in combination with other antimicrobial agents and frequently with a corticosteroid.

Dexamethasone is a synthetic glucocorticoid and has the general properties as other corticosteroids.

Framycetin sulphate absorption occurs from inflamed skin and wounds. Once absorbed it is rapidly excreted by the kidneys in active form. It has been reported to have a half-life of 2 – 3 hours

Gramicidin has properties similar to those of Tyrothricin and is too toxic to be administered systemically.

Dexamethasone is readily absorbed from the gastro-intestinal tract. It has a biological half-life in plasma of about 190 minutes.

Not applicable.

Citric Acid Monohydrate

Sodium Citrate

Lithium Chloride

Phenylethyl Alcohol

Industrial Methylated Spirits 95%

Polysorbate 80

Water for Injection

Sodium Hydroxide (for pH-adjustment)

Hydrochloric Acid (for pH-adjustment)

Not applicable.

2 years

Discard contents 28 days after opening.

Store below 25° C, do not refrigerate.

Glass bottle fitted with a special dropper attachment: Pack size of 8 or 10ml.

Plastic dropper bottle: Pack size of 5, 8 or 10ml.

Not all pack sizes may be marketed.

No special requirements.