SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Optrex Infected Eye Drops

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Chloramphenicol 0.5% w/v.

For excipients, see 6.1.

3    PHARMACEUTICAL FORM

Eye drops, solution. A clear, slightly yellow solution.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of acute bacterial conjunctivitis.

4.2    Posology and method of administration

Adults, children aged 2 years and over and elderly

One drop instilled into the infected eye every 2 hours for the first 48 hours and 4 hourly thereafter. To be used during waking hours only. The course of treatment is 5 days.

Treatment should continue for 5 days even if symptoms improve.

For ocular use.

4.3    Contraindications

Chloramphenicol eye drops must not be administered to:

• Patients who have a history of hypersensitivity to chloramphenicol or to any other ingredient of the drops.

•    Patients who have experienced myelosuppression during previous exposure to chloramphenicol.

•    Patients with a family history of blood dyscrasias.

4.4 Special warnings and precautions for use

Chloramphenicol is absorbed systemically from the eye and systemic toxicity has been reported (see section 4.8).

In severe bacterial conjunctivitis and in cases where infection is not confined to the conjunctivae, the topical use of chloramphenicol should be supplemented by appropriate systemic treatment. Therefore, the patient should be referred to seek medical advice.

The use of topical chloramphenicol may occasionally result in overgrowth of non-susceptible organisms including fungi. If any new infection appears during treatment, the patient should be referred to the doctor.

Prolonged or frequent intermittent topical application of chloramphenicol should be avoided since it may increase the likelihood of sensitisation and emergence of resistant organisms.

Do not use for more than 5 days without consulting your doctor.

The label will state:

•    If symptoms do not improve within 48 hours talk to your doctor

•    Seek further immediate medical advice at any time if symptoms worsen

•    Do not use if you are allergic to chloramphenicol or any of the ingredients

•    Discard any remaining eye drops after the five day course of treatment

For external use only.

Keep all medicines out of the sight and reach of children.

Phenylmercuric nitrate is irritant to the skin. Topical application to eyes has been associated with mercurialentis and atypical band keratopathy.

Patients should be referred to a doctor if any of the following apply: • Disturbed vision

•    Severe pain within the eye

•    Photophobia

•    Eye inflammation associated with a rash on the scalp or face

•    The eye looks cloudy

•    The pupil looks unusual

•    Suspected foreign body in the eye

Patients should also be referred to their doctor if any of the following in his/her medical history apply:

•    Previous conjunctivitis in the recent past

•    Glaucoma

•    Dry eye syndrome

•    Eye surgery or laser treatment in the last 6 months

•    Eye injury

•    Current use of other eye drops or eye ointment

•    Contact lens use

If this product is used following advice from a contact lens practitioner or doctor contact lenses should not be worn during the course of treatment. Soft contact lenses should not be replaced for 24 hours after completing the treatment.

4.5    Interaction with other medicinal products and other forms of interaction

Bone marrow depressant drugs

4.6    Pregnancy and lactation

The safety of chloramphenicol eye drops during pregnancy and lactation has not been established. As this product is for sale without prescription it is not recommended for use during pregnancy.

In view of the fact that chloramphenicol may appear in breast milk, use of the product during lactation should be avoided.

4.7    Effects on ability to drive and use machines

Blurring of vision can occur with the drops and patients should be warned not to drive or operate machinery unless their vision is clear.

4.8 Undesirable effects

Transient burning or stinging sensations may occur with the use of chloramphenicol eye drops. Serious side effects include hypersensitivity reactions that may manifest as angioneurotic oedema, anaphylaxis, urticaria, fever, and vesicular and maculopapular dermatitis. Treatment must be discontinued immediately in such cases.

Bone marrow depression, including the idiosyncratic type of irreversible and fatal aplastic anaemia that is recognised to occur with systemic therapy, has been reported in association with topical administration of chloramphenicol.

4.9 Overdose

In view of the relatively small amount of chloramphenicol in chloramphenicol eye drops, overdosage with this product is unlikely to constitute a hazard. No specific treatment would be required.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Chloramphenicol is a broad spectrum bacteriostatic antibiotic active against a wide variety of gram-negative and gram-positive organisms.

Mechanism of action

Chloramphenicol exerts its antibacterial effect by binding to bacterial ribosomes and inhibiting bacterial protein synthesis at an early stage.

Susceptibility

The following bacterial species are recognised conjunctival pathogens and may be susceptible to chloramphenicol. However due to the prevalence of acquired resistance to chloramphenicol in these species, the results of susceptibility testing should be taken into account if these are available. If no susceptibility test result is available, the choice of antibacterial agent should be influenced by local information on the likely prevalence of resistance to chloramphenicol in species that are commonly pathogenic in the eye.

Staphylococcus aureus Streptococcus pyogenes Streptococcus pneumoniae Other beta-haemolytic streptococci

Haemophilius influenze Moraxella catarrhalis

Resistance

Acquired resistance to chloramphenicol has been described in all the above species. Most commonly this is mediated by bacterial production of a chloramphenicol acetyl transferase that inactivates the drug. Chloramphenicol is not generally active against the enterobacteriaceae and is not active against non-fermenters such as Pseudomonas aeruginosa.

5.2 Pharmacokinetic properties

Following topical application to the eye, chloramphenicol may be absorbed into the aqueous humour. Sufficient chloramphenicol may be absorbed from the eye to appear in the systemic circulation.

Specific data on systemic absorption from this dosage presentation is not available.

Chloramphenicol is readily absorbed when given by mouth. Blood concentrations of 10pg per ml or more may be reached about 1 or 2 hours after a single dose of 1g by mouth, and blood concentrations of about 18.5pg per ml have been reported after multiple 1g doses. Choramphenicol palmitate is hydrolysed to chloramphenicol in the gastrointestinal tract prior to absorption, and the sodium succinate, which is given parenterally is probably hydrolysed to free drug mainly in the liver, lungs, and kidneys; such hydrolysis may be incomplete in infants and neonates, contributing to the variable pharmacokinetics in this age group. Chloramphenicol sodium succinate is, even in adults, only partially and variably hydrolysed, so that blood concentrations of chloramphenicol obtained after parenteral administration of the sodium succinate are often lower than those obtained after administration of chloramphenicol by mouth, with up to 30% of a dose excreted unchanged in the urine before hydrolysis can take place.

Chloramphenicol is widely distributed in body tissues and fluids; it enters the cerebrospinal fluid, giving concentrations of about 50% of those existing in the blood even in the absence of inflamed meninges; it diffuses across the placenta into the foetal circulation, into breast milk, and into the aqueous and vitreous humours of the eye. Up to about 60% in the circulation is bound to plasma protein. The half-life of chloramphenicol has been reported to range from 1.5 to 4 hours; the half-life is prolonged in patients with severe hepatic impairment and is also much longer in neonates. Renal impairment has relatively little effect on the half-life of the active drug, due to its extensive metabolism, but may lead to accumulation of the inactive metabolites.

Chloramphenicol is excreted mainly in the urine but only 5 to 10% of an oral dose appears unchanged; the remainder is inactivated in the liver, mostly by conjugation with glucorinic acid. About 3% is excreted in the bile. However,

most is reabsorbed and only about 1%, mainly in the inactive form, is excreted in the faeces.

The absorption, metabolism, and excretion of chloramphenicol are subject to considerable interindividual variation, especially in infants and children, making monitoring of plasma concentrations necessary to determine pharmacokinetics in a given patient.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Borax powder Boric acid powder Phenylmercuric nitrate Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

18 months unopened.

Although the shelf life once opened is 28 days, patients should be advised to discard the medicine after a 5 day course of treatment.

6.4 Special precautions for storage

Store at 2° to 8°C.

Protect from light.

6.5 Nature and contents of container

White pigmented bottle of high density polyethylene/low density polyethylene mix with white pigmented low density polyethylene plug and red pigmented polyethylene tamper evident cap.

Pack size: 10 ml.

6.6 Special precautions for disposal

None

7.    MARKETING AUTHORISATION HOLDER

Optrex Limited 103-105 Bath Road Slough SL1 3UH UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 00062/0051

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10 March 2004

10 DATE OF REVISION OF THE TEXT

23/06/2015