Mollifeye 5 mg/ml eye drops, solution

Mollifeye 5 mg/ml eye drops solution contains 5 mg/ml chloramphenicol.

Excipient with known effect

One ml of solution contains 2.9 mg boron.

For the full list of excipients, see section 6.1.

Eye drops, solution.

Clear, colourless, aqueous eye drops solution

Osmolality: 260-320 mOsm/Kg

pH: 6.8 -7.8

Chloramphenicol is indicated in adults and children aged 2 years and over for the treatment of acute bacterial conjunctivitis.

Considerations should be given to official guidance on the appropriate use of antibacterial agents.

Posology

Adults (including the elderly) and children aged 2 years and over:

• put one drop into the affected eye(s) every 2 hours for the first 48 hours and 4 hourly thereafter.

• To be used during waking hours only.

• The course of treatment should be 5 days.

Systemic absorption may be reduced by compressing the lacrimal sac at the medial canthus for a minute following instillation of the drops.

Method of administration

For ocular use.

Mollifeye 5 mg/ml eye drops solution is a sterile solution that does not contain a preservative.

Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with the eye or surrounding structures as this could cause injury to the eye.

Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

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

• Myelosuppression during previous exposure to chloramphenicol.

• Family or personal history of blood dyscrasias including aplastic anaemia.

Chloramphenicol is absorbed systemically from the eye and systemic toxicity has been reported. 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 the drops via the naso lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.)

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

Prolonged use of chloramphenicol eye drops is not advisable. Prolonged or frequent intermittent topical application of chloramphenicol should be avoided since it may increase the likelihood of sensitisation and the emergence of resistant organisms.

Patients with a history of contact hypersensitivity to silver should not use this product as dispensed drops may contain traces of silver.

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

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.

The label will state:

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

• Consult your doctor if your eye infection does not start to improve within 48 hours.

• Discard the medicine after a 5 day course of treatment.

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

• For external use/use in the eye only

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

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 period of treatment. Contact lens users may use glasses during treatment with chloramphenicol eye drops.

Soft contact lens wearers should wait 24 hours after completing a course of treatment before starting to use their lenses again.

The concomitant administration of chloramphenicol with other drugs liable to depress bone marrow function should be avoided.

The safety of chloramphenicol eye drops in pregnancy and lactation has not been established.

Pregnancy

As this product is for sale without prescription it is not recommended for use during pregnancy.

Breast-feeding

Chloramphenicol may appear in breast milk, use of the product during lactation should be avoided.

Fertility

No fertility data are available.

The use of the eye drops may cause transient blurring of vision. Patients should not drive or operate hazardous machinery unless vision is clear.

Eye disorders:

Transient irritation, burning, stinging and sensitivity reactions such as itching and dermatitis.

Immune System Disorders:

Hypersensitivity reactions including angioedema, anaphylaxis, urticaria, fever, vesicular and maculopapular dermatitis. Treatment must be discontinued immediately in such cases.

Blood and lymphatic system disorders:

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.

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).

Accidental ingestion of the drops is unlikely to cause systemic toxicity due to the low content of the antibiotic in the product.

In view of the relatively small amount of chloramphenicol in Mollifeye, overdosage with this product is unlikely to constitute a hazard.

No specific treatment would be required. If irritation, pain, swelling, lacrimation or photophobia occur after undesired eye contact, the exposed eye(s) should be irrigated for at least 15 minutes. If symptoms persist after this, an ophthalmological examination should be considered.

Pharmacotherapeutic group: Ophthalmological antibiotic, ATC code: S01AA01

Chloramphenicol is a broad spectrum antibiotic with bacteriostatic activity which has activity against many types of Gram-positive and Gram-negative bacteria. Chloramphenicol is not effective against fungi, protozoa, and viruses.

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

Neisseria gonorrhoeae

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.

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 10μg 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 18.5μg 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.

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

Boric acid

Borax

Sodium hydroxide or/and Hydrochloric acid (for pH adjustment)

Water for injection

Not applicable

2 years.

After opening: 28 days

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

Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the bottle in the outer carton in order to protect from light.

The eye drop solution is presented as a 10 ml clear, colourless aqueous solution in a white opaque 11 ml LDPE bottle and white Novelia nozzle (HDPE and silicone) with a white HDPE cap.

Pack sizes: 1 bottle in a cardboard box.

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

Aspire Pharma Ltd

Unit 4, Rotherbrook Court,

Bedford Road,

Petersfield,

Hampshire,

GU32 3QG

United Kingdom

PL35533/0178

12/01/2022

12/04/2022