In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
Floxedol® is contra-indicated in individuals who have shown hypersensitivity to ofloxacin, any of its excipients or any other quinolones.
None known.
General
Serious reactions after use of systemic ofloxacin are rare and most symptoms are reversible. Since a small amount of ofloxacin is systemically absorbed after topical administration, side-effects reported with systemic use could possibly occur.
Frequency categories: Very common (>1/10); Common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100); Rare (>1/10,000 to <1/1,000); Very rare (<1/10,000) and not known (cannot be estimated from the available data):
Immune System Disorders
Not Known: Hypersensitivity reaction including signs or symptoms of Eye allergy (such as Eye pruritus and Eyelid pruritus) and Anaphylactic reactions (such as angioedema, dyspnea, anaphylactic shock, oropharyngeal swelling, facial oedema and tongue swollen)
Nervous System Disorders
Not known: Dizziness
Eye Disorders
Common: Eye irritation; Ocular discomfort
Not known: Keratitis; Conjunctivitis; Vision blurred; Photophobia; Eye oedema; Foreign body sensation in eyes; Lacrimation increased; Dry eye; Eye pain; Ocular hyperaemia; Periorbital oedema (including eyelid oedema)
Cardiac disorders
Not known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation); ECG QT prolonged
Gastrointestinal Disorders
Not known: Nausea
Skin and Subcutaneous Tissue Disorders
Not Known: Stevens-Johnson syndrome; Toxic epidermal necrolysis
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
Website: www.mhra.gov.uk/yellowcard
There are no toxicological safety issues with this product in man as the level of systemic absorption from topical ocular administration of ofloxacin is minimal.
Animal studies in the dog have found cases of arthropathy in weight bearing joints of juvenile animals after high oral doses of certain quinolones. However, these findings have not been seen in clinical studies and their relevance to man is unknown.
Floxedol® is indicated for the topical treatment of external ocular infections (such as conjunctivitis and keratoconjunctivitis) in adults and children caused by ofloxacin - sensitive organisms. Safety and efficacy in the treatment of ophthalmia neonatorum has not been established.
Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, fluoroquinolones
ATC code: S01AE01.
Ofloxacin is a synthetic fluorinated 4-quinolone antibacterial agent with activity against a broad spectrum of Gram negative and to a lesser degree Gram positive organisms.
Ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically in ophthalmic infections. Clinical trial evidence of the efficacy of Floxedol® against S. pneumoniae was based on a limited number of isolates.
Gram-negative bacteria: Acinetobacter calcoaceticus var. anitratum, and A. calcoaceticus var. iwoffi; Enterobacter Sp. including E. cloacae; Haemophilis Sp, including H. influenza and H. aegyptius; Klebsiella Sp., including K. Pneumoniae; Moraxella Sp., Morganella morganii; Proteus Sp., including P. Mirabilis; Pseudomonas Sp.; including P. Aeruginosa, P. cepacia, and P. fluoroscens; and Serratia Sp., including S. marcescens.
Gram-positive bacteria: Bacillus Sp.; Corynebacterium Sp.; Micrococcus Sp.; Staphylococcus Sp., including S. aureus and S. epidermidis; Streptococcus Sp., including S. Pneumoniae (see above), S. viridans and Beta-haemolytic.
The primary mechanisms of action is through inhibition of bacterial DNA gyrase, the enzyme responsible for maintaining the structure of DNA.
Ofloxacin is not subject to degradation by beta-lactamase enzymes nor is it modified by enzymes such as aminoglycoside adenylases or phosphorylases, or chloramphenicol acetyltransferase.
After ophthalmic instillation, ofloxacin is well maintained in the tear-film.
In a healthy volunteer study, mean tear film concentrations of ofloxacin measured four hours after topical dosing (9.2 µg/g) were higher than the 2µg/ml minimum concentration of ofloxacin necessary to inhibit 90% of most ocular bacterial strains (MIC90) in-vitro.
Maximum serum ofloxacin concentrations after ten days of topical dosing were about 1000 times lower than those reported after standard oral doses of ofloxacin, and no systemic side-effects attributable to topical ofloxacin were observed.
Floxedol® is not for injection.
Safety and effectiveness in infants below the age of one year have not been established.
Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin.5, section 4.8, section 4.9).
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including Floxedol®, in these populations.
Use Floxedol® with caution in patients who have exhibited sensitivities to other quinolone antibacterial agents.
Data are very limited to establish efficacy and safety of Floxedol® eye drops 0.3% in the treatment of conjunctivitis in neonates.
The use of Floxedol® eye drops in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients.
Use in elderly: No comparative data are available with topical dosing in elderly versus other age groups.
Clinical and non-clinical publications have reported the occurrence of corneal perforation in patients with pre-existing corneal epithelial defect or corneal ulcer, when treated with topical fluoroquinolone antibiotics. However, significant confounding factors were involved in many of these reports, including advanced age, presence of large ulcers, concomitant ocular conditions (e.g. severe dry eye), systemic inflammatory diseases (e.g. rheumatoid arthritis), and concomitant use of ocular steroids or non-steroidal anti-inflammatory drugs. Nevertheless, it is necessary to advise caution regarding the risk of corneal perforation when using product to treat patients with corneal epithelial defects or corneal ulcers.
Corneal precipitates have been reported during treatment with topical ophthalmic ofloxacin. However, a causal relationship has not been established.
Long-term, high-dose use of other fluoroquinolones in experimental animals has caused lenticular opacities. However, this effect has not been reported in human patients, nor has it been noted following topical ophthalmic treatment with ofloxacin for up to six months in animal studies including studies in monkeys.
Floxedol® contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.
Sun or UV-exposition should be avoided during use of ofloxacin due to the potential for photosensitivity.
Use of contact lenses is not recommended in patients receiving treatment for an eye infection.
No studies on the effects on the ability to drive and use machines have been performed.
Transient blurring of vision may occur on instillation of eye drops. Do not drive or operate hazardous machinery unless vision is clear.
Topical ocular instillation.
For all ages: one to two drops in the affected eye(s) every two to four hours for the first two days and then four times daily. The length of treatment should not exceed ten days.
There is no special requirement for disposal.
Any unused product or waste material should be disposed of in accordance with local requirements.
