Exocin

Section Number

Subject

Change

4.4

Special Warnings and Precautions for Use

Text Added:

EXOCIN is not for injection.

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.

If an allergic reaction to ofloxacin occurs, discontinue the drug. Use EXOCIN with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents.

When using EXOCIN eye drops the risk of rhinopharyngeal passage which can contribute to the occurrence and the diffusion of bacterial resistance should be considered. As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms. If infection worsens, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.

Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established.

Data are very limited to establish efficacy and safety of ofloxacin eye drops 0.3% in the treatment of conjunctivitis in neonates.

The use of ofloxacin 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. Neonates with ophthalmia neonatorum should receive appropriate treatment for their condition, e.g. systemic treatment in cases caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Use in the elderly: No comparative data are available with topical dosing in elderly versus other groups.

The following precautions are relevant for the systemic absorption of oxoquinolone antibacterial agents. However, the plasma levels of ofloxacin following absorption from topically applied EXOCIN eye drops are minimal.

Persons with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions with systemically absorbed oxoquinolone antibacterial agents.

Patients with pre-existent significant renal or hepatic disorders should be carefully monitored to detect any deterioration in function. Dosage reduction may be required.

EXOCIN should be administered with caution to persons with existent central nervous system disorders, epilepsy, hepatic or renal insufficiency, or severe dehydration. Photosensitivity reactions may be induced. Evidence of CNS irritability has been reported particularly in the elderly, leading occasionally to psychosis.

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.

Caution should be taken when using fluoroquinolones, including EXOCIN, in patients with known risk factors for prolongation of the QT interval such as, for example:

- Congenital long QT syndrome

- Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)

- Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)

- Elderly

- Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

(see section 4.2 elderly, section 4.5, section 4.8, section 4.9)

EXOCIN contains the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.

Use of contact lenses is not recommended in patients receiving treatment for an eye infection.

4.5

Interaction with other medicinal products and other forms of interactions

Text Added

It has been shown that the systemic administration of some quinolones inhibits the metabolic clearance of caffeine and theophylline. Drug interaction studies conducted with systemic ofloxacin have demonstrated that metabolic clearance of caffeine and theophylline are not significantly affected by ofloxacin.

Although there have been reports of an increased prevalence of CNS toxicity with systemic dosing of fluoroquinolones when used concomitantly with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.

Mineral antacids used simultaneously may effect systemic absorption. Concomitant use of systemic quinolones with some phenylproprionic acid derived non-steroidal anti-inflammatory drugs may lead to toxicity possibly because of renal effects.

A study of concurrent administration with a coumarin anticoagulant showed no interaction.

EXOCIN, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4)

4.8

Undesirable effects

Text Added:

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, adverse events 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), not known (cannot be estimated from the available data).

Immune System Disorders:

Not known: Hypersensitivity (including Eye allergy)

Nervous System Disorders:

Not known: Dizziness

Headache

Hypoaesthesia

Eye Disorders:

Common: Eye irritation

Ocular discomfort

Not known:  Keratitis,

        Conjunctivitis,

        Vision blurred,

        Photophobia,

        Eyelid oedema,

        Foreign body sensation in eyes,

        Lacrimation increased,

        Dry eye,

        Eye pain,

        Eye/Eyelids pruritus,

        Ocular hyperaemia

Cardiac disorders:

Not known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9)

Gastrointestinal Disorders

Not known: Nausea

Skin and Subcutaneous Tissue Disorders

Not known: Periorbital oedema

General Disorders and Administrative Site Conditions

Not known: Facial oedema

4.9

Overdose

Text Added

No case of overdose has been reported.

In the event of a topical overdose, flush the eye with water.

In the event of an overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

10

DATE OF REVISION OF TEXT

Text Removed/Added

26^th August 2009 07 June 2011

Section Number

Subject

Change

4.4

Special Warnings and Precautions for Use

The following text was added:

EXOCIN is not for injection.

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching.

If an allergic reaction to ofloxacin occurs, discontinue the drug. Use EXOCIN with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents

Stevens-Johnson syndrome has been reported in patients receiving topical ophthalmic ofloxacin, however, a causal relationship has not been established.

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.

Text has been amended as follows:

Exocin The multidose eye drop presentation contains the preservative benzalkonium chloride which may cause eye ocular irritation and discolour soft contact lenses.

Exocin contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses and discolour them. Contact lenses should be removed prior to instillation and may be reinserted 15 minutes following administration.

Use of contact lenses is not recommended in patients receiving treatment for an eye infection.

4.5

Interaction with other medicinal products and other forms of interactions

The following text was added:

It has been shown that the systemic administration of some quinolones inhibits the metabolic clearance of caffeine and theophylline. Drug interaction studies conducted with systemic ofloxacin have demonstrated that metabolic clearance of caffeine and theophylline are not significantly affected by ofloxacin.

Although there have been reports of an increased prevalence of CNS toxicity with systemic dosing of fluoroquinolones when used concomitantly with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.

4.7

Effects on the ability to Drive and Use Machines

The following text was added:

No studies on the effects on the ability to drive and use machines have been performed.

4.8

Undesirable Effects

Text has been amended as follows:

a) The most frequently reported ADR is eye irritation which was reported with an incidence of 1.6% in clinical trials.

General

4.9

Overdose

The following text was added:

No case of overdose has been reported.

5.1

Pharmacodynamic properties

The following text was added:

Pharmacotherapeutic group: Ophthalmologicals, anti-infectives, quinolones

ATC code: S 01 AX 11

6.6

Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

Text has been amended as follows:

No special requirements.

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

Due to the nature of Benzalkonium chloride, EXOCIN should not be used by soft (hydrophilic) contact lens wearers.

10

Date of revision of text

26^th August 2009 replaces 28th October 2006