INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo EXOCIN Ophthalmic Solution
SCHEDULING STATUS:
Schedule 4

PROPRIETARY NAME
(and dosage form):

EXOCIN Ophthalmic Solution

COMPOSITION:
EXOCIN Ophthalmic Solution contains:
Ofloxacin 3,0 mg/mL
Preservative:
Benzalkonium chloride 0,005% m/v.

PHARMACOLOGICAL CLASSIFICATION.
A. 15.1 Ophthalmic preparations with antibiotics.

PHARMACOLOGICAL ACTION.
Ofloxacin has in vitro activity against a broad range of gram-positive and gram-negative aerobic and anaerobic bacteria. Ofloxacin is bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Ofloxacin is thought to exert a bactericidal effect on susceptible bacterial cells by inhibiting DNA gyrase, an essential bacterial enzyme which is a critical catalyst in the duplication, transcription and repair of bacterial DNA.
Cross resistance has been observed between ofloxacin and other fluoroquinolones. There is generally no cross-resistance between ofloxacin and other classes of antibacterial agents such as beta-lactams or aminoglycosides.
Ofloxacin has been shown to be active against most strains of the following organisms both in vitro and clinically, in conjunctival and/or corneal ulcer infections as described in the INDICATIONS section.
AEROBES, GRAM-POSITIVE: AEROBES, GRAM-NEGATIVE:
        Staphylococcus aureus        Enterobacter cloacae
        Staphylococcus epidermidis        Haemophilus influenzae
        Streptococcus pneumoniae        Proteus mirabilis
ANAEROBIC SPECIES: Pseudomomas aeruginosa
        Propionibacteriam acnes        Serratia marcescens*
* Efficacy for this organism was studied in fewer than 10 infections.

The safety and effectiveness of EXOCIN in treating ophthalmologic infections due to these microorganisms have not been established in adequate and well-controlled clinical trials. EXOCIN has been shown to be active in vitro against most strains of the following organisms but the clinical significance in ophthalmic infections is unknown.
AEROBES, GRAM-POSITIVE:
        Enterococcus faecalis        Staphylococcus hominus
        Listeria monocytogene        Staphylococcus simulans
        Staphylococcus capiti        Streptococcus mitis
        Streptococcus pyogenes
AEROBES, GRAM-NEGATIVE:
        Acinetobacter calcoaceticus var. anitratum Klebsiella pneumoniae
        Acinetobacter calcoaceticus var. wolffii Moraxella (branhameila) catarrhalis
        Citrobacter diversus        Moraxella lacunata
        Citrobacter freundii        Morganella morganii
        Enterobacter aerogenes        Neisseria gonorrhoeae
        Enterobacter agglomerans        Pseudomonas acidovorans
        Escherichia coli        Pseudomonas fluorescens
        Haemophilus parainfluenzae        Shigella sonnei
  Klebsiella oxytoca
OTHER:
Chlamydia trachomatis

Pharmacokinetics (Ocular administration):
Systemic absorption of ofloxacin was detected following ocular drug administration. In all species tested (rabbits, monkeys, and man), the systemic absorption of ofloxacin was in the low ng/mL range.
The maximal serum concentration observed after topical ocular doses to man (+ 1,9 ng/mL) was about a thousand fold lower than that achieved after a standard dose. Therefore, the pharmacokinetic parameters of ofloxacin following oral administration of therapeutic systemic dosages may not be clinically relevant to topical ocular administration due to the extremely low serum levels following topical administration.

INDICATIONS
EXOCINis indicated for the treatment of infections caused by susceptible strains of the following bacteria in the conditions listed below:

CONJUNCTIVITIS                CORNEAL ULCERS
Gram-positive bacteria:        Gram-positive bacteria:
        Staphylococcus aureus        Staphylococcus aureus
        Staphylococcus epidermidis Staphylococcus epidermidis
        Streptococcus pneomoniae        Streptococcus pneomoniae

Gram-negative bacteria:                Gram-negative bacteria:
        Enterobacter cloacae Pseudomonas aeroginsa
        Haemophilus influenzae Serratia marcescens*
        Proteus mirabilis         
        Pseudomonas aeruginosa Anaerobic species:
                Propionibacterium acnes
* Efficacy for this organism was studied in fewer than 10 infections.

CONTRA-INDICATIONS
EXOCIN is contra-indicated in patients hypersensitive to ofloxacin or any of its components. Since systemic quinolones have been shown to cause arthropathy in immature animals, it is recommended that EXOCIN not be used by pregnant or lactating women.
Safety and effectiveness in infants below the age of one year have not been established.

WARNINGS
As the possibility of adverse effects on the corneal permeability and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride preserved ophthalmic preparations cannot be excluded, regular ophthalmological examination is required.
Caution should be exercised in the use of benzalkonium chloride preserved topical medication over an extended period in patients with extensive ocular surface disease.

DOSAGE AND DIRECTIONS FOR USE
The recommended dosage for the treatment of bacterial conjunctivitis is:
One drop every two to four hours for the first two days, then four times daily in the affected eye(s).
Treatment should not exceed ten days.
The recommended dosage regimen for the treatment of bacterial corneal ulcer is:
Days 1 and 2: Instill one to two drops into the affected eye every 30 minutes, while awake. Awaken at approximately four and six hours after retiring and instill one to two drops.
Days 3 through 7 to 9: Instill one or two drops hourly, while awake.
Days 7 to 9 through treatment completion: Instill one to two drops, four times daily.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Transient ocular irritation (burning, stinging, redness, itching and photophobia) was reported in clinical trials. Haemorrhagic conjunctivitis with palbebral oedema due to an allergic reaction may rarely occur.
Long-term, high-dose use of 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 monkeys.
The systemic administration of quinolones, including ofloxacin, has led to lesions or erosions of the cartilage in weight bearing joints and other signs of arthropathy in immature animals of various species. Ofloxacin, administered systemically at 10 mg/kg/day in young dogs (equivalent to 150 times the maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.
A rare occurrence of Stevens-Johnson syndrome, which progressed to toxic epidermal necrolysis, has been reported in a patient who was receiving topical ophthalmic ofloxacin. If an allergic reaction to ofloxacin occurs, discontinue the drug.
Since a small amount of ofloxacin is systemically absorbed after topical administration, side-effects reported with systemic use could possibly occur.
The following effects have been reported with systemic use of ofloxacin:
Allergic manifestations may occur, in particular hypersensitivity reactions of the skin. There have been fleabite-like haemorrhages (petechiae), the formation of blood blisters (haemorrhagic bullae), and small nodules (papules) with crust formation indicating vessel involvement (vasculitis).
There have been symptoms such as facial oedema, swollen tongue, glottal oedema, tachycardia, dyspnoea and signs of imminent shock and acute anaphylaxis. Skin reactions on exposure to strong sunlight have been reported.
Disturbances of the nervous system e.g., headaches, dizziness, sleep disturbances, nightmares, unsteady gait and tremor (disturbance of muscular coordination), numbness and tingling in the limbs (parasthesiae), visual disturbances such as double vision and abnormal colour vision, disturbances of the senses of taste and smell, hallucinations, epilepsy, convulsions and psychotic reactions such as restlessness, agitation, anxiety and confusion may occur. These reactions have occurred mainly in elderly patients and patients with impaired renal functions, but not extensively.
There have been reports of pain in joints and muscles. There have been cases of changes in the blood picture (leucopenia, agranulocytosis, thrombocytopenia, anameia), transient increases in liver enzymes and/or bilirubin and in serum creatinine.
Crystalluria may also occur.
Gastro-intestinal symptoms may occur (gastric or abdominal symptoms, loss of appetite, nausea, vomiting, diarrhoea). If severe and persistent diarrhoea occurs during or after therapy, the doctor should be informed because in a few cases this may point to a serious intestinal disorder (pseudomembranous colitis) which requires immediate treatment. In such cases EXOCIN, must be discontinued immediately and suitable therapy initiated.
The doctor should always be informed of side-effects that have occurred. Prolonged use may result in overgrowth of nonsusceptible organisms. If superinfection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute appropriate therapy.
Use EXOCIN with caution in patients who have exhibited hypersensitivities to other quinolone antibacterial agents.
The use of EXOCIN while wearing contact lenses is not recommended.
No comparative data are available with topical dosing in the elderly versus other age groups.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In event of accidental ingestion of 10 mL of EXOCIN, 30 mg of ofloxacin would be ingested. This amount does not appear to be clinically significant in terms of overdosage. However, there would be an increased potential for systemic reactions. (See Side-Effects).
In the event of a topical overdosage, flush the eye with a topical ocular irrigant.
Treatment is symptomatic and supportive.

IDENTIFICATION
EXOCIN is a clear, pale to light yellow-green solution practically free from particulate matter.

PRESENTATION
EXOCIN is supplied in sterile dropper bottles containing 5 mL solution.

STORAGE INSTRUCTIONS
Store below 25°C. Do not use more than 30 days after opening.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER.
Z/15.1/347

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Allergan Pharmaceuticals (Pty) Ltd
Mount Royal Industrial Park
James Crescent
Halfway House
Johannesburg, South Africa

DATE OF PUBLICATION OF THIS PACKAGE INSERT
5 September 1997

Updated on this site: Aug 2007
Source: Pharmaceutical Industry

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