Dexaflox Ophthalmic Suspension is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial ocular infection or a risk of infection exists.

Posology
Adults (including the elderly)
The usual dose in adults, including the elderly, is 1 drop, 4 to 6 times daily.
In severe conditions, the treatment can be used more frequently at first (1 drop every hour), and then reduced to 1 drop every 4 hours as the eye inflammation subsides. Dexamethasone sodium phosphate dosage should be progressively reduced.
Paediatric population
Use of Dexaflox in children and adolescents must be restricted. No data on safety and efficacy are available for children aged less than 2 years. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made. In children, long- term continuous corticosteroid therapy should be avoided due to possible adrenal suppression (see section 4.4).
Method of administration
Ocular use.

Ofloxacin Contra-indicated in individuals who have shown hypersensitivity to ofloxacin, any of its excipients or any other quinolones. Dexamethasone Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Use is contra-indicated in herpes simplex and other viral diseases of the cornea and conjunctiva, fungal disease, ocular tuberculosis, untreated purulent infections, patients with a history of acute epithelial herpes simplex keratitis or hypersensitivity to any component of the preparation.

Ofloxacin
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. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial oedema), airway obstruction, dyspnoea, urticaria, and itching.
If an allergic reaction to Ofloxacin occurs, discontinue the drug. Use Ofloxacin with caution in patients who have exhibited sensitivities to other quinolones antibacterial agents.
When using Ofloxacin 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 worsening infection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.
Cardiac disorders
Caution should be taken when using fluoroquinolones, including Ofloxacin 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)
- Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including Ofloxacin, in these populations.
Use Ofloxacin with caution in patients who have exhibited sensitivities to other quinolone antibacterial agents.
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.
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.
Ofloxacin 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.
Dexamethasone
For ocular use only. Not for injection into the eye.
In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical corticosteroids.
Caution is also necessary when used in conjunction with antiviral therapy in the treatment of stromal keratitis or uveitis and use of periodic slit-lamp microscopy.
Corticosteroids may reduce resistance to and aid in the establishment of bacterial, viral and fungal infections and mask the clinical signs of infections, preventing recognition of ineffectiveness of the antibiotic. In such cases antibiotic therapy is mandatory. Fungal infection should be suspected in patients with persistent corneal ulceration who have been or are receiving these drugs, and corticosteroids therapy should be discontinued if fungal infection occurs.
This medicinal product contains phosphates which may lead to corneal deposits or corneal opacity when topically administered. It should be used with caution in patients presenting with compromised cornea and in instances where the patient is receiving polypharmacy with other phosphate-containing eye medications (see section 4.5).

Topical corticosteroids should not be used for longer than one week except under ophthalmic supervision. Prolonged use of topical ophthalmic corticosteroids may result in ocular hypertension and/or glaucoma, with damage to the optic nerve, reduced visual acuity, visual field defects and posterior subcapsular cataract formation. In patients receiving prolonged ophthalmic corticosteroid therapy, intraocular pressure and the lens should be checked routinely and frequently, particularly in patients with a history or presence of glaucoma. The dose of anti-glaucoma medication may need to be adjusted in these patients. Prolonged use may also increase the hazard of secondary ocular infections. Topical ophthalmic corticosteroids may slow corneal wound healing.
Cushing's syndrome and/or adrenal suppression associated with systemic absorption of ophthalmic dexamethasone may occur after intensive or long-term continuous therapy in predisposed patients, including children and patients treated with CYP3A4 inhibitors (including ritonavir and cobicistat). In these cases, treatment should be progressively discontinued.
Contact lenses should not be worn during treatment with corticosteroid eye drops due to increased risk of infection.
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 drops via the naso-lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.)
Paediatric population
In children, long-term, continuous corticosteroid therapy should be avoided due to possible adrenal suppression.

Ofloxacin No interaction studies have been performed.
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.
Ofloxacin, 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).
Dexamethasone
The risk of increased intraocular pressure associated with prolonged corticosteroid therapy may be more likely to occur with concomitant use of anticholinergics, especially atropine and related compounds, in patients predisposed to acute angle closure.
The risk of corneal deposits or corneal opacity may be more likely to occur in patients presenting with compromised cornea and receiving polypharmacy with other phosphate-containing eye medications.
The therapeutic efficacy of dexamethasone may be reduced by phenytoin, phenobarbitone, ephedrine and rifampicin.
Glucocorticoids may increase the need for salicylates as plasma salicylate clearance is increased.
CYP3A4 inhibitors (including ritanovir and cobicistat) may decrease dexamethasone clearance resulting in increased effects and adrenal suppression/Cushing's syndrome. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid effects.
If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

Ofloxacin Use in pregnancy: There have been no adequate and well-controlled studies performed in pregnant women. Since systemic quinolones have been shown to cause arthropathy in immature animals, it is recommended that Ofloxacin not be used in pregnant women.
Use during lactation: Because ofloxacin and other quinolones taken systemically are excreted in breast milk, and there is potential for harm to nursing infants, a decision should be made whether to temporarily discontinue nursing or not to administer the drug, taking into account the importance of the drug to the mother
Dexamethasone
Pregnancy
There are no or limited amount of data from the use of dexamethasone eye drops in pregnant women. Studies in animals have shown that topically applied steroids can be absorbed systemically and can cause abnormalities of fetal development in pregnant animals. Although the relevance of these findings to human beings has not been established, the use of Dexamethasone during pregnancy should be avoided.
Breastfeeding
Systemically administered corticosteroids appear in human milk in quantities that could affect the child being breastfed. However, when instilled topically, systemic exposure is low. It is unknown whether dexamethasone is excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from dexamethasone therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Ofloxacin 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.
Dexamethasone
Have no or negligible influence on the ability to drive and use machines; however, instillation of eye drops may cause transient blurring of vision. Warn patients not to drive or operate hazardous machinery until vision is clear.

Ofloxacin
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 edema and tongue swollen)
Nervous System Disorders
Not known: Dizziness
Eye Disorders
Common: Eye irritation; Ocular discomfort
Not known: Keratitis; Conjunctivitis; Vision blurred; Photophobia; Eye edema; Foreign body sensation in eyes; Lacrimation increased; Dry eye; Eye pain; Ocular hyperaemia; Periorbital edema (including eyelid edema)
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
Dexamethasone
The following undesirable effects are classified according to the following convention: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1000), very rare (<1/10,000), or not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness.
Endocrine disorders
- Not known (cannot be estimated from the available data): Cushing's syndrome, adrenal suppression.
Ocular disorders:
- Very common (>1/10): intraocular pressure increased (after 2 weeks of treatment).
- Common (>1/100, <1/10): ocular discomfort after instillation, irritation, burning, eye pruritus and blurred vision. These symptoms are mild and transient with no consequences.
- Uncommon (>1/1,000, <1/100): signs and symptoms of allergic or hypersensitive reactions can occur. The following corticoid specific undesirable effects can occur: delay in healing, risk of posterior subcapsular cataract formation, opportunist infections and glaucoma.
- Very rare (<1/10,000, including isolated reports): conjunctivitis, eyelid oedema, corticoid-induced uveitis, keratitis, corneal thinning, corneal oedema and ulcerations. Cases of corneal calcification have been reported in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas. Due to the steroid component, in diseases causing thinning of the cornea or sclera, there is a higher risk for perforation especially after topical long treatments.
General disorders and administration site conditions:
- Uncommon (>1/1,000, <1/100): after long treatment posology, systemic absorption can occur with an inhibition of the adrenal function
To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222,
Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
• Other GCC States: − Please contact the relevant competent authority.

Ofloxacin
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
Dexamethasone
Excess Dexamethasone Eye Drops may be wiped away with a clean tissue.

Ofloxacin
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 Ofloxacin 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.

Dexamethasone
Pharmacotherapeutic group: Corticosteroids, plain, ATC code: S01 BA01
Dexamethasone is a highly potent and long-acting glucocorticoid. It has an approximately 7 times greater anti-inflammatory potency than prednisolone, another commonly prescribed corticosteroid.
The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.
Corticosteroids will inhibit phospholipase A2 thereby preventing the generation of substances which mediate inflammation, for example, prostaglandins. Corticosteroids also produce a marked, though transient, lymphocytopaenia. This depletion is due to redistribution of the cells, the T lymphocytes being affected to a greater degree than the B lymphocytes. Lymphokine production is reduced, as is the sensitivity of macrophages to activation by lymphokines. Corticosteroids also retard epithelial regeneration, diminish post-inflammatory neo- vascularisation and reduce towards normal levels the excessive permeability of inflamed capillaries.
The actions of corticosteroids described above are exhibited by dexamethasone and they all contribute to its anti-inflammatory effect.

Ofloxacin
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.

Dexamethasone
Absorption
When given topically to the eye, dexamethasone is absorbed into the aqueous humour, cornea, iris, choroid, ciliary body and retina. Systemic absorption occurs but may be significant only at higher dosages or in extended paediatric therapy. Up to 90% of dexamethasone is absorbed when given by mouth; peak plasma levels are reached between 1 and 2 hours after ingestion and show wide individual variations.
Distribution
Tissue distribution studies in animals show a high uptake of dexamethasone by the liver, kidney and adrenal glands; a volume of distribution has been quoted as 0.58 l/kg. In man, over 60% of circulating steroids are excreted in the urine within 24 hours, largely as unconjugated steroid.
Biotransformation
Dexamethasone sodium phosphate is rapidly converted to dexamethasone within the circulation. Up to 77% of dexamethasone is bound to plasma proteins, mainly albumin. This percentage, unlike cortisol, remains practically unchanged with increasing steroid concentrations. The mean plasma half-life of dexamethasone is 3.6 ± 0.9h.
Elimination
Dexamethasone also appears to be cleared more rapidly from the circulation of the foetus and neonate than in the mother; plasma dexamethasone levels in the foetus and the mother have been found in the ratio of 0.32:1.

Ofloxacin 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

 

Dexamethasone
Repeat dose topical ocular safety studies with dexamethasone in rabbits have shown systemic corticosteroid effects. Such effects are considered to be unlikely when dexamethasone eye drops are used as recommended.
Dexamethasone was clastogenic in the in vitro human lymphocyte assay and in vivo in the mouse micronucleus assay at doses in excess of those obtained following topical application. Conventional carcinogenicity studies with dexamethasone have not been performed.
Dexamethasone has been found to be teratogenic in animal models. Dexamethasone induced abnormalities of fetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development.
There are no other preclinical data of relevance to the prescriber which are additional to that included in other sections of the SPC.

Benzalkonium chloride
Disodium edetate
Hydroxypropyl methylcellulose
Sodium chloride
Sodium hydroxide
Sodium sulphate anhydrous
Sulphuric acid
Tyloxapol
Water for injection.

None known. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

2 years, unopened.

 

Keep out of sight and reach of children.
Do not store above 30°C.

Discard after 30 days of opening

5 ml LDPE Opaque bottles

Not Applicable