Qualitative and Quantitative Composition
OFLOX Eye/Ear Drops
Each ml contains:
Ofloxacin USP …................................................................................................0.3% w/v
Benzalkonium Chloride NF …............................................................................0.01% w/v
Sterile aqueous vehicle …..................................................................................q.s.
Dosage Form and Strength
Ofloxacin Ophthalmic Solution, 0.3%
OFLOX Eye/Ear Drops are indicated for the treatment of ocular infections caused by susceptible strains of the following bacteria in the conditions listed below:
*Efficacy for this organism was studied in fewer than 10 infections
Posology and Method of Administration
The recommended dosage regimen for the treatment of bacterial conjunctivitis is as follows:
Days 1 and 2
Instill one to two drops every 2–4 hours in the affected eye(s).
Days 3 through 7
Instill one to two drops four times daily.
The recommended dosage regimen for the treatment of bacterial corneal ulcer is as follows:
Days 1 and 2
Instill one to two drops into the affected eye every 30 minutes, while awake. Awaken at approximately 4 and 6 hours after retiring and instill one to two drops.
Days 3 through 7 to 9
Instill one to two drops hourly, while awake.
Days 7 to 9 through
Instill one to two drops, four times daily.
The length of treatment should not exceed 10 days.
The use of OFLOX Eye/Ear Drops is contraindicated in patients with hypersensitivity to ofloxacin, any of its excipients or any other quinolones.
Special Warnings and Precautions for Use
NOT FOR INJECTION.
OFLOX Eye/Ear Drops should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
There are rare reports of anaphylactic reaction/shock and fatal hypersensitivity reactions in patients receiving systemic quinolones, some following the first dose, including ofloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angio-oedema (including laryngeal, pharyngeal or facial oedema), airway obstruction, dyspnoea, urticaria, and itching. 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. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation, should be administered as clinically indicated.
As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgement dictates, the patient should be examined with the aid of magnification, such as slit-lamp biomicroscopy and, where appropriate, fluorescein staining. Ofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.
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 110 times the maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.
When using ofloxacin ophthalmic solution, the risk of rhinopharyngeal passage, which can contribute to the occurrence and the diffusion of bacterial resistance, should be considered.
If worsening infection occurs, or if clinical improvement is not noted within a reasonable period, discontinue use and institute alternative therapy.
Caution should be taken when using fluoroquinolones, including ofloxacin ophthalmic solution, in patients with known risk factors for prolongation of the QT interval such as the following:
- 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 ophthalmic solution, in these populations.
Data are very limited to establish efficacy and safety of ofloxacin ophthalmic 0.3% solution, in the treatment of conjunctivitis in neonates.
The use of ofloxacin ophthalmic solution in neonates with ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended as it has not been evaluated in such patients.
No comparative data are available with topical dosing in the 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 (NSAIDs). 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 6 months in animal studies, including studies in monkeys.
Sun or UV exposure should be avoided during use of ofloxacin due to the potential for photosensitivity.
OFLOX Eye/Ear Drops contain the preservative benzalkonium chloride which may cause ocular irritation and discolour soft contact lenses.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies to determine the carcinogenic potential of ofloxacin have not been conducted.
Ofloxacin was not mutagenic in the Ames test, in vitro and in vivo cytogenic assay, sister chromatid exchange assay (Chinese hamster and human cell lines), unscheduled DMA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay, or mouse micronucleus assay. Ofloxacin was positive in the UDS test using rat hepatocyte, and in the mouse lymphoma assay.
In fertility studies in rats, ofloxacin did not affect male or female fertility or morphological or reproductive performance at oral dosing up to 360 mg/kg/day (equivalent to 4,000 times the maximum recommended daily ophthalmic dose).
Specific drug interaction studies have not been conducted with OFLOX Eye/Ear Drops. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.
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 NSAIDs, this has not been reported with the concomitant systemic use of NSAIDs and ofloxacin.
Ofloxacin ophthalmic solution, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval.
Use in Special Populations
Pregnancy Category C Drug
Ofloxacin has been shown to have an embryocidal effect in rats and in rabbits when given in doses of 810 mg/kg/day (equivalent to 9,000 times the maximum recommended daily ophthalmic dose) and 160 mg/kg/day (equivalent to 1,800 times the maximum recommended daily ophthalmic dose). These dosages resulted in decreased foetal body weight and increased foetal mortality in rats and rabbits, respectively. Minor foetal skeletal variations were reported in rats receiving doses of 810 mg/kg/day. Ofloxacin has not been shown to be teratogenic at doses as high as 810 mg/kg/day and 160 mg/kg/day when administered to pregnant rats and rabbits, respectively.
There are no adequate and well-controlled studies in pregnant women. OFLOX Eye/Ear Drops should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the embryo or foetus.
Additional studies in rats with doses up to 360 mg/kg/day during late gestation showed no adverse effect on late foetal development, labour, delivery, lactation, neonatal viability, or growth of the newborn.
There are, however, no adequate and well-controlled studies in pregnant women. Ofloxacin ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
In nursing women, a single 200 mg oral dose resulted in concentrations of ofloxacin in milk, which were like those found in plasma.
Because ofloxacin and other quinolones taken systemically are excreted in breast milk, there is potential for harm to nursing infants. Similarly, 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 not known whether ofloxacin ophthalmic solution is excreted in human milk following topical administration. Because of the potential for serious adverse reactions from ofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in infants below the age of 1 year have not been established.
Quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals after oral administration; however, topical ocular administration of ofloxacin to immature animals has not shown any arthropathy. There is no evidence that the ophthalmic dosage form of ofloxacin has any effect on weight-bearing joints.
No overall differences in safety or effectiveness have been observed between the elderly and younger patients.
Effects on Ability to Drive and Use Machines
As with any topical ophthalmic medicinal product, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs upon instillation, the patient must wait until the vision clears before driving or using machinery.
The most frequently reported drug-related adverse reaction was transient ocular burning or discomfort. Other reported reactions include stinging, redness, itching, chemical conjunctivitis/keratitis, ocular/periocular/facial oedema, foreign-body sensation, photophobia, blurred vision, tearing, dryness, and eye pain. Rare reports of dizziness and nausea have been received.
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 under the following 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 reactions, including signs or symptoms of eye allergy (such as eye pruritus and eyelid pruritus) and anaphylactic reactions (such as angio-oedema, dyspnoea, anaphylactic shock, oropharyngeal swelling, facial oedema and tongue swollen)
Nervous System Disorders
Not Known: dizziness
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)
Not Known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation); ECG QT prolonged
Not Known: nausea
Skin and Subcutaneous Tissue Disorders
Not Known: Stevens-Johnson syndrome; toxic epidermal necrolysis
Systemic absorption of fluoroquinolones has been reported to cause the adverse effects such as low blood sugar and mental health-related side effects. Low blood sugar levels, also called hypoglycaemia, can lead to coma. The mental health side effects that are more prominent and more consistent across the systemic fluoroquinolone drug class are as mentioned below:
- Disturbances in attention
- Memory impairment
- Serious disturbances in mental abilities (delirium)
If you experience any side effects, talk to your doctor or pharmacist or write to firstname.lastname@example.org. You can also report side effects directly via the National Pharmacovigilance Programme of India (PvPI) by calling on 1800 267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product.
An ocular overdose can be flushed from the eye(s) with lukewarm water. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
Mechanism of Action
Ofloxacin has in vitro activity against a broad range of Gram-positive and Gram-negative aerobic and anaerobic bacteria. It 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 that is a critical catalyst in the duplication, transcription, and repair of bacterial DNA.
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. The primary mechanisms of action through inhibition of bacterial DNA gyrase, the enzyme responsible for maintaining the structure of 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:
*Efficacy for this organism was studied in fewer than ten infections.
The safety and effectiveness of ofloxacin ophthalmic solution in treating ophthalmologic infections due to the following organisms have not been established in adequate and well-controlled clinical trials. Ofloxacin ophthalmic solution has been shown to be active in vitro against most strains of these organisms but the clinical significance in ophthalmologic infections is unknown.
Acinetobacter calcoaceticus var. anitratus
Acinetobacter calcoaceticus var. lwoffii
Moraxella (Branhamella) catarrhalis
In a randomised, double-masked, multicentre clinical trial, ofloxacin ophthalmic solution was superior to its vehicle after 2 days of treatment in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trial demonstrated a clinical improvement rate of 86% (54/63) for the ofloxacin-treated group versus 72% (48/67) for the placebo-treated group after 2 days of therapy. Microbiological outcomes for the same clinical trial demonstrated an eradication rate for causative pathogens of 65% (41/63) for the ofloxacin-treated group versus 25% (17/67) for the vehicle-treated group after 2 days of therapy. Please note that microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.
In a randomised, double-masked, multicentre clinical trial of 140 subjects with positive cultures, ofloxacin ophthalmic solution-treated subjects had an overall clinical success rate (complete re-epithelialisation and no progression of the infiltrate for two consecutive visits) of 82% (61/74) compared with 80% (53/66) for the fortified-antibiotic group, consisting of 1.5% tobramycin and 10% cefazolin solutions. The median time to clinical success was 11 days for the ofloxacin-treated group and 10 days for the fortified-treatment group.
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 4 hours after topical dosing (9.2 µg/g) were higher than the 2 µg/ml minimum concentration of ofloxacin necessary to inhibit 90% of most ocular bacterial strains (MIC90) in vitro.
Maximum serum ofloxacin concentrations after 10 days of topical dosing were about 1,000 times lower than those reported after standard oral doses of ofloxacin, and no systemic side effects attributable to topical ofloxacin were observed.
Serum, urine and tear concentrations of ofloxacin were measured in 30 healthy women at various time points during a 10-day course of treatment with ofloxacin ophthalmic solution. The mean serum ofloxacin concentration ranged from 0.4 ng/mL to 1.9 ng/mL. Maximum ofloxacin concentration increased from 1.1 ng/mL (day 1) to 1.9 ng/mL (day 11) after QID dosing for 10½ days. Maximum serum ofloxacin concentrations after 10 days of topical ophthalmic dosing were more than 1,000 times lower than those reported after standard oral doses of ofloxacin.
Tear ofloxacin concentrations ranged from 5.7 to 31 mcg/g during the 40-minute period following the last dose on day 11. Mean tear concentration measured 4 hours after topical ophthalmic dosing was 9.2 mcg/g.
Corneal tissue concentrations of 4.4 mcg/mL were observed 4 hours after beginning topical ocular application of two drops of ofloxacin ophthalmic solution every 30 minutes. Ofloxacin was excreted in the urine primarily unmodified.
Animal Toxicology or Pharmacology
There are no toxicological safety issues with this product in humans 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 humans is unknown.
OFLOX Eye/Ear Drops (ofloxacin ophthalmic solution), 0.3%, is a sterile ophthalmic solution. It is a fluorinated carboxyquinolone anti-infective for topical ophthalmic use.
Incompatible with alkaline solutions.
OFLOX Eye/Ear Drops:…………………..Vial of 5ml
Storage and Handling Instructions
Protect from light
Keep out of reach of children
Patient Counselling Information
What is OFLOX Eye/Ear Drops?
OFLOX Eye/Ear Drops contain ofloxacin, a fluoroquinolone, which shows an antimicrobial effect.
Do not use if you have an allergy to OFLOX Eye/Ear Drops
Do not use if you are allergic (hypersensitive) to ofloxacin, benzalkonium chloride, any of the other ingredients, or any other quinolones.
Before you use OFLOX Eye/Ear Drops, tell your HCP about other medication.
Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including medicines obtained without prescription.
You must tell your doctor if you are taking other medicines that can alter your heart rhythm: medicines that belong to the group of anti-arrhythmics (e.g. quindine, hydroquindine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (that belong to the group of macrolides), and some antipsychotics.
How should I use OFLOX Eye/Ear Drops?
Always use OFLOX Eye/Ear Drops exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.
What are the possible side effects?
Like all medicines, OFLOX Eye/Ear Drops can cause side effects, but not everyone gets them.
Serious side effects
If you have one or more of the following side effects, you may have had a serious
allergic reaction. Stop using OFLOX Eye/Ear Drops immediately and contact your physician.
Frequency not known (cannot be estimated from available data)
- Allergic reactions in the eye (including itchiness of the eye and/or eyelid)
- Inflammation of the skin due to allergy (including rash, itching or hives)
- Severe sudden life-threatening allergic reaction (anaphylactic) presenting as a swelling beneath the skin that can occur in areas such as the face, lips or other parts of the body and/or swelling of the mouth, tongue or throat that can obstruct the airways, which may cause wheezing, difficulty swallowing, breathing or shortness of breath
- Potentially life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported with the use of OFLOX Eye/Ear Drops, appearing initially as reddish target-like spots or circular patches, often with central blisters on the trunk.
The following side effects are also known to occur. You should see your doctor if any of the following side effects prove troublesome or if they are long-lasting.
Common side effects (may affect up to 1 in 10 people)
- Eye irritation
- Ocular discomfort
In very rare cases, cornea of eye has developed cloudy patches on the cornea due to calcium build-up during treatment.
Frequency not known (cannot be estimated from available data)
Side effects affecting the eye:
- Visual disturbance
- Sensitivity to light
- A feeling that something is in your eye
- Eye swelling
- Swelling around the eyes (including eyelid swelling)
- Eye pain
- Dryness (mild stinging or burning)
Side effects affecting the body:
Side effects affecting the heart:
- Abnormal fast heart rhythm
- Life-threatening irregular heart rhythm
- Alteration of the heart rhythm (called ‘prolongation of QT interval’, seen on ECG electrical activity of the heart)
How should I store OFLOX Eye/Ear Drops?
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date, which is stated on the pack.
General information about the safe and effective use of this drug.
OFLOX Eye/Ear Drops are a combination of ofloxacin, a fluoroquinolone, which is an antibacterial agent indicated for the treatment of ocular infections caused by susceptible strains. This product should be used with caution in patients sensitive to other quinolone antibacterial agents.
- This product should be used with caution in patients with a defect or ulceration of the surface of the eye.
- Ofloxacin ophthalmic solution potentially increases sensitivity to sunlight. You should avoid exposure to direct sunlight or sun during use of OFLOX Eye/Ear Drops.
- Heart problems: Caution should be taken when using this kind of medicine, if you were born with or have family history of prolonged QT interval (seen on an ECG, which is an electrical recording of the heart), have salt imbalance in the blood (especially low levels of potassium or magnesium in the blood), have a very slow heart rhythm (called ‘bradycardia’), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), you are female or elderly, or you are taking other medicines that result in abnormal ECG changes.
- Tell your doctor before you start using OFLOX Eye/Ear Drops if you are pregnant or if you are breastfeeding. Your doctor can then decide whether you can use OFLOX Eye/Ear Drops.
- Children: There is limited experience of the use of ofloxacin ophthalmic solution in children. Talk to your doctor before you start using ofloxacin ophthalmic solution in children. OFLOX Eye/Ear Drops is not recommended for use in infants below the age of 1 year.
- Driving and using machines: Your eyesight may become blurred for a short time just after using ofloxacin ophthalmic solution. Hence, you should not drive or use machines until your sight is clear again.
Important information about some of the ingredients in OFLOX Eye/Ear Drops if you wear contact lenses
- Normally, you should not wear contact lenses whilst being treated with this product. However, there may be situations where the use of contact lenses is unavoidable. In these situations, remove the lenses before using OFLOX Eye/Ear Drops. Wait at least 15 minutes after using the eye drops before putting your lenses back in your eyes.
- A preservative in OFLOX Eye/Ear Drops (benzalkonium chloride) may cause eye irritation and is also known to discolour soft contact lenses.
What are the ingredients in OFLOX Eye/Ear Drops?
The active substance is ofloxacin (0.3% w/v). The other ingredients are benzalkonium chloride (0.01% w/v) and purified water.
Any other information
- Avoid contaminating the applicator tip with material from the eye, fingers or other source. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions
- Systemic quinolones, including ofloxacin, have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.
- The preservative in OFLOX Eye/Ear Drops, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling OFLOX Eye/Ear Drops before they insert their lenses.
Details of the Manufacturer
OFLOX Eye/Ear Drops
Mfd. By CIPLA LTD.
Solapur 413006 INDIA
Mfd By CIPLA LTD
Plot No.9 & 10 Pharma Zone, Phase II,
Indore Special Economic zone,
Pithampur (M.P.) – 454775 INDIA
Details of Permission or Licence Number with Date
Permitted vide letter No.721/(27)/MFG/DFDA/5985 Dated: 10/06/2009
Date of Revision
24 September 2019