Consumer medicine information

Ciloxan 0.3% Ear Drops

Ciprofloxacin

BRAND INFORMATION

Brand name

Ciloxan Ear Drops

Active ingredient

Ciprofloxacin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ciloxan 0.3% Ear Drops.

SUMMARY CMI

Ciloxan® 0.3% Ear Drops

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Ciloxan Ear Drops?

Ciloxan Ear Drops contain the active ingredient Ciprofloxacin hydrochloride. Ciloxan Ear Drops are used to treat chronic suppurative otitis media (CSOM) in adults and children 1 month old or above. It is a chronic infection of the middle ear.

For more information, see Section 1. Why am I using Ciloxan Ear Drops? in the full CMI.

2. What should I know before I use Ciloxan Ear Drops?

Do not use if you have ever had an allergic reaction to Ciloxan Ear Drops or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Ciloxan Ear Drops? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Ciloxan Ear Drops and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Ciloxan?

  • Follow the instructions provided by your doctor and use Ciloxan Ear Drops carefully.
  • Put five Ciloxan Ear Drops into the affected ear(s) twice daily for 9 days.

More instructions can be found in Section 4. How do I use Ciloxan Ear Drops? in the full CMI.

5. What should I know while using Ciloxan Ear Drops?

Things you should do
  • Remind any doctor, dentist, pharmacist or specialist you visit that you are using Ciloxan Ear Drops.
  • Tell your doctor immediately if you develop any signs of allergic reaction.
  • Avoid excessive exposure to sunlight during treatment with Ciloxan Ear Drops.
Things you should not do
  • Do not stop using this medicine suddenly.
  • Do not touch the dropper tip with your fingers or to your ear or any other surface.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Ciloxan Ear Drops affect you.
Looking after your medicine
  • Store below 25°C.
  • Do not refrigerate or freeze.
  • Do not leave the cap off the bottle for any length of time. Put the cap back on the bottle immediately after use.

For more information, see Section 5. What should I know while using Ciloxan Ear Drops? in the full CMI.

6. Are there any side effects?

Common side effects include ear pain, vertigo, fever, ear itching, headache, buzzing, hissing, whistling, ringing or other persistent noise in the ear(s).

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Ciloxan® 0.3% Ear Drops

Active ingredient: Ciprofloxacin hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using Ciloxan Ear Drops. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Ciloxan Ear Drops.

Where to find information in this leaflet:

1. Why am I using Ciloxan Ear Drops?
2. What should I know before I use Ciloxan Ear Drops?
3. What if I am taking other medicines?
4. How do I use Ciloxan Ear Drops?
5. What should I know while using Ciloxan Ear Drops?
6. Are there any side effects?
7. Product details

1. Why am I using Ciloxan Ear Drops?

Ciloxan Ear Drops contain the active ingredient Ciprofloxacin hydrochloride. Ciloxan Ear Drops belong to class of drugs called fluoroquinolone which are used to treat different types of infections caused by bacteria.

Ciloxan Ear Drops are used to treat chronic suppurative otitis media (CSOM) in adults and children 1 month old or above. It is a chronic infection of the middle ear. Symptoms include severe ear pain, discharge, hearing loss, fever. Ciloxan Ear Drops help to kill the bacteria that causes infection. It does not work against infections caused by viruses or fungus.

2. What should I know before I use Ciloxan Ear Drops?

Warnings

Do not use Ciloxan Ear Drops:

  • If you are allergic to Ciprofloxacin hydrochloride, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • If you are allergic to other quinolone antibiotics e.g. nalidixic acid, Levaquin.
    Symptoms of allergic reaction may include:
    shortness of breath, difficulty breathing
    swelling of the face, lips, tongue or other parts of the body, rash, hives
  • If you suffer from any muscle problem or have any swelling to your tendons (strands of connective tissue between muscles and bones).

Check with your doctor if you:

  • have any other medical conditions
  • take any medicines for any other condition
  • develop any skin reactions as Ciloxan Ear Drops contain benzalkonium chloride which may be an irritant.

Do not use this medicine after the expiry date printed on the pack or bottle, or if the seal around the pack is broken or shows signs of tampering.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

As a precautionary measure, it is preferable to avoid the use of Ciloxan Ear Drops during pregnancy. Your doctor will advise you regarding the possible risks and benefits of using Ciloxan Ear Drops during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will advise you regarding the possible risks and benefits of using Ciloxan Ear Drops during breast feeding.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Ciloxan Ear Drops and affect how it works.

Tell your doctor if you take any of the following medicines:

  • medicines that help to thin your blood e.g. warfarin
  • medicines to prevent tissue rejection e.g. cyclosporin
  • medicines such as theophylline which are used for asthma or other breathing problems
  • caffeine for the treatment of migraines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Ciloxan Ear Drops.

4. How do I use Ciloxan Ear Drops?

How much to use

For adults and children 1 month old or above:

  • Put five Ciloxan Ear Drops into the affected ear(s) twice daily for 9 days.
  • Follow the instructions provided when Ciloxan Ear Drops were prescribed, including the number of days it should be taken.
  • If you do not understand your dose consult your doctor or pharmacist.

When to use Ciloxan Ear Drops

  • Ciloxan Ear Drops should be used at about the same time every day unless your doctor tells you otherwise.

How to use Ciloxan Ear Drops

  • Follow the instructions provided by your doctor and use Ciloxan Ear Drops carefully.

Below are steps to use Ciloxan Ear Drops:

  • Wash your hands thoroughly.
  • To open a new bottle of Ciloxan Ear Drops, remove the cap and replace it with the dropper cap supplied in the carton. Your pharmacist may have already done this for you.
  • Do not touch the dropper tip with your fingers or to your ear or any other surface. This will help prevent the ear drops getting contaminated.
  • Shake the bottle well prior to use.
  • If the solution is cold, warm it by holding the bottle in your hand for one or two minutes before putting it in your ear.
  • This will help to prevent dizziness which may be associated with putting a cold solution into the ear.
  • Put Ciloxan Ear Drops in sitting or lying down position with the affected ear turned upwards (see Diagram 1).

  • Gently squeeze the bulb on the dropper cap to draw up the liquid into the dropper.
  • Put the tip of the dropper close to the ear and gently squeeze three drops into the ear. (see Diagram 2)

  • Hold the head in the same position for about one min. This will help the drops to reach deeper into the ear. (see Diagram 3).

  • Repeat the above steps for the other ear if necessary.
  • There might be a slightly unpleasant feeling since the drops flow all the way into the ear. If it persists, or is very uncomfortable, contact your doctor or pharmacist immediately.
  • Place the cap on the bottle and close it tightly.
  • Wash your hands again with soap and water to remove any residue.

If you forget to use Ciloxan Ear Drops

Ciloxan Ear Drops should be used as prescribed by your doctor. If you miss your dose at the usual time, use the drop(s) as soon as you remember, and then go back to use them as you would normally do.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much Ciloxan Ear Drops

If you think that you have used too much Ciloxan Ear Drops, you may need urgent medical attention.

If you have accidentally put too many Ciloxan Ear drops in your ear(s) immediately rinse your ear(s) with warm tap water.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Ciloxan Ear Drops?

Things you should do

Avoid excessive exposure to sunlight as it may cause moderate to severe phototoxicity (increased sensitivity of the skin to sun having symptoms such as redness, itching, swelling).

Call your doctor straight away if you:

  • develop any signs of an allergic reaction.
  • become pregnant or if you are breast feeding while using Ciloxan Ear Drops.
  • are taking any other medicines for any other medical conditions.

Remind any doctor, dentist, pharmacist or specialist you visit that you are using Ciloxan Ear Drops.

Things you should not do

  • Do not stop using this medicine suddenly.
  • Do not give Ciloxan Ear Drops to anyone else, even if they seem to have the same condition as you.
  • Do not touch the dropper tip with your fingers or to your ear or any other surface.
  • Do not use Ciloxan Ear Drops just before having a bath, shower or going swimming.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Ciloxan Ear Drops affect you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Store below 25°C
  • Do not refrigerate or freeze.
  • Protect from light

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

Discard Ciloxan Ear Drops container 4 weeks after opening.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Ear Problems:
  • Ear itching
  • Mild local uncomfortable feeling in ear(s)
Nervous system problems:
  • Bitter taste in mouth (dysgeusia)
  • Transient dizziness
  • Vertigo
  • Headache
General problems:
  • Fever
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Ear problems:
  • Otomycosis, fungal infection of ear (symptoms such as itching, hearing loss, pain).
  • Uncomfortable feeling in ear(s), burning sensation or tingling in, on, or around the ear (stinging)
  • Buzzing, hissing, whistling, ringing or other persistent noise in the ear(s)
  • Ear pain
  • Allergic reaction with symptoms such as:
    - shortness of breath, difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, hives
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Ciloxan Ear Drops contain

Active ingredient
(main ingredient)		Ciprofloxacin hydrochloride
Other ingredients
(inactive ingredients)		Sodium acetate, glacial acetic acid, mannitol, disodium edetate, hydrochloric acid and/or sodium hydroxide (to adjust pH), purified water and benzalkonium chloride (0.06 mg/mL) as preservative.

Do not take this medicine if you are allergic to any of these ingredients.

What Ciloxan Ear Drops looks like

Ciloxan Ear Drops are a sterile otic solution that comes in a 1 mL, 2.5 mL and 5 mL plastic bottle. The safety seal must be removed before use.

Who distributes Ciloxan Ear Drops

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone: 1800 671 203
Web Site: www.novartis.com.au

Australian Registration Number:
AUST R: 121897

This leaflet was prepared in April 2025.

Internal document code:

(cix_ear261023c_v2) based on PI (cix_ear261023i)

Published by MIMS July 2025

BRAND INFORMATION

Brand name

Ciloxan Ear Drops

Active ingredient

Ciprofloxacin

Schedule

S4

 

1 Name of Medicine

Ciprofloxacin hydrochloride.

2 Qualitative and Quantitative Composition

Ciloxan Ear Drops contain ciprofloxacin hydrochloride (equivalent to 3 mg/mL ciprofloxacin base).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ciloxan Ear Drops is a sterile, multiple dose product, for topical otic use.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of chronic suppurative otitis media (CSOM) when caused by organisms susceptible to ciprofloxacin in adults and children 1 month or older.

4.2 Dose and Method of Administration

Chronic suppurative otitis media (adults and children 1 month or older).

The recommended dosage is: five (5) drops into the affected ear canal(s) twice daily for 9 days.
If the solution is cold, it should be warmed by holding the bottle in the hand for one or two minutes before instillation, to avoid dizziness which may be associated with instillation of a cold solution into the ear.
Patients should be advised to avoid contamination of the dispensing tip.

4.3 Contraindications

A history of hypersensitivity to ciprofloxacin or any other component of the medication. A history of hypersensitivity to other quinolones, including nalidixic acid, may also contraindicate the topical use of ciprofloxacin.

4.4 Special Warnings and Precautions for Use

For topical use only - not for injection.
For otic use only.

Identified precautions.

Ciloxan Ear Drops should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnoea, urticaria and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with adrenaline and other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management, as clinically required.
Moderate to severe phototoxicity manifested by an exaggerated sunburn reaction has been observed in some patients who were exposed to direct sunlight while receiving some members of the quinolone class of drugs, including oral ciprofloxacin. Excessive sunlight should be avoided.

General.

As with other antibacterial preparations, prolonged use of ciprofloxacin may result in overgrowth of nonsusceptible organisms, including yeast and fungi. If the infection has not improved after 9 days of treatment, cultures should be obtained to guide further treatment. If otorrhea persists after a full course of therapy, or if two or more episodes of otorrhea occur within six months, further evaluation is recommended to exclude an underlying condition such as cholesteatoma, foreign body or a tumour.
Safety and efficacy of ciprofloxacin ear drops have not been established for treatment periods longer than 14 days.
The systemic administration of quinolones, including ciprofloxacin at doses much higher than given or absorbed by the otic route, has led to lesions or erosions of the cartilage in weight bearing joints and other signs of arthropathy in immature animals of various species.
Tendon inflammation and rupture may occur with systemic fluoroquinolone therapy including ciprofloxacin, particularly in elderly patients and in those treated concurrently with corticosteroids. Therefore treatment with Ciloxan 0.3% Ear Drops should be discontinued at the first sign of tendon inflammation.
Ciloxan 0.3% Ear Drops contain benzalkonium chloride which may be an irritant and cause skin reactions.

Use in hepatic impairment.

Safety and effectiveness in patients with hepatic impairment have not been established.

Use in renal impairment.

Safety and effectiveness in patients with renal impairment have not been established.

Use in the elderly.

No data available.

Paediatric use.

Efficacy and safety in children less than one year old have not been assessed. Oral administration of ciprofloxacin and other quinolones has been shown to cause arthropathy in immature animals of most species tested. However, there is no evidence that otic dosing has any effect on the weight bearing joints. Caution should be exercised when ciprofloxacin is administered to very young children. In otic use, frequent medical monitoring is required in order to be able to determine in a timely manner the possible necessity of other therapeutic measures.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Specific drug interaction studies have not been conducted with otic ciprofloxacin. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, enhance the effects of the oral anticoagulant warfarin and its derivatives and have been associated with transient elevations in serum creatinine in patients receiving ciclosporin concomitantly.
Given the low systemic concentration of ciprofloxacin following topical otic administration, drug interactions are unlikely to occur.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies have not been performed in humans to evaluate the effect of topical administration of ciprofloxacin on fertility.
Studies performed in rats and mice at oral doses of ciprofloxacin up to 100 mg/kg/day (based on body surface area 0.6 and 0.3 times, respectively, the maximal recommended daily human oral dose) revealed no evidence of impairment of fertility due to ciprofloxacin.
(Category B3)
Reproduction studies in rats and mice at oral doses of up to 100 mg/kg/day (based on body surface area 0.6 and 0.3 times, respectively, the maximal recommended human oral dose) and intravenous doses of up to 30 mg/kg have revealed no evidence of harm to the fetus due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin (30 and 100 mg/kg orally, based on body surface area 0.4 and 1.2 times, respectively, the maximal recommended human oral dose) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, intrauterine deaths and fetal retardation, but no teratogenicity was observed at either dose. After intravenous administration at doses up to 20 mg/kg, no maternal toxicity was produced and no embryo-toxicity or teratogenicity was observed at either dose. In rabbits, intravenous administration of doses up to 20 mg/kg did not elicit maternal toxicity, embryo-toxicity or teratogenicity.
There are no adequate and well controlled studies in pregnant women. Like other drugs in its class, ciprofloxacin causes arthropathy in immature animals. As a precautionary measure, it is preferable to avoid the use of Ciloxan during pregnancy. Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
 Ciprofloxacin is excreted in human milk with systemic use. It is not known whether topically applied ciprofloxacin is excreted in human milk. Since ciprofloxacin causes arthtopathy in immature animals, caution should be exercised when ciprofloxacin is administered to a nursing mother.

4.7 Effects on Ability to Drive and Use Machines

There are no known effects of Ciloxan Ear Drops on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

No serious adverse effects have been reported in published studies when ciprofloxacin ear drops have been used ototopically within the recommended dosage. Following otic administration, the following adverse events have been reported the most frequently (≥ 1%):

Ear and labyrinth disorders.

Mild local intolerance, ear pain, ear discomfort (stinging), ear pruritus, ear infection (fungal; otomycosis).

Nervous system disorders.

Dysgeusia (bitter taste), transient dizziness, vertigo, headache (cephalea).
Overall Ciloxan Ear Drops is well tolerated.

Postmarketing events.

The following adverse reactions are classified according to the following convention: very common, common, uncommon, rare, very rare, or not known (cannot be estimated from the available data), according to system organ classes. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions have been observed during clinical trials and postmarketing experience.

Nervous system disorders.

Uncommon (> 0.1% to ≤ 1%): crying, headache.

Ear and labyrinth disorders.

Uncommon (> 0.1% to ≤ 1%): ear pain, ear congestion, otorrhoea, ear pruritus.
Not known: tinnitus.

Skin and subcutaneous tissue disorders.

Uncommon (> 0.1% to ≤ 1%): dermatitis.

General disorders and administration site conditions.

Uncommon (> 0.1% to ≤ 1%): pyrexia.
With locally applied fluoroquinolones (generalized) rash, toxic epidermolysis, dermatitis exfoliative, Stevens-Johnson syndrome and urticaria occur very rarely.
In otic use the ingredients rarely are sensitizing. However as with any substance that is applied to the skin, an allergic reaction to any of the ingredients of the preparation can always occur.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnoea, urticaria, and itching.
Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving systemic fluoroquinolones. Studies and postmarketing experience with systemic fluoroquinolones indicate that the risk of these ruptures may be increased in patients receiving corticosteroids, especially geriatric patients and in tendons under high stress, including the Achilles tendon. To date, clinical and postmarketing data have not demonstrated a clear association between Ciloxan and musculoskeletal and connective tissue adverse reactions.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

A topical overdose of Ciloxan Ear Drops may be flushed from the ear(s) with warm tap water. Accidental oral ingestion of Ciloxan is not likely to be associated with toxicity. Treatment of any exposure is symptomatic and supportive.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. Ciprofloxacin has in vitro activity against a wide range of Gram negative and Gram positive organisms.
The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase which is needed for the synthesis of bacterial DNA.
Ciprofloxacin has been shown to be active against most strains of the following organisms both in vitro and in chronic suppurative otitis media (CSOM):

Gram positive.

Staphylococcus species, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae, β-hemolytic Streptococcus.

Gram negative.

Haemophilus influenzae, Pseudomonas species, including Pseudomonas aeruginosa, Serratia species, Proteus species, including Proteus mirabilis, Klebsiella species, including Klebsiella aerogenes, Enterobacteriaceae species, including Escherichia coli.
Resistance to ciprofloxacin in vitro usually develops slowly (multiple step mutation). The plasmid mediated bacterial resistance does not appear to occur with the fluoroquinolone class of antibiotics, however, parallel resistance is seen with this group of gyrase inhibitors.
Due to its special mode of action there is no crossover resistance between ciprofloxacin and other antibacterial compounds with different chemical structures, such as β-lactam antibiotics, aminoglycosides, tetracyclines, macrolide and peptide antibiotics as well as sulfonamides, trimethoprim and nitrofuran derivatives, therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin.
Co-selection of resistance to β-lactam antibiotics and tetracyclines via over expression of multidrug resistance efflux has been shown in ciprofloxacin resistant Staphylococcus aureus strains.

Toxicological properties.

An ototoxic study was conducted in which guinea pigs received 0.3% ciprofloxacin solution, twice a day, directly onto the round window membrane. Auditory brainstem response findings following two and four weeks of treatment revealed no significant differences in intra-aural threshold response (treated vs. untreated ear) or in absolute threshold at any of the frequencies tested (2, 8 and 16 kHz). Histopathologic evaluation of the cochlear hair cells demonstrated that the ciprofloxacin 0.3% and saline control groups had hair cell loss within the normal range for guinea pigs. Profound hair cell loss, corresponding with loss of auditory function, was observed in the neomycin group.

Clinical trials.

Based on a review of 24 published studies (n = 1210) ciprofloxacin solution has been demonstrated to be safe and effective in the treatment of CSOM. The pivotal study was a double blind, randomised controlled trial in Australian Aboriginal and Torres Strait Islander children (n = 111) with CSOM, from 1 to 14 years and compared the effectiveness of ototopical ciprofloxacin 0.3% (CIP) with framycetin (0.5%), gramicidin, dexamethasone (FGD) eardrops when dosed 5 drops twice daily for 9 days (Couzos et al). Regular aural toilet (povidone iodine (0.5%)) was also employed. The primary endpoint was resolution of otorrhoea (clinical cure).
Clinical cure was significantly higher in patients treated with CIP (76.4%; p = 0.009, absolute difference of 24.6% [95% CI, 15.8%-33.4%]) compared with patients treated with FGD (51.8%).
No change in hearing or tympanic membrane healing was evident in the short follow-up period of 10-21 days after treatment in this study. Longer term data is needed to determine the effect of topical antibiotic therapy on tympanic membrane healing and the level of healing impairment.
The safety profile from these published studies support that the otic administration of ciprofloxacin 0.3% is well tolerated. There have been no reports of ototoxicity associated with ciprofloxacin 0.3% ear drops.

5.2 Pharmacokinetic Properties

After instillation to the ear canal, ciprofloxacin is concentrated directly at the site of infection (approximately 3000 microgram/mL in the middle ear).
Published studies in paediatric and adult patients with a tympanic perforation (artificial or natural), showed minimal systemic absorption of ciprofloxacin following ototopical administration. Following tympanostomy tube insertion in paediatric patients who received a single bilateral topical otic dose of an ear drop containing ciprofloxacin 0.3%, plasma concentrations of ciprofloxacin (up to 6 hours following administration) were quantifiable in only 2 of 9 patients. The mean peak plasma concentrations of ciprofloxacin was 1.39 nanogram/mL. Peak plasma concentrations ranged from 0.54 nanogram/mL to 3.45 nanogram/mL and were on average approximately 0.1% of peak plasma concentrations achieved with an oral dose of 250 mg. Peak plasma concentrations were observed within 15 minutes to 2 hours post dose application.

5.3 Preclinical Safety Data

Genotoxicity.

In a battery of genotoxicity assays, ciprofloxacin was positive in the mouse lymphoma assay and the rat hepatocyte DNA repair assay in vitro, but negative in bacterial gene mutation assays, in assays for chromosomal damage in vitro and in vivo, in a cell transformation in vitro and in the rat hepatocyte DNA repair assay in vivo.

Carcinogenicity.

Carcinogenicity studies in mice (oral doses up to 1090 mg/kg/day and 1455 mg/kg/day in males and females, respectively; based on body surface area 3-4 times the maximal recommended human oral dose of 1500 mg/day based on body surface area) and rats (oral doses up to 241 mg/kg/day and 328 mg/kg/day in males and females, respectively; based on body surface area 1-2 times the maximal recommended human oral dose of 1500 mg/day) showed no evidence of ciprofloxacin induced carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ciloxan Ear Drops also contain sodium acetate, glacial acetic acid, mannitol, disodium edetate, hydrochloric acid and/or sodium hydroxide (to adjust pH), purified water and benzalkonium chloride (0.06 mg/mL) as preservative.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Do not refrigerate or freeze. Protect from light.
Discard container 4 weeks after opening.

6.5 Nature and Contents of Container

As a sterile otic solution 1 mL, 2.5 mL and 5 mL in plastic bottle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Ciprofloxacin, a faint to light yellow crystalline powder which is soluble in water, is a fluoroquinolone antibacterial active against a broad spectrum of Gram positive and Gram negative otic pathogens.
The pH of Ciloxan Ear Drops is approximately 4.5 and the osmolality is approximately 300 mOsm.

Chemical structure.

The chemical structure of ciprofloxacin hydrochloride is represented as:
Chemical name: monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro- 1,4-dihydro-4-oxo-7- piperazin-1-ylquinoline- 3-carboxylic acid.
Empirical formula: C17H18FN3O3.HCl.H2O.
Molecular weight: 385.8.

CAS number.

86393-32-0.

References

Couzos et al. Effectiveness of ototopical antibiotics for chronic suppurative otitis media in Aboriginal children: a community-based, multicentre, double-blind randomized controlled trial. MJA 2003; 179: 185-190.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes