Consumer medicine information

Ciloquin 0.3% Ear Drops

Ciprofloxacin

BRAND INFORMATION

Brand name

Ciloquin Ear Drops

Active ingredient

Ciprofloxacin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

What is in this leaflet

Please read this leaflet carefully before you use Ciloquin Ear Drops.

This leaflet answers some common questions about Ciloquin Ear Drops. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet from www.novartis.com.au

The updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the expected benefits of you using Ciloquin Ear Drops against the risks this medicine could have for you.

The information in this leaflet applies to Ciloquin only. This information does not apply to similar products, even if they contain the same ingredients.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Ciloquin is used for

Ciloquin is used to treat certain types of ear infections caused by bacteria. Your doctor will usually prescribe this medicine because you have a middle ear infection.

Ciloquin contains ciprofloxacin hydrochloride and is an antibiotic that belongs to a group of medicines called fluoroquinolones. This antibiotic works by killing the bacteria that are causing your infection.

Ciloquin will not work against infections caused by viruses, such as colds or the flu, or infections caused by fungus.

Before prescribing Ciloquin, the doctor will have examined your ear(s) and decided that Ciloquin is the right medicine for you.

Your doctor may have prescribed Ciloquin for another reason.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Ciloquin Ear Drops are only available on a doctor's prescription.

Use in children

Do not use Ciloquin Ear Drops in children under 12 months of age. The safety and effectiveness of Ciloquin Ear Drops in this age group has not been established.

Before you use Ciloquin

When you must not use it

Do not use Ciloquin Ear Drops if you have an allergy to:

  • Ciprofloxacin
  • Any other "quinolone" antibiotics e.g. nalidixic acid
  • Any of the other ingredients in Ciloquin Ear Drops that are listed under "Product description".

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

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.

If it is has expired or is damaged, return it to your pharmacist for disposal.

If you use this medicine after the expiry date has passed, it may not work.

Do not use Ciloquin Ear Drops just before having a bath, shower or going swimming. If you do, you may reduce the effectiveness of this medicine.

If you are not sure whether you should start using Ciloquin, talk to your doctor.

Before you start to use it

Tell your doctor if you have had an allergy to any other medicines or any other substances, such as foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the possible risks and benefits of using Ciloquin during pregnancy.

Tell your doctor if you are breastfeeding. Your doctor will discuss the possible risks and benefits of using Ciloquin when you are breastfeeding.

If you have not told your doctor about any of the above, tell him/ her before you use Ciloquin.

Using or taking other medicines

Tell your doctor or pharmacist if you are using or taking any other medicines, including other ear drops and any other medicines that you get without a prescription from a pharmacy, supermarket or health food shop. Some medicines and ciprofloxacin may interfere with each other.

Tell your doctor if you are taking any of the following:

  • medicines to thin your blood e.g. warfarin
  • medicines to prevent tissue rejection e.g. cyclosporin
  • theophylline for asthma or breathing problems
  • caffeine for the treatment of migraines.

Your doctor and pharmacist will have more information on medicines to be careful with or avoid while using this medicine.

How to use Ciloquin

Carefully follow all directions given to you by your doctor and pharmacist. They may differ from the information contained in this leaflet.

If you are being changed from one medicine to another, follow your doctor’s instructions carefully as to when to stop this medicine and when to start the new ear drops.

If you do not understand the instructions on the carton / bottle, ask your doctor or pharmacist for help.

How much to use

The usual dose in adults and children (1 month and older) is five drops of Ciloquin in the affected ear(s), twice each day for nine days.

Your doctor will tell you how many drops you need to use each day. These dosing instructions will be printed on the label your pharmacist puts on the bottle or carton.

How to use it

It is important to use Ciloquin exactly as your doctor or pharmacist has told you. If you use the drops less often than your doctor has advised, your medicine may not work as well and your ear infection may not improve. If you use the drops more often than your doctor has advised, your ear infection may not improve any faster and this may lead to increased side effects.

Before opening the bottle for the first time, make sure the safety seal joining the cap to the bottle is not broken. If it is, do not use the bottle and return it to your pharmacist.

To open a new bottle of Ciloquin, break the safety seal by removing the cap from the bottle. Remove the lower portion of the safety seal and discard.

Follow these steps to use the ear drops:

  1. Wash your hands thoroughly with soap and water.
  2. Shake the bottle.
  3. Remove the cap from the bottle.
  4. Hold the bottle upside down in one hand between your thumb and middle finger (see Diagram 1).

  1. Tilt your head to one side so that the affected ear is facing up. This may be easier in the sitting or lying down position (see Diagram 2).

  1. Place the dropper tip close to, but not touching, your ear and gently tap or press the base of the bottle with your forefinger to release drops (see Diagram 3).

  1. Hold the head in the same position for about one minute. This will help the drops to reach deeper into the ear.
  2. Repeat the above steps for the other ear if necessary.
  3. Place the cap on the bottle and close it tightly.
  4. Wash your hands again with soap and water to remove any residue.

There might be a slightly unpleasant feeling as the drops flow all the way into the ear. If this persists, or is very uncomfortable, contact your doctor or pharmacist.

Be careful not to touch the dropper tip against your fingers or the ear, or anything else. This will help prevent the ear drops becoming dirty or contaminated.

When to use it

Use Ciloquin, at about the same time every day unless your doctor tells you otherwise. Using your ear drops at the same time each day will have the best effect on your ear infection. It will also help you remember when to use it.

How long to use it

Continue using your medicine for as long as your doctor tells you.

As Ciloquin Ear Drops start to kill the bacteria that are causing the infection in your ear(s) you will start to feel better. However, it is very important that you continue to use Ciloquin Ear Drops for the full treatment period advised by your doctor to ensure that the infection does not return.

If you are unsure about when to stop using Ciloquin Ear Drops you should talk to your doctor or pharmacist.

If you forget to use it

If it is almost time for your next drop(s), skip the drop(s) you missed and use your next drop(s) when you are meant to.

Otherwise, use the drop(s) as soon as you remember, and then go back to using them as you would normally.

Do not use a double dose to make up for the drop(s) that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to use your medicine, ask your pharmacist for some hints.

If you use too much (overdose)

If you accidentally put too many Ciloquin drops in your ear(s) immediately rinse your ear(s) with warm water.

If you think that you or someone else has swallowed any, or all, of the contents of Ciloquin, or used too many drops, immediately telephone your doctor or the Poisons Information Centre on 13 11 26 for advice or go to Accident and Emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

While you are using Ciloquin

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

Tell your doctor if, for any reason, you have not used Ciloquin Ear Drops exactly as prescribed. Otherwise your doctor may think that the ear drops were not effective and change the treatment unnecessarily.

If you become pregnant while you are using this medicine, tell your doctor immediately,

If you are about to be started on any new medicine, remind your doctor or pharmacist that you are using Ciloquin Ear Drops.

Tell all the doctors, dentists and pharmacists who are treating you that you are using Ciloquin.

Things you must not do

Do not use Ciloquin Ear Drops to treat other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they appear to have the same condition as you.

Do not stop using Ciloquin Ear Drops or lower the dose without first asking your doctor.

Do not let children handle Ciloquin Ear Drops.

Things to be careful of

Be careful driving or operating machinery until you know how Ciloquin affects you and your hearing. This medicine may cause dizziness or light-headedness in some people. Make sure you know how you react to the ear drops before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If you drink alcohol, dizziness or light-headedness may by worse.

Be careful of sun exposure. These medicines cause some people to sunburn more readily.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Ciloquin.

This medicine helps most people with middle ear infection, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • bad taste in the mouth following the use of Ciloquin
  • ear stinging or discomfort following use of Ciloquin
  • headache
  • ear pain
  • vertigo and transient dizziness
  • ear itching (pruritus)
  • inflammation, itching and scaling of the outer ear (fungus infection of the ear; otomycosis)
  • fever
  • weeping ear
  • ear congestion.

These are the more common side effects of your medicine. They are usually mild and short-lived.

If any of the following happen, stop using Ciloquin and tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • skin rash
  • swelling of the face, hands or feet
  • wheezing, difficulty in breathing
  • severe and sudden onset of pinkish, itchy swellings on the skin, also called hives or nettle rash

These hypersensitivity reactions can be very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

If you are over 65 years of age and taking inflammatory inhibiting medicines similar to cortisone, you have a higher risk of getting tendon problems during treatment with Ciloquin Ear Drops. If this occurs, stop treatment and immediately consult your doctor.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell. Other side effects not listed above may also occur in some people.

After using Ciloquin

Storage

Keep Ciloquin Ear Drops in a cool dry place, where the temperature stays below 25°C. Do not refrigerate or freeze. Cold ear drops may hurt your ear(s) or cause temporary dizziness.

Protect from light.

Do not store Ciloquin Ear Drops or any other medicine in the car, the bathroom or any other warm, damp place. Heat and dampness can destroy some medicines.

Do not carry the ear drops in the pockets of your clothes.

Do not leave the top off the bottle for any length of time, to avoid contaminating the ear drops.

Do not use the ear drops if the solution is discoloured brown.

Keep it out of the sight and reach of children.

Disposal

Write the date on the bottle when you open the ear drops and throw out any remaining solution after four weeks. Ciloquin contains a preservative which helps prevent germs growing in the solution for the first four weeks after opening the bottle. After this time there is a greater risk that the drops may become contaminated and cause an ear infection. A new bottle should be opened.

If your doctor tells you to stop using Ciloquin or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Ciloquin Ear Drops are a sterile liquid that comes in a 1 mL, 2.5 mL or a 5 mL oval dropper bottle with a screw cap. The safety seal must be removed before use.

Ingredients

The active ingredient in Ciloquin Ear Drops is ciprofloxacin (base) 3mg in 1 mL.

Ciloquin Ear Drops also contain:

  • Benzalkonium chloride (0.06 mg/mL) as a preservative
  • Sodium acetate
  • Acetic acid
  • Mannitol
  • Disodium edetate
  • Purified water
  • Hydrochloric acid and/or sodium hydroxide to adjust pH.

Supplier

This product is supplied in Australia by:

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 No: 121898

Date of preparation

This leaflet was prepared in October 2023.

© Novartis Pharmaceuticals Australia Pty Limited 2021

® Registered trademark

Internal document code:
(cil_ear261023c) based on PI (cil_ear261023i)

Published by MIMS December 2023

BRAND INFORMATION

Brand name

Ciloquin Ear Drops

Active ingredient

Ciprofloxacin

Schedule

S4

 

1 Name of Medicine

Ciprofloxacin hydrochloride.

2 Qualitative and Quantitative Composition

Ciloquin 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

Ciloquin 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.

Ciloquin 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 Ciloquin 0.3% Ear Drops should be discontinued at the first sign of tendon inflammation.
Ciloquin 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 Ciloquin 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 arthropathy 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 Ciloquin 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 Ciloquin Ear Drops is well tolerated.

Post-marketing 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 post-marketing 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 post-marketing 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 post-marketing data have not demonstrated a clear association between Ciloquin 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 Ciloquin Ear Drops may be flushed from the ear(s) with warm tap water. Accidental oral ingestion of Ciloquin 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). A 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 cross-over 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 multi-drug 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

Ciloquin 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 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 Ciloquin 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