Consumer medicine information

Ciprofloxacin GH

Ciprofloxacin

BRAND INFORMATION

Brand name

Ciprofloxacin GH

Active ingredient

Ciprofloxacin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ciprofloxacin GH.

What is in this leaflet

This leaflet answers some common questions about Ciprofloxacin GH.

This leaflet does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Ciprofloxacin GH against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What Ciprofloxacin GH is used for

Ciprofloxacin GH is used for the treatment of infections of the lungs, skin, bones, joints, kidneys, bladder, prostate and bowel. Ciprofloxacin GH is also used to treat inhalational anthrax (an infection caused by breathing in the spores of bacteria).

Ciprofloxacin GH contains the active ingredient ciprofloxacin (present as hydrochloride monohydrate) which is an antibiotic belonging to a group of medicines called quinolones (pronounced kwin-o-lones). These antibiotics work by killing the bacteria that are causing your infection.

Ciprofloxacin GH will not work against infections caused by viruses such as colds or the flu.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

Before you take Ciprofloxacin GH

When you must not take it

Do not take Ciprofloxacin GH if you have an allergy to:

  • ciprofloxacin, the active ingredient in Ciprofloxacin GH;
  • any of the ingredients listed at the end of this leaflet;
  • other medicines belonging to the quinolone chemical family (eg. moxifloxacin, norfloxacin, nalidixic acid).

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 take Ciprofloxacin GH if you are also taking a medicine called tizanidine a muscle relaxant used to treat spasticity associated with multiple sclerosis, injury or diseases of the spinal cord. Ciprofloxacin GH can interfere with tizanidine and can lead to undesirable side effects.

Do not take this medicine after the expiry date printed on the pack and blister. The expiry date is printed on the carton and on each blister (eg. EXP 11-09 refers to November 2009). The expiry date refers to the last day of that month. If it has expired return it to your pharmacist for disposal.

Do not take this medicine if the packaging is torn or shows signs of tampering. If the packaging is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant. Ciprofloxacin GH is not recommended if you are pregnant, but your doctor will assess the benefit if required. Medicines similar to Ciprofloxacin GH have caused joint disease in immature animals.

Tell your doctor if you are breastfeeding. Ciprofloxacin GH is excreted into the breast milk. Your doctor will tell you whether you should take it and temporarily stop breastfeeding while you are taking the tablets.

Ciprofloxacin GH is not recommended in children under 18 years of age except for use in inhalation anthrax.

Ciprofloxacin GH should be used with caution in elderly patients as they are more prone to side effects.

Tell your doctor if you:

  • suffer from epilepsy (seizures, convulsions), have had a stroke, or have kidney or liver disease.
  • have arrhythmias (fast or irregular heartbeats). Ciprofloxacin GH may increase the risk of arrhythmias, especially in the elderly or patients with low potassium levels.
  • have previously taken corticosteroids. You may be at increased risk of swelling of the tendons. Symptoms include pain, tenderness and sometimes restricted movement.
  • have myasthenia gravis, a condition where the muscles become weak. Ciprofloxacin GH can worsen the symptoms of this condition.
  • have a history of tendon disorders with the use of quinolones (eg. moxifloxacin, norfloxacin, nalidixic acid);
  • have or have had a mental illness;
  • have diabetes.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Ciprofloxacin GH.

Taking other medicines

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

Some medicines may be affected by Ciprofloxacin GH. These include:

  • medicines used to treat arrhythmias (fast or irregular heartbeats);
  • theophylline, a medicine used to treat asthma;
  • oral anticoagulants, warfarin and its derivatives, medicines used to stop blood clots;
  • phenytoin, a medicine used to treat epilepsy;
  • oral antidiabetic agents;
  • didanosine, a medicine used to treat viral infections;
  • cyclosporin, a medicine used to suppress the immune system;
  • non-steroidal anti-inflammatory drugs (NSAIDs), medicines used to treat pain, arthritis and other inflammatory conditions;
  • methotrexate, a medicine used to treat certain types of cancers, severe psoriasis or severe rheumatoid arthritis;
  • duloxetine, a medicine used to treat depression, anxiety, and nerve pain in people with diabetes;
  • clozapine, a medicine used to treat schizophrenia;
  • ropinirole, a medicine used to treat Parkinson’s disease or restless legs syndrome;
  • the local anaesthetic lidocaine, a medicine used to numb pain or cause loss of sensation;
  • oxpentifylline, a medicine used to treat circulation disorders;
  • sildenafil, a medicine used to treat erectile dysfunction;
  • agomelatine, a medicine used to treat depression;
  • zolpidem, a medicine used to treat sleep disorders.

These medicines may be affected by Ciprofloxacin GH or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Some medicines may interfere with the absorption of Ciprofloxacin GH. These include:

  • multivitamins, mineral supplements, antacids (used for indigestion) and other medicines containing iron, zinc, magnesium, aluminium or calcium;
  • sucralfate, a medicine used to treat duodenal or stomach ulcers;
  • medicines used to treat HIV infection;
  • probenecid, a medicine used to treat gout;
  • omeprazole, a medicine used to treat stomach ulcers and other conditions where stomach produces too much acid;
  • sevelamer, a medicine used to treat high blood levels of phosphorus in patients with kidney disease who are on dialysis;
  • metoclopramide, a medicine used to relieve nausea and vomiting; heartburn, and stomach pain.

You can still take these medicines while you are taking Ciprofloxacin GH. However, you must take Ciprofloxacin GH at least 2 hours before or 2 hours after taking any of these medicines. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take Ciprofloxacin GH

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions printed on the pharmacist label, ask your doctor or pharmacist for help.

How much to take

Your doctor or pharmacist will tell you how much and how often you should take Ciprofloxacin GH. This will depend on the type of infection and any medical conditions you may have.

The usual adult dosage for most infections is one tablet twice daily for 7 to 14 days. You may need to take your tablets for a longer period for some types of infection. The dose will be determined by your doctor as it depends upon the type of infection you have.

When to take it

Ciprofloxacin GH tablets are usually taken twice a day. Take your tablets at the same time each day preferably on an empty stomach. However, they can be taken with or without food.

How long to take it

The length of treatment may vary from 1 to 28 days or longer depending on the type of infection.

Continue taking Ciprofloxacin GH until you have finished the blister pack or for as long as your doctor tells you. Do not stop taking your tablets because you are feeling better.

If you do not complete the full course prescribed by your doctor, the infection may not clear completely or your symptoms may return.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

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

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

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

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone in Australia 13 11 26, in New Zealand 0800 POISON or 0800 764 766), or go to the Accident and Emergency department at your nearest hospital, if you think you or anyone else may have taken too much Ciprofloxacin GH. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking it

Things you must do

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Ciprofloxacin GH.

Tell your doctor if you need to have a surgical or dental procedure that you are taking Ciprofloxacin GH.

Ciprofloxacin GH may affect the results of certain laboratory tests. If you are about to have any tests, tell your doctor that you are taking this medicine.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Ciprofloxacin GH.

Drink plenty of water while you are taking Ciprofloxacin GH. This helps to stop crystals forming in your urine.

If you become pregnant while you are taking Ciprofloxacin GH, tell your doctor immediately.

If you develop diarrhoea, tell your doctor or pharmacist immediately. Do it even if it occurs several weeks after you have stopped taking Ciprofloxacin GH. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any medications for diarrhoea without checking with your doctor or pharmacist.

Tell your doctor immediately if you experience symptoms of depression or self-endangering behaviour. Ciprofloxacin should be discontinued immediately.

Tell your doctor immediately if you develop pain, burning, tingling, numbness or weakness in any part of the body. Ciprofloxacin GH should be discontinued immediately.

Things you must not do

Do not give your Ciprofloxacin GH tablets to anyone else, even if they have the same condition as you.

Do not use Ciprofloxacin GH to treat other conditions unless your doctor tells you to.

Do not stop taking your tablets because you are feeling better, unless your doctor told you to do so.

If you do not complete the full course prescribed by your doctor, some of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear up completely or it may return.

Things to be careful of

Avoid excessive exposure to direct sunlight. Your skin may become more prone to sunburn. If such a reaction occurs, stop taking Ciprofloxacin GH immediately and tell your doctor.

Be careful driving or operating machinery until you know how Ciprofloxacin GH affects you. Ciprofloxacin GH tablets may cause dizziness in some patients, especially after the first few doses. Your ability to drive and/or operate machinery may be impaired. If you drink alcohol while taking this medicine, dizziness may be worse.

Ciprofloxacin GH tablets may increase the stimulatory effects of caffeine.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Ciprofloxacin GH.

All medicines have side effects. Sometimes they are serious, most of the time they are not. In serious cases, you may need medical attention.

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

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

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

  • nausea;
  • diarrhoea.

These are the common side effects of Ciprofloxacin GH. They are usually mild and short-lived.

Tell your doctor immediately, or go to the Accident and Emergency department at your nearest hospital if you notice any of the following:

  • severe skin rashes, peeling of the skin and/or mucosal reactions;
  • signs of allergy such as rash, swelling of the face, lips, mouth, throat or other parts of the body, shortness of breath, wheezing or trouble breathing;
  • fainting;
  • yellowing of the skin and eyes, also called jaundice;
  • severe watery or bloody diarrhoea, even if it occurs several weeks after taking your tablets;
  • fits (seizures, convulsions);
  • confusion, nightmares, hallucinations, and psychotic reaction (even progressing to self-endangering behaviour);
  • fast or irregular heart beats;
  • visual disturbances (eyesight problems);
  • ringing in the ear, loss of hearing;
  • abdominal pain/cramps. Very rarely this can progress to a serious condition accompanied by fever and fatigue;
  • pain, burning, tingling, numbness and/or weakness in your limbs.

These serious side effects are rare. If you have them, you may need urgent medical attention.

In isolated instances, some serious side effects may be long-lasting (>30 days) and disabling, such as tendonitis, tendon rupture, musculoskeletal disorders and other reactions affecting the nervous system including mental health disorders and disturbance of senses.

Photosensitivity (getting sunburnt very easily) can occasionally occur with Ciprofloxacin GH. However, it is temporary and staying out of direct sunlight while on Ciprofloxacin GH will prevent it from happening.

Rarely, there can be a worsening of the symptoms of myasthenia gravis. This is a condition in which the muscles become weak and tire easily, causing drooping eyelids, double vision, difficulty in speaking and swallowing and sometimes muscle weakness in the arms or legs.

Rarely, the Achilles tendon (extending from the calf to the heel of the foot) or other tendons have been torn after Ciprofloxacin GH therapy. This may occur even within the first 48 hours of treatment and up to several months after completing treatment with Ciprofloxacin GH. This risk of tendon damage may be increased in elderly patients, during strenuous physical activity, if you are currently being treated with a type of medicine called corticosteroids, if you have reduced kidney function or have received solid organ transplants. Tell your doctor immediately if you feel any discomfort, pain or inflammation of a tendon.

Rarely, you may experience hyperglycaemia (high blood sugar), or hypoglycaemia (low blood sugar). Symptoms of hyperglycaemia include increased thirst, appetite and urination. Symptoms of hypoglycaemia include weakness, shaking, sweating, light headedness, headache, behavioural changes, confusion, numbness/pins and needles in the lips, fingers or toes, irritability and hunger.

Tell your doctor if you experience these symptoms.

If you experience any of these symptoms during treatment with Ciprofloxacin GH tablets, tell your doctor or pharmacist immediately. Ciprofloxacin GH may need to be discontinued.

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

After taking Ciprofloxacin GH

Storage

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the box or the blister pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store Ciprofloxacin GH or any other medicine in the bathroom, near a sink or on a window sill.

Do not leave it in the car. Heat and damp can destroy some medicines.

Keep your tablets where children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Ciprofloxacin GH tablets or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

Ciprofloxacin GH 500 mg tablets: White to creamish white, capsule shaped film-coated tablets, embossed with “CPR 500” and a break line on one side and “BL” on the reverse.

Ciprofloxacin GH 500 mg tablets are supplied in blister packs of 14 tablets.

Ingredients

Active ingredient

Ciprofloxacin GH 500 mg tablets contain 500 mg ciprofloxacin (as hydrochloride monohydrate).

Other ingredients

  • maize starch;
  • microcrystalline cellulose;
  • sodium starch glycollate;
  • colloidal anhydrous silica;
  • magnesium stearate;
  • hypromellose;
  • purified talc;
  • titanium dioxide;
  • macrogol 4000.

Australian Registration Numbers

Ciprofloxacin GH 500 mg tablets: AUST R 127781.

Sponsor

Generic Health Pty Ltd
Suite 2, Level 2
19-23 Prospect Street
Box Hill VIC 3128

E-mail: [email protected]
Telephone: +61 3 9809 7900
Website: www.generichealth.com.au

This leaflet was prepared in February 2023.

Published by MIMS April 2023

BRAND INFORMATION

Brand name

Ciprofloxacin GH

Active ingredient

Ciprofloxacin

Schedule

S4

 

1 Name of Medicine

Ciprofloxacin hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Each Ciprofloxacin GH 500 mg tablets contains 500 mg ciprofloxacin (as hydrochloride monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ciprofloxacin GH 500 mg tablets are white to creamish white, capsule-shaped, film-coated tablets with "CPR 500" embossed and break line on one side, and "BL" embossed on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Ciprofloxacin is indicated for the treatment of infections caused by susceptible organisms in the conditions listed below:
urinary tract infections;
gonorrhoeal urethritis and cervicitis;
gastroenteritis;
bronchial infections;
skin and skin structure infections;
bone and joint infections;
chronic bacterial prostatitis of mild to moderate severity.
Inhalational anthrax (postexposure): to reduce the incidence or progression of disease following exposure to aerosolised Bacillus anthracis. Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication.

Note.

1. Typhoid and paratyphoid infections and infections due to multiresistant Staphylococcus aureus are excluded from the above due to insufficient data.
2. Because Gram-positive organisms are generally less sensitive to ciprofloxacin, it may not be the drug of choice in cases with Gram-positive infections, such as pneumonia due to Streptococcus pneumoniae.
3. Chronic bacterial prostatitis should be demonstrated by microbiological evidence localising infection to the prostate.
Strains of Neisseria gonorrhoea resistant to ciprofloxacin have been reported in Australia.
Appropriate culture and susceptibility tests should be performed before treatment in order to determine the organism susceptibility to ciprofloxacin and after treatment as warranted by the clinical condition. Therapy with ciprofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.
Ciprofloxacin is suitable to treat mixed infections caused by susceptible strains of both Gram-negative and Gram-positive aerobic bacteria. If anaerobic organisms are suspected as accompanying aetiologic agents, additional therapy should be considered.
Consideration should be given to available official guidance on the appropriate use of antibacterial agents.

4.2 Dose and Method of Administration

The dosage of Ciprofloxacin GH tablets is determined by the severity and type of infection, the sensitivity of the causative organism(s) and the age, weight and renal function of the patient. Ciprofloxacin GH tablets should be swallowed whole with an adequate amount of liquid.
The following dosages for specific types of infection are recommended:

Urinary tract infections.

The usual adult dosage is 250 mg every 12 hours. For patients with complicated infections caused by organisms not highly susceptible, such as Enterococcus faecalis, 500 mg may be administered every 12 hours.

Bronchial infections, skin and skin structure infections.

The usual dose is 500 mg every 12 hours. For more severe or complicated infections, a dosage of 750 mg may be given every 12 hours.

Bone and joint infections.

750 mg every 12 hours.

Gastroenteritis (infectious diarrhoea).

500 mg every 12 hours.

Acute, uncomplicated gonorrhoeal urethritis.

A single dose of 250 mg.

Chronic bacterial prostatitis.

250 mg to 500 mg every 12 hours.

Inhalational anthrax (post-exposure).

For adults, the recommended dose is 500 mg every 12 hours. For paediatric patients, the recommended dose is 15 mg/kg per dose (not to exceed 500 mg per dose), every 12 hours. Drug administration should begin as soon as possible after suspected or confirmed exposure.
The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient's host defence mechanisms, and the status of renal function.
Because Gram-positive organisms are generally less sensitive than Gram-negative organisms, the use of higher doses should be considered in patients with Gram-positive infections. In such cases, 8 hourly administration of 500 mg ciprofloxacin may be preferable.

Duration.

The duration of treatment depends upon the severity of infection. Generally, ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration is 7 to 14 days, however for severe and complicated infections more prolonged therapy may be required.
Bone and joint infections may require treatment for 4 to 6 weeks or longer. Gastrointestinal infections (infectious diarrhoea) need treatment for only 5 days. Chronic bacterial prostatitis should be treated for 14 to 28 days.
Inhalational anthrax (postexposure) should be treated for 60 days. Drug administration should begin as soon as possible after suspected or confirmed exposure.
In certain deep-seated infections involving abscess formation, appropriate surgical drainage should be performed in conjunction with antimicrobial therapy.

Missed dose.

If a dose is missed, it should be taken as soon as the patient remembers and then treatment should be continued as prescribed. Double doses should not be taken to compensate for a missed dose.

Impaired renal function.

Dosage adjustments for patients with creatinine clearance between 31-60 mL/min/1.73 m2, the maximum daily dose should be 1000 mg/day for oral administration. For creatinine clearance equal or less than 30 mL/min/1.73 m2, the maximum daily dose should be 500 mg/day for oral administration.
When only data for serum creatinine are available, the following formula (Cockcroft's equation) may be used to estimate creatinine clearance.

4.3 Contraindications

A history of hypersensitivity to ciprofloxacin or other quinolones, including nalidixic acid, or any of the excipients.
Concurrent administration of ciprofloxacin and tizanidine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially persistent adverse reactions involving different body systems that have occurred together in the same patient. These include, but are not limited to, serious adverse reactions involving the nervous system (see CNS effects and Psychiatric reactions) and musculoskeletal system (see Tendonitis and tendon rupture).

Streptococcus pneumoniae infections.

Ciprofloxacin is not recommended for treatment of pneumococcal infections due to inadequate efficacy against Streptococcus pneumoniae.

Cardiac disorders.

Ciprofloxacin is associated with cases of QT prolongation (see Section 4.8 Adverse Effects (Undesirable Effects)). In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Women may also be more sensitive to QT prolongation medicine compared to men as they tend to have a longer baseline QTc interval. Precaution should be taken when using ciprofloxacin with concomitant drugs that can result in prolongation with the QT interval (e.g. class IA or III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions) or in patients with risk factors for QT prolongation or torsade de pointes (e.g. congenital long QT syndrome, uncorrected electrolyte imbalance such as hypokalaemia or hypomagnesaemia and cardiac disease such as heart failure, myocardial infarction, or bradycardia).

Antibiotic-associated colitis.

Antibiotic-associated colitis has been rarely reported with ciprofloxacin, but it should be considered in patients who develop diarrhoea.
Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including ciprofloxacin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy such as oral antibacterial agents effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil), may prolong and/or worsen the condition and should not be used.

Myasthenia gravis.

Ciprofloxacin should be used with caution in patients with myasthenia gravis because symptoms can be exacerbated. Therefore, at any clinical sign or symptom of an exacerbation of myasthenia gravis, a physician should be consulted.

Tendonitis and tendon rupture.

Tendonitis and tendon rupture (predominantly Achilles tendon), sometimes bilateral, that required surgical repair or resulted in prolonged disability have been reported with ciprofloxacin and other quinolones. This may occur even within the first 48 hours of treatment, and cases occurring up to several months after completion of therapy have been reported. The risk of tendinopathy may be increased in elderly patients, during strenuous physical activity, in patients treated concomitantly with corticosteroids, in patients with renal impairment and in patients with solid organ transplants. Ciprofloxacin should be used with caution in patients with a history of tendon disorders related to quinolone treatment. At any sign of tendonitis (e.g. painful swelling, inflammation), the affected extremity should be kept at rest, any inappropriate physical exercise should be avoided, a physician should be consulted and the antibiotic treatment should be discontinued.

Superinfections.

As with other broad-spectrum antimicrobial agents, prolonged use of ciprofloxacin may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Pseudomonas aeruginosa infections in cystic fibrosis.

Although clinical improvement has been observed in patients with respiratory exacerbation of cystic fibrosis associated with Pseudomonas aeruginosa, bacterial eradication is usually not achieved. Resistance to ciprofloxacin has been shown to develop in a significant proportion of Pseudomonas aeruginosa infections in cystic fibrosis patients following a single course of the drug.

Anaphylactoid reactions.

In some instances, hypersensitivity and allergic reactions may occur following a single dose, a physician should be informed immediately.
Serious, and occasionally fatal, anaphylactoid reactions, some following the first dose, have been reported in patients receiving quinolones (including ciprofloxacin). In these cases, ciprofloxacin should be discontinued, and appropriate medical treatment given.

Phototoxicity.

Ciprofloxacin has been shown to be phototoxic in a number of in vitro and in vivo studies. Nalidixic acid, the prototype quinolone antibiotic and other quinolone antibiotics, produce photosensitivity reactions. Patients taking ciprofloxacin should avoid direct exposure to sunlight. Therapy should be discontinued if photosensitisation occurs.

CNS effects.

As with other quinolones, ciprofloxacin may cause central nervous system (CNS) stimulation, which may lead to transient tremor, restlessness, lightheadedness, confusion and very rarely to hallucination or convulsive seizures. In some instances, CNS reactions may occur even after the first administration of fluoroquinolones, including ciprofloxacin.
Ciprofloxacin should be used with caution in patients with CNS disorders such as severe cerebral arteriosclerosis or epilepsy.
Even when taken as prescribed, this drug can alter patients' responsiveness, impairing the ability to drive or operate machinery. This is even more applicable when the drug is taken in conjunction with alcohol.

Psychiatric reactions.

Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of psychiatric adverse reactions including: toxic psychosis, psychotic reactions progressing to suicidal ideations/thoughts, hallucinations or paranoia; depression, or self-injurious behaviour such as attempted or completed suicide; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; memory impairment. These reactions may occur following the first dose. Advise patients receiving ciprofloxacin to inform their healthcare provider immediately if these reactions occur, discontinue the drug and institute appropriate care.

Peripheral neuropathy.

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving fluoroquinolones including ciprofloxacin. Ciprofloxacin should be discontinued in patients experiencing symptoms of neuropathy, including pain, burning, tingling, numbness, and/or weakness in order to prevent the development of an irreversible condition (see Section 4.8 Adverse Effects (Undesirable Effects)).

Vision disorders.

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see Section 4.8 Adverse Effects (Undesirable Effects)).

Cytochrome P450.

Ciprofloxacin is known to be a moderate inhibitor of the CYP450 1A2 enzymes. Care should be taken when other drugs are administered concomitantly which are metabolised via the same enzymatic pathway (e.g. theophylline, methylxanthines, caffeine, duloxetine, clozapine, olanzapine, ropinirole, agomelatine). Increased plasma concentrations associated with drug specific side effects may be observed due to inhibition of their metabolic clearance by ciprofloxacin (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Dysglycaemia.

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported with ciprofloxacin. In ciprofloxacin-treated patients, dysglycaemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g. sulfonylurea) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended (see Section 4.8 Adverse Effects (Undesirable Effects)).

Aortic aneurysm and dissection.

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population. Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or dissection, or in the presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, known atherosclerosis). In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Crystalluria.

The solubility of ciprofloxacin is pH dependent and is greatly reduced between pH 5 and 9. Crystals of ciprofloxacin have been observed in the urine of laboratory animals given high doses of the drug, but also in some patients receiving standard therapeutic doses. Crystalluria seems to occur under alkaline conditions of the urine and is less likely in nonvegetarians who usually have an acidic urine. Patients receiving ciprofloxacin should be well hydrated and alkalinity of the urine should be avoided. It should, however, be noted that the activity of ciprofloxacin is significantly reduced in acid media.

Epileptic patients.

Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower seizure threshold. Ciprofloxacin should be used with caution in epileptics and in patients who have suffered from previous CNS disorders (e.g. lowered convulsion threshold, previous history of convulsion, reduced cerebral blood flow, altered brain structure or stroke). Ciprofloxacin should only be used where the benefits of treatment exceed the risks, since these patients are endangered because of possible central nervous system adverse effects. Cases of status epilepticus have been reported. If seizures occur, ciprofloxacin should be discontinued.

Use in hepatic impairment.

Cases of hepatic necrosis and life-threatening hepatic failure have been reported with ciprofloxacin. In the event of any signs and symptoms of hepatic disease (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), treatment should be discontinued (see Section 4.8 Adverse Effects (Undesirable Effects)). There can be temporary increase in transaminases, alkaline phosphatase, or cholestatic jaundice, especially in patients with previous liver damage, who are treated with ciprofloxacin.

Use in renal impairment.

Alteration of the dosage regimen is necessary for patients with impairment of renal function (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

Ciprofloxacin should be used with caution in the elderly after taking into account the severity of the illness and the creatinine clearance (see Section 4.2 Dose and Method of Administration).

Paediatric use.

Ciprofloxacin is not recommended for use in prepubertal children, except for use in inhalational anthrax (postexposure). Toxicological studies have shown that ciprofloxacin and related drugs such as nalidixic acid and cinoxacin, can produce erosions of cartilage of weight bearing joints and other signs of arthropathy in immature animals of various species. Long-term safety data, including effects on cartilage, following the administration of ciprofloxacin to paediatric patients are limited.
For the indication of inhalational anthrax (postexposure), the risk/benefit assessment indicates that administration of ciprofloxacin to paediatric patients is appropriate. For information regarding paediatric dosing in inhalational anthrax (postexposure) (see Section 4.2 Dose and Method of Administration).
The safety and effectiveness of ciprofloxacin in prepubertal children except for use in inhalational anthrax (postexposure) have not been established.

Effects on laboratory tests.

Ciprofloxacin in vitro potency may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth, causing false negative results in specimens from patients currently taking ciprofloxacin.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs known to prolong QT interval.

Ciprofloxacin, like other fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Theophylline.

Concurrent administration of ciprofloxacin with theophylline may lead to elevated plasma concentrations of theophylline and prolongation of its elimination half-life. This can lead to theophylline induced side effects; in very rare cases these side effects can be life threatening or fatal. If concomitant use cannot be avoided, the plasma levels of theophylline should be monitored, and appropriate dosage adjustments should be made.

Omeprazole.

Concomitant administration of ciprofloxacin and omeprazole results in a slight reduction of Cmax and AUC of ciprofloxacin.

Probenecid.

Coadministration of probenecid with ciprofloxacin result in a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its AUC, without altering the peak concentration, time to peak and half-life of elimination.

Anticoagulants.

Quinolones, including ciprofloxacin, have been reported to enhance the effects of oral anticoagulants, warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of ciprofloxacin to the increase in INR (international normalised ratio) is difficult to assess.

Ciclosporin.

Some quinolones, including ciprofloxacin, have been associated with transient elevations of serum creatinine in patients receiving ciclosporin concomitantly. Therefore, it is frequently (twice a week) necessary to control the serum creatinine concentrations in these patients.

Metoclopramide.

Metoclopramide accelerates the absorption of ciprofloxacin resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.

Oral antidiabetic agents.

Hypoglycaemia has been reported when ciprofloxacin and oral antidiabetic agents, mainly sulfonylureas (e.g. glibenclamide, glimepiride), where coadministered, presumably by intensifying the action of the oral antidiabetic agent.

NSAIDs.

Animal studies have shown that the combination of very high doses of fluoroquinolones (gyrase inhibitors) and certain nonsteroidal anti-inflammatory agents (but not acetylsalicylic acid) can provoke convulsions.

Other xanthine derivatives.

On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) containing products, raised serum concentrations of these xanthine derivatives were reported. Quinolones may reduce the clearance of caffeine and prolong its plasma half-life, and therefore may enhance the effects of caffeine.

Phenytoin.

Altered (decreased or increased) serum levels of phenytoin were observed in patients receiving ciprofloxacin and phenytoin simultaneously. To avoid the loss of seizure control associated with decreased phenytoin levels, and to prevent phenytoin overdose-related adverse effects when ciprofloxacin is discontinued in patients receiving both agents, monitoring of phenytoin therapy, including phenytoin serum concentration measurements, is recommended during and shortly after coadministration of ciprofloxacin with phenytoin.

Methotrexate.

Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate associated toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated.

Chelation complex formation.

The simultaneous administration of ciprofloxacin and multivalent cation-containing medicinal products and mineral supplements (e.g. calcium, magnesium, aluminium, iron), polymeric phosphate binders (e.g. sevelamer, lanthanum carbonate), sucralfate or antacids, and highly buffered drugs (e.g. antiretrovirals) containing magnesium, aluminium or calcium reduce the absorption of ciprofloxacin. Consequently, ciprofloxacin should be administered either 1-2 hours before or at least 4 hours after these preparations.

Tizanidine.

Tizanidine serum concentrations increase with concomitant administration with ciprofloxacin. Associated with the increased serum concentrations was a potentiated hypotensive and sedative effect. Tizanidine must not be administered together with ciprofloxacin (see Section 4.3 Contraindications).

Duloxetine.

In clinical studies it was demonstrated that concurrent use of duloxetine with strong inhibitors of the CYP450 1A2 isoenzyme such as fluvoxamine, may result in an increase of AUC and Cmax of duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar effects can be expected upon concomitant administration.

Ropinirole.

In a clinical study it was shown that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isozyme, resulted in increases in the Cmax and AUC of ropinirole of 60% and 84%, respectively. Although ropinirole treatment was well tolerated, case reports suggest that a possible interaction with ciprofloxacin associated with side effects may occur upon concomitant administration. Ropinirole-related side effects should be monitored during and shortly after coadministration with ciprofloxacin; dose adjustment is recommended if necessary.

Lidocaine.

It was demonstrated in healthy subjects that concomitant use of lidocaine with ciprofloxacin, a moderate inhibitor of CYP450 1A2 isozyme, reduces clearance of intravenous lidocaine by 22%. Although lidocaine treatment was well tolerated, a possible interaction with ciprofloxacin associated with side effects may occur upon concomitant administration.

Clozapine.

Following concomitant administration of 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical surveillance and appropriate adjustment of clozapine dosage during and shortly after coadministration with ciprofloxacin are advised.

Sildenafil.

Cmax and AUC of sildenafil were increased approximately twofold in healthy subjects after an oral dose of 50 mg given concomitantly with 500 mg ciprofloxacin. Therefore, caution should be used prescribing ciprofloxacin concomitantly with sildenafil taking into consideration the risks and the benefits.

Agomelatine.

In clinical studies, it was demonstrated that fluvoxamine, as a strong inhibitor of the CYP450 1A2 isoenzyme, markedly inhibits the metabolism of agomelatine resulting in a large increase in agomelatine exposure. Although no clinical data are available, ciprofloxacin is a moderate inhibitor of CYP450 1A2 and similar effect can be expected upon concomitant administration. Therefore concurrent use of ciprofloxacin with agomelatine is not recommended (see Section 4.4 Special Warnings and Precautions for Use, Cytochrome P450).

Zolpidem.

Coadministration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Reproduction studies have been performed in rats and mice at doses up to 100 mg/kg (0.6 and 0.3 times the maximum daily human dose based upon body surface area, respectively) and intravenous doses of up to 30 mg/kg and have revealed no evidence of impaired fertility or harm to the foetus due to ciprofloxacin. In rabbits, ciprofloxacin (30 and 100 mg/kg orally, 0.4 and 1.2 times the maximum daily human dose based upon body surface area, respectively) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, intrauterine deaths and foetal retardation, but no teratogenicity was observed at either dose. After intravenous administration, at doses up to 20 mg/kg, no maternal toxicity was produced in the rabbits and no embryotoxicity or teratogenicity was observed. There are however no adequate and well controlled studies in pregnant women. Like other drugs in its class, ciprofloxacin causes arthropathy in immature animals.
Ciprofloxacin should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus (e.g. potential damage to articular cartilage in the immature foetal organism).
 Ciprofloxacin is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ciprofloxacin, a decision should be made to discontinue nursing or to avoid using the drug taking into account the importance of the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

Even when taken as prescribed, this drug can alter patients' responsiveness, impairing the ability to drive or operate machinery. This is even more applicable when the drug is taken in conjunction with alcohol.

4.8 Adverse Effects (Undesirable Effects)

Adverse drug reactions (ADRs) based on all clinical studies with ciprofloxacin (oral, parenteral) sorted by CIOMS III categories of frequency are listed in Table 1 (overall n = 51,721, data lock point: 15 May 2005).
ADRs derived from postmarketing reports (status: 31 July 2005) for which a frequency could not be estimated are listed in Table 2.
In isolated instances, some serious adverse drug reactions may be long-lasting (> 30 days) and disabling; such as tendonitis, tendon rupture, musculoskeletal disorders, and other reactions affecting the nervous system including psychiatric disorders and disturbance of senses.
The following undesirable effects have a higher frequency category in the subgroups of patients receiving intravenous or sequential (intravenous to oral) treatment (see Table 3).

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

In the event of acute, excessive oral overdosage, reversible renal toxicity has been reported in some cases. Therefore, apart from routine emergency measures, it is recommended to monitor renal function, including urinary pH and acidity, if required, to prevent crystalluria. Patients should be kept well hydrated - calcium or magnesium containing antacids reduce the absorption of ciprofloxacin in overdoses.
Only a small quantity of ciprofloxacin (< 10%) is eliminated from the body after haemodialysis or peritoneal dialysis.
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 appears to result from interference with the enzyme, DNA gyrase. Ciprofloxacin is usually active against the following organisms in vitro.

Gram-negative.

Escherichia coli; Klebsiella species (including Klebsiella pneumoniae and Klebsiella oxytoca); Enterobacter species; Citrobacter species; Salmonella species; Shigella species; Proteus mirabilis; Proteus vulgaris; Providencia stuartii, Providencia rettgeri (formerly Proteus rettgen); Morganella morganii (formerly Proteus morganii); Serratia species* (including Serratia marcescens); Pseudomonas aeruginosa; Pseudomonas fluorescens; Campylobacter species; Haemophilus influenzae; Moraxella (Branhamella) catarrhalis.

Gram-positive*.

Staphylococcus aureus (including methicillin susceptible and methicillin resistant strains); coagulase negative Staphylococcus species (including Staphylococcus epidermidis); Streptococcus pyogenes (group A); Streptococcus pneumoniae; Enterococcus faecalis.

* Note.

1. Gram-positive organisms are generally less sensitive to ciprofloxacin than Gram-negative organisms.
2. Most strains of Streptococci are only moderately susceptible to ciprofloxacin. Clinical studies have shown the drug to be effective for urinary tract infections caused by Enterococcus faecalis; however failures and reinfections have been observed with prostatitis. Although bronchial infections caused by Streptococcus pneumoniae and skin infections caused by Streptococcus pyogenes have been shown to respond to ciprofloxacin, it is not the drug of first choice in such infections, particularly Streptococcus pneumoniae infection of the lower respiratory tract.
3. Most strains of Burkholderia cepacia and many strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.
4. Enterococcus faecium, Ureaplasma urealyticum and Nocardia asteroides are generally resistant. Ciprofloxacin is ineffective against Treponema pallidum.
5. The in vitro MIC of several strains of Serratia approaches or exceeds the peak plasma concentrations with the recommended doses of ciprofloxacin.
The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance whether microorganisms will be susceptible for ciprofloxacin or not.
Ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker.
Ciprofloxacin is less active when tested in acidic pH and its antibacterial activity may be reduced by up to 100-fold in acidic urine. The inoculum size has little effect when tested in vitro. The minimal bactericidal concentration (MBC) is generally 2-8 times the minimal inhibitory concentration (MIC).
Resistance to ciprofloxacin in vitro develops slowly (multiple step mutation). Rapid one step development of resistance has not been observed. However, in practice, resistance to ciprofloxacin may develop during the course of a treatment, particularly in a significant proportion of Pseudomonas aeruginosa infections, especially in patients with cystic fibrosis, and in Staphylococcus aureus infections.
Ciprofloxacin does not exhibit cross resistance with nonquinolone antibacterial agents such as β-lactams and aminoglycosides. However, organisms which are resistant to other quinolone agents (e.g. nalidixic acid, cinoxacin, etc.) are usually less sensitive to ciprofloxacin.
In vitro studies have shown that when ciprofloxacin is combined with other antimicrobial agents, particularly β-lactams, the combination behaves either in an indifferent or additive manner. Synergism or antagonism have, however, been observed rarely.
Appropriate culture and susceptibility tests should be performed before treatment in order to determine organism susceptibility to ciprofloxacin and after treatment as warranted by the clinical condition. Therapy with ciprofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.
Disc susceptibility tests. Dilution or infusion techniques, either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory controlled microorganisms to control the technical aspects of the laboratory procedures.
A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "intermediate" indicates that the result should be considered equivocal and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available. For further information, see Section 5.1 Pharmacodynamic Properties.

5.2 Pharmacokinetic Properties

Absorption.

Ciprofloxacin are rapidly and well absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability is approximately 70% with no substantial loss by first pass metabolism. Coadministration of ciprofloxacin with food appears to lower peak serum levels and delay the absorption of ciprofloxacin, resulting in peak concentrations closer to 2 hours after dosing rather than 1 hour. The overall absorption, however, is not substantially affected. Absorption also appears to be greatly reduced by prior administration of antacids.

Distribution.

After oral dosing, ciprofloxacin is widely distributed throughout the body. The binding of ciprofloxacin to serum proteins is 20 to 40%. Serum concentrations increase in a dose-proportional manner and were, after multiple doses, as shown in Table 4.
Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean concentrations 12 hours after dosing with 250, 500 or 750 mg are 0.1, 0.2 and 0.4 microgram/mL respectively.

Metabolism.

Ciprofloxacin is also metabolised. Four metabolites have been identified in human urine which together account for approximately 15% of an oral dose. The metabolites have less antimicrobial activity than unchanged ciprofloxacin.

Excretion.

The serum elimination half-life in subjects with normal renal function is approximately 4 hours. Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug. During the first 2 hours after an oral dose of 250 mg, the urine concentration of ciprofloxacin usually exceeds 200 microgram/mL. Eight to 12 hours after the same dose, urine levels are approximately 30 microgram/mL. Urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin is approximately 18 L/h which exceeds the normal glomerular filtration rate of 7.2 L/h. Thus, active tubular secretion would seem to play a significant role in its elimination. In patients with creatinine clearance between 21-40 mL/min, the half-life of ciprofloxacin is only slightly prolonged. Dosage adjustments are usually not required in such cases. However, in patients with severe renal impairment, with creatinine clearance less than 20 mL/min, the half-life of ciprofloxacin is nearly doubled, and dosage adjustment is necessary (see Section 4.2 Dose and Method of Administration).
Although bile concentrations of ciprofloxacin are 3-4 times higher than serum concentrations after oral dosing, only a small amount of the dose administered is recovered from the bile. Approximately 20 to 35% of an oral dose is recovered from the faeces within 5 days after dosing.

Inhalational anthrax.

The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and paediatric patients receiving oral and intravenous regimens (see Section 4.2 Dose and Method of Administration). Ciprofloxacin pharmacokinetics have been evaluated in various human populations. The mean peak serum concentration achieved at steady state in human adults receiving 500 mg orally every 12 hours is 2.97 microgram/mL, and 4.56 microgram/mL following 400 mg intravenously every 12 hours. The mean trough serum concentration at steady state for both of these regimens is 0.2 microgram/mL. In a study of 10 paediatric patients between 6 and 16 years of age, the mean peak plasma concentration achieved is 8.3 microgram/mL, and trough concentration ranges from 0.09 to 0.26 microgram/mL, following two 30 minute intravenous infusions of 10 mg/kg, administered 12 hours apart. After the second intravenous infusion, patients switched to 15 mg/kg orally every 12 hours achieve a mean peak concentration of 3.6 microgram/mL after the initial oral dose. Long-term safety data, including effects on cartilage, following the administration of ciprofloxacin to paediatric patients are limited. (For additional information, see Section 4.4 Special Warnings and Precautions for Use, Paediatric use). Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for the indication.
A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD50 (-5.5 x 105) spores (range 5-30 LD50) of B. anthracis was conducted. The minimal inhibitory concentration (MIC) of ciprofloxacin for the anthrax strain used in this study was 0.08 microgram/mL. In the animals studied, mean serum concentrations of ciprofloxacin achieved at expected Tmax (1-hour postdose) following oral dosing to steady state ranged from 0.98 to 1.69 microgram/mL. Mean steady state trough concentrations at 12 hours postdose ranged from 0.12 to 0.19 microgram/mL. Mortality due to anthrax for animals that received a 30-day regimen of oral ciprofloxacin beginning 24 hours postexposure was significantly lower (1/9), compared to the placebo group (9/10) [p = 0.001]. The one ciprofloxacin treated animal that died of anthrax did so following the 30-day drug administration period.

5.3 Preclinical Safety Data

Genotoxicity.

Ciprofloxacin was mutagenic in the mouse lymphoma assay and the rat primary hepatocyte culture/DNA repair assay in vitro, but not in other mammalian systems in vitro or in microbial systems.
In a small study on the chromosomal effects of ciprofloxacin on white blood cells, the drug did not exhibit any cytogenetic effect.

Carcinogenicity.

Carcinogenicity studies in mice (oral doses up to 1090 mg/kg/day and 1455 mg/kg/day in males and females, respectively; 1.4 and 1.8 times the highest recommended human dose of 1500 mg/day based upon body surface area) and rats (241 mg/kg/day and 328 mg/kg/day in males and females, respectively; 3.1 and 4.2 times the highest recommended human dose of 1500 mg/day based upon body surface area) showed no evidence of carcinogenicity.
Results from photo cocarcinogenicity testing indicate that ciprofloxacin does not reduce the time to appearance of UV induced skin tumours as compared to vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours five times every two weeks for up to 78 weeks while concurrently being administered ciprofloxacin. The time to development of the first skin tumour was 50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately equal to maximum recommended human dose based upon mg/m2), as opposed to 34 weeks when animals were treated with both UVA and vehicle. The times to development of skin tumours ranged from 16-32 weeks in mice treated concomitantly with UVA and other quinolones. In this model, mice treated with ciprofloxacin alone did not develop skin or systemic tumours. There are no data from similar models using pigmented mice and/or fully haired mice. The clinical significance of these findings to humans is unknown.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ciprofloxacin GH tablets contain the following excipients: maize starch, microcrystalline cellulose, sodium starch glycollate, colloidal anhydrous silica, magnesium stearate, hypromellose, purified talc, titanium dioxide, macrogol 4000.

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

Do not store above 25°C. Store in the original package.

6.5 Nature and Contents of Container

Ciprofloxacin GH 500 mg tablets are available in PVC/Al blisters packs enclosed in an outer carton. Pack size: 14 tablets.

Australian registration numbers.

Ciprofloxacin GH 500 mg: AUST R 127781.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

A pale yellow, crystalline powder, soluble in water, slightly soluble in methanol, very slightly soluble in ethanol, practically insoluble in acetone, in ethyl acetate and in methylene chloride. Ciprofloxacin has a melting point of 318-320°C.

Chemical structure.


Chemical Name: (1-cyclopropyl-6-fluoro-1,4- dihydro-4-oxo-7- (1-piperazinyl)-3-quinolinecarboxylic acid).
Molecular Formula: C17H18FN3O3.HCl.H2O.
Molecular Weight: 385.8.
PKa: 6, 8.8.

CAS number.

86393-32-0.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes