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CIPROFLOXACIN 2MG|ML INTRAVENOUS INFUSION

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PACKAGE LEAFLET: INFORMATION FOR THE USER
Ciprofloxacin 2mg/ml Solution for Infusion
Ciprofloxacin
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even
if their sign of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What Ciprofloxacin Infusion is and what it is used for
2. What you need to know before you are given Ciprofloxacin Infusion
3. How to use Ciprofloxacin Infusion
4. Possible side effects
5. How to store Ciprofloxacin Infusion
6. Contents of the pack and other information

1 What Ciprofloxacin Infusion is and what it is used for
Ciprofloxacin is an antibiotic belonging to the fluoroquinolones family Ciprofloxacin works by killing
bacteria that cause infections. It only works with specific strains of bacteria.
Adults
Ciprofloxacin is used in adults to treat the following bacterial infections:
• respiratory tract infections
• long lasting or recurring ear or sinus infections
• urinary tract infections
• genital tract infections in men and women
• gastro-intestinal tract infections and intra-abdominal infections
• skin and soft tissue infections
• bone and joint infections
• anthrax inhalation exposure
Ciprofloxacin may be used in the management of patients with low white blood cell counts
(neutropenia) who have a fever that is suspected to be due to a bacterial infection.
If you have a severe infection or one that is caused by more than one type of bacterium, you may be
given additional antibiotic treatment in addition to Ciprofloxacin.
Children and adolescents
Ciprofloxacin is used in children and adolescents, under specialist medical supervision, to treat the
following bacterial infections:
• lung and bronchial infections in children and adolescents suffering from cystic fibrosis




complicated urinary tract infections, including infections that have reached the kidneys
(pyelonephritis)
anthrax inhalation exposure

Ciprofloxacin may also be used to treat other specific severe infections in children and adolescents
when your doctor considered this necessary..
2 What you need to know before you are given Ciprofloxacin Infusion
DO NOT USE Ciprofloxacin Infusion:
• if you are allergic(hypersensitive) to ciprofloxacin or to other quinolone drugs or to any of the
other ingredients of Ciprofloxacin Infusion (see section 6)
• taking tizanidine (see section 2: Taking other medicines)
If any of these apply to you, talk to a doctor or nurse before you are given this medicine.
Warning and precautions
Before using Ciprofloxacin Infusion
Tell your doctor if you:









have ever had kidney problems because your treatment may need to be adjusted
suffer from epilepsy or other neurological conditions
have a history of tendon problems during previous treatment with antibiotics such as
ciprofloxacin
have myasthenia gravis (a type of muscle weakness)
have diabetes
have heart problems. Caution should be taken when using ciprofloxacin, if you were born
with or have family history of prolonged QT interval (seen on ECG, electrical recording of
the heart), have salt imbalance in the blood (especially low level of potassium or magnesium
in the blood), have a very slow heart rhythm (called ‘bradycardia’), have a weak heart (heart
failure), have a history of heart attack (myocardial infarction), you are female or elderly or
you are taking other medicines that result in abnormal ECG changes (see section: Taking
other medicines)
or a member of your family is known to have a deficiency in glucose-6-phosphate
dehydrogenase (G6PD), since you may experience a risk of anaemia with ciprofloxacin

For the treatment of some genital tract infections, your doctor can prescribe another antibiotic in
addition to ciprofloxacin. If there is no improvement in symptoms after 3 days of treatment, please
consult your doctor.If any of these apply to you, talk to a doctor or nurse before you are given this
medicine.
While under treatment with Ciprofloxacin Infusion
Tell your doctor immediately, if any of the following occurs during treatment with ciprofloxacin.
Your doctor will decide whether treatment with ciprofloxacin needs to be stopped.


Severe, sudden allergic reaction (an anaphylactic reaction/shock, angio-oedema). Even with
the first dose, there is a rare chance that you may experience a severe allergic reaction with
the following symptoms: tightness in the chest, feeling dizzy, feeling sick or faint, or

















experience dizziness on standing. If this happens, tell your doctor immediately since the
administration of ciprofloxacin will have to be stopped.
Pain and swelling in the joints, and tendinitis may occur occasionally, particularly if you
are elderly and are also being treated with corticosteroids. Inflammation and ruptures of
tendons may occur even within the first 48 hours of treatment or up to several months after
discontinuation of ciprofloxacin therapy. At the first sign of any pain or inflammation
ciprofloxacin will have to be stopped, rest the painful area. Avoid any unnecessary exercise as
this might increase the risk of a tendon rupture.
If you suffer from epilepsy or other neurological conditions such as cerebral ischemia or
stroke, you may experience side effects associated with the central nervous system. If this
happens, stop taking ciprofloxacin and contact your doctor immediately.
You may experience psychiatric reactions after first administration of ciprofloxacin. If you
suffer from depression or psychosis, your symptoms may become worse under treatment
with ciprofloxacin. In rare cases, depression or psychosis can progress to thoughts of suicide,
suicide attempts, or completed suicide. If this happens, stop taking ciprofloxacin and contact
your doctor immediately.
You may experience symptoms of neuropathy such as pain, burning, tingling, numbness
and/or weakness. If this happens, stop taking ciprofloxacin and contact your doctor
immediately.
Diarrhoea may develop while you are on antibiotics, including ciprofloxacin, or even several
weeks after you have stopped using them. If it becomes severe or persistent or you notice that
your stool contains blood or mucus tell your doctor immediately. Ciprofloxacin treatment will
have to be stopped immediately, as this can be life-threatening. Do not take medicines that
stop or slow down bowel movements.
Tell the doctor or laboratory staff that you are taking ciprofloxacin if you have to provide a
blood or urine sample.
Ciprofloxacin may cause liver damage. If you notice any symptoms such as loss of appetite,
jaundice (yellowing of the skin), dark urine, itching, or tenderness of the stomach,
ciprofloxacin must be stopped immediately.
Ciprofloxacin may cause a reduction in the number of white blood cells and your resistance
to infection may be decreased. If you experience an infection with symptoms such as fever
and serious deterioration of your general condition, or fever with local infection symptoms
such as sore throat/pharynx/mouth or urinary problems you should see your doctor
immediately. A blood test will be taken to check possible reduction of white blood cells
(agranulocytosis). It is important to inform your doctor about your medicine.
Tell your doctor if you or a member of your family is known to have a deficiency in glucose6-phosphate dehydrogenase (G6PD), since you may experience a risk of anemia with
ciprofloxacin.
If you suffer from kidney problems, tell the doctor because your dose may need to be
adjusted.
Your skin becomes more sensitive to sunlight or ultraviolet (UV) light under treatment with
ciprofloxacin. Avoid exposure to strong sunlight or artificial UV light such as sunbeds.

Other medicines and Ciprofloxacin Infusion:
Please tell your doctor, nurse or pharmacist if you are taking, or have recently taken, any other
medicines, including medicines obtained without a prescription.
Do not use ciprofloxacin together with tizanidine, because this may cause side effects such as low
blood pressure and sleepiness (see Section 2: "You must not be given Ciprofloxacin if you are").

The following medicines are known to interact with ciprofloxacin in your body. Using ciprofloxacin
together with these medicines can influence the therapeutic effect of these medicines. It can also
increase the probability of experiencing side effects.
Tell your doctor if you are taking:
• Vitamin K antagonists (e.g: warfarin) or other oral anti-coagulants (to thin the blood)
• probenecid (for gout)
• methotrexate (for certain types of cancer, psoriasis, rheumatoid arthritis)
• theophylline (for breathing problems)
• tizanidine (for muscle spasticity in multiple sclerosis)
• olanzapine (an antipsychotic)
• clozapine (an antipsychotic)
• ropinirole (for Parkinson’s disease)
• phenytoin (for epilepsy)
• cyclosporin (for skin conditions, rheumatoid arthritis and in organ transplantation)
• glibenclamide (for diabetes)
• other medicines that can alter your heart rhythm: medicines that belong to the group of
antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol,
dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (that belong to the group
of macrolides), some antipsychotics.
Ciprofloxacin may increase the levels of the following medicines in your blood:






pentoxifylline (for circulatory disorders)
caffeine
duloxetine (for depression, diabetic nerve damage or incontinence)
lidocaine (for heart conditions or anesthetic use)
sildenafil (e.g. for erectile dysfunction)

Taking Ciprofloxacin Infusion with food and drink
Food and drink does not affect your treatment with Ciprofloxacin Infusion..
Pregnancy, breast-feeding and fertility
Ask your doctor for advice before taking any medicine.
It is preferable to avoid the use of ciprofloxacin during pregnancy. Tell your doctor if you are
planning to get pregnant.
Do not take ciprofloxacin during breast feeding because ciprofloxacin is excreted in breast milk and
can be harmful for your child. .
Driving and using machines
Ciprofloxacin Infusion may make you feel less alert.
Some neurological adverse events can occur. Therefore, make sure you know how you react to
ciprofloxacin before driving a vehicle or operating machinery. If in doubt, talk to your doctor.
Important information about some of the ingredients of Ciprofloxacin Infusion

Ciprofloxacin Infusion contains 900mg sodium chloride in 100ml of infusion. This may make the
infusion unsuitable for you if you are on a low sodium diet.
3 How to use Ciprofloxacin Infusion
Your doctor will explain to you exactly how much Ciprofloxacin Infusion you will be given as well as
how often and for how long. This will depend on the type of infection you have and how bad it is.
Tell your doctor if you suffer from kidney problems because your dose may need to be adjusted.
Treatment usually lasts between 5 and 21 days, but may be longer for severe infections.
Your doctor will give you each dose by slow infusion through a vein into your bloodstream. For
children, the infusion duration is 60 minutes. In adult patients, infusion time is 60 minutes for 400 mg
Ciprofloxacin Infusion and 30 minutes for 200 mg Ciprofloxacin Infusion. Administering the infusion
slowly helps prevent immediate side effects occurring.
Remember to drink plenty of fluids while you are taking Ciprofloxacin Infusion.
If you stop your course of Ciprofloxacin Infusion
It is important that you finish the course of treatment even if you begin to feel better after a few
days. If you stop using this medicine too soon your infection may not be completely cured and the
symptoms of the infection may return or get worse. You might also develop resistance to the
antibiotic.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can have side effects although not everyone gets them.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your
doctor or pharmacist.
Common side effects (between 1 and 10 in every 100 people are likely to get these):





nausea, diarrhoea, vomiting
joint pains in children
local reaction at the injection site, rash
temporary increased amounts of substances in the blood (transaminases)

Uncommon side effects (between 1 and 10 in every 1,000 people are likely to get these):






fungal superinfections
a high concentration of eosinophils, a type of white blood cell, increased or decreased
amounts of a blood cloting factor (thrombocytes)
loss of appetite (anorexia)
hyperactivity, agitation, confusion, disorientation, hallucinations
headache, dizziness, sleeping problems, taste disorders, pins and needles, unusual sensitivity
to stimuli of the senses, seizures (see Section 2: Take special care with Ciproxin), giddiness













eyesight problems including double vision
loss of hearing
rapid heartbeat (tachycardia)
expansion of the blood vessels (vasodilation), low blood pressure
abdominal pain, digestive problems such as stomach upset (indigestion/heartburn), wind
liver disorders, increased amounts of one substance in the blood (bilirubin), jaundice
(cholestatic icterus)
itching, hives
joint pain in adults
poor kidney function, kidney failure
pains in your muscles and bones, feeling unwell (asthenia), fever, fluid retention
increase in blood alkaline phosphatase (a certain substance in the blood)

Rare side effects (between 1 and 10 in every 10,000 people are likely to get these):




















inflammation of the bowel (colitis) linked to antibiotic use (can be fatal in rare cases) (see
Section 2: Take special care with Ciprofloxacin Infusion)
changes to the blood count (leukopenia, leukocytosis, neutropenia, anaemia), a drop in the
number of red and white blood cells and platelets (pancytopenia), which may be fatal, bone
marrow depression which may also be fatal (see Section 2: Take special care with
Ciprofloxacin Infusion)
allergic reaction, allergic swelling (oedema), rapid swelling of the skin and mucous
membranes (angiooedema), severe allergic reaction (anaphylactic shock) which can be lifethreatening (see Section 2: Take special care with Ciprofloxacin Infusion)
increased blood sugar (hyperglycemia)
low blood sugar (hypoglycaemia)
anxiety reaction, strange dreams, depression (potentially leading to thoughts of suicide,
suicide attempts, or completed suicide), mental disturbances (psychotic reactions potentially
leading to thoughts of suicide, suicide attempts, or completed suicide) (see Section 2: Take
special care with Ciprofloxacin Infusion)
decreased skin sensitivity, tremor, migraine, disorder of sense of smell (olfactory disorders)
tinnitus, impaired hearing
fainting, inflammation of the blood vessel (vasculitis)
shortness of breath including asthmatic symptoms
pancreatitis
hepatitis, death of liver cells (liver necrosis) very rarely leading to life-threatening liver
failure
sensitivity to light (see Section 2: Take special care with Ciprofloxacin Infusion), small, pinpoint bleeding under the skin (petechiae)
muscle pain, inflammation of the joints, increased muscle tone, cramping, tendon rupture –
especially of the large tendon at the back of the ankle (Achilles tendon) (see Section 2: Take
special care with Ciprofloxacin Infusion)
blood or crystals in the urine (see Section 2: Take special care with Ciprofloxacin Infusion),
urinary tract inflammation
excessive sweating
increased levels of the enzyme amylase

Very rare side effects (less than 1 in every 10,000 people are likely to get these):


a special type of reduced red blood cell count (haemolytic anaemia); a dangerous drop in a
type of white blood cells (agranulocytosis )







severe allergic reaction (anaphylactic reaction, anaphylactic shock, serum sickness) which can
be fatal (see Section 2: Take special care with Ciprofloxacin Infusion)
disturbed coordination, unsteady walk (gait disturbance), pressure on the brain (intracranial
pressure)
visual colour distortions
various skin eruptions or rashes (e.g. the potentially fatal Stevens-Johnson syndrome or toxic
epidermal necrolysis)
muscle weakness, tendon inflammation, worsening of the symptoms of myasthenia gravis
(see Section 2: Take special care with Ciprofloxacin Infusion)

Frequency not known (cannot be estimated from the available data)
• troubles associated with the nervous system such as pain, burning, tingling, numbness and/ or
weakness in extremities
• abnormal fast heart rhythm, life-threatening irregular heart rhythm, alteration of the heart
rhythm (called ‘prolongation of QT interval’, seen on ECG, electrical activity of the heart)
• pustular rash
• influence on blood clotting (in patients treated with Vitamin K antagonists)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the Yellow Card
Scheme at: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more information on the safety of this
medicine.
5. How to store Ciprofloxacin Infusion
Keep this medicine out of the sight and reach of children. Do not use Ciprofloxacin Infusion after the
expiry date which is stated on the carton and vial. The expiry date refers to the last date of that month.
Do not refrigerate or freeze.
Keep container in the outer carton.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the pack and other information
What Ciprofloxacin Infusion contains
The active substance is ciprofloxacin (as ciprofloxacin lactate). The other ingredients are lactic acid,
sodium chloride, hydrochloric acid and water for injections.
What Ciprofloxacin Infusion looks like and contents of the pack
Ciprofloxacin Infusion is a clear, yellowish to slightly yellow solution, and comes in 50ml, 100ml and
200ml vials containing 100mg, 200mg and 400mg ciprofloxacin (as lactate). You will normally be
given this infusion in hospital.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
PLIVA Pharma Ltd,

Vision House,
Bedford Road,
Petersfield,
Hampshire, GU32 3QB,
England.
Manufacturer:
Pharmathen Ltd,
Dervenakion 6
Pallini 15351
Attiki, Greece
This Medicinal product is authorised in the Member States of the EEA under the following names:
United Kingdom:
Ciprofloxacin 2mg/ml Solution for Infusion
Ireland:
Ciprofloxacin 2mg/ml Solution for Infusion
Date of preparation: June 2014
-------------------------------------------------------------------------------------------------------------------------Technical leaflet

1. Name of the Medicial Product
Ciprofloxacin 2mg/ml Solution for Infusion.
2. Qualitative and Quantitative Composition
Each presentation of Ciprofloxacin 2mg/ml Solution for Infusion in glass vials contains the following:
50ml pack size: 100mg Ciprofloxacin (as lactate)
100ml pack size: 200mg Ciprofloxacin (as lactate)
200ml pack size: 400mg Ciprofloxacin (as lactate)
Excipient(s) with known effect:
Sodium (354mg/100ml equivalent to 154mmol sodium per litre). For a full list of excipients, see
section 6.1.
For the full list of excipients, see section 6.1.
3. Pharmaceutical Form
Solution for Infusion. Clear, yellowish to slightly yellow solution.
4. Clinical Particulars
4.1. Therapeutic indications

Ciprofloxacin solution for infusion is indicated for the treatment of the following infections
(see sections 4.4 and 5.1). Special attention should be paid to available information on
resistance to ciprofloxacin before commencing therapy.
Consideration should be given to official guidance on the appropriate use of antibacterial
agents.
Adults
• Lower respiratory tract infections due to Gram-negative bacteria
o exacerbations of chronic obstructive pulmonary disease
o broncho-pulmonary infections in cystic fibrosis or in bronchiectasis
o pneumonia
• Chronic suppurative otitis media
• Acute exacerbation of chronic sinusitis especially if these are caused by Gramnegative bacteria
• Urinary tract infections
• Genital tract infections
o epididymo-orchitis including cases due to susceptible Neisseria gonorrhoeae
o pelvic inflammatory disease including cases due to susceptible Neisseria
gonorrhoeae
In the above genital tract infections when thought or known to be due to Neisseria
gonorrhoeae it is particularly important to obtain local information on the prevalence
of resistance to ciprofloxacin and to confirm susceptibility based on laboratory
testing.
• Infections of the gastro-intestinal tract (e.g. travellers` diarrhoea)
• Intra-abdominal infections
• Infections of the skin and soft tissue caused by Gram-negative bacteria
• Malignant external otitis
• Infections of the bones and joints
• Inhalation anthrax (post-exposure prophylaxis and curative treatment)
Ciprofloxacin may be used in the management of neutropenic patients with fever that is
suspected to be due to a bacterial infection..
Children and adolescents:
• Broncho-pulmonary infections in cystic fibrosis caused by Pseudomonas aeruginosa
• Complicated urinary tract infections and pyelonephritis
• Inhalation anthrax (post-exposure prophylaxis and curative treatment)
Ciprofloxacin may also be used to treat severe infections in children and adolescents when
this is considered to be necessary.
Treatment should be initiated only by physicians who are experienced in the treatment of cystic
fibrosis and/or severe infections in children and adolescents (see sections 4.4 and 5.1).

4.2. Posology and method of administration
The dosage is determined by the indication, the severity and the site of the infection, the
susceptibility to ciprofloxacin of the causative organism(s), the renal function of the patient
and, in children and adolescents the body weight.
The duration of treatment depends on the severity of the illness and on the clinical and
bacteriological course.

After intravenous initiation of treatment, the treatment can be switched to oral treatment with
tablet or suspension if clinically indicated at the discretion of the physician. IV treatment
should be followed by oral route as soon as possible.
In severe cases or if the patient is unable to take tablets (e.g. patients on enteral nutrition), it is
recommended to commence therapy with intravenous ciprofloxacin until a switch to oral
administration is possible.
Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosa, Acinetobacter
or Staphylococci) may require higher ciprofloxacin doses and co-administration with other
appropriate antibacterial agents.
Treatment of some infections (e.g. pelvic inflammatory disease, intra-abdominal infections,
infections in neutropenic patients and infections of bones and joints) may require coadministration with other appropriate antibacterial agents depending on the pathogens
involved.
Adults:
Indications

Daily dose in mg

Infections of the lower respiratory tract

400 mg twice daily
to 400 mg three
times a day
400 mg twice daily
to 400 mg three
times a day
400 mg twice daily
to 400 mg three
times a day
400 mg three times
a day
400 mg twice daily
to 400 mg three
times a day

Infections of the
upper respiratory
tract

Urinary tract
infections
(see section 4.4)

Acute exacerbation
of chronic sinusitis
Chronic
suppurative otitis
media
Malignant external
otitis
Complicated and
uncomplicated
pyelonephritis

Prostatitis

Genital tract
infections

Infections of the
gastrointestinal
tract and intraabdominal
infections

Epididymo-orchitis
and pelvic
inflammatory
diseases
Diarrhoea caused
by bacterial
pathogens
including Shigella
spp. other than
Shigella

400 mg twice daily
to 400 mg three
times a day
400 mg twice daily
to 400 mg three
times a day
400 mg twice daily

Total duration of
treatment
(including switch
to oral therapy as
soon as possible)
7 to 14 days

7 to 14 days

7 to 14 days

28 days up to 3
months
7 to 21 days, it can
be continued for
longer than 21 days
in some specific
circumstances
(such as abscesses)
2 to 4 weeks
(acute)
at least 14 days

1 day

dysenteriae type 1
and empirical
treatment of severe
travellers'
diarrhoea
Diarrhoea caused
by Shigella
dysenteriae type 1
Diarrhoea caused
by Vibrio cholerae
Typhoid fever
Intra-abdominal
infections due
to Gram-negative
bacteria
Infections of the skin and soft tissue

Bone and joint infections

Neutropenic patients with fever that is
suspected to be due to a bacterial
infection.
Ciprofloxacin should be co-administered
with appropriate antibacterial agent(s) in
accordance to official guidance.
Inhalation anthrax post-exposure
prophylaxis and curative treatment for
persons requiring parenteral treatment

400 mg twice daily

5 days

400 mg twice daily

3 days

400 mg twice daily
400 mg twice daily
to 400 mg three
times a day

7 days
5 to 14 days

400 mg twice daily
to 400 mg three
times a day
400 mg twice daily
to 400 mg three
times a day
400 mg twice daily
to 400 mg three
times a day

7 to 14 days

400 mg twice daily

60 days from the
confirmation of
Bacillus anthracis
exposure

max. of 3 months

Therapy should be
continued over
the entire period of
neutropenia

Drug administration should begin as soon
as possible after suspected or confirmed
exposure

Paediatric population
Indications

Cystic fibrosis

Complicated urinary tract
infections and pyelonephritis

Inhalation anthrax postexposure prophylaxis and
curative treatment for persons
able to receive treatment by

Daily dose in mg

10 mg/kg body weight three times
daily with a maximum of 400 mg
per dose.
6 mg/kg body weight three times
daily to 10 mg/kg body weight three
times a day with a maximum of 400
mg per dose.
10 mg/kg body weight twice daily
to 15 mg/kg body weight twice
daily with a maximum of 400 mg
per dose.

Total duration of treatment
(potentially including initial
parenteral treatment with
ciprofloxacin)
10 to 14 days

10 to 21 days

60 days from the
confirmation of Bacillus
anthracis exposure

oral route when clinically
appropriate.
Drug administration should
begin as soon as possible after
suspected or confirmed
exposure.
Other severe infections

10 mg/kg body weight three times a
day with a maximum of 400 mg per
dose.

According to the type of
infections

Geriatric patients
Geriatric patients should receive a dose selected according to the severity of the infection and
the patient`s creatinine clearance.
Renal and hepatic impairment
Recommended starting and maintenance doses for patients with impaired renal function:
Creatinine Clearance
[ml/min/1.73 m2]
> 60
30-60
< 30
Patients on haemodialysis

Serum Creatinine
[µmol/l]
< 124
124 to 168
> 169
> 169

Patients on peritoneal dialysis

> 169

Intravenous Dose
[mg]
See Usual Dosage.
200-400 mg every 12 h
200-400 mg every 24 h
200-400 mg every 24 h
(after dialysis)
200-400 mg every 24 h

In patients with impaired liver function no dose adjustment is required.
Dosing in children with impaired renal and/or hepatic function has not been studied.
Method of administration
Ciprofloxacin solution for infusion should be checked visually prior to use. It must not be
used if cloudy.
Ciprofloxacin should be administered by intravenous infusion. For children, the infusion
duration is 60 minutes.
In adult patients, infusion time is 60 minutes for 400 mg Ciprofloxacin solution for infusion
and 30 minutes for 200 mg Ciprofloxacin solution for infusion. Slow infusion into a large
vein will minimise patient discomfort and reduce the risk of venous irritation.
The infusion solution can be infused either directly or after mixing with other compatible
infusion solutions (see section 6.6).
4.3. Contraindications
Hypersensitivity to the active substance, to other quinolones or to any of the excipients (see
section 6.1).
Concomitant administration of ciprofloxacin and tizanidine (see section 4.5).
4.4. Special warnings and precautions for use

Severe infections and mixed infections with Gram-positive and anaerobic pathogens
Ciprofloxacin monotherapy is not suited for treatment of severe infections and infections that
might be due to Gram-positive or anaerobic pathogens. In such infections ciprofloxacin must
be co-administered with other appropriate antibacterial agents.
Streptococcal Infections (including Streptococcus pneumoniae)
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to
inadequate efficacy.
Genital tract infections
Epididymo-orchitis and pelvic inflammatory diseases may be caused by fluoroquinoloneresistant Neisseria gonorrhoeae isolates.
For epididymo-orchitis and pelvic inflammatory diseases, empirical ciprofloxacin should only
be considered in combination with another appropriate antibacterial agent (e.g. a
cephalosporin) unless ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded. If
clinical improvement is not achieved after 3 days of treatment, the therapy should be
reconsidered.
Urinary tract infections
Resistance to fluoroquinolones of Escherichia coli– the most common pathogen involved in
urinary tract infections – varies across the European Union. Prescribers are advised to take
into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.
Intra-abdominal infections
There are limited data on the efficacy of ciprofloxacin in the treatment of post-surgical intraabdominal infections.
Travellers' diarrhoea
The choice of ciprofloxacin should take into account information on resistance to
ciprofloxacin in relevant pathogens in the countries visited.
Infections of the bones and joints
Ciprofloxacin should be used in combination with other antimicrobial agents depending on
the results of the microbiological documentation.
Inhalational anthrax
Use in humans is based on in-vitro susceptibility data and on animal experimental data
together with limited human data. Treating physicians should refer to national and /or
international consensus documents regarding the treatment of anthrax.
Children and adolescents
The use of ciprofloxacin in children and adolescents should follow available official guidance.
Ciprofloxacin treatment should be initiated only by physicians who are experienced in the
treatment of cystic fibrosis and/or severe infections in children and adolescents.
Ciprofloxacin has been shown to cause arthropathy in weight-bearing joints of immature
animals. Safety data from a randomised double-blind study on ciprofloxacin use in children
(ciprofloxacin: n = 335, mean age = 6.3 years; comparators: n = 349, mean age = 6.2 years;
age range = 1 to 17 years) revealed an incidence of suspected drug-related arthropathy
(discerned from joint-related clinical signs and symptoms) by Day +42 of 7.2% and 4.6%.
Respectively, an incidence of drug-related arthropathy by 1-year follow-up was 9.0% and
5.7%. The increase of suspected drug-related arthropathy cases over time was not statistically
significant between groups. Treatment should be initiated only after a careful benefit/risk
evaluation, due to possible adverse events related to joints and/or surrounding tissue.

Broncho-pulmonary infections in cystic fibrosis
Clinical trials have included children and adolescents aged 5-17 years. More limited
experience is available in treating children between 1 and 5 years of age.
Complicated urinary tract infections and pyelonephritis
Ciprofloxacin treatment of urinary tract infections should be considered when other
treatments cannot be used, and should be based on the results of the microbiological
documentation.
Clinical trials have included children and adolescents aged 1-17 years.
Other specific severe infections
Other severe infections in accordance with official guidance, or after careful benefit-risk
evaluation when other treatments cannot be used, or after failure to conventional therapy and
when the microbiological documentation can justify a ciprofloxacin use.
The use of ciprofloxacin for specific severe infections other than those mentioned above has
not been evaluated in clinical trials and the clinical experience is limited. Consequently,
caution is advised when treating patients with these infections.
Hypersensitivity
Hypersensitivity and allergic reactions, including anaphylaxis and anaphylactoid reactions,
may occur following a single dose (see section 4.8) and may be life-threatening. If such
reaction occurs, ciprofloxacin should be discontinued and an adequate medical treatment is
required.
Musculoskeletal System
Ciprofloxacin should generally not be used in patients with a history of tendon
disease/disorder related to quinolone treatment. Nevertheless, in very rare instances, after
microbiological documentation of the causative organism and evaluation of the risk/benefit
balance, ciprofloxacin may be prescribed to these patients for the treatment of certain severe
infections, particularly in the event of failure of the standard therapy or bacterial resistance,
where the microbiological data may justify the use of ciprofloxacin.
Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may occur
with ciprofloxacin, even within the first 48 hours of treatment. Inflammation and ruptures of
tendon may occur even up to several months after discontinuation of ciprofloxacin therapy.
The risk of tendinopathy may be increased in elderly patients or in patients concomitantly
treated with corticosteroids (see section 4.8).
At any sign of tendinitis (e.g. painful swelling, inflammation), ciprofloxacin treatment should
be discontinued. Care should be taken to keep the affected limb at rest.
Ciprofloxacin should be used with caution in patients with myasthenia gravis (see section
4.8).
Photosensitivity
Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking
ciprofloxacin should be advised to avoid direct exposure to either extensive sunlight or UV
irradiation during treatment (see section 4.8).
Central Nervous System
Ciprofloxacin like other quinolones are known to trigger seizures or lower the seizure
threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with
caution in patients with CNS disorders which may be predisposed to seizure. If seizures occur
ciprofloxacin should be discontinued (see section 4.8). Psychiatric reactions may occur even
after first administration of ciprofloxacin. In rare cases, depression or psychosis can progress
to suicidal ideations/thoughts culminating in attempted suicide or completed suicide. In the
occurrence of such cases, ciprofloxacin should be discontinued.

Cases of polyneuropathy (based on neurological symptoms such as pain, burning, sensory
disturbances or muscle weakness, alone or in combination) have been reported in patients
receiving 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).
Cardiac disorders
Caution should be taken when using fluoroquinolones, including ciprofloxacin, in patients
with known risk factors for prolongation of the QT interval such as, for example:
• congenital long QT syndrome
• concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and
III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
• uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
• cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patients and women may be more sensitive to QTc-prolonging medications.
Therefore, caution should be taken when using fluoroquinolones, including ciprofloxacin, in
these populations.
(See section 4.2 Geriatric patients, section 4.5, section 4.8, section 4.9).
Gastrointestinal System
The occurrence of severe and persistent diarrhoea during or after treatment (including several
weeks after treatment) may indicate an antibiotic-associated colitis (life-threatening with
possible fatal outcome), requiring immediate treatment (see section 4.8). In such cases,
ciprofloxacin should immediately be discontinued, and an appropriate therapy initiated. Antiperistaltic drugs are contraindicated in this situation.

Hypoglycemia
As with other quinolones, hypoglycemia has been reported most often in diabetic
patients, predominantly in the elderly population. In all diabetic patients, careful
monitoring of blood glucose is recommended (see section 4.8).
Renal and urinary system
Crystalluria related to the use of ciprofloxacin has been reported (see section 4.8). Patients
receiving ciprofloxacin should be well hydrated and excessive alkalinity of the urine should
be avoided.
Impaired renal function
Since ciprofloxacin is largely excreted unchanged via renal pathway dose adjustment is
needed in patients with impaired renal function as described in section 4.2 to avoid an
increase in adverse drug reactions due to accumulation of ciprofloxacin.
Hepatobiliary system
Cases of hepatic necrosis and life-threatening hepatic failure have been reported with
ciprofloxacin (see section 4.8). 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.
Glucose-6-phosphate dehydrogenase deficiency
Haemolytic reactions have been reported with ciprofloxacin in patients with glucose-6phosphate dehydrogenase deficiency. Ciprofloxacin should be avoided in these patients unless
the potential benefit is considered to outweigh the possible risk. In this case, potential
occurrence of haemolysis should be monitored.
Resistance

During or following a course of treatment with ciprofloxacin bacteria that demonstrate
resistance to ciprofloxacin may be isolated, with or without a clinically apparent
superinfection. There may be a particular risk of selecting for ciprofloxacin-resistant bacteria
during extended durations of treatment and when treating nosocomial infections and/or
infections caused by Staphylococcus and Pseudomonas species .
Cytochrome P450
Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of
concomitantly administered substances metabolised by this enzyme (e.g. theophylline,
clozapine,olanzapine ropinirole, tizanidine, duloxetine). Co-administration of ciprofloxacin
and tizanidine is contra-indicated. Therefore, patients taking these substances concomitantly
with ciprofloxacin should be monitored closely for clinical signs of overdose, and
determination of serum concentrations (e.g. of theophylline) may be necessary (see section
4.5).
Methotrexate
The concomitant use of ciprofloxacin with methotrexate is not recommended (see section
4.5).
Interaction with tests
The in-vitro activity of ciprofloxacin against Mycobacterium tuberculosis might give false
negative bacteriological test results in specimens from patients currently taking ciprofloxacin.
Injection Site Reaction
Local intravenous site reactions have been reported with the intravenous administration of
ciprofloxacin. These reactions are more frequent if the infusion time is 30 minutes or less.
These may appear as local skin reactions which resolve rapidly upon completion of the
infusion. Subsequent intravenous administration is not contraindicated unless the reactions
recur or worsen.
NaCl Load
In patients for whom sodium intake is of medical concern (patients with congestive heart
failure, renal failure, nephritic syndrome, etc.), the additional sodium load should be taken
into account (for sodium chloride content, see section 2).
4.5. Interactions with other medicinal products and other forms of interaction
Effects of other products on ciprofloxacin:
Drugs known to prolong QT interval
Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients receiving
drugs known to prolong QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic
antidepressants, macrolides, antipsychotics) (see section 4.4).
Probenecid
Probenecid interferes with renal secretion of ciprofloxacin. Co-administration of probenecid
and ciprofloxacin increases ciprofloxacin serum concentrations.
Effects of ciprofloxacin on other medicinal products:
Tizanidine
Tizanidine must not be administered together with ciprofloxacin (see section 4.3). In a clinical
study with healthy subjects, there was an increase in serum tizanidine concentration (Cmax
increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given

concomitantly with ciprofloxacin. Increased serum tizanidine concentration is associated with
a potentiated hypotensive and sedative effect.
Methotrexate
Renal tubular transport of methotrexate may be inhibited by concomitant administration of
ciprofloxacin, potentially leading to increased plasma levels of methotrexate and increased
risk of methotrexate-associated toxic reactions. The concomitant use is not recommended (see
section 4.4).
Theophylline
Concurrent administration of ciprofloxacin and theophylline can cause an undesirable
increase in serum theophylline concentration. This can lead to theophylline-induced side
effects that may rarely be life threatening or fatal. During the combination, serum
theophylline concentrations should be checked and the theophylline dose reduced as
necessary (see section 4.4).
Other xanthine derivatives
On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline),
raised serum concentrations of these xanthine derivatives were reported.
Phenytoin
Simultaneous administration of ciprofloxacin and phenytoin may result in increased or
reduced serum levels of phenytoin such that monitoring of drug levels is recommended.
Cyclosporin
A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and
cyclosporin containing medicinal products were administered simultaneously. Therefore, it is
frequently (twice a week) necessary to control the serum creatinine concentrations in these
patients.
Vitamin K antagonists
Simultaneous administration of ciprofloxacin with a vitamin K antagonist may augment its
anti-coagulant effects. 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. The INR should be monitored frequently during and
shortly after coadministration of ciprofloxacin with a vitamin K antagonist (e.g., warfarin,
acenocoumarol, phenprocoumon, or fluindione).
Glibenclamide
In particular cases, concurrent administration of ciprofloxacin and glibenclamide containing
medicinal products can intensify the action of glibenclamide (hypoglycaemia).
Duloxetine
In clinical studies, it was demonstrated that concomitant use of duloxetine with strong
inhibitors of the CYP450 1A2 isozyme 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 (see section 4.4).
Ropinirole
It was shown in a clinical study that concomitant use of ropinirole with ciprofloxacin, a
moderate inhibitor of the CYP450 1A2 isozyme, results in an increase of Cmax and AUC of
ropinirole by 60% and 84%, respectively. Monitoring of ropinirole-related side effects and
dose adjustment as appropriate is recommended during and shortly after co-administration
with ciprofloxacin (see section 4.4).

Lidocaine
It was demonstrated in healthy subjects that concomitant use of lidocaine containing
medicinal products 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 co-administration with ciprofloxacin are advised (see section 4.4).
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.
4.6. Pregnancy and lactation
Pregnancy
The data that are available on administration of ciprofloxacin to pregnant women indicates no
malformative or feto/neonatal toxicity of ciprofloxacin. Animal studies do not indicate direct
or indirect harmful effects with respect to reproductive toxicity. In juvenile and prenatal
animals exposed to quinolones, effects on immature cartilage have been observed, thus, it
cannot be excluded that the drug could cause damage to articular cartilage in the human
immature organism / foetus (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of ciprofloxacin during
pregnancy.
Breast-feedingCiprofloxacin is excreted in breast milk. Due to the potential risk of articular
damage, ciprofloxacin should not be used duringbreast-feeding.
4.7. Effects on ability to drive and use machines
Due to its neurological effects, ciprofloxacin may affect reaction time. Thus, the ability to
drive or to operate machinery may be impaired..
4.8. Undesirable effects
The most frequently reported adverse reactions (ADRs) are: nausea, diarrhoea, vomiting,
transioetn increase in transaminases, rash, and injection and infusion site reactions.
ADRs derived from clinical studies and post-marketing surveillance with Ciprofloxacin (oral,
intravenous and sequential therapy)
sorted by categories of frequency are listed below. The frequency analysis takes into account
data from both oral and intravenous administration of ciprofloxacin.
System
Organ Class

Common
≥ 1/100 to
< 1/10

Uncommon
≥ 1/1000 to
< 1/100

Rare
≥ 1/10 000 to
< 1/1000

Very Rare
< 1/10 000

Frequency
not known
(cannot be
estimated
from

available
data)
Infections and
Infestations

Mycotic
superinfections

Blood and
Lymphatic
System
Disorders

Eosinophilia

Immune
System
Disorders

Metabolism
and Nutrition
Disorders

Anorexia

Psychiatric
Disorders

Psychomotor
hyperactivity/
agitation

Nervous
System
Disorders

Headache
Dizziness
Sleep
disorders
Taste
disorders

Antibiotic
associated
colitis (very
rarely with
possible fatal
outcome) (see
section 4.4)
Leukopenia
Anaemia
Neutropenia
Leukocytosis
Thrombocyto
penia
Thrombocytaemia
Allergic
reaction
Allergic
oedema/
angiooedema

Hyperglycaemia
Hypoglycaem
ia
Confusion
and
disorientation
Anxiety
reaction
Abnormal
dreams
Depression
(potentially
culminating
in suicidal
ideations/thou
ghts or
suicide
attempts and
completed
suicide) (see
section 4.4)
Hallucinations
Par- and
Dysaesthesia
Hypoaesthesia
Tremor
Seizures (incl.

Haemolytic
anaemia
Agranulocytosis
Pancytopenia
(life-threatening)
Bone marrow
depression (lifethreatening)
Anaphylactic
reaction
Anaphylactic
shock (lifethreatening) (see
section 4.4)
Serum sicknesslike reaction

Psychotic
reactions
(potentially
culminating in
suicidal
ideations/though
ts or suicide
attempts and
completed
suicide) (see
section 4.4)

Migraine
Disturbed
coordination
Gait disturbance
Olfactory nerve
disorders

Peripheral
neuropathy
(see section
4.4)

status
epilepticus,
see section
4.4)
Vertigo
Visual
disturbances
(e.g. diplopia)
Tinnitus
Hearing loss/
Hearing
impaired
Tachycardia

Eye Disorders

Ear and
Labyrinth
Disorders
Cardiac
Disorders

Vascular
Disorders
Respiratory,
Thoracic and
Mediastinal
Disorders
Gastrointestinal
Disorders

Hepatobiliary
Disorders

Skin and
Subcutaneous
Tissue
Disorders

Nausea
Diarrhoea

Vomiting
Gastrointestinal and
abdominal
pains
Dyspepsia
Flatulence
Increase in
transaminases
Increased
bilirubin

Rash
Pruritus
Urticaria

Intracranial
hypertension

Visual colour
distortions

Ventricular
arrhythmia
and torsades
de pointes
(reported
predominantl
y in patients
with risk
factors for
QT
prolongation)
, ECG QT
prolonged
(see section
4.4 and 4.9)

Vasodilatation Vasculitis
Hypotension
Syncope
Dyspnoea
(including
asthmatic
condition)
Pancreatitis

Hepatic
impairment
Cholestatic
icterus
Hepatitis
Photosensitivity
reactions (see
section 4.4)

Liver necrosis
(very rarely
progressing to
life-threatening
hepatic failure)
(see section 4.4)
Petechiae
Erythema
multiforme
Erythema
nodosum
Stevens-Johnson
syndrome

Acute
generalised
exanthematou
s pustulosis
(AGEP)

Musculoskeletal,
Connective
Tissue and
Bone
Disorders

Musculoskeletal pain
(e.g.
extremity
pain, back
pain, chest
pain)
Arthralgia

Myalgia
Arthritis
Increased
muscle tone
and cramping

Renal and
Urinary
Disorders

Renal
impairment

(potentially lifethreatening)
Toxic epidermal
necrolysis
(potentially lifethreatening)
Muscular
weakness
Tendinitis
Tendon rupture
(pre-dominantly
Achilles tendon)
(see section 4.4)
Exacerbation of
symptoms of
myasthenia
gravis (see
section 4.4)

Renal failure
Haematuria
Crystalluria
(see section
4.4)
Tubulointerstitial
nephritis
Oedema
Sweating
(hyperhidrosis)

General
Disorders and
Administration
Site Conditions

Investigations

Injectio
n and
infusio
n site
reactio
ns
(only
intrave
nous
admini
stration
)

Asthenia
Fever

Increase in
blood alkaline
phosphatase

Increased
amylase

International
normalised
ratio
increased (in
patients
treated with
Vitamin K
antagonists)

The following undesirable effects have a higher frequency category in the subgroups of
patients receiving intravenous or sequential (intravenous to oral) treatment:
Common
Uncommon

Vomiting, Transient increase in transaminases, Rash
Thrombocytopenia,
Thrombocytaemia,
Confusion
and
disorientation, Hallucinations, Par- and dysaesthesia, Seizures,
Vertigo, Visual disturbances, Hearing loss, Tachycardia,

Vasodilatation, Hypotension, Transient hepatic impairment,
Cholestatic icterus, Renal failure, Oedema
Pancytopenia, Bone marrow depression, Anaphylactic shock,
Psychotic reactions, Migraine, Olfactory nerve disorders, Hearing
impaired, Vasculitis, Pancreatitis, Liver necrosis, Petechiae,
Tendon rupture

Rare

Paediatric patients
The incidence of arthropathy, mentioned above, is referring to data collected in studies with
adults. In children, arthropathy is reported to occur commonly (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow
Card Scheme at: www.mhra.gov.uk/yellowcard
4.9. Overdose
An overdose of 12 g has been reported to lead to mild symptoms of toxicity. An acute
overdose of 16 g has been reported to cause acute renal failure.
Symptoms in overdose consist of dizziness, tremor, headache, tiredness, seizures,
hallucinations, confusion, abdominal discomfort, renal and hepatic impairment as well as
crystalluria and haematuria. Reversible renal toxicity has been reported.
Apart from routine emergency measures, ,e.g. ventricular emptying followed by medical
carbon, it is recommended to monitor renal function, including urinary pH and acidify, if
required, to prevent crystalluria. Patients should be kept well hydrated. Calcium or
magnesium containing antacids may theoretically reduce the absorption of ciprofloxacin in
overdoses.
Only a small quantity of ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal
dialysis.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring
should be undertaken, because of the possibility of QT interval prolongation.

5. Pharmacological Properties
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Fluoroquinolones, ATC code: J 01 MA 02
Mechanism of action:
As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from
the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for
bacterial DNA replication, transcription, repair and recombination.
PK/PD relationship:
Efficacy mainly depends on the relation between the maximum concentration in serum
(Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial
pathogen and the relation between the area under the curve (AUC) and the MIC.
Mechanism of resistance

In-vitro resistance to ciprofloxacin can be acquired through a stepwise process by target site
mutations in both DNA gyrase and topoisomerase IV. The degree of cross-resistance between
ciprofloxacin and other fluoroquinolones that results is variable. Single mutations may not
result in clinical resistance, but multiple mutations generally result in clinical resistance to
many or all active substances within the class.
Impermeability and/or active substance efflux pump mechanisms of resistance may have a
variable effect on susceptibility to fluoroquinolones, which depends on the physiochemical
properties of the various active substances within the class and the affinity of transport
systems for each active substance. All in-vitro mechanisms of resistance are commonly
observed in clinical isolates. Resistance mechanisms that inactivate other antibiotics such as
permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may
affect susceptibility to ciprofloxacin.
Plasmid-mediated resistance encoded by qnr-genes has been reported.
Spectrum of antibacterial activity:
Breakpoints separate susceptible strains from strains with intermediate susceptibility and the
latter from resistant strains:
EUCAST Recommendations
Microorganisms
Susceptible
Resistant
Enterobacteriaceae
S ≤ 0.5 mg/l
R > 1mg/l
Pseudomonas spp
S ≤ 0.5 mg/l
R > 1mg/l
Acinetobacter spp
S ≤ 1 mg/l
R > 1 mg/l
1
Staphylococcus spp.
S ≤ 1 mg/l
R > 1 mg/l
Haemophilus influenzae and S ≤ 0.5 mg/l
R > 0.5 mg/l
Moraxella catarrhalis
Neisseria gonorrhoeae
S ≤ 0.03 mg/l
R > 0.06 mg/l
Neisseria meningitidis
S ≤ 0.03 mg/l
R > 0.06 mg/l
Non-species-related
S ≤ 0.5 mg/l
R > 1 mg/l
breakpoints*
1
Staphylococcus spp. - breakpoints for ciprofloxacin relate to high dose therapy.
* Non-species-related breakpoints have been determined mainly on the basis of PK/PD data
and are independent of MIC distributions of specific species. They are for use only for species
that have not been given a species-specific breakpoint and not for those species where
susceptibility testing is not recommended.
The prevalence of acquired resistance may vary geographically and with time for selected
species and local information on resistance is desirable, particularly when treating severe
infections. As necessary, expert advice should be sought when the local prevalence of
resistance is such that the utility of the agent in at least some types of infections is questionable.
Groupings of relevant species according to ciprofloxacin susceptibility (for Streptococcus
species see section 4.4)
COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive micro-organisms
Bacillus anthracis (1)
Aerobic Gram-negative micro-organisms
Aeromonas spp.
Brucella spp.
Citrobacter koseri
Francisella tularensis
Haemophilus ducreyi

Haemophilus influenzae*
Legionella spp.
Moraxella catarrhalis*
Neisseria meningitidis
Pasteurella spp.
Salmonella spp.*
Shigella spp.*
Vibrio spp.
Yersinia pestis
Anaerobic micro-organisms
Mobiluncus
Other micro-organisms
Chlamydia trachomatis ($)
Chlamydia pneumoniae ($)
Mycoplasma hominis ($)
Mycoplasma pneumoniae ($)
SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM
Aerobic Gram-positive micro-organisms
Enterococcus faecalis ($)
Staphylococcus spp.* (2)
Aerobic Gram-negative micro-organisms
Acinetobacter baumannii+
Burkholderia cepacia+*
Campylobacter spp.+*
Citrobacter freundii*
Enterobacter aerogenes
Enterobacter cloacae*
Escherichia coli*
Klebsiella oxytoca
Klebsiella pneumoniae*
Morganella morganii*
Neisseria gonorrhoeae*
Proteus mirabilis*
Proteus vulgaris*
Providencia spp.
Pseudomonas aeruginosa*
Pseudomonas fluorescens
Serratia marcescens*
Anaerobic micro-organisms
Peptostreptococcus spp.
Propionibacterium acnes
INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive micro-organisms
Actinomyces
Enterococcus faecium
Listeria monocytogenes
Aerobic Gram-negative micro-organisms
Stenotrophomonas maltophilia
Anaerobic micro-organisms
Excepted as listed above
Other micro-organisms
Mycoplasma genitalium
Ureaplasma urealitycum
* Clinical efficacy has been demonstrated for susceptible isolates in approved clinical

indications
Resistance rate ≥ 50% in one or more EU countries
($): Natural intermediate susceptibility in the absence of acquired mechanism of resistance
(1): Studies have been conducted in experimental animal infections due to inhalations of
Bacillus anthracis spores; these studies reveal that antibiotics starting early after
exposition avoid the occurrence of the disease if the treatment is made up to the decrease
of the number of spores in the organism under the infective dose. The recommended use
in human subjects is based primarily on in-vitro susceptibility and on animal experimental
data together with limited human data. Two-month treatment duration in adults with oral
ciprofloxacin given at the following dose, 500 mg bid, is considered as effective to
prevent anthrax infection in humans. The treating physician should refer to national and/or
international consensus documents regarding treatment of anthrax.
(2): Methicillin-resistant S. aureus very commonly express co-resistance to fluoroquinolones.
The rate of resistance to methicillin is around 20 to 50% among all staphylococcal species
and is usually higher in nosocomial isolates.
+

5.2. Pharmacokinetic properties
Absorption
Following an intravenous infusion of ciprofloxacin the mean maximum serum concentrations
were achieved at the end of infusion. Pharmacokinetics of ciprofloxacin were linear over the
dose range up to 400 mg administered intravenously.
Comparison of the pharmacokinetic parameters for a twice a day and three times a day
intravenous dose regimen indicated no evidence of drug accumulation for ciprofloxacin and its
metabolites.
A 60-minute intravenous infusion of 200 mg ciprofloxacin or the oral administration of 250 mg
ciprofloxacin, both given every 12 hours, produced an equivalent area under the serum
concentration time curve (AUC).
A 60-minute intravenous infusion of 400 mg ciprofloxacin every 12 hours was bioequivalent to
a 500 mg oral dose every 12 hours with regard to AUC.
The 400 mg intravenous dose administered over 60 minutes every 12 hours resulted in a Cmax
similar to that observed with a 750 mg oral dose.
A 60-minute infusion of 400 mg ciprofloxacin every 8 hours is equivalent with respect to AUC
to 750 mg oral regimen given every 12 hours.
Distribution
Protein binding of ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma largely in
a non-ionised form and has a large steady state distribution volume of 2-3 L/kg body weight.
Ciprofloxacin reaches high concentrations in a variety of tissues such as lung (epithelial fluid,
alveolar macrophages, biopsy tissue), sinuses, inflamed lesions (cantharides blister fluid), and
the urogenital tract (urine, prostate, endometrium) where total concentrations exceeding those
of plasma concentrations are reached.
Metabolism
Low concentrations of four metabolites have been reported, which were identified as:
desethyleneciprofloxacin (M 1), sulphociprofloxacin (M 2), oxociprofloxacin (M 3) and
formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a
lower degree than the parent compound.
Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 iso-enzymes.
Elimination
Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, faecally.
Excretion of ciprofloxacin (% of dose)

Ciprofloxacin
Metabolites (M1-M4)

Intrevenous Administration
Urine
Faeces
61.5
15.2
9.5
2.6

Renal clearance is between 180-300 mL/kg/h and the total body clearance is between 480-600
mL/kg/h. Ciprofloxacin undergoes both glomerular filtration and tubular secretion. Severely
impaired renal function leads to increased half lives of ciprofloxacin of up to 12 h.
Non-renal clearance of ciprofloxacin is mainly due to active trans-intestinal secretion and
metabolism. 1% of the dose is excreted via the biliary route. Ciprofloxacin is present in the bile
in high concentrations.
Paediatric patients
The pharmacokinetic data in paediatric patients are limited.
In a study in children Cmax and AUC were not age-dependent (above one year of age). No
notable increase in Cmax and AUC upon multiple dosing (10 mg/kg three times daily) was
observed.
In 10 children with severe sepsis Cmax was 6.1 mg/L (range 4.6-8.3 mg/L) after a 1-hour
intravenous infusion of 10 mg/kg in children aged less than 1 year compared to 7.2 mg/L (range
4.7-11.8 mg/L) for children between 1 and 5 years of age. The AUC values were 17.4 mg*h/L
(range 11.8-32.0 mg*h/L) and 16.5 mg*h/L (range 11.0-23.8 mg*h/L) in the respective age
groups.
These values are within the range reported for adults at therapeutic doses. Based on population
pharmacokinetic analysis of paediatric patients with various infections, the predicted mean halflife in children is approx. 4-5 hours and the bioavailability of the oral suspension ranges from
50 to 80%.
5.3. Preclinical safety data
Non-clinical data reveal no special hazards for humans based on conventional studies of
single dose toxicity, repeated dose toxicity, carcinogenic potential, or toxicity to reproduction.
Like a number of other quinolones, ciprofloxacin is phototoxic in animals at clinically
relevant exposure levels. Data on photomutagenicity/ photocarcinogenicity show a weak
photomutagenic or phototumorigenic effect of ciprofloxacin in-vitro and in animal
experiments. This effect was comparable to that of other gyrase inhibitors.
Articular tolerability:
As reported for other gyrase inhibitors, ciprofloxacin causes damage to the large weightbearing joints in immature animals. The extent of the cartilage damage varies according to
age, species and dose; the damage can be reduced by taking the weight off the joints. Studies
with mature animals (rat, dog) revealed no evidence of cartilage lesions. In a study in young
beagle dogs, ciprofloxacin caused severe articular changes at therapeutic doses after two
weeks of treatment, which were still observed after 5 months.
6. Pharmaceutical Particulars
6.1. List of excipients
Lactic Acid, Sodium Chloride, Hydrochloric Acid (for pH adjustment) and Water for
Injections.
6.2. Incompatibilities

Ciprofloxacin 2mg/ml Solution for Infusion is incompatible with injection solutions (e.g.
penicillins, heparin solutions) which are chemically or physically unstable at its pH of 3.9 –
4.5. Unless compatibility is proven, the infusion should always be administered separately.
This medical product must not be mixed with other medicinal products except those
mentioned in section 6.6.
6.3. Shelf life
3 years.
Following dilution, as outlined in section 6.6, chemical and physical in-use stability has been
demonstrated for 4 hours at 25°C. From a microbiological point of view, the product should
be used immediately. If not used immediately, the in-use storage times and conditions prior to
use are the
responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless
dilution has taken place in controlled and validated aseptic conditions.
6.4. Special precautions for storage
Do not refrigerate or freeze.
Keep container in the outer carton.
For storage conditions of the diluted medicinal product, see section 6.3.
6.5. Nature and contents of container
Vials (glass type 1) containing 50ml, 100ml or 200ml of solution with a rubber stopper and
aluminium cap, with a cardboard outer. Not all pack sizes may be marketed.
6.6. Instruction for disposal and other handling
Ciprofloxacin 2mg/ml Solution for Infusion has been shown to be compatible with Ringer’s
solution, 0.9% sodium chloride solution, 5% and 10% glucose solutions, glucose/saline and
fructose 10% solution. For single use only.
Discard any unused portion of the product immediately after use. If the product is
inadvertently refrigerated, crystals may form.
Do not use if crystals are present. These crystals will, however, redissolve at room
temperature and do not adversely affect the quality of the product.
7. Marketing Authorisation Holder
PLIVA Pharma Ltd
Vision House
Bedford Road
Petersfield
Hampshire, GU32 3QB
United Kingdom.
8. Marketing Authorisation Number(s)
PL 10622/0072
PA 585/10/4
9. Date of First Authorisation/Renewal of the Authorisation

UK 29/07/03
IE 10/08/07
10. Date of Revision of the Text
To be completed upon approval.

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