Cipflox

New Zealand - English - Medsafe (Medicines Safety Authority)

Buy It Now

Active ingredient:
Ciprofloxacin hydrochloride 277.5 mg equivalent to ciprofloxacin 250 mg (anhydrous);  ;  
Available from:
Mylan New Zealand Ltd
INN (International Name):
Ciprofloxacin hydrochloride 277.5 mg (equivalent to ciprofloxacin 250 mg; anhydrous)
Dosage:
250 mg
Pharmaceutical form:
Film coated tablet
Composition:
Active: Ciprofloxacin hydrochloride 277.5 mg equivalent to ciprofloxacin 250 mg (anhydrous)     Excipient: Colloidal silicon dioxide Crospovidone Hypromellose Macrogols Magnesium stearate Maize starch Microcrystalline cellulose Opadry white Y-22-7719 Polydextrose Pregelatinised maize starch Purified water Titanium dioxide Triacetin
Units in package:
Blister pack, PVC/PVDC/Al foil, 14 tablets
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Neuland Laboratories Limited
Therapeutic indications:
For complicated urinary tract infections or pyelonephritis due to E.coli in paediatric patients aged 1-17 years. The risk-benefit assessment indicates that administration of ciprofloxacin to paediatric patients is appropriate. Treatment should only be initiated after careful benefit/risk evaluation, due to possible adverse events related to joints/surrounding tissues. The use of ciprofloxacin for other indications is not recommended in children.
Product summary:
Package - Contents - Shelf Life: Blister pack, PVC/PVDC/Al foil - 14 tablets - 36 months from date of manufacture stored at or below 25°C - Blister pack, PVC/PVDC/Al foil - 28 tablets - 36 months from date of manufacture stored at or below 25°C
Authorization number:
TT50-6617
Authorization date:
2000-08-01

Page 1 of 5

NEW ZEALAND CONSUMER MEDICINE INFORMATION

CIPFLOX

Ciprofloxacin film coated tablets

250 mg, 500 mg and 750 mg

What is in this leaflet

Please read this leaflet carefully

before you start taking CIPFLOX.

This leaflet answers some common

questions about CIPFLOX tablets.

It 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 CIPFLOX

against the benefits it is expected to

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 CIPFLOX is

used for

CIPFLOX is used to treat infections

of the

bronchial tubes and lungs,

skin,

bones and joints,

kidneys,

bladder,

genital organs including

prostate,

abdomen,

blood.

CIPFLOX is also used to treat

inhalational anthrax (an infection

caused by breathing in the spores

of bacteria).

CIPFLOX tablets contain the active

ingredient ciprofloxacin. It belongs

to a group of antibiotics called

quinolones.

These antibiotics work by killing the

bacteria that are causing your

infection.

Your doctor may have prescribed it

for another reason.

Ask your doctor if you have any

questions about why this

medicine has been prescribed for

you.

CIPFLOX is available only with a

doctor’s prescription.

There is no evidence that CIPFLOX

is addictive.

Before you take

CIPFLOX

When you must not take

it

Do not take CIPFLOX if you have

an allergy to:

ciprofloxacin or any other

ingredients listed at the end

of this leaflet

any of the other quinolone

antibiotics, including

nalidixic acid, moxifloxacin

and norfloxacin.

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 CIPFLOX if you are

taking a medicine called

tizanidine, a muscle relaxant

used to treat spasticity

associated with multiple

sclerosis, injury or diseases of

the spinal cord. CIPFLOX can

interfere with tizanidine and this can

lead to undesirable side effects.

Do not take this medicine after

the expiry date printed on the

pack or if the packaging is torn or

shows signs of tampering.

If it has expired or 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

CIPFLOX

Tell your doctor if you have

allergies to any other medicines,

foods, preservatives or dyes.

Tell your doctor if you have or

have had any of the following

medical conditions:

fits, seizures or convulsions

stroke or reduced blood

flow in the brain

liver or kidney disease or

other medical problems

if you are taking

corticosteroids. You may be

at increased risk of damage

of the tendons. Symptoms

include pain, swelling and

sometimes restricted

movement.

any heart conditions such

as heart attack (myocardial

infarction) or heart failure

fast, slow or irregular

heartbeat (arrhythmias), or

congenital long QT

syndrome. CIPFLOX may

increase the risk of

arrhythmias.

uncorrected electrolyte

imbalances such as low

potassium or magnesium

levels

myasthenia gravis, a

condition where the

Page 2 of 5

muscles become weak.

CIPFLOX can make the

symptoms of this condition

worse

tendon problems such as

inflamed or ruptured

tendons, especially when

these occurred with the use

of quinolones (such as

naladixic acid, norfloxacin

or moxifloxacin)

aortic aneurysm

Marfan syndrome, Ehlers-

Danlos syndrome

(disorders that affects the

connective tissue)

inflamed blood vessels

high blood pressure

narrow blood vessels.

Tell your doctor if you are

pregnant or plan to become

pregnant. CIPFLOX is not

recommended if you are pregnant

as safety in pregnancy has not been

established. Your doctor can

discuss with you the risks and

benefits involved.

Tell your doctor if you are breast

feeding. The use of CIPFLOX is not

recommended during breast feeding

as CIPFLOX is excreted into the

breast milk. Talk to you doctor

about whether you should take

CIPFLOX and temporarily stop

breastfeeding while taking the

tablets.

Do not give CIPFLOX to children

under 18 years of age unless you

are told to do so by a doctor.

If you have not told your doctor

about any of the above, tell them

before you start taking CIPFLOX.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including medicines

that you buy without a

prescription from your pharmacy,

supermarket or health food shop.

You should also tell any health

professional who is prescribing a

new medication for you that you are

taking CIPFLOX.

Some medicines may interfere with

CIPFLOX. These include:

corticosteroids

anti-arrhythmic medicines used

to help control heart rhythm

tricyclic antidepressant, such as

amitriptyline or nortriptyline

antipsychotic medicines used to

treat mental health disorders

erythromycin, roxithromycin or

other macrolide antibiotics used

to treat infections

multivitamins, mineral

supplements and other

medicines containing iron, zinc,

magnesium, aluminium or

calcium

antacids, medicines used to

treat indigestion, heartburn or

upset stomachs

sucralfate, a medicine used to

treat duodenal or stomach

ulcers

omeprazole, a medicine used to

treat ulcers and other conditions

where the stomach produces

too much acid

medicines used to treat high

levels of phosphates in patients

with kidney diseases such as

sevelamer or lanthanum

carbonate

metoclopramide, a medicine

used to relieve nausea and

vomiting

didanosine, a medicine used to

treat viral infections.

probenecid, a medicine used to

treat gout

theophylline, a medicine used

to treat asthma

caffeine containing products

pentoxifylline, a medicine used

to treat muscle pain

phenytoin, a medicine used to

control seizures (epilepsy)

NSAIDs, medicines used to

relieve pain, swelling and other

symptoms of inflammation,

including arthritis

cyclosporin, an

immunosuppressant medicine

used to help prevent organ

transplant rejection

medicines used to stop blood

clots such as warfarin,

acenocoumarol,

phenprocoumon or fluindione

methotrexate, a medicine used

to treat certain types of cancers,

severe psoriasis and severe

rheumatoid arthritis

metoclopramide, a medicine

used to treat slow gastric

emptying in people with

diabetes

medicines used to treat

diabetes such as glibenclamide

or glimepiride

tizanidine, a medicine used to

treat spasticity

duloxetine, a medicine used to

treat depression, anxiety and

stress urinary incontinence

ropinirole, a medicine used to

treat Parkinson’s Disease

lidocaine, a local anaesthetic

and medicine used to treat

arrhythmias

clozapine, a medicine used to

treat schizophrenia

sildenafil, a medicine used to

treat erectile dysfunction

agomelatine, a medicine used

to treat depression

zolpidem, a medicine used to

treat insomnia.

These medicines may be affected

by CIPFLOX or may affect how well

it works. You may need different

amounts of your medicines, or you

may need to take different

medicines.

Your doctor and pharmacist have

more information on medicines to

be careful with or avoid while taking

CIPFLOX.

How to take

CIPFLOX

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 on the label, ask

your doctor or pharmacist for

help.

How much to take

Your doctor will tell you how much

CIPFLOX you need to take each

day. It is important that you take

CIPFLOX as directed by your

doctor. Do not take more than the

recommended dose.

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

Page 3 of 5

doctor as it depends upon the type

of infection you have.

The dosage for children depends on

your child’s body weight. Your

doctor or pharmacist will advise you

on the dosing for your child.

How to take it

Swallow CIPFLOX 100 mg, 250

mg and 750 mg tablets whole

with a glass of water or other

fluid. Scored CIPFLOX 500 mg

tablets may be halved and

swallowed with a glass of water.

Do not take CIPFLOX with milk,

yoghurt or other products very high

in calcium; otherwise CIPFLOX will

not be absorbed completely from

the stomach.

However, if milk, yoghurt or other

high calcium products are

ingredients of a meal, they will NOT

interfere with CIPFLOX absorption.

When to take it

Take your medicine at about the

same time each day.

Taking it at the same time each day

will have the best effect. It will also

help you remember when to take it.

It does not matter if you take this

medicine before or after food.

If you need to take multivitamins,

mineral supplements, other

medicines containing iron, zinc,

magnesium, aluminium or

calcium, antacids, sucralfate,

omeprazole, sevelamer,

metoclopramide, didanosine or

lanthanum carbonate, take them

at least 1 to 2 hours before or 4

hours after your dose of

CIPFLOX.

How long to take it

Continue taking CIPFLOX until

you have finished all the tablets

or for as long as your doctor tells

you to.

The length of treatment may vary

from 1 to 28 days or longer

depending on the type of infection.

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 or get

worse. You might also develop

resistance to the antibiotic.

Check with your doctor if you are

unsure how long you should take

CIPFLOX for.

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 to

take your medicine, ask your

pharmacist for some hints.

While you are taking

CIPFLOX

Things you must do

If you are about to be started on

any new medicine, remind your

doctor and pharmacist that you

are taking CIPFLOX.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are taking CIPFLOX.

If you are going to have a

surgical or dental procedure, tell

the surgeon, anaesthetist or

dentist that you are taking

CIPFLOX.

It may affect other medicines used

during the procedure.

If you become pregnant while

taking this medicine, tell your

doctor immediately.

If you are about to have any

blood or culture tests, tell your

doctor that you are taking this

medicine.

It may interfere with the results of

some tests.

Drink plenty of water while taking

CIPFLOX. This helps stop crystals

forming in the urine.

If you develop diarrhoea, tell your

doctor or pharmacist immediately

– even if it occurs several weeks

after you have stopped taking

CIPFLOX. 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. CIPFLOX should be

discontinued immediately.

Things you must not do

Do not take CIPFLOX to treat any

other complaints unless your

doctor tells you to.

Do not give your CIPFLOX to

anyone else, even if they have

the same condition as you.

Do not stop taking your tablets or

lower the dosage without

checking with your doctor.

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

CIPFLOX immediately and tell your

doctor.

Be careful driving or operating

machinery until you know how

CIPFLOX affects you.

This medicine may cause dizziness,

headache, tremors, blurred vision

and numbness in some patients.

Your ability to drive or operate

machinery may be impaired. If you

drink alcohol while taking this

medicine the symptoms may be

worse.

Children should be careful when

riding bicycles or climbing trees.

Page 4 of 5

Be careful when drinking alcohol

while you are given this

medicine. If you drink alcohol while

being given this medicine dizziness,

headache, tremors, blurred vision,

numbness or light-headedness may

be worse. CIPFLOX may increase

the stimulatory effects of caffeine.

In case of overdose

If you take too much

(overdose)

Immediately telephone your

doctor or the National Poisons

Information Centre (telephone

0800 POISON or 0800 764 766), or

go to Accident and Emergency at

your nearest hospital, if you think

that you or anyone else may have

taken too much CIPFLOX. Do this

even if there are no signs of

discomfort or poisoning. You may

need urgent medical attention.

Symptoms of an overdose may

include cloudy urine.

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not

feel well while you are taking

CIPFLOX.

This medicine helps most people

with a bacterial infection but it may

have unwanted side effects in a few

people.

If you are elderly you may have an

increased chance of getting side

effects.

All medicines can have side

effects. Sometimes they are

serious, most of the time they are

not. You may need medical

attention if you get some of the

side effects.

Ask your doctor or pharmacist to

answer any questions you may

have.

Tell your doctor or pharmacist if

you notice any of the following

and they worry you:

nausea or vomiting

headache, dizziness or light

headedness

flatulence

dyspepsia (heartburn)

loss of appetite

itching, hives or rash

agitation

anxiety

sleep disorders

altered taste and/or smell

swollen and/or painful joints

muscle pain

nonspecific pain, numbness

or weakness

feeling unwell, fever

sweating

burning, tingling or

numbness

feeling of skin pricking,

tingling or creeping when

there is no visible cause

decreased or increased

sense of feeling, especially

in the skin

looking pale

sore throat

red spots under the skin.

The above list includes some of the

more common side effects of your

CIPFLOX.

If any of the following happen,

tell your doctor immediately or

go to Accident and Emergency at

your nearest hospital:

severe skin rashes, peeling

or blistering of the skin

swelling of the face, lips,

mouth or throat which may

cause difficulties in

swallowing or breathing

unusual bleeding or

bruising

fainting

yellowing of the skin and

eyes, also called jaundice

dark urine or pale stools

diarrhoea which may be

waterly or bloody with

stomach pain and fever -

even if it occurs several

weeks after taking your

tablets

fits (seizures, convulsions)

and tremors

fast or irregular heart beats

confusion, disorientation,

depression, abnormal

dreams, hallucinations, and

psychotic reactions (even

progressing to self-injuring

behaviour or thoughts of

suicide)

wheezing or difficulty in

breathing

shortness of breath

visual disturbances

ringing in the ear, loss of

hearing, hearing impairment

bleeding or bruising more

easily than normal

abdominal, chest or back

pains

enlarged lymph nodes

disturbed coordination

little or no urine

bloody urine

cloudy urine.

The above list includes very serious

side effects. You may need urgent

medical attention or hospitalisation.

Photosensitivity (getting skin

reactions more easily after sun

exposure) can occur with CIPFLOX.

Staying out of direct sunlight while

on CIPFLOX will help to prevent it

from happening.

Rarely, tendons, (particularly the

Achilles tendon which extends from

the calf to the foot) have torn or

become inflamed after taking

CIPFLOX – sometimes as much as

6 months later. Tell your doctor

immediately if a tendon becomes

painful and stiff, and sometimes hot,

swollen and red.

Rarely, there can be a worsening of

the symptoms of myasthenia gravis.

This is a condition where the

muscles become weak and tire

easily, causing droopy eyelids,

double vision, difficulty in speaking

and swallowing, and sometimes

muscle weakness in the arms and

legs. Tell your doctor if you have

any concerns.

Rarely, you may experience

hyperglycaemia (high blood sugar).

Symptoms include increased thirst,

increased appetite and increased

frequency of urination. Tell your

doctor if you experience these

symptoms.

Some people taking anti-diabetic

medicines may experience

hypoglycaemia (low blood sugar).

Symptoms may include sweating,

weakness, hunger, dizziness,

trembling and a fast heartbeat. Tell

your doctor if you experience these

symptoms.

Tell your doctor or pharmacist if

you notice anything that is

Page 5 of 5

making you feel unwell.

Other side effects not listed above

may also occur in some people. Tell

your doctor if you notice any other

effects.

Some of the side effects (for

example, increased liver enzymes,

changes in numbers of blood cells

and changes in your blood

pressure) can only be found when

your doctor does tests from time to

time to check your progress.

Do not be alarmed by these lists

of possible side effects. You may

not experience any of them.

After using CIPFLOX

Storage

Keep your tablets in the bottle or

blister pack until it is time to take

them.

If you take the tablets out of the

bottle or 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 CIPFLOX or any other

medicine in the bathroom or near a

sink. Do not leave it on a window sill

or in the car.

Heat and dampness can destroy

some medicines.

Keep it where children cannot

reach it.

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 this medicine or the expiry

date has passed, ask your

pharmacist what to do with any

medicine that is left over.

Product description

What CIPFLOX looks like

CIPFLOX 250 mg: a white bi-

convex round film coated tablet

marked “CF” and “250” on either

side of the score line on one side

and “G” on the other side.

CIPFLOX 500 mg in blisters: a

white bi-convex capsule shaped film

coated tablet marked “CF” and

“500” on either side of the score line

on one side and “G” on the other

side. Scored CIPFLOX 500 mg

tablets may be halved.

CIPFLOX 500 mg in bottles: a

white bi-convex capsule shaped film

coated tablet marked “CF 500” on

one side and “G” on the other side.

Unscored CIPFLOX 500 mg tablets

must not be halved.

CIPFLOX 750 mg: a white bi-

convex capsule shaped film coated

tablet marked “CF” and “750” on

either side of the score line on one

side and “G” on the other side.

Ingredients

Active ingredient:

CIPFLOX tablets contain the active

ingredient ciprofloxacin.

Inactive ingredients:

The tablets also contain:

microcrystalline cellulose

maize starch

crospovidone

pregelatinised maize starch

colloidal silicon dioxide

magnesium stearate

hypromellose

titanium dioxide

polydextrose

glycerol triacetate

macrogol.

This medicine does not contain

lactose, sucrose, gluten, tartrazine

or any other azo dyes.

If you want to know

more

Should you have any questions

regarding this product, please

contact your pharmacist or doctor.

Who supplies CIPFLOX

CIPFLOX is supplied in New

Zealand by:

Mylan New Zealand Ltd,

PO Box 11183,

Ellerslie,

Auckland

NEW ZEALAND

Telephone: (09) 579 2792

Date of Information

22 August 2019

(Based on datasheet dated

22 August 2019)

Page 1 of 23

NEW ZEALAND DATA SHEET

CIPFLOX

1. Product Name

CIPFLOX,100 mg, 250 mg, 500 mg and 750 mg, film-coated tablets.

CIPFLOX INFUSION, 2 mg/mL, solution for infusion.

2. Qualitative and Quantitative Composition

Each film-coated tablet contains 100 mg, 250 mg, 500 mg or 750 mg of ciprofloxacin.

Each 100 mL bag of infusion contains 200 mg of ciprofloxacin and each 200 mL bag of infusion

contains 400 mg of ciprofloxacin.

For the full list of excipients, see section 6.1.

This product is not able to deliver all approved dose regimens.

3. Pharmaceutical Form

CIPFLOX 100 mg tablets: White bi-convex round, film-coated tablets marked “CF” on one side and

“G” on the other side.

CIPFLOX 250 mg tablets: White bi-convex round, film-coated tablets marked “CF”, “250” on either

side of a score line on one side and “G” on the other side. The score line is not intended for breaking

the tablet.

CIPFLOX 500 mg tablets in blisters: White bi-convex capsule shaped, film-coated tablets marked

“CF”, “500” on either side of a score line on one side and “G” on the other side. Scored CIPFLOX

500 mg tablets can be divided into equal doses.

CIPFLOX 500 mg tablets in bottles: White bi-convex capsule shaped, film-coated tablets debossed

with “G” on one side of the tablet and “CF 500” on the other side. Unscored CIPFLOX 500 mg tablets

must not be halved.

CIPFLOX 750 mg tablets: White bi-convex capsule shaped, film-coated tablets marked “CF”, “750”

on either side of a score line on one side and “G” on the other side. The score line is not intended

for breaking the tablet.

CIPFLOX INFUSION, 2 mg/mL infusion: Clear, odourless, sterile solution in a plastic bag. The pH-

value of the solution for infusion ranges from 3.5 to 4.6.

Page 2 of 23

4. Clinical Particulars

4.1

Therapeutic indications

Adults

Uncomplicated and complicated infections caused by ciprofloxacin sensitive pathogens:

Infections of the lower respiratory tract.

In the treatment of outpatients with pneumonia due to Pneumococcus, ciprofloxacin should not be

used as a medicine of first choice. Ciprofloxacin can be regarded as a suitable treatment for

pneumonias caused by Klebsiella, Enterobacter, Proteus, E. coli, Pseudomonas, Haemophilus,

Branhamella, Legionella, and Staphylococcus

Infections of the kidneys and/or the efferent urinary tract.

Infections of the genital organs, including adnexitis, gonorrhoea, prostatitis.

Infections of the abdominal cavity (e.g. infections of the gastrointestinal tract or of the biliary tract,

peritonitis).

Infections of the skin and soft tissue.

Infections of the bones and joints.

Sepsis.

Inhalational anthrax (post-exposure): To reduce the incidence or progression of disease following

exposure to aerosolized 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.

According to in vitro investigations, the following pathogens can be regarded as sensitive:

E. coli, Shigella, Salmonella, Citrobacter, Klebsiella, Enterobacter, Serratia, Hafnia, Edwardsiella,

Proteus (indole-positive and indole-negative), Providencia, Morganella, Yersinia; Vibrio, Aeromonas,

Plesiomonas, Pasteurella, Haemophilus, Campylobacter, Pseudomonas, Legionella, Moraxella,

Acinetobacter, Brucella; Staphylococcus, Listeria, Corynebacterium, Chlamydia.

The following show varying degrees of sensitivity:

Neisseria,

Gardnerella,

Flavobacterium,

Alcaligenes,

Streptococcus

agalactiae,

Enterococcus

faecalis,

Streptococcus

pyogenes,

Streptococcus

pneumoniae,

Viridans

group

Streptococci,

Mycoplasma hominis, Mycobacterium tuberculosis, and Mycobacterium fortuitum.

The following are usually resistant:

Enterococcus faecium, Ureaplasma urealyticum, Nocardia asteroides.

With a few exceptions anaerobes are moderately sensitive e.g. Peptococcus, Peptostreptococcus

to resistant e.g. Bacteroides.

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 ineffective against Treponema pallidum.

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

Page 3 of 23

gives only an approximate guidance whether microorganisms will be susceptible for ciprofloxacin or

not.

Consideration should be given to available official guidance on the appropriate use of antibacterial

agents.

Children

Cystic fibrosis

For the treatment of acute pulmonary exacerbation of cystic fibrosis associated with P. aeruginosa

infection in paediatric patients aged 5 to 17 years.

Inhalational anthrax (post-exposure)

For the indication of inhalational anthrax (post-exposure).

Complicated urinary tract infections and pyelonephritis

For complicated urinary tract infections or pyelonephritis due to E.coli in paediatric patients aged 1

to 17 years.

The risk-benefit assessment indicates that administration of ciprofloxacin to paediatric patients is

appropriate. Treatment should only be initiated after careful benefit/risk evaluation, due to possible

adverse events related to joints/surrounding tissues. The use of ciprofloxacin for other indications is

not recommended in children.

4.2

Dose and method of administration

Dose

Adults

Unless otherwise prescribed, the following guideline doses are recommended:

Tablets

Intravenous

Respiratory tract infection

(according to severity and organism)

2 x 250 - 500 mg

2 x 200 - 400 mg

Urinary tract infections:

- acute, uncomplicated

1 - 2 x 250 mg

2 x 100mg

- cystitis in women (before menopause)

single dose 250 mg

single dose 100 mg

- complicated

2 x 250 - 500 mg

2 x 200 mg

Gonorrhoea

- extragenital

1 x 250 mg

2 x 100 mg

- acute, uncomplicated

single dose 250 mg

single dose 100 mg

Diarrhoea

1 - 2 x 500 mg

2 x 200 mg

Other infections

(see section 4.1)

2 x 500 mg

2 x 200 - 400 mg

Particularly severe, life threatening infections,

i.e.

-Streptococcal pneumonia

-Recurrent infections in cystic fibrosis

-Bone and joint infections

-Septicaemia

-Peritonitis

In particular when Pseudomonas,

Staphylococcus or Streptococcus is present

2 x 750 mg

3 x 400 mg

Inhalational anthrax (post-exposure)

2 x 500 mg

2 x 400 mg

Page 4 of 23

Drug administration should begin as soon as

possible after suspected or confirmed exposure

Special populations

Paediatric

Cystic Fibrosis

Clinical and pharmacokinetic data support the use of ciprofloxacin in paediatric cystic fibrosis

patients (aged 5 to 17 years) with acute pulmonary exacerbation associated with P. aeruginosa

infection, at a dose of 20 mg/kg orally twice daily (maximum daily dose 1500 mg) or 10 mg/kg i.v.

three times daily (maximum dose 1200 mg).

Inhalational anthrax (post-exposure)

For the indication of inhalational anthrax (post-exposure), the risk-benefit assessment indicates that

treatment of paediatric patients with ciprofloxacin is appropriate. For paediatric patients, the

recommended oral dose is 15 mg/kg twice daily (not to exceed a maximum dose of 500 mg per dose,

1000 mg per day). For intravenous infusion, the recommended dose is 10 mg/kg twice daily (not to

exceed a maximum dose of 400 mg per dose, 800 mg per day). Drug administration should begin

as soon as possible after suspected or confirmed exposure.

Complicated urinary tract infections and pyelonephritis

For the indication of complicated urinary tract infections and pyelonephritis, the recommended dose

is 6 to 10 mg/kg i.v. every 8 hours with a maximum of 400 mg per dose or 10 to 20 mg/kg orally

every 12 hours with a maximum of 750 mg per dose.

Elderly

Elderly patients should receive a dose as low as possible depending on the severity of their illness

and the creatinine clearance.

Renal and hepatic impairment

Adults

Impaired renal function

1.1. Where creatinine clearance is between 30 and 60 mL/min/1.73 m

or where the serum

creatinine concentration is between 1.4 and 1.9 mg/100 mL the maximum daily dose should

be 1000 mg per day for oral administration or 800 mg per day for an intravenous regimen.

1.2. Where creatinine clearance is equal or is less than 30 mL/min/1.73 m

or where the serum

creatinine concentration is equal or higher than 2.0 mg/100 mL the maximum daily dose

should be 500 mg per day for oral administration or 400 mg per day for an intravenous

regimen.

Impaired renal function + haemodialysis

Dose as in 1.2; on dialysis days after dialysis.

Impaired renal function + continuous ambulatory peritoneal dialysis (CAPD)

3.1. Addition

ciprofloxacin

infusion

solution

dialysate

(intraperitoneal):

ciprofloxacin / litre dialysate administered 4 times a day every 6 hours.

3.2. Administration of ciprofloxacin film coated tablets (oral) as 1 x 500 mg film coated tablet (or

2 x 250 mg film coated tablets).

Impaired liver function.

No dose adjustment is required.

Impaired renal and liver function

Dose adjustment as in 1.1 and 1.2

Page 5 of 23

Children

Dosing in children with impaired renal and or hepatic function has not been studied.

Method of administration

Oral

CIPFLOX 100 mg, 250 mg and 750 mg tablets should be swallowed whole with a small amount of

fluid. Unscored CIPFLOX 500 mg tablets must also be swallowed whole with a small amount of

liquid. Scored CIPFLOX 500 mg tablets may be halved and swallowed with a small amount of liquid.

Tablets can be taken independent of mealtimes. If the tablets are taken on an empty stomach, the

active substance is absorbed more rapidly. In this case, tablets should not be taken concurrently

with dairy products or with mineral fortified drinks alone (e.g. milk, yoghurt, calcium fortified orange

juice). However, dietary calcium as part of a meal does not significantly affect ciprofloxacin

absorption.

If the patient is unable to take the tablets because of the severity of the illness or for other reasons,

it is recommended to commence the therapy with an intravenous form of ciprofloxacin. After

intravenous administration the treatment can be continued orally.

Intravenous

Ciprofloxacin should be administered by intravenous infusion over a period of 60 minutes. 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.

Unless compatibility with other infusion solutions/drugs has been confirmed, the infusion solution

must always be administered separately. The visual signs of incompatibility are e.g. precipitation,

clouding, and discolouration.

Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at

the pH of the solution (e.g. penicillins, heparin solutions), especially in combination with solutions

adjusted to an alkaline pH (pH of the ciprofloxacin infusion solutions: 3.5 - 4.6). Only clear solutions

are to be used.

Duration of treatment

The duration of treatment depends on the severity of the illness and on the clinical and bacteriological

course. It is essential to continue therapy for at least 3 days after disappearance of the fever or of

the clinical symptoms.

Mean duration of treatment:

Adults

1 day for acute uncomplicated gonorrhoea and cystitis

up to 7 days for infections of the kidneys, urinary tract, and abdominal cavity

a maximum of 2 months in osteomyelitis

60 days in inhalational anthrax (post-exposure)

and 7 to 14 days in all other infections

In streptococcal infections the treatment must last at least 10 days because of the risk of late

complications.

Infections caused by Chlamydia should also be treated for a minimum of 10 days.

Page 6 of 23

Children

Cystic fibrosis

For acute pulmonary exacerbation of cystic fibrosis associated with P. aeruginosa infection in

paediatric patients (aged 5 to 17 years), the duration of treatment is 10 to 14 days.

Inhalation anthrax (post-exposure)

For inhalational anthrax (post-exposure), the duration of treatment is 60 days.

Complicated urinary tract infections and pyelonephritis

For complicated urinary tract infections or pyelonephritis due to E. coli, the duration of treatment is

10 to 21 days.

4.3

Contraindications

Hypersensitivity to ciprofloxacin or other quinolone or to any of the excipients listed in section 6.1.

Concurrent administration of ciprofloxacin and tizanidine (see section 4.5).

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 Nervous system in section 4.4) and musculoskeletal system (see Musculoskeletal

system in section 4.4).

May cause tendonitis, hypoglycaemia.

Severe infections and/or infections due to Gram-positive or anaerobic bacteria

For the treatment of severe infections, staphylococcal infections and infections involving anaerobic

bacteria, ciprofloxacin should be used in combination with an appropriate antibacterial agent.

Streptococcus pneumoniae infections

Ciprofloxacin is not recommended for treatment of pneumococcal infections due to limited efficacy

against Streptococcus pneumoniae.

Genital tract infections

Genital tract infections may be caused by fluoroquinolone-resistant Neisseria gonorrhoea isolates.

In genital tract infections thought or known to be due to N. gonorrhoea, it is particularly important to

obtain local information on the prevalence of resistance to ciprofloxacin and to confirm susceptibility

based on laboratory testing.

Cardiac disorders

Ciprofloxacin is associated with cases of QT prolongation (see section 4.8). As women tend to have

a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging

medications. Elderly patients may also be more susceptible to drug-associated effects on the QT

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) 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).

Page 7 of 23

Children and adolescents

As with medicinal products in its class, ciprofloxacin has been shown to cause arthropathy in weight-

bearing joints of immature animals (see section 4.8). The analysis of available safety data from

ciprofloxacin use in patients less than 18 years of age, the majority of whom had cystic fibrosis, did

not disclose any evidence of drug related cartilage or articular damage. The use of ciprofloxacin for

indications other than the treatment of acute pulmonary exacerbation of cystic fibrosis caused by P.

aeruginosa infection (children aged 5 to 17 years), complicated urinary tract infections and

pyelonephritis due to E.coli (children aged 1 to 17 years) and for the use in inhalational anthrax (post-

exposure) was not studied. For other indications clinical experience is limited.

For the indication of inhalational anthrax (post-exposure), the risk-benefit assessment indicates that

administration of ciprofloxacin to paediatric patients is appropriate. For information regarding

paediatric dosing in inhalational anthrax (post-exposure) (see sections 4.2 and 5.1).

Hypersensitivity

In some instances, the hypersensitivity and allergic reactions occurred after the first administration

(see section 4.8). The doctor should be informed immediately.

Anaphylactic/anaphylactoid reactions in very rare instances can progress to a life-threatening shock,

in some instances after the first administration (see section 4.8). In these cases, ciprofloxacin has to

be discontinued, medical treatment (e.g. treatment for shock) is required.

Gastrointestinal system

In the event of severe and persistent diarrhoea during or after treatment a doctor must be consulted,

since this symptom can hide a serious intestinal disease (life threatening pseudomembranous colitis

with possible fatal outcome), requiring immediate treatment (see section 4.8). In such cases

ciprofloxacin must be discontinued and appropriate therapy initiated (e.g. vancomycin, orally, 4 x

250 mg/day). Drugs that inhibit peristalsis are contraindicated in this situation.

Hepatobiliary system

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). There can be a

temporary increase in transaminases, alkaline phosphatase or cholestatic jaundice, especially in

patients with previous liver damage, who are treated with ciprofloxacin (see section 4.8).

Musculoskeletal system

Ciprofloxacin should be used with caution in patients with myasthenia gravis, because symptoms

can be exacerbated.

Tendinitis and tendon rupture (predominantly 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.

At any sign of tendinitis (e.g. painful swelling, inflammation), a physician should be consulted and

the antibiotic treatment should be discontinued. Care should be taken to keep the affected extremity

at rest and avoid any inappropriate physical exercise due to increased risk of tendon rupture.

Ciprofloxacin should be used with caution in patients with a history of tendon disorders related to

quinolone treatment.

Nervous system

Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold.

In epileptics and in patients who have suffered from previous CNS-disorders (e.g. lowered

Page 8 of 23

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 at risk because of possible undesirable CNS effects. Cases of status

epilepticus have been reported (see section 4.8). If seizures occur, ciprofloxacin should be

discontinued.

Psychiatric reactions may occur even after the first administration of fluoroquinolones, including

ciprofloxacin.

rare

cases

depression

psychotic

reactions

progress

suicidal

ideations/thoughts and self-injurious behaviour, such as attempted or completed suicide (see section

4.8). If depression, psychotic reactions, suicide-related thoughts or behavior occur, ciprofloxacin

should be discontinued and the appropriate measures instituted.

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoesthesias,

dysesthesias, or weakness have been reported in patients receiving fluoroquinolones including

ciprofloxacin. Patients under treatment with ciprofloxacin should be advised to inform their doctor

prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness

or weakness develop (see section 4.8).

Skin and appendages

Ciprofloxacin has been shown to produce photosensitivity reactions. Patients taking ciprofloxacin

should avoid direct exposure to excessive sunlight or UV-light. Therapy should be discontinued if

photosensitisation (i.e. sunburn-like skin reactions) occurs (see section 4.8).

Cytochrome P450

Ciprofloxacin is known to be a moderate inhibitor of the CYP450 1A2 enzymes. Care should be taken

when other medicinal products are administered concomitantly which are metabolised via the same

enzymatic pathway (e.g. tizanidine, theophylline, methylxantines, caffeine, duloxetine, ropinirole,

clozapine, olanzapine, agomelatine). Increased plasma concentrations associated with drug specific

undesirable effects may be observed due to inhibition of their metabolic clearance by ciprofloxacin

(see section 4.5).

Aortic aneurysm and dissection

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 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.

Injection site reaction

Local i.v. site reactions have been reported with the intravenous administration of ciprofloxacin (see

section 4.8). 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.

Interference with laboratory tests

Ciprofloxacin in vitro potency may interfere with the Mycobacterium tuberculosis culture test by

suppression of mycobacterial growth, causing false negative results in specimens from patients

currently taking ciprofloxacin.

Page 9 of 23

4.5

Interaction with other medicines and other forms of interaction

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 anti-arrhythmics, tricyclic antidepressants,

macrolides, antipsychotics) (see section 4.4).

Chelation complex formulation

The simultaneous administration of ciprofloxacin (oral) 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. didanosine tablets), containing magnesium, aluminium, or calcium reduce the absorption of

ciprofloxacin. Consequently, ciprofloxacin should be administered either 1 to 2 hours before, or at

least 4 hours after these preparations.

This restriction does not apply to antacids belonging to the class of H

receptor blockers.

Food and dairy products

The concurrent administration of dairy products or mineral fortified drinks alone (e.g. milk, yoghurt,

calcium fortified orange juice) and oral ciprofloxacin should be avoided because absorption of

ciprofloxacin may be reduced. Dietary calcium as part of a meal, however, does not significantly

affect absorption.

Probenecid

Probenecid

interferes

with

renal

secretion

ciprofloxacin.

Co-administration

probenecid

containing medicinal products and ciprofloxacin increases the ciprofloxacin serum concentrations.

Omeprazole

Concomitant administration of oral ciprofloxacin and omeprazole results in a slight reduction of C

and AUC of ciprofloxacin.

Theophylline

Concurrent administration of ciprofloxacin and theophylline containing medicinal products can cause

an undesirable increase in the serum theophylline concentration. This can lead to theophylline-

induced side effects. In very rare cases these side effects can be life threatening or fatal. If concurrent

use of the two products is unavoidable, the serum theophylline concentration should therefore be

checked and the theophylline dose appropriately reduced (see Cytochrome P450 in section 4.4).

Other xanthine derivatives

On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) containing

products, raised serum concentrations of these xanthine derivatives were reported.

Phenytoin

Altered (increased or decreased) 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

co-administration of ciprofloxacin with phenytoin.

NSAID

Animal studies have shown that the combination of very high doses of quinolones (gyrase inhibitors)

and certain non-steroidal anti-inflammatory agents (but not acetylsalicylic acid) can provoke

convulsions.

Page 10 of 23

Cyclosporine

A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and

cyclosporine were administered simultaneously. Therefore, it is necessary to monitor the serum

creatinine concentrations in these patients frequently (twice a week).

Vitamin K antagonists

Simultaneous

administration

ciprofloxacin

with

Vitamin

antagonist

augment

anticoagulant 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 normalized ratio)

is difficult to assess. The INR should be monitored frequently during and shortly after co-

administration

ciprofloxacin

with

Vitamin

antagonist

(e.g.

warfarin,

acenocoumarol,

phenprocoumon, or fluindione).

Oral anti-diabetic agents

Hypoglycaemia

been

reported

when

ciprofloxacin

and oral

anti-diabetic agents,

mainly

sulfonylureas (e.g. glibenclamide, glimepiride), where co-administered, presumably by intensifying

the action of the oral anti-diabetic agent (see section 4.8).

Methotrexate

Renal

tubular

transport

methotrexate

inhibited

concomitant

administration

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.

Metoclopramide

Metoclopramide accelerates the absorption of ciprofloxacin (oral) resulting in a shorter time to reach

maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.

Tizanidine

In a clinical study in healthy subjects, there was an increase in tizanidine serum concentrations (C

increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given

concomitantly with ciprofloxacin. Associated with the increased serum concentrations was a

potentiated hypotensive and sedative effect (see Cytochrome P450 in section 4.4). Tizanidine must

not be administered together with ciprofloxacin (see section 4.3).

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 C

duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar

effects can be expected upon concomitant administration (see Cytochrome P450 in section 4.4).

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 C

and AUC of ropinirole of 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

Cytochrome P450 in section 4.4).

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.

Page 11 of 23

Clozapine

Following concomitant administration of 250 mg ciprofloxacin for 7 days, serum concentration of

clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical

surveillance

appropriate

adjustment

clozapine

dosage

during

shortly

after

administration with ciprofloxacin are advised (see Cytochrome P450 in section 4.4).

Sildenafil

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

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 of

agomelatine exposure. Although no clinical data are available for a possible interaction with

ciprofloxacin, a moderate inhibitor of CYP450 1A2, similar effects can be expected upon concomitant

administration (see Cytochrome P450 in section 4.4).

Zolpidem

Co-administration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not

recommended.

4.6

Fertility, pregnancy and lactation

Pregnancy

The data that are available from the use of ciprofloxacin in pregnant women, indicate neither

malformative nor feto/neonatal toxicity. Animal studies do not indicate reproductive toxicity. Based

on animal studies, it cannot be excluded that the drug could cause damage to articular cartilage in

immature

foetal

organism

(see

section

5.3),

therefore

ciprofloxacin

recommended during pregnancy.

Animal studies have not shown any evidence of teratogenic effects (malformations) (see section

5.3).

Breast-feeding

Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, the use of

ciprofloxacin is not recommended during breast-feeding (see section 5.3).

Fertility

Fertility studies in rats

Fertility, the intrauterine and postnatal development of the young, and the fertility of F1 generation

were not affected by ciprofloxacin.

Embryotoxicity studies

These yielded no evidence of any embryotoxic or teratogenic action of ciprofloxacin.

Perinatal and postnatal development in rats

No effects on the perinatal or postnatal development of the animals were detected. At the end of the

rearing period histological investigations did not bring to light any sign of articular damage in the

young.

Page 12 of 23

4.7

Effects on ability to drive and use machines

Fluoroquinolones including ciprofloxacin may result in an impairment of the patient's ability to drive

or operate machinery due to CNS reactions (see section 4.8). This applies particularly in combination

with alcohol.

4.8

Undesirable effects

Adverse effects with ciprofloxacin (oral and parenteral) sorted by CIOMS III categories of frequency

are listed below.

The frequencies of Adverse Drug Reactions (ADRs) reported with ciprofloxacin are summarised in

the table below. Within each frequency grouping, undesirable effects are presented in order of

decreasing seriousness. Frequencies are defined as:

Very common (≥ 1/10)

Common

(≥ 1/100 to < 1/10)

Uncommon

(≥ 1/1000 to < 1/100)

Rare

(≥ 1/10000 to < 1/1000)

Very rare

(< 1/10000)

Not known

(cannot be estimated from the available data)

The ADRs identified only during post-marketing surveillance, and for which a frequency could not be

estimated, are listed under "not known".

System organ

class

Common

Uncommon

Rare

Very Rare

Not Known

Infections and

infestations

Mycotic

superinfections

Antibiotic

associated colitis

(very rarely with

possible fatal

outcome)

Blood and

lymphatic

system

disorders

Eosinophilia

Leukopenia,

Anaemia,

Neutropenia,

Leukocytosis,

Thrombocytopenia,

Thrombocytaemia

Haemolytic

anaemia,

Agranulocytosis,

Pancytopenia

(life-

threatening),

Bone marrow

depression (life-

threatening)

Immune system

disorders

Allergic reaction,

Allergic oedema /

angiooedema

Anaphylactic

reaction,

Anaphylactic

shock (life-

threatening),

Serum

sickness-like

reaction

Metabolism and

nutrition

disorders

Decreased

appetite and

food intake

Hyperglycaemia,

Hypoglycaemia

Psychiatric

disorders

Psychomotor

hyperactivity /

agitation

Confusion and

disorientation,

Anxiety reaction,

Abnormal dreams,

Psychotic

reactions

(potentially

culminating in

Page 13 of 23

System organ

class

Common

Uncommon

Rare

Very Rare

Not Known

Depression

(potentially

culminating in self-

injurious behavior,

such as suicidal

ideations / thoughts

and attempted or

completed suicide),

Hallucinations

self-injurious

behavior, such

as suicidal

ideations /

thoughts and

attempted or

completed

suicide)

Nervous system

disorders

Headache,

Dizziness,

Sleep disorders,

Taste disorders

Par- and

Dysaesthesia,

Hypoaesthesia,

Tremor,

Seizures (including

status epilepticus),

Vertigo

Migraine,

Disturbed

coordination,

Smell disorders,

Hyperesthesia,

Intracranial

hypertension

(pseudotumour

cerebri)

Peripheral

neuropathy and

polyneuropathy

Eye disorders

Visual disturbances

Visual colour

distortions

Ear and

labyrinth

disorders

Tinnitus,

Hearing loss

Hearing

impaired

Cardiac

disorders

Tachycardia

prolongation,

Ventricular

arrhythmia,

Torsades de

pointes

Vascular

disorders

Vasodilatation,

Hypotension,

Syncope

Vasculitis

Respiratory,

thoracic and

mediastinal

disorders

Dyspnoea

(including

asthmatic

condition)

Gastrointestinal

disorders

Nausea,

Diarrhoea

Vomiting,

Gastrointestinal

and abdominal

pains,

Dyspepsia,

Flatulence

Pancreatitis

Hepatobiliary

disorders

Increase in

transaminases,

Increased

bilirubin

Hepatic

impairment,

Jaundice,

Hepatitis (non-

infective)

Liver necrosis

(very rarely

progressing to

life-threatening

hepatic failure)

These events were reported during the post-marketing period and were observed predominantly

among patients with further risk factors for QT prolongation (see section 4.4).

Page 14 of 23

System organ

class

Common

Uncommon

Rare

Very Rare

Not Known

Skin and

subcutaneous

tissue disorders

Rash,

Pruritus,

Urticaria

Photosensitivity

reactions,

Blistering

Petechiae,

Erythema

multiforme,

Erythema

nodosum,

Stevens-

Johnson

syndrome

(potentially life-

threatening),

Toxic epidermal

necrolysis

(potentially life-

threatening)

Acute

generalised

exanthematous

pustulosis

(AGEP)

Musculoskeletal

, connective

tissue and bone

disorders

Arthralgia

Myalgia,

Arthritis,

Increased muscle

tone and cramping

Muscular

weakness,

Tendonitis,

Tendon rupture

(predominantly

Achilles

tendon),

Exacerbation of

symptoms of

myasthenia

gravis

Renal and

urinary

disorders

Renal

impairment

Renal failure,

Haematuria,

Crystalluria,

Tubulointerstitial

nephritis

General

disorders and

administration

site conditions

Injection

site

reaction

Unspecific pain,

Feeling unwell,

Fever

Oedema,

Sweating

(hyperhidrosis)

Gait disturbance

Investigations

Increase in

blood alkaline

phosphatase

Abnormal

prothrombin level,

Increased amylase

International

Normalised

Ratio (INR)

increased (in

patients treated

with Vitamin K

antagonists)

For ciprofloxacin solution for infusion only.

Page 15 of 23

The following undesirable effects have a higher frequency category in the subgroups of patients

receiving intravenous or sequential (intravenous to oral) treatment:

Common

Vomiting, Transient increase in transaminases, Rash

Uncommon

Thrombocytopenia,

Thrombocytaemia,

Confusion

disorientation,

Hallucinations,

Par-

dysaesthesia,

Seizures,

Vertigo,

Visual

disturbances,

Hearing

loss,

Tachycardia,

Vasodilatation,

Hypotension,

Transient hepatic impairment, Jaundice, Renal failure, Oedema

Rare

Pancytopenia, Bone marrow depression, Anaphylactic shock, Psychotic

reactions,

Migraine,

Smell

disorders,

Hearing

impaired,

Vasculitis,

Pancreatitis, Liver necrosis, Petechiae, Tendon rupture

Additional information on special populations

Paediatric population

The incidence of arthropathy (arthralgia, arthritis), 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 medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

4.9

Overdose

In the event of acute, excessive oral overdosage, reversible renal toxicity has been reported in some

cases.

Apart from routine emergency measures, 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 reduce the absorption of ciprofloxacin in overdoses.

Only a small quantity of ciprofloxacin (< 10%) is eliminated by haemodialysis or peritoneal dialysis.

For further advice on management of overdose please contact the National Poisons Information

Centre (0800 POISON or 0800 764 766).

5. Pharmacological Properties

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Quinolone antibacterials,

ATC code:

J01MA02

Ciprofloxacin is a synthetic broad spectrum antibacterial agent.

Mechanism of action

Ciprofloxacin is effective in vitro against a wide range of Gram-negative and Gram-positive

organisms. The bactericidal action of ciprofloxacin results from inhibition of bacterial type II

Page 16 of 23

topoisomerases (DNA gyrase and topoisomerase IV), which are required for bacterial DNA

replication, transcription, repair, and recombination.

Mechanism of resistance

In vitro resistance to ciprofloxacin is commonly due to mutations in bacterial topoisomerases and

DNA gyrase through multiple-step mutations. Single mutations may result in reduced susceptibility

rather than clinical resistance, but multiple mutations generally result in clinical resistance to

ciprofloxacin and cross-resistance across the quinolone class.

Resistance mechanisms that inactivate other antibiotics such as permeation barriers (common in

Pseudomonas

aeruginosa) and efflux

mechanisms

may affect

susceptibility

ciprofloxacin.

Plasmid-mediated resistance encoded by the qnr gene has been reported. Resistance mechanisms

that inactivate penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines may not

interfere with the antibacterial activity of ciprofloxacin and there is no known cross-resistance

between ciprofloxacin and other classes of antimicrobials. Organisms resistant to these drugs may

be susceptible to ciprofloxacin.

The minimum bactericidal concentration (MBC) generally does not exceed the minimal inhibitory

concentration (MIC) by more than a factor of 2.

In vitro susceptibility to ciprofloxacin

The prevalence of acquired resistance may vary geographically and with time for selected species

and local information of resistance is desirable, particularly when treating severe infections. As

necessary, expert advice should be sought where the local prevalence of resistance is such that

utility of the agent, in at least some types of infections, is questionable.

The bacterial genus and species listed below have been shown to commonly be susceptible

to ciprofloxacin in vitro:

Aerobic Gram-positive microorganisms

Bacillus anthracis

Staphylococcus aureus (methicillin-susceptible)

Staphylococcus saprophyticus

Streptococcus spp.

Aerobic Gram-negative microorganisms

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 microorganisms

Mobiluncus

Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

Mycoplasma hominis

Mycoplasma pneumoniae

The following microorganisms show varying degrees of susceptibility to ciprofloxacin:

Acinetobacter

baumann,

Burkholderia

cepacia,

Campylobacter

spp.,

Citrobacterfreudii,

Enterococcus faecalis, Enterobacter aerogenes, Enterobacter clocae, Escherichia coli, Klebsiella

pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis,

Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia

marcescens, Streptococcus pneumoniae, Peptostreptococcus spp., Propionibacterium acnes.

Page 17 of 23

The following microorganisms are considered inherently resistant to ciprofloxacin:

Staphylococcus aureus (methicillin-resistant) and Stenotrophomonas maltophilia, Actinomyces,

Enterococcus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealyticum,

Anaerobic microorganisms (except Mobiluncus, Peptostreptococcus, Propionibacterium acnes).

Inhalational anthrax - additional information

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 is referred to national and/or international

consensus documents regarding treatment of anthrax.

mean

serum

concentrations

ciprofloxacin

associated

with

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).

A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 11 LD

(~ 5.5 x 10

) spores (range 5 to 30 LD

) 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 T

(1hour

post-dose) following oral dosing to steady state ranged from 0.98 to 1.69 microgramg/mL. Mean

steady-state trough concentrations at 12 hours post-dose 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 post-exposure 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.

5.2

Pharmacokinetic properties

Absorption

Film-coated tablets

Following oral administration of single doses of 250 mg, 500 mg, and 750 mg of ciprofloxacin film-

coated tablets, ciprofloxacin is absorbed rapidly and extensively mainly from the small intestine,

reaching maximum serum concentrations 1 to 2 hours later.

Mean ciprofloxacin serum concentrations (mg/L)

after oral administration

[Time from tablet intake]

Time (h)

250 mg

500 mg

750 mg

12.0

The absolute bioavailability is approximately 70 to 80%. Maximum serum concentrations (C

) and

total areas under serum concentration vs. time curves (AUC) increased in proportion to dose.

Page 18 of 23

Solution for infusion

Following an intravenous infusion of ciprofloxacin the mean maximum serum concentrations were

achieved at the end of infusion. Pharmacokinetics of ciprofloxacin was linear over the dose range

up to 400 mg administered intravenously.

Mean ciprofloxacin serum concentrations

(mg/l) after intravenous administration

[Time from start of infusion (in hours)]

Time (h)

200 mg i.v. (30 min inf.)

0.50

0.75

1.40

1.00

1.00

1.50

0.70

2.50

0.50

4.50

0.30

8.50

0.10

12.50

0.10

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).

Distribution

The protein binding of ciprofloxacin is low (20 to 30%), and the substance is present in plasma largely

in a non-ionised form. Ciprofloxacin can diffuse freely into the extravascular space. The large steady-

state volume of distribution of 2 to 3 L/kg body weight shows that ciprofloxacin penetrates into tissues

resulting in concentrations which clearly exceed the corresponding serum levels.

Biotransformation

Small

concentrations

metabolites

have

been

reported.

They

were

identified

desethyleneciprofloxacin

sulphociprofloxacin

oxociprofloxacin

formylciprofloxacin (M

). M

to M

display antibacterial activity comparable to or inferior to that of

nalidixic acid. M

, with the smallest quantity, is largely equivalent to norfloxacin in its antimicrobial

activity.

Elimination

Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, non-renally.

Excretion of ciprofloxacin (% of dose)

Urine

Faeces

Oral administration

Ciprofloxacin

44.7

25.0

Metabolites (M

– M

11.3

Intravenous administration

Ciprofloxacin

61.5

15.2

Metabolites (M

– M

Page 19 of 23

Renal clearance is between 0.18 to 0.3 L/h/kg and the total body clearance between 0.48 to 0.60

L/h/kg. Ciprofloxacin undergoes both glomerular filtration and tubular secretion.

Non-renal clearance of ciprofloxacin is mainly due to active transintestinal secretion as well as

metabolisation. 1% of the dose is via the biliary excreted route. Ciprofloxacin is present in the bile in

high concentrations.

Children

In a study in children, C

and AUC were not age-dependent. No notable increase in C

and AUC

upon multiple dosing (10 mg/kg/TID) was observed. In 10 children with severe sepsis, less than 1

year of age, C

was 6.1 mg/L (range 4.6 to 8.3 mg/L) after a 1-hour intravenous infusion at a dose

level of 10 mg/kg; and 7.2 mg/L (range 4.7 to 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 to 32.0 mg*h/L) and 16.5 mg*h/L (range 11.0 to 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 half-life in children is approximately 4 to 5 hours and the bioavailability

of the oral suspension approximately 60%.

5.3

Preclinical safety data

The acute toxicity of ciprofloxacin after oral administration can be classified as very low. Depending

on the individual species, the LD

after intravenous infusion is 125 to 290 mg/kg.

Species

Mode of administration

LD

50

(mg/kg)

Mouse

p.o.

Approx. 5000

p.o.

Approx. 5000

Rabbit

p.o.

Approx. 2500

Mouse

i.v.

Approx. 290

i.v.

Approx. 145

Rabbit

i.v.

Approx. 125

i.v.

Approx. 250

Chronic Toxicity

Subacute tolerability studies over 4 weeks

Oral administration

Doses up to and including 100 mg/kg were tolerated without damage by rats. Pseudoallergic

reactions due to histamine release were observed in dogs.

Parenteral administration

In the highest-dose group in each case (rats 80 mg/kg and monkeys 30 mg/kg), crystals containing

ciprofloxacin were found in the urine sediment. There were also changes in individual renal tubules,

with typical foreign-body reactions due to crystal-like precipitates.

The tubular changes observed should not (as e.g. in the case of aminoglycosides) be interpreted as

a primary toxic effect of ciprofloxacin, but as secondary inflammatory foreign-body reactions due to

the precipitation of a crystalline complex in the distal renal tubule system (cf. also the subchronic

and chronic tolerability studies).

Subchronic toxicity studies over 3 months

Oral administration

All doses up to and including 500 mg/kg were tolerated without damage by rats. In monkeys,

crystalluria and changes in the renal tubules were observed in the highest-dose group (135 mg/kg).

Page 20 of 23

Parenteral administration

Although the changes in the renal tubules observed in rats were in some cases very slight, they were

present in every dose group. In monkeys they were found only in the highest-dose group (18 mg/kg)

and were associated with slightly reduced erythrocyte counts and haemoglobin values.

Chronic tolerability studies over 6 months

Oral administration

Doses up to and including 500 mg/kg and 30 mg/kg were tolerated without damage by rats and

monkeys, respectively. Changes in the distal renal tubules were again observed in some monkeys

in the highest-dose group (90 mg/kg).

Parenteral administration

In monkeys slightly elevated urea and creatinine concentrations and changes in the distal renal

tubules were recorded in the highest-dose group (20 mg/kg).

Carcinogenicity

In carcinogenicity studies in mice (21 months) and rats (24 months) with doses up to approx. 1000

mg/kg bw/day in mice and 125 mg/kg bw/day in rats (increased to 250 mg/kg bw/day after 22 weeks),

there was no evidence of a carcinogenic potential at any dose level.

Mutagenicity

Eight in vitro mutagenicity tests have been conducted with ciprofloxacin.

Test results are listed below:

Salmonella: Microsome Test (Negative)

E. coli: DNA Repair Assay (Negative)

Mouse Lymphoma Cell Forward Mutation Assay (Positive)

Chinese Hamster V

Cell HGPRT Test (Negative)

Syrian Hamster Embryo Cell Transformation Assay (Negative)

Saccharomyces cerev.: Point Mutation Assay (Negative), Mitotic Crossover and Gene

Conversion Assay (Negative)

Rat Hepatocyte Primary Culture DNA Repair Assay (UDS) (Positive)

Thus, two of the eight tests were positive, but results of the following four in vivo test systems gave

negative results:

Rat Hepatocyte DNA Repair Assay

Micronucleus Test (Mice)

Dominant Lethal Test (Mice)

Chinese Hamster Bone Marrow

Although two of the eight in vitro assays (i.e. the Mouse Lymphoma Cell Forward Mutation Assay

and the Rat Hepatocyte Primary Culture DNA Repair Assay [UDS]) were positive, all of the in vivo

test systems covering all relevant endpoints gave negative results.

In summary, ciprofloxacin poses no significant mutagenic potential. This assessment is confirmed

by the negative outcome of the long-term carcinogenicity studies in mice and rats.

Special tolerability studies

It is known from comparative studies in animals, both with the older gyrase inhibitors (e.g. nalidixic

and pipemidic acid) and the more recent ones (e.g. norfloxacin and ofloxacin), that this substance

class produces a characteristic damage pattern. Kidney damage, cartilage damage in weight-

bearing joints of immature animals, and eye damage may be encountered.

Page 21 of 23

Renal tolerability

The crystallisation observed in the animal studies occurred preferentially under pH conditions that

do not apply in man.

Compared to rapid infusion, a

slow infusion of ciprofloxacin reduces the danger of crystal

precipitation.

The precipitation of crystals in renal tubules does not immediately and automatically lead to kidney

damage. In the animal studies damage occurred only after high doses, with correspondingly high

levels of crystalluria. For example, although they always caused crystalluria, even high doses were

tolerated over 6 months without damage and without foreign-body reactions occurring in individual

distal renal tubules.

Damage to the kidneys without the presence of crystalluria has not been observed. The renal

damage observed in animal studies must not, therefore, as is the case e.g. with the aminoglycosides,

be regarded as a primary toxic action of ciprofloxacin on the kidney tissue, but as typical secondary

inflammatory foreign-body reactions due to the precipitation of a crystalline complex of ciprofloxacin,

magnesium, and protein.

Articular tolerability studies

As with other gyrase inhibitors, ciprofloxacin causes damage to the large, weight-bearing 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 at high doses (1.3 to 3.5

times the therapeutic dose) caused articular changes after two weeks of treatment, which were still

observed after 5 months. At therapeutic doses, no effects were observed.

Studies aimed at excluding cataractogenic effects

On the basis of the investigations it may be stated from a toxicological point of view that ciprofloxacin

treatment

does

involve

risk

cataract

induction,

particularly

because

parental

administration maximal bioavailability can be assumed and the duration of administration was 6

months.

Retina

tolerability studies

Ciprofloxacin binds to the melanin containing structures including the retina. Potential effects of

ciprofloxacin on the retina were assessed in various pigmented animal species. Ciprofloxacin

treatment had no effect on the morphological structures of the retina and on electroretinographic

findings.

6. Pharmaceutical Particulars

6.1

List of excipients

CIPFLOX tablets

CIPFLOX 100 mg, 250 mg, 500 mg and 750 mg tablets also contain

microcrystalline cellulose,

maize starch,

pregelatinised maize starch,

crospovidone,

colloidal anhydrous silica,

magnesium stearate,titanium dioxide,

polydextrose,

Page 22 of 23

hypromellose,

glycerol triacetate,

macrogol.

CIPFLOX tablets are gluten and lactose free.

CIPFLOX infusion

CIPFLOX INFUSION, 2 mg/mL solution for infusion also contains

lactic acid,

glucose monohydrate,

hydrochloric acid,

water for injection.

6.2

Incompatibilities

The ciprofloxacin infusion solution is compatible with physiological saline, Ringer solution and Ringer

lactate solution, 5% and 10% glucose solutions, 10% fructose solution, and 5% glucose solution with

0.225% NaCl or 0.45% NaCl. When ciprofloxacin infusion solutions are mixed with compatible

infusion solutions, they should be administered shortly after admixture for microbiological and light

sensitivity reasons.

Unless compatibility with other infusion solutions/drugs has been confirmed, the infusion solution

must always be administered separately. The visual signs of incompatibility are e.g. precipitation,

clouding, and discolouration. Only clear solutions are to be used.

Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at

the pH of the solution (e.g. penicillins, heparin solutions), especially in combination with solutions

adjusted to an alkaline pH (pH of the ciprofloxacin infusion solutions: 3.5 to 4.6).

6.3

Shelf life

CIPFLOX tablets

Blister pack: 3 years.

Bottle pack: 2 years.

CIPFLOX infusion

3 years.

6.4

Special precautions for storage

Store at or below 25°C.

Since the infusion solution is photosensitive, the infusion bags should be removed from the overwrap

only immediately before use.

At cool storage temperatures precipitation may occur, which will re-dissolve at room temperature. It

is therefore recommended not to store the infusion solution in a refrigerator.

6.5

Nature and contents of container

CIPFLOX tablets

Blister pack, PVC/PVDC/Al foil. Pack sizes of 14 and 28 film-coated tablets.

White HDPE bottles with white screw caps. Pack size of 100 film-coated tablets.

Blue HDPE bottle with blue child resistant closure. Pack size of 100 film-coated tablets.

Not all pack types and sizes may be marketed.

Page 23 of 23

CIPFLOX infusion

Polyolefin (non-PVC) bags with an opaque overwrap and packed in an outer carton in quantities of

10 x 100 mL and 10 x 200 mL.

Not all pack types and sizes may be marketed.

6.6

Special precautions for disposal and other handling

Any unused medicine or waste material should be disposed of in accordance with local requirements.

7. Medicines Schedule

Prescription Medicine

8. Sponsor Details

Mylan New Zealand Ltd

PO Box 11183

Ellerslie

AUCKLAND

Telephone 09-579-2792

9. Date of First Approval

19 July 2001

10. Date of Revision of the Text

22 August 2019 Summary of Changes

Section changed

Summary of changes

Minor editorial updates

Dosing for children added

Addition of aortic aneurysm and dissection

Similar products

Search alerts related to this product

Share this information