Ciprofloxacin (AFT)

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Ciprofloxacin lactate 2.653 mg/mL equivalent to Ciprofloxacin 2 mg/mL
Available from:
Baxter Healthcare Ltd
INN (International Name):
Ciprofloxacin lactate 2.653 mg/mL (equivalent to Ciprofloxacin 2 mg/mL)
Dosage:
0.2% w/v
Pharmaceutical form:
Solution for infusion
Composition:
Active: Ciprofloxacin lactate 2.653 mg/mL equivalent to Ciprofloxacin 2 mg/mL Excipient: Hydrochloric acid Lactic acid Sodium chloride Water for injection
Units in package:
Bottle, glass, Clear Type II colourless bottle with grey bromobutyl rubber closure 50 mL, 50 mL
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Mylan Laboratories Limited
Product summary:
Package - Contents - Shelf Life: Bottle, glass, Clear Type II colourless bottle with grey bromobutyl rubber closure 50 mL - 50 mL - 36 months from date of manufacture stored at or below 30°C protect from light. do not freeze - Bottle, glass, Clear Type II colourless bottle with grey bromobutyl rubber closure 100 mL - 100 mL - 36 months from date of manufacture stored at or below 30°C protect from light. do not freeze - Bottle, glass, Clear Type II colourless bottle with grey bromobutyl rubber closure 200 mL - 200 mL - 36 months from date of manufacture stored at or below 30°C protect from light. do not freeze
Authorization number:
TT50-7768
Authorization date:
2006-07-13

NEW ZEALAND DATA SHEET

CIPROFLOXACIN Data Sheet 14 March 2018 Page 1 of 12

Baxter Healthcare Ltd

1 CIPROFLOXACIN (0.2%w/v, solution for infusion)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active ingredient

Ciprofloxacin lactate 2.653mg/mL (equivalent to ciprofloxacin 2mg/mL).

For the full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

Solution for infusion.

CIPROFLOXACIN 2mg/mL is a clear, colourless to slightly yellow infusion solution containing

ciprofloxacin lactate equivalent to 2mg of ciprofloxacin per mL.

The pH of CIPROFLOXACIN solution for infusion is 3.9 ‐ 4.5.

4 CLINICAL PARTICULARS

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 and prostatitis.

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

peritonitis).

Infections of the skin and soft tissue.

Infections of the bones and joints.

Sepsis.

Inhalation 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.

Children

For the treatment

of acute pulmonary exacerbation of cystic fibrosis associated with

P. aeruginosa infection in paediatric patients aged 5 ‐ 17 years.

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 ‐ 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 and/or surrounding tissues. The use of CIPROFLOXACIN for other

indications is not recommended in children.

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Dose and method of administration

CIPROFLOXACIN solution for infusion should be administered by intravenous infusion over a period of

60 minutes. Slow infusion into a large vein will minimize patient discomfort and reduce the risk of

venous irritation. The infusion solution can be infused either directly or after mixing with compatible

infusion solutions.

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

solution must always be administered separately. The visual signs of incompatibility include

precipitation, clouding and discolouration.

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

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

solutions adjusted to an alkaline pH. The pH of CIPROFLOXACIN solution is 3.9 ‐ 4.5.

Dosage in adults

Unless otherwise prescribed the following guideline doses are recommended:

Respiratory tract infection

200 ‐ 400mg at 12‐hourly intervals depending upon severity and organism

Urinary tract infections

Acute, uncomplicated ‐ 100mg at 12‐hourly intervals

Cystitis in women (before menopause) ‐ a single dose of 100mg

Complicated ‐ 200mg at 12‐hourly intervals

Gonorrhoea

Extragenital ‐ 100mg at 12‐hourly intervals

Acute, uncomplicated ‐ a single dose of 100mg

Diarrhoea

200mg at 12‐hourly intervals

Other infections (see section 4.1)

200 ‐ 400mg at

12‐hourly intervals

Severe, life threatening infections e.g. Streptococcal pneumonia, recurrent infections in cystic fibrosis,

bone and joint infections, septicaemia, peritonitis. In particular, when Pseudomonas, Staphylococcus

or Streptococcus is present

400mg at 8‐hourly intervals

Inhalation anthrax (post exposure)

400mg at 12‐hourly intervals. CIPROFLOXACIN solution for infusion administration should begin as

soon as possible after suspected or confirmed exposure.

Dosage in elderly

Elderly patients should receive as low a dose as possible depending on the

severity of their illness and

the creatinine clearance.

Dosage in children

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

(aged 5 ‐ 17 years) with acute pulmonary exacerbation associated with P. aeruginosa infection, at a

dose of 10mg/kg i.v. three times daily with a maximum daily dose of 1200mg.

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Baxter Healthcare Ltd

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 intravenous infusion dose is 10mg/kg twice daily (not to exceed a

maximum dose of

400mg per dose, 800mg per day). CIPROFLOXACIN solution for infusion administration should begin

as soon as possible after suspected or confirmed exposure.

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

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

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 the clinical symptoms.

Mean duration of treatment

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)

7 ‐ 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 be treated for a minimum of 10 days.

Duration of treatment in children

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

paediatric patents aged 5 ‐ 17 years the duration of treatment is 10 ‐ 14 days.

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

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

10 ‐ 21 days.

Renal impairment

Where creatinine clearance is between 31 ‐ 60mL/min/1.73m

or where the serum creatinine

concentration is between 1.4 ‐ 1.9mg/100mL the maximum daily dose for an intravenous regimen

should be 800mg per day.

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

or where the serum creatinine

concentration is equal to or greater than 2.0mg/100mL the maximum daily dose for an intravenous

regimen should be 400mg per day.

Where the patient has renal impairment and is receiving dialysis the dose for an intravenous regimen

should be 400mg per day and after dialysis

on dialysis days. Where the patient has renal impairment

plus CAPD, CIPROFLOXACIN infusion should be added to the intraperitoneal dialysate at the rate of

50mg ciprofloxacin per litre dialysate administered every 6 hours.

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

Hepatic impairment

No dose adjustment is required for impaired liver function.

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Baxter Healthcare Ltd

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

Contraindications

Hypersensitivity to ciprofloxacin or other quinolone chemotherapeutics.

Concurrent administration of ciprofloxacin and tizanidine is contraindicated because an undesirable

increase in serum tizanidine concentrations associated with

clinically relevant tizanidine‐induced side

effects (hypotension, somnolence, drowsiness) can occur.

Ciprofloxacin must not be prescribed for pregnant women or nursing mothers as there is no

experience regarding safety in these patient groups and on the basis of animal studies, it is possible

that the medicine may cause damage to

articular cartilage in the foetus or infant. Animal studies

have not shown any evidence of teratogenic effects. When considering treatment for inhalational

anthrax (post‐exposure), the risks and benefits of ciprofloxacin and alternative antibiotic therapies

must be carefully considered, and explained to the patient.

Special warnings and precautions for use

Ciprofloxacin is associated with cases of QT prolongation (see section 4.8). In general, elderly patients

maybe more susceptible to medicine‐associated effects on the QT interval. Precautions should be

taken when using ciprofloxacin with concomitant medicines that can result in prolongation with the

QT interval (e.g., class IA or III anti‐arrhythmics) or in patients with risk factors for torsades de pointes

(e.g., known QT prolongation, uncorrected hypokalaemia).

Ciprofloxacin may cause tendonitis, tendon rupture or hypoglycaemia. The risk of tendonitis or

tendon rupture is increased in patients: over the age of 60 years; on concomitant systemic steroid

therapy; who have received a kidney, heart or lung transplant. Ciprofloxacin should not be used in

patients with a history of fluoroquinolone associated tendonopathy. Tendonitis and tendon rupture

risk is present during use and for 6 months following use of ciprofloxacin. Prescribers should advise

patients that at the first sign of tendon pain, inflammation or tendon rupture, to stop using

ciprofloxacin, avoid exercise or use of the affected area and immediately contact their doctor.

Paediatric use

Ciprofloxacin has been shown to cause arthropathy in weight‐bearing joints of immature animals.

Analysis of available 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 medicine 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 ‐ 17 years),

complicated urinary tract infections and pyelonephritis due to E. coli (children aged 1 ‐ 17 years) and

for the use in inhalation anthrax (post‐exposure) was not studies. 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.

Cytochrome P450

Ciprofloxacin is

a moderate inhibitor of the CYP 450 1A2 enzymes. Care should be taken when other

medicines are administered concomitantly which are metabolised via the same enzymatic pathway

e.g. theophylline, methylxantines, caffeine. Increased plasma concentrations associated with

medicine specific side effects may be observed due to inhibition of their metabolic clearance by

ciprofloxacin.

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Gastrointestinal system

A doctor must be consulted in the event of severe or persistent diarrhoea during or after treatment,

because of the possibility that this may be concealing pseudomembraneous colitis with a potentially

fatal outcome. In such cases, ciprofloxacin must be discontinued and appropriate therapy (e.g. oral

vancomycin 4 x 250mg daily) initiated. Medicines that inhibit peristalsis are contraindicated.

A temporary increase in transaminases, alkaline phosphatase or cholestatic jaundice may occur

especially in patients with previous hepatic damage.

Nervous system

Ciprofloxacin should only be used in epileptics and patients who have

suffered from previous CNS‐

disorders e.g. lowered convulsion threshold, previous history of convulsion, reduced cerebral blood

flow, altered brain structure or stroke, where the benefits exceed the risks due to possible central‐

nervous effects. In some cases CNS reactions occurred after the first administration of ciprofloxacin.

In rare cases, depression or psychosis can progress to self‐endangering behaviour. In these cases

ciprofloxacin is to be discontinued immediately.

Hypersensitivity

Hypersensitivity and allergic reactions have occurred after the first administration. The doctor should

be informed immediately.

Anaphylactic/anaphylactoid reactions can progress to a life‐threatening shock. Ciprofloxacin should

be discontinued in these cases and appropriate medical treatment started.

Injection site reaction

Local I.V. site reactions have been reported with the intravenous administration of Ciprofloxacin.

These reactions occur more frequently if the infusion time is 30 minutes or less. They 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.

Musculo‐skeletal system

At any sign of tendonitis, e.g. the administration of ciprofloxacin should be discontinued, physical

exercise avoided and a physician consulted. Tendon rupture (predominantly the Achilles tendon) has

been reported predominantly in the elderly on prior systemic treatment with glucocortocoids.

Skin and appendages

Ciprofloxacin can cause photosensitivity reactions. Patients should avoid direct exposure to excessive

sunlight or UV‐light. Therapy should be discontinued if photo‐ sensitisation occurs.

Hypoglycaemia

Hypoglycaemia has been noted with enoxacin lomefloxacin but it is not known whether it occurs with

ciprofloxacin.

Sodium load

The additional sodium load should be taken into account when using ciprofloxacin

in patients where

sodium intake is restricted e.g. patients with congestive heart failure, renal failure, nephritic

syndrome. Each 100mL of CIPROFLOXACIN infusion contains 900mg of sodium chloride.

Interaction with other medicines and other forms of interaction

Class IA or III antiarrhythmics

Precautions should be taken when using ciprofloxacin together with class IA or III antiarrhythmics as

ciprofloxacin may have an additive effect on the QT interval.

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Concurrent administration of ciprofloxacin and theophylline can cause an increase in the serum

theophylline concentration. This can result in theophylline induced side effects which in rare cases

may be life threatening or fatal. If concurrent use of the

two products is unavoidable, the serum

theophylline concentration should be monitored and the theophylline dose reduced as appropriate.

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

and some NSAIDs (not acetylsalicylic acid) can cause convulsions.

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

were administered simultaneously. Serum creatinine concentrations should be monitored twice

weekly in these patients.

The simultaneous administration of ciprofloxacin and warfarin may intensify the action of warfarin.

Concurrent administration of ciprofloxacin and glibenclamide may cause hypoglycaemia.

Probenicid interferes with the renal secretion of ciprofloxacin. Co‐administration of probenicid and

Ciprofloxacin increases ciprofloxacin serum concentrations. Renal tubular transport of methotrexate

may be inhibited by concomitant administration of Ciprofloxacin potentially leading to increased

plasma levels of methotrexate. This may increase the risk of methotrexate associated toxic reactions.

Patients receiving methotrexate therapy should be carefully monitored when concomitant

ciprofloxacin therapy is indicated.

Tizanidine serum concentrations increase with concomitant administration of Ciprofloxacin with an

associated potentiated hypotensive and sedative effect. Tizanidine must not be administered

together with ciprofloxacin.

Fertility, pregnancy and lactation

Fertility

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

4.3.

Pregnancy (Category B3)

Ciprofloxacin must

not be prescribed for pregnant women since there is no experience on the

medicine's safety in these patient groups and since, on the basis of animal studies, it is possible that

the medicine could cause damage to articular cartilage in the foetus or infant. Also see section 4.3.

Lactation

Ciprofloxacin must not be prescribed for nursing mothers, since there is no experience on the

medicine's safety in these patient groups and since, on the basis of animal studies, it is possible that

the medicine could cause damage to articular cartilage in the foetus or infant. Also see section 4.3.

Effects on ability to drive and use machines

Ciprofloxacin can affect the speed of reaction to such an extent that the ability to drive or operate

machinery is impaired. This is particularly true when Ciprofloxacin is taken in combination with

alcohol.

Undesirable effects

The most common adverse effects that have been observed during clinical studies and spontaneous

reporting (both oral and parenteral) are as follows:

Digestive System

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Incidence ≥1% and <10%: nausea, diarrhoea.

Incidence ≥0.1% and <1%: SGOT increased, SGPT increased, vomiting, dyspepsia, abnormal liver

function test, alkaline phosphatase increased, anorexia, flatulence, bilirubinemia.

Incidence ≥0.01% and <0.1%: moniliasis (oral), jaundice, cholestatic jaundice, pseudomembranous

colitis.

Incidence <0.01%: moniliasis (gastrointestinal), hepatitis, liver necrosis (very rarely progressing to life‐

threatening hepatic failure), life threatening pseudomembranous colitis with possible fatal outcome.

Skin and appendages

Incidence ≥1% and <10%: rash.

Incidence ≥0.1% and <1%: pruritus, maculopapular rash, urticaria.

Incidence ≥0.01% and <0.1%: photosensitivity reaction.

Incidence <0.01%: petechiae, erythema multiforme (minor), erythema nodosum, fixed eruption,

Stevens‐Johnson‐Syndrome, epidermal necrolysis (Lyell‐Syndrome).

Body as a Whole

Incidence ≥0.1% and <1%: abdominal pain, moniliasis, asthenia (general feeling of weakness,

tiredness).

Incidence ≥0.01% and <0.1%: pain, pain in extremities, back pain, chest pain.

Cardiovascular

Incidence ≥0.1% and <1%: thrombophlebitis.

Incidence ≥0.01% and <0.1%: tachycardia, migraine, syncope (fainting), vasodilatation (hot flushes),

hypotension.

Incidence <0.01%: vasculitis (petechiae, haemorrhagic bullae, papules, crust formation).

Incidence of Frequency Unknown: QT prolongation, ventricular arrhythmia, torsades de pointes.

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).

Haemic and Lymphatic System

Incidence ≥0.1% and <1%:

eosinophilia, leucopoenia.

Incidence ≥0.01% and <0.1%: anaemia, leucopoenia (granulocytopenia), leucocytosis, altered

prothrombin values, thrombocytopenia, thrombocytemia (thrombocytosis).

Incidence <0.01%: haemolytic anaemia, petechiae (punctuate skin haemorrhages), pancytopenia (life‐

threatening), bone marrow, depression (life‐threatening), agranulocytosis.

Injection Site Reaction

Incidence ≥0.1% and <1%: injection site reaction.

Metabolic Disorders

Incidence ≥0.1% and <1%: creatinine increased, BUN (urea) increased.

Incidence

≥0.01% and <0.1%: oedema (peripheral, vascular, face), hyperglycaemia.

Musculo‐Skeletal System

Incidence ≥0.1% and <1%: arthralgia (joint pain).

Incidence ≥0.01% and <0.1%: myalgia (muscular pain), joint disorder (joint swelling).

Incidence <0.01%: myasthenia, tendinitis (predominantly achillotendinitis); partial or complete

tendon rupture (predominantly achilles tendon), exacerbation of symptoms of myasthenia gravis.

Nervous System

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Incidence ≥0.1% and <1%: headache, dizziness, insomnia, agitation, confusion Incidence ≥0.01% and

<0.1%: hallucination, sweating, paresthesia (peripheral paralgesia), anxiety, abnormal dreams

(nightmares), depression, tremor (trembling), convulsion, hypaesthesia.

Incidence <0.01%: grand mal convulsion, abnormal (unsteady) gait, psychosis, intracranial

hypertension,

ataxia, hypertonia, twitching.

Special Senses

Incidence ≥0.1% and <1%: taste perversion.

Incidence ≥0.01% and <0.1%: tinnitus, transitory deafness (especially at high frequencies), abnormal

vision (visual disturbances), diplopia, chromatopsia, taste loss (impaired taste).

Incidence <0.01%: parosmia (impaired smell) anosmia (usually reversible on discontinuation).

Hypersensitivity

Incidence ≥0.01% and <0.1%: allergic reaction, drug fever, anaphylactoid (anaphylactic) reaction.

Incidence <0.01%: shock (anaphylactic; life threatening), pruritic rash, serum sickness like reaction.

Respiratory System

Incidence ≥0.01% and <0.1%: dyspnea, larynx oedema.

Urogenital System

Incidence ≥0.01% and <0.1%: acute kidney failure, kidney function abnormal, vaginal moniliasis,

haematuria, crystalluria, nephritis interstitial.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It

allows

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

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

Overdose

In addition to normal emergency measures, it is recommended that renal function be monitored.

Less than 10% of Ciprofloxacin is removed from the body after haemodialysis or peritoneal dialysis.

For advice on the management of overdose please contact the National Poisons Centre on phone

number: 0800 764 766 [0800 POISON] in New Zealand (or 131126 in Australia).

5 PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

Pharmacotherapeutic group

Antiinfectives for systemic use, Antivirals for systemic use, Direct acting antivirals, Nucleosides and

nucleotides excl. reverse transcriptase inhibitors.

ATC code

J05AB01.

Actions

Ciprofloxacin is a synthetic carboxyquinolone derivative with broad spectrum antibacterial activity. It

acts by inhibiting the A subunit of DNA gyrase (topoisomerase) which is essential in the reproduction

of bacterial DNA. Resistance to ciprofloxacin develops slowly and in stages.

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Plasmid‐mediated resistance development of the kind that occurs with β‐lactam antibiotics,

aminoglycosides and tetracyclines has not been observed with ciprofloxacin. It is of clinical interest

that plasmid‐carrying bacteria are also completely sensitive to ciprofloxacin.

Parallel resistance to other active substance groups such as β‐lactam antibiotics, aminoglycosides,

tetracyclines, macrolide or peptide antibiotics, sulphonamides, trimethoprim or nitrofuran derivatives

is not generally seen with ciprofloxacin. Ciprofloxacin is effective on pathogens resistant to the above

mentioned groups of antibiotics.

Parallel resistance is observed within the group of gyrase inhibitors. However because of the high

primary sensitivity to ciprofloxacin shown by most organisms, parallel resistance is less pronounced

with this medicine, Ciprofloxacin is often effective on pathogens that are resistant to the less effective

gyrase inhibitors.

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, Neisseria,

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

The following show varying degrees of sensitivity:

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,

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.

Ciprofloxacin is less active when tested in acidic pH. The inoculum size has little effect when tested in

vitro. Minimal bactericidal concentration (MBC) is generally not more than double the minimal

inhibitory concentration (MIC).

In vitro studies have

shown that additive activity often results when ciprofloxacin is used in

combination with other agents e.g. β‐lactams, aminogylcosides, clindamycin, metronidazole.

Pharmacokinetic properties

Pharmacokinetics

Immediately following a 30 minute I.V. infusion of ciprofloxacin 200mg serum concentrations average

3µg/mL. During the first hour after completion of infusion serum concentration decreases to

approximately 30% of the peak value but after that serum concentrations decline with a half‐life of

approximately 4 hours.

Time (post dose)

End of

Infusion

0.5 hours

1 hour

3 hours

6 hours

8 hours

12 hours

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Serum

concentration

(microgram/mL)

Pharmacokinetics of ciprofloxacin are linear over the dose range 100 ‐ 400mg administered

intravenously.

Approximately 50 ‐ 70% of an intravenous dose is excreted unchanged in the urine. During the first 2

hours after a 200mg IV dose, the urine concentration of ciprofloxacin usually exceeds 200µg.

Comparison of the pharmacokinetic parameters for a twice daily and three times daily i.v. dose

regimen indicated no evidence of medicine accumulation for ciprofloxacin and its metabolites.

Metabolism

Four metabolites, desethyleneciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3) and

formylciprofloxacon (M4) have been identified in human urine, which together account for

approximately 12% of an intravenous dose. The metabolites

have less antimicrobial activity than

unchanged ciprofloxacin.

Excretion

Urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal

clearance of ciprofloxacin is approximately 18L/hour which exceeds the normal glomerular filtration

rate of 7.2L/hour. Therefore, active tubular secretion would seem to play a significant role in its

elimination.

Although bile concentrations of ciprofloxacin are 3 ‐ 4 times higher than serum concentrations after

intravenous dosing less than 1% is recovered from bile as unchanged medicine. A further 1 ‐ 2% of

the dose is recovered from bile in the form of metabolites.

Approximately 15% of an intravenous dose is recovered

from the faeces within 5 days after dosing.

Distribution

Protein binding of ciprofloxacin is low (20 ‐ 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 ‐ 3L/kg body weight shows that ciprofloxacin penetrates into tissues

resulting in concentrations which clearly exceed the corresponding serum levels.

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. In 10 children with severe sepsis, less

than 1 year of age C

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

dose level of 10mg/kg; and 7.2mg/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 ‐

23.8mg*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 approx. 4 ‐ 5 hours.

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Elderly patients

The higher levels of ciprofloxacin and its metabolites seen in elderly patients are possibly due to

reduced renal function and volume of distribution.

Impaired Renal Function

In patients with creatinine clearance 21 ‐ 40mL/minutes, the half‐life of ciprofloxacin is slightly

prolonged but dosage adjustments are not usually required.

In patients with creatinine clearance < 20mL/minute, the half‐life is nearly doubled and dosage

adjustments are necessary. Serum metabolite concentrations (especially M2 and M3) are higher than

in patients with normal renal function.

Preclinical safety data

Please refer to the following sections 4.3, 4.4, 4.5 and 4.6 for findings in the non‐clinical testing.

6 PHARMACEUTICAL PARTICULARS

List of excipients

Lactic acid

Sodium hydrochloride

Hydrochloric acid and

Water for Injection.

Incompatibilities

If compatibility with other infusible solutions or medication has not been established, ciprofloxacin

must be administered separately. Visible incompatibility indicators are sedimentation, turbidity and

discolouration.

Incompatibility appears with all infusion solutions/medicines that are physically or

chemically unstable

at the pH of the solution e.g. penicillins and heparin solutions, especially in combination with

solutions adjusted to an alkaline pH. The pH of CIPROFLOXACIN solution for infusion is 3.9 ‐ 4.5.

Compatible solutions are physiological saline, Ringer solution and Ringer lactate solution, 5% and 10%

dextrose solutions, 10%

fructose solution and 5% dextrose solution with 0.225% or 0.45% sodium

chloride. When CIPROFLOXACIN solution for infusions are mixed with compatible infusion solutions

they should be administered shortly after mixing for microbiological and light sensitivity reasons.

Shelf life

36 months from date of manufacture.

Special precautions for storage

Store

at or below 30°C. Protect from heat, light and moisture. Do not freeze.

The product should not be stored in a refrigerator as precipitation which will re‐dissolve at room

temperature, may occur at cool storage temperatures.

The infusion solution is photosensitive therefore the product should only be removed from the carton

immediately before use.

Nature and contents of container

CIPROFLOXACIN solution for infusion is available in bottles of:

50mL which contain 100mg ciprofloxacin

NEW ZEALAND DATA SHEET

CIPROFLOXACIN Data Sheet 14 March 2018 Page 12 of 12

Baxter Healthcare Ltd

100mL which contain 200mg ciprofloxacin and

200mL which contain 400mg ciprofloxacin.

Package quantities

50mL:

Packs of 1 vial which are packed into a carton of 6 packs

100mL and 200mL:

Packs of 1 vial.

Special precautions for disposal and other handling

Disposal

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

7 MEDICINE SCHEDULE

Prescription only medicine.

8 SPONSOR

CIPROFLOXACIN is distributed in New Zealand by:

Baxter Healthcare Ltd

33 Vestey Drive

Mt Wellington

Auckland 1060.

Baxter Healthcare Ltd

PO Box 14 062

Panmure

Auckland 1741

Phone (09) 574 2400.

9 DATE OF FIRST APPROVAL

Date of publication in the New Zealand Gazette of consent to distribute the medicine:

19 October 2006.

10 DATE OF REVISION OF THE TEXT

14 March 2018.

SUMMARY TABLE OF CHANGES

Section changed

Summary of new information

Data sheet converted to SPC format.

Sponsor details updated.

Date of revision, and footer date updated.

Please refer to the Medsafe website (www.medsafe.govt.nz) for most recent data sheet.

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