Ciprofloxacin 2 mg/ml Solution for Infusion

Summary of Product Characteristics Updated 16-Aug-2021 | Hospira UK Ltd

1. Name of the medicinal product

Ciprofloxacin 2 mg/ml solution for infusion

2. Qualitative and quantitative composition

1 ml solution for infusion contains: 2 mg ciprofloxacin (as ciprofloxacin lactate).

Excipients with known effect: 1 ml solution contains: 50 mg glucose monohydrate: equivalent to 45 mg glucose.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Solution for infusion.

Clear, colourless or slightly yellow solution.

The pH-value of the solution for infusion ranges from 3.9 to 4.5.

4. Clinical particulars
4.1 Therapeutic indications

Ciprofloxacin solution for infusion is indicated for the treatment of the following infections (see sections 4.4 and 5.1). Special attention should be paid to available information on resistance to ciprofloxacin before commencing therapy.

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


• Lower respiratory tract infections due to Gram-negative bacteria

- exacerbation of chronic obstructive pulmonary disease. In exacerbation of chronic obstructive pulmonary disease Ciprofloxacin should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections.

- broncho-pulmonary infections in cystic fibrosis or in bronchiectasis

- pneumonia

• Chronic suppurative otitis media

• Acute exacerbation of chronic sinusitis especially if these are caused by Gram-negative bacteria

• Urinary tract infections

- Acute pyelonephritis

- Complicated pyelonephritis

- Bacterial prostatitis

• Genital tract infections

- epididymo-orchitis including cases due to susceptible Neisseria gonorrhoeae

- pelvic inflammatory disease including cases due to susceptible Neisseria gonorrhoeae

• Infections of the gastrointestinal tract (e.g. travellers` diarrhoea)

• Intra-abdominal infections

• Infections of the skin and soft tissue caused by Gram-negative bacteria

• Malignant external otitis

• Infections of the bones and joints

• Inhalation anthrax (post-exposure prophylaxis and curative treatment)

Ciprofloxacin may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.

Children and adolescents

• Broncho-pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis

• Complicated urinary tract infections and acute pyelonephritis

• Inhalation anthrax (post-exposure prophylaxis and curative treatment)

Ciprofloxacin may also be used to treat severe infections in children and adolescents when this is considered to be necessary.

Treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents (see sections 4.4 and 5.1).

4.2 Posology and method of administration


The dosage is determined by the indication, the severity and the site of the infection, the susceptibility to ciprofloxacin of the causative organism(s), the renal function of the patient and, in children and adolescents the body weight.

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

After intravenous initiation of treatment, the treatment can be switched to oral treatment with tablet or suspension if clinically indicated at the discretion of the physician. IV treatment should be followed by oral route as soon as possible.

In severe cases or if the patient is unable to take tablets (e.g. patients on enteral nutrition), it is recommended to commence therapy with intravenous ciprofloxacin until a switch to oral administration is possible.

Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosa, Acinetobacter or Staphylococci) may require higher ciprofloxacin doses and co-administration with other appropriate antibacterial agents.

Treatment of some infections (e.g. pelvic inflammatory disease, intra-abdominal infections, infections in neutropenic patients and infections of bones and joints) may require co-administration with other appropriate antibacterial agents depending on the pathogens involved.



Daily dose in mg

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

Infections of the lower respiratory tract

400 mg twice daily to 400 mg three times a day

7 to 14 days

Infections of the upper respiratory tract

Acute exacerbation of chronic sinusitis

400 mg twice daily to 400 mg three times a day

7 to 14 days

Chronic suppurative otitis media

400 mg twice daily to 400 mg three times a day

7 to 14 days

Malignant external otitis

400 mg three times a day

28 days up to 3 months

Urinary tract infections

(see section 4.4)

Acute and complicated pyelonephritis

400 mg twice daily to 400 mg three times a day

7 to 21 days, it can be continued for longer than 21 days in some specific circumstances (such as abscesses)

Bacterial prostatitis

400 mg twice daily to 400 mg three times a day

2 to 4 weeks (acute)

Genital tract infections

Epididymo-orchitis and pelvic inflammatory diseases including cases due to susceptible Neisserria gonorrhoeae

400 mg twice daily to 400 mg three times a day

at least 14 days

Infections of the gastro-intestinal tract and intra-abdominal infections

Diarrhoea caused by bacterial pathogens including Shigella spp. other than Shigella dysenteriae type 1 and empirical treatment of severe travellers' diarrhoea

400 mg twice daily

1 day

Diarrhoea caused by Shigella dysenteriae type 1

400 mg twice daily

5 days

Diarrhoea caused by Vibrio cholerae

400 mg twice daily

3 days

Typhoid fever

400 mg twice daily

7 days

Intra-abdominal infections due to Gram-negative bacteria

400 mg twice daily to 400 mg three times a day

5 to 14 days

Infections of the skin and soft tissue caused by Gram-negative bacteria

400 mg twice daily to 400 mg three times a day

7 to 14 days

Bone and joint infections

400 mg twice daily to 400 mg three times a day

max. of 3 months

Neutropenic patients with fever that is suspected to be due to a bacterial infection.

Ciprofloxacin should be co-administered with appropriate antibacterial agent(s) in accordance to official guidance.

400 mg twice daily to 400 mg three times a day

Therapy should be continued over the entire period of neutropenia

Inhalation anthrax post-exposure prophylaxis and curative treatment for persons requiring parenteral treatment

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

400 mg twice daily

60 days from the confirmation of Bacillus anthracis exposure

Paediatric population


Daily dose in mg

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

Cystic fibrosis

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

10 to 14 days

Complicated urinary tract infections and acute pyelonephritis

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

10 to 21 days

Inhalation anthrax post-exposure curative treatment for persons requiring parenteral treatment

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

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

60 days from the confirmation of Bacillus anthracis exposure

Other severe infections

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

According to the type of infections

Elderly patients

Elderly patients should receive a dose selected according to the severity of the infection and the patient`s creatinine clearance.

Patients with renal and hepatic impairment

Recommended starting and maintenance doses for patients with impaired renal function:

Creatinine Clearance

[mL/min/1.73 m2]

Serum Creatinine


Intravenous Dose


> 60

< 124

See Usual Dosage.


124 to 168

200-400 mg every 12 h

< 30

> 169

200-400 mg every 24 h

Patients on haemodialysis

> 169

200-400 mg every 24 h (after dialysis)

Patients on peritoneal dialysis

> 169

200-400 mg every 24 h

In patients with impaired liver function no dose adjustment is required.

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

Method of administration

Ciprofloxacin solution for infusion should be checked visually prior to use. It must not be used if cloudy.

Ciprofloxacin should be administered by intravenous infusion. For children, the infusion duration is 60 minutes.

In adult patients, infusion time is 60 minutes for 400 mg Ciprofloxacin solution for infusion and 30 minutes for 200 mg Ciprofloxacin solution for infusion. Slow infusion into a large vein will minimise patient discomfort and reduce the risk of venous irritation.

The infusion solution can be infused either directly or after mixing with other compatible infusion solutions (see section 6.6).

4.3 Contraindications

• Hypersensitivity to the active substance, to other quinolones or to any of the excipients listed in section 6.1.

• Concomitant administration of ciprofloxacin and tizanidine (see section 4.5).

4.4 Special warnings and precautions for use

The use of ciprofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with ciprofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see section 4.3).

Severe infections and mixed infections with Gram-positive and anaerobic pathogens

Ciprofloxacin monotherapy is not suited for treatment of severe infections and infections that might be due to Gram-positive or anaerobic pathogens. In such infections ciprofloxacin must be co-administered with other appropriate antibacterial agents.

Streptococcal infections (including Streptococcus pneumoniae)

Ciprofloxacin is not recommended for the treatment of streptococcal infections due to inadequate efficacy.

Genital tract infections

Epididymo-orchitis and pelvic inflammatory diseases may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae isolates.

For epididymo-orchitis and pelvic inflammatory diseases, empirical ciprofloxacin should only be considered in combination with another appropriate antibacterial agent (e.g. a cephalosporin) unless ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.

Urinary tract infections

Resistance to fluoroquinolones of Escherichia coli – the most common pathogen involved in urinary tract infections – varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.

Intra-abdominal infections

There are limited data on the efficacy of ciprofloxacin in the treatment of post-surgical intra-abdominal infections.

Travellers' diarrhoea

The choice of ciprofloxacin should take into account information on resistance to ciprofloxacin in relevant pathogens in the countries visited.

Infections of the bones and joints

Ciprofloxacin should be used in combination with other antimicrobial agents depending on the results of the microbiological documentation.

Inhalational anthrax

Use in humans is based on in-vitro susceptibility data and on animal experimental data together with limited human data. Treating physicians should refer to national and /or international consensus documents regarding the treatment of anthrax.

Paediatric population

The use of ciprofloxacin in children and adolescents should follow available official guidance. Ciprofloxacin treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents.

Ciprofloxacin has been shown to cause arthropathy in weight-bearing joints of immature animals. Safety data from a randomised double-blind study on ciprofloxacin use in children (ciprofloxacin: n=335, mean age = 6.3 years; comparators: n=349, mean age = 6.2 years; age range = 1 to 17 years) revealed an incidence of suspected drug-related arthropathy (discerned from joint-related clinical signs and symptoms) by Day +42 of 7.2% and 4.6%. Respectively, an incidence of drug-related arthropathy by 1-year follow-up was 9.0% and 5.7%. The increase of suspected drug-related arthropathy cases over time was not statistically significant between groups. Treatment should be initiated only after a careful benefit/risk evaluation, due to possible adverse events related to joints and/or surrounding tissue (see section 4.8).

Broncho-pulmonary infections in cystic fibrosis

Clinical trials have included children and adolescents aged 5-17 years. More limited experience is available in treating children between 1 and 5 years of age.

Complicated urinary tract infections and pyelonephritis

Ciprofloxacin treatment of urinary tract infections should be considered when other treatments cannot be used, and should be based on the results of the microbiological documentation.

Clinical trials have included children and adolescents aged 1-17 years.

Other specific severe infections

Other severe infections in accordance with official guidance, or after careful benefit-risk evaluation when other treatments cannot be used, or after failure to conventional therapy and when the microbiological documentation can justify a ciprofloxacin use.

The use of ciprofloxacin for specific severe infections other than those mentioned above has not been evaluated in clinical trials and the clinical experience is limited. Consequently, caution is advised when treating patients with these infections.


Hypersensitivity and allergic reactions, including anaphylaxis and anaphylactoid reactions, may occur following a single dose (see section 4.8) and may be life-threatening. If such reaction occurs, ciprofloxacin should be discontinued and an adequate medical treatment is required.

Prolonged, disabling and potentially irreversible serious adverse drug reactions

Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Ciprofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.

Tendinitis and tendon rupture

Ciprofloxacin should generally not be used in patients with a history of tendon disease/disorder related to quinolone treatment. Nevertheless, in very rare instances, after microbiological documentation of the causative organism and evaluation of the risk/benefit balance, ciprofloxacin may be prescribed to these patients for the treatment of certain severe infections, particularly in the event of failure of the standard therapy or bacterial resistance, where the microbiological data may justify the use of ciprofloxacin.

Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment (see section 4.8). The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

At the first sign of tendinitis (e.g. painful swelling, inflammation), the treatment with ciprofloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.

Patients with myasthenia gravis

Ciprofloxacin should be used with caution in patients with myasthenia gravis, because symptoms can be exacerbated (see section 4.8).

Aortic aneurysm and dissection, and heart valve regurgitation/incompetence

Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8).

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 congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or dissection or heart valve disease, or in presence of other risk factors or conditions predisposing:

- for both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis) or additionally

- for aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome) or additionally

- for heart valve regurgitation/incompetence (e.g. infective endocarditis).

The risk of aortic aneurysm and dissection, and their rupture may also be increased in patients treated concurrently with systemic corticosteroids.

In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients should be advised to seek immediate medical attention in case of acute dyspnoea, new onset of heart palpitations, or development of oedema of the abdomen or lower extremities.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.


Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking ciprofloxacin should be advised to avoid direct exposure to either extensive sunlight or UV irradiation during treatment (see section 4.8).


Ciprofloxacin like other quinolones are known to trigger seizures or lower the seizure threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders which may be predisposed to seizure. If seizures occur ciprofloxacin should be discontinued (see section 4.8).

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypoaesthesia, dysaesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. 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 in order to prevent the development of potentially irreversible condition (see section 4.8).

Psychiatric reactions

Psychiatric reactions may occur even after first administration of ciprofloxacin. In rare cases, depression or psychosis can progress to suicidal ideations/thoughts culminating in attempted suicide or completed suicide. If depression, psychotic reactions, suicide-related thoughts or behaviour occur, ciprofloxacin should be discontinued.

Cardiac disorders

Caution should be taken when using fluoroquinolones, including ciprofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:

- congenital long QT syndrome

- concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)

- uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)

- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ciprofloxacin, in these populations. (See section 4.2 Elderly patients, section 4.5, section 4.8, section 4.9).


As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported (see section 4.8), usually in elderly diabetic patients, receiving concomitant treatment with an oral hypoglycaemic agent (e.g. glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.

Gastrointestinal system

The occurrence of severe and persistent diarrhoea during or after treatment (including several weeks after treatment) may indicate an antibiotic-associated colitis (life-threatening with possible fatal outcome), requiring immediate treatment (see section 4.8). In such cases, ciprofloxacin should immediately be discontinued, and an appropriate therapy initiated. Anti-peristaltic drugs are contraindicated in this situation.

Renal and urinary system

Crystalluria related to the use of ciprofloxacin has been reported (see section 4.8). Patients receiving ciprofloxacin should be well hydrated and excessive alkalinity of the urine should be avoided.

Impaired renal function

Since ciprofloxacin is largely excreted unchanged via renal pathway dose adjustment is needed in patients with impaired renal function as described in section 4.2 to avoid an increase in adverse drug reactions due to accumulation of ciprofloxacin.

Hepatobiliary system

Cases of hepatic necrosis and life-threatening hepatic failure have been reported with ciprofloxacin (see section 4.8). In the event of any signs and symptoms of hepatic disease (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), treatment should be discontinued.

Glucose-6-phosphate dehydrogenase deficiency

Haemolytic reactions have been reported with ciprofloxacin in patients with glucose-6-phosphate dehydrogenase deficiency. Ciprofloxacin should be avoided in these patients unless the potential benefit is considered to outweigh the possible risk. In this case, potential occurrence of haemolysis should be monitored.


During or following a course of treatment with ciprofloxacin bacteria that demonstrate resistance to ciprofloxacin may be isolated, with or without a clinically apparent superinfection. There may be a particular risk of selecting for ciprofloxacin-resistant bacteria during extended durations of treatment and when treating nosocomial infections and/or infections caused by Staphylococcus and Pseudomonas species.

Cytochrome P450

Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme (e.g. theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine, agomelatine). Therefore, patients taking these substances concomitantly with ciprofloxacin should be monitored closely for clinical signs of overdose, and determination of serum concentrations (e.g. of theophylline) may be necessary (see section 4.5). Co-administration of ciprofloxacin and tizanidine is contraindicated.


The concomitant use of ciprofloxacin with methotrexate is not recommended (see section 4.5).

Interaction with tests

The in vitro activity of ciprofloxacin against Mycobacterium tuberculosis might give false negative bacteriological test results in specimens from patients currently taking ciprofloxacin.

Injection site reaction

Local intravenous site reactions have been reported with the intravenous administration of ciprofloxacin. These reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions which resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen.

4.5 Interaction with other medicinal products and other forms of interaction

Effects of other products on ciprofloxacin

Drugs known to prolong QT interval

Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).


Probenecid interferes with renal secretion of ciprofloxacin. Co-administration of probenecid and ciprofloxacin increases ciprofloxacin serum concentrations.

Effects of ciprofloxacin on other medicinal products


Tizanidine must not be administered together with ciprofloxacin (see section 4.3). In a clinical study with healthy subjects, there was an increase in serum tizanidine concentration (Cmax increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given concomitantly with ciprofloxacin. Increased serum tizanidine concentration is associated with a potentiated hypotensive and sedative effect.


Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and increased risk of methotrexate-associated toxic reactions. The concomitant use is not recommended (see section 4.4).


Concurrent administration of ciprofloxacin and theophylline can cause an undesirable increase in serum theophylline concentration. This can lead to theophylline-induced side effects that may rarely be life-threatening or fatal. During the combination, serum theophylline concentrations should be checked and the theophylline dose reduced as necessary (see section 4.4).

Other xanthine derivatives

On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline), raised serum concentrations of these xanthine derivatives were reported.


Simultaneous administration of ciprofloxacin and phenytoin may result in increased or reduced serum levels of phenytoin such that monitoring of drug levels is recommended.


A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and cyclosporin containing medicinal products were administered simultaneously. Therefore, it is frequently (twice a week) necessary to control the serum creatinine concentrations in these patients.

Vitamin K antagonists

Simultaneous administration of ciprofloxacin with a vitamin K antagonist may augment its anti-coagulant effects. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of ciprofloxacin to the increase in INR (international normalised ratio) is difficult to assess. The INR should be monitored frequently during and shortly after co-administration of ciprofloxacin with a vitamin K antagonist (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione).


In clinical studies, it was demonstrated that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isozyme such as fluvoxamine, may result in an increase of AUC and Cmax of duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar effects can be expected upon concomitant administration (see section 4.4).


It was shown in a clinical study that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isozyme, results in an increase of Cmax and AUC of ropinirole by 60% and 84%, respectively. Monitoring of ropinirole-related side effects and dose adjustment as appropriate is recommended during and shortly after co-administration with ciprofloxacin (see section 4.4).


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


Following concomitant administration of 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical surveillance and appropriate adjustment of clozapine dosage during and shortly after co-administration with ciprofloxacin are advised (see section 4.4).


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


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 60-fold 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 section 4.4).


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

4.6 Pregnancy and lactation


The data that are available on administration of ciprofloxacin to pregnant women indicates no malformative or feto/neonatal toxicity of ciprofloxacin. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. In juvenile and prenatal animals exposed to quinolones, effects on immature cartilage have been observed, thus, it cannot be excluded that the drug could cause damage to articular cartilage in the human immature organism / foetus (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of ciprofloxacin during pregnancy.


Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, ciprofloxacin should not be used during breast-feeding.

4.7 Effects on ability to drive and use machines

Due to its neurological effects, ciprofloxacin may affect reaction time. Thus, the ability to drive or to operate machinery may be impaired.

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are nausea, diarrhoea, vomiting, transient increase in transaminases, rash, and injection and infusion site reactions.

ADRs derived from clinical studies and post-marketing surveillance with Ciprofloxacin (oral, intravenous and sequential therapy) sorted by categories of frequency are listed below. The frequency analysis takes into account data from both oral and intravenous administration of ciprofloxacin.

System Organ Class


≥ 1/100 to < 1/10


≥ 1/1,000 to < 1/100


≥ 1/10,000 to < 1/1,000

Very Rare

< 1/10,000

Frequency not known

(cannot be estimated from the available data)

Infections and Infestations

Mycotic super-infections

Blood and lymphatic system disorders








Haemolytic anaemia


Pancytopenia (life-threatening)

Bone marrow depression (life-threatening)

Immune system disorders

Allergic reaction

Allergic oedema / angioedema

Anaphylactic reaction

Anaphylactic shock (life-threatening) (see section 4.4)

Serum sickness-like reaction

Endocrine disorders

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Metabolism and nutrition disorders

Decreased appetite


Hypoglycaemia (see section 4.4)

Hypoglycaemic coma (see section 4.4)

Psychiatric disorders*

Psychomotor hyperactivity / agitation

Confusion and disorientation

Anxiety reaction

Abnormal dreams

Depression (potentially culminating in suicidal ideations/thoughts or suicide attempts and completed suicide) (see section 4.4)


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

Mania, incl. hypomania

Nervous system disorders*



Sleep disorders

Taste disorders

Par- and Dysaesthesia



Seizures (including status epilepticus see section 4.4)



Disturbed coordination

Gait disturbance

Olfactory nerve disorders

Intracranial hypertension and pseudotumor cerebri

Peripheral neuropathy and polyneur-opathy (see section 4.4)

Eye disorders*

Visual disturbances (e.g. diplopia)

Visual colour distortions

Ear and labyrinth disorders*


Hearing loss / Hearing impaired

Cardiac disorders**


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

Vascular disorders**





Respiratory, thoracic and mediastinal disorders

Dyspnoea (including asthmatic condition)

Gastrointestinal disorders




Gastrointestinal and abdominal pains



Antibiotic-associated colitis (very rarely with possible fatal outcome) (see section 4.4)


Hepatobiliary disorders

Increase in transaminases

Increased bilirubin

Hepatic impairment

Cholestatic icterus


Liver necrosis (very rarely progressing to life-threatening hepatic failure) (see section 4.4)

Skin and subcutaneous tissue disorders




Photosensitivity reactions (see section 4.4)


Erythema multiforme

Erythema nodosum

Stevens-Johnson syndrome (potentially life-threatening)

Toxic epidermal necrolysis (potentially life-threatening)

Acute Generalised Exanthematous Pustulosis (AGEP)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Musculoskeletal and connective tissue disorders*

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




Increased muscle tone and cramping

Muscular weakness


Tendon rupture (predominantly Achilles tendon) (see section 4.4)

Exacerbation of symptoms of myasthenia gravis (see section 4.4)

Renal and urinary disorders

Renal impairment

Renal failure


Crystalluria (see section 4.4)

Tubulointerstitial nephritis

General disorders and administration site conditions*

Injection and infusion site reactions (only intravenous administration)




Sweating (hyperhidrosis)


Increase in blood alkaline phosphatase

Increased amylase

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

*Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see section 4.4).

**Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).

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


Vomiting, Transient increase in transaminases, Rash


Thrombocytopenia, Thrombocytaemia, Confusion and disorientation, Hallucinations, Par- and dysaesthesia, Seizures, Vertigo, Visual disturbances, Hearing loss, Tachycardia, Vasodilatation, Hypotension, Transient hepatic impairment, Cholestatic icterus, Renal failure, Oedema


Pancytopenia, Bone marrow depression, Anaphylactic shock, Psychotic reactions, Migraine, Olfactory nerve disorders, Hearing impaired, Vasculitis, Pancreatitis, Liver necrosis, Petechiae, Tendon rupture

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 authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at; or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

An overdose of 12 g has been reported to lead to mild symptoms of toxicity. An acute overdose of 16 g has been reported to cause acute renal failure.

Symptoms in overdose consist of dizziness, tremor, headache, tiredness, seizures, hallucinations, confusion, abdominal discomfort, renal and hepatic impairment as well as crystalluria and haematuria. Reversible renal toxicity has been reported.

Apart from routine emergency measures, e.g. ventricular emptying followed by medical carbon, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria. Patients should be kept well hydrated. Calcium or magnesium containing antacids may theoretically reduce the absorption of ciprofloxacin in overdoses.

Only a small quantity of ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal dialysis. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Fluoroquinolones, ATC code: J01MA02

Mechanism of action

As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial DNA replication, transcription, repair and recombination.

Pharmacokinetic/pharmacodynamic relationship

Efficacy mainly depends on the relation between the maximum concentration in serum (Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation between the area under the curve (AUC) and the MIC.

Mechanism of resistance

In-vitro resistance to ciprofloxacin can be acquired through a stepwise process by target site mutations in both DNA gyrase and topoisomerase IV. The degree of cross-resistance between ciprofloxacin and other fluoroquinolones that results is variable. Single mutations may not result in clinical resistance, but multiple mutations generally result in clinical resistance to many or all active substances within the class.

Impermeability and/or active substance efflux pump mechanisms of resistance may have a variable effect on susceptibility to fluoroquinolones, which depends on the physiochemical properties of the various active substances within the class and the affinity of transport systems for each active substance. All in-vitro mechanisms of resistance are commonly observed in clinical isolates. Resistance mechanisms that inactivate other antibiotics such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may affect susceptibility to ciprofloxacin.

Plasmid-mediated resistance encoded by qnr-genes has been reported.

Spectrum of antibacterial activity

Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains:

EUCAST Recommendations





S ≤ 0.25 mg/L

R > 0.5 mg/L

Salmonella spp.

S ≤ 0.06 mg/L

R > 0.06 mg/L

Pseudomonas spp.

S ≤ 0.5 mg/L

R > 0.5 mg/L

Acinetobacter spp.

S ≤ 1 mg/L

R > 1 mg/L

Staphylococcus spp.1

S ≤ 1 mg/L

R > 1 mg/L

Haemophilus influenzae

S ≤ 0.06 mg/L

R > 0.06 mg/L

Moraxella catarrhalis

S ≤ 0.125 mg/L

R > 0.125 mg/L

Neisseria gonorrhoeae

S ≤ 0.03 mg/L

R > 0.06 mg/L

Neisseria meningitidis

S ≤ 0.03 mg/L

R > 0.03 mg/L

Non-species-related breakpoints*

S ≤ 0.25 mg/L

R > 0.5 mg/L

1: Staphylococcus spp. - breakpoints for ciprofloxacin relate to high dose therapy.

*: Non-species-related breakpoints have been determined mainly on the basis of PK/PD data and are independent of MIC distributions of specific species. They are for use only for species that have not been given a species-specific breakpoint and not for those species where susceptibility testing is not recommended.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Groupings of relevant species according to ciprofloxacin susceptibility (for Streptococcus species see section 4.4).


Aerobic Gram-positive micro-organisms

Bacillus anthracis (1)

Aerobic Gram-negative micro-organisms

Aeromonas spp.

Brucella spp.

Citrobacter koseri

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae*

Legionella spp.

Moraxella catarrhalis*

Neisseria meningitidis

Pasteurella spp.

Salmonella spp.*

Shigella spp.*

Vibrio spp.

Yersinia pestis

Anaerobic micro-organisms


Other micro-organisms

Chlamydia trachomatis ($)

Chlamydia pneumoniae ($)

Mycoplasma hominis ($)

Mycoplasma pneumoniae ($)


Aerobic Gram-positive micro-organisms

Enterococcus faecalis ($)

Staphylococcus spp.*(2)

Aerobic Gram-negative micro-organisms

Acinetobacter baumannii +

Burkholderia cepacia +*

Campylobacter spp.+*

Citrobacter freundii*

Enterobacter aerogenes

Enterobacter cloacae*

Escherichia coli*

Klebsiella oxytoca

Klebsiella pneumoniae*

Morganella morganii*

Neisseria gonorrhoeae*

Proteus mirabilis*

Proteus vulgaris*

Providencia spp.

Pseudomonas aeruginosa*

Pseudomonas fluorescens

Serratia marcescens*

Anaerobic micro-organisms

Peptostreptococcus spp.

Propionibacterium acne


Aerobic Gram-positive micro-organisms


Enteroccus faecium

Listeria monocytogenes

Aerobic Gram-negative micro-organisms

Stenotrophomonas maltophilia

Anaerobic micro-organisms

Excepted as listed above

Other micro-organisms

Mycoplasma genitalium

Ureaplasma urealitycum

*: Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications

+: Resistance rate ≥ 50% in one or more EU countries

($): Natural intermediate susceptibility in the absence of acquired mechanism of resistance

(1): Studies have been conducted in experimental animal infections due to inhalations of Bacillus anthracis spores; these studies reveal that antibiotics starting early after exposition avoid the occurrence of the disease if the treatment is made up to the decrease of the number of spores in the organism under the infective dose. The recommended use in human subjects is based primarily on in-vitro susceptibility and on animal experimental data together with limited human data. Two-month treatment duration in adults with oral ciprofloxacin given at the following dose, 500 mg bid, is considered as effective to prevent anthrax infection in humans. The treating physician should refer to national and/or international consensus documents regarding treatment of anthrax.

(2): Methicillin-resistant S. aureus very commonly express co-resistance to fluoroquinolones. The rate of resistance to methicillin is around 20 to 50% among all staphylococcal species and is usually higher in nosocomial isolates.

5.2 Pharmacokinetic properties


Following an intravenous infusion of ciprofloxacin the mean maximum serum concentrations were achieved at the end of infusion. Pharmacokinetics of ciprofloxacin were linear over the dose range up to 400 mg administered intravenously.

Comparison of the pharmacokinetic parameters for a twice a day and three times a day intravenous dose regimen indicated no evidence of drug accumulation for ciprofloxacin and its metabolites.

A 60-minute intravenous infusion of 200 mg ciprofloxacin or the oral administration of 250 mg ciprofloxacin, both given every 12 hours, produced an equivalent area under the serum concentration time curve (AUC).

A 60-minute intravenous infusion of 400 mg ciprofloxacin every 12 hours was bioequivalent to a 500 mg oral dose every 12 hours with regard to AUC.

The 400 mg intravenous dose administered over 60 minutes every 12 hours resulted in a Cmax similar to that observed with a 750 mg oral dose.

A 60-minute infusion of 400 mg ciprofloxacin every 8 hours is equivalent with respect to AUC to 750 mg oral regimen given every 12 hours.


Protein binding of ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma largely in a non-ionised form and has a large steady state distribution volume of 2-3 L/kg body weight. Ciprofloxacin reaches high concentrations in a variety of tissues such as lung (epithelial fluid, alveolar macrophages, biopsy tissue), sinuses, inflamed lesions (cantharides blister fluid), and the urogenital tract (urine, prostate, endometrium) where total concentrations exceeding those of plasma concentrations are reached.


Low concentrations of four metabolites have been reported, which were identified as: desethyleneciprofloxacin (M 1), sulphociprofloxacin (M 2), oxociprofloxacin (M 3) and formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a lower degree than the parent compound.

Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 iso-enzymes.


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

Excretion of ciprofloxacin (% of dose)

Intravenous Administration






Metabolites (M1-M4)



Renal clearance is between 180-300 mL/kg/h and the total body clearance is between 480-600 mL/kg/h. Ciprofloxacin undergoes both glomerular filtration and tubular secretion. Severely impaired renal function leads to increased half lives of ciprofloxacin of up to 12 h.

Non-renal clearance of ciprofloxacin is mainly due to active trans-intestinal secretion and metabolism. 1% of the dose is excreted via the biliary route. Ciprofloxacin is present in the bile in high concentrations.

Paediatric patients

The pharmacokinetic data in paediatric patients are limited.

In a study in children Cmax and AUC were not age-dependent (above one year of age). No notable increase in Cmax and AUC upon multiple dosing (10 mg/kg three times daily) was observed.

In 10 children with severe sepsis Cmax was 6.1 mg/L (range 4.6-8.3 mg/L) after a 1-hour intravenous infusion of 10 mg/kg in children aged less than 1 year compared to 7.2 mg/L (range 4.7-11.8 mg/L) for children between 1 and 5 years of age. The AUC values were 17.4 mg*h/L (range 11.8-32.0 mg*h/L) and 16.5 mg*h/L (range 11.0-23.8 mg*h/L) in the respective age groups.

These values are within the range reported for adults at therapeutic doses. Based on population pharmacokinetic analysis of paediatric patients with various infections, the predicted mean half-life in children is approx. 4-5 hours and the bioavailability of the oral suspension ranges from 50 to 80%.

5.3 Preclinical safety data

Non-clinical data reveal no special hazards for humans based on conventional studies of single dose toxicity, repeated dose toxicity, carcinogenic potential, or toxicity to reproduction.

Like a number of other quinolones, ciprofloxacin is phototoxic in animals at clinically relevant exposure levels. Data on photomutagenicity/ photocarcinogenicity show a weak photomutagenic or phototumorigenic effect of ciprofloxacin in-vitro and in animal experiments. This effect was comparable to that of other gyrase inhibitors.

Articular tolerability

As reported for other gyrase inhibitors, ciprofloxacin causes damage to the large 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 caused severe articular changes at therapeutic doses after two weeks of treatment, which were still observed after 5 months.

6. Pharmaceutical particulars
6.1 List of excipients

Glucose monohydrate

Lactic acid 50 %

Water for injection

Hydrochloric acid for pH adjustment

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Unless compatibility with other solutions/drugs has been confirmed, the infusion solution must always be administered separately. The visual signs of incompatibility are e.g. precipitation, clouding, and discoloration.

Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at the pH of the solutions (e.g. penicillins, heparin solutions), especially in combination with solutions adjusted to an alkaline pH (pH of ciprofloxacin solutions: 3.9 – 4.5).

6.3 Shelf life

100 mg/50 ml: 18 months

200 mg/100 ml: 24 months

400 mg/200 ml: 24 months

6.4 Special precautions for storage

Do not store above 25°C.

Do not refrigerate or freeze.

Keep infusion bag within the sealed outer foil wrap before use, in order to protect from light and evaporation.

The infusion solution must be used immediately after opening.

6.5 Nature and contents of container

Ciprofloxacin solution for infusion is supplied in transparent infusion bags (PVC or polyolefin) containing 50ml, 100ml or 200ml of sterile solution of ciprofloxacin 2 mg/ml. The bags are in an outer packaging of a double sheet of metallised polyethylene terephthalate.

Pack sizes:

5 x 50 ml, 10 x 50 ml, 50 x 50 ml

5 x 100 ml, 10 x 100 ml, 50 x 100 ml

5 x 200 ml, 10 x 200 ml, 20 x 200 ml

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Ciprofloxacin solution for infusion should be administered without mixing with any other substances or infusion fluids. Ciprofloxacin infusion has been shown to be compatible with Ringer's solution, Sodium chloride 9 mg/ml (0.9%) solution for infusion, Glucose 50 mg/ml (5%) and 100 mg/ml (10%) solution for infusion and Fructose 100 mg/ml (10%) solution for infusion when infused in parallel. Unless compatibility is proven, the infusion solution should always be administered separately.

When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbial reasons and light sensitivity these solutions must be administered shortly after admixture.

For single use only.

At cool temperatures precipitation may occur, which will re-dissolve at room temperature (15°C – 25°C).

The solution should be visually inspected for particulate matter and discoloration prior to administration. Only clear and colourless or slightly yellow solution should be used.

Any unused solution and the bags should be adequately disposed of, in accordance with local requirements.

7. Marketing authorisation holder

Hospira UK Limited


Honey Lane




United Kingdom

8. Marketing authorisation number(s)

PL 04515/0208

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 1st June 2007

Date of the last renewal: 7th April 2011

10. Date of revision of the text


Ref: UK gxCI 6_1

Company Contact Details
Hospira UK Ltd

Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, UK

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+44 (0)1304 616161


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