1. NAME OF THE MEDICINAL PRODUCT

Ciprofloxacin Intravenous Infusion BP 200mg/100ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of Infusion contains:
Ciprofloxacin BP………………….2mg

Excipients:

100ml bag: The sodium chloride content is 900mg (15.4 mmol).

For a full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Solution for infusion.

Clear, colourless solution

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Ciprofloxacin 200mg/100ml solution for infusion is indicated for the treatment of the following infections (see sections 4.4 and 5.1). Special attention should be paid to available information on resistance to ciprofloxacin before commencing therapy.

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

Adults

  • Lower respiratory tract infections due to Gram-negative bacteria

– exacerbations of chronic obstructive pulmonary disease

– 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
  • Genital tract infections

– Epididymo-orchitis including cases due to Neisseria gonorrhoeae

– Pelvic inflammatory disease including cases due to Neisseria gonorrhoeae

  • Infections of the gastro-intestinal tract (e.g. travellers` diarrhoea)
  • Intra-abdominal infections
  • Infections of the skin and soft tissue caused by Gram-negative bacteria
  • Malignant external otitis
  • Infections of the bones and joints
  • Inhalation anthrax (post-exposure prophylaxis and curative treatment)

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

Children and adolescents

  • Broncho-pulmonary infections in cystic fibrosis caused by Pseudomonas aeruginosa
  • Complicated urinary tract infections and pyelonephritis
  • Inhalation anthrax (post-exposure prophylaxis and curative treatment)

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

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

4.2 Posology and method of administration

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

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

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

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

Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosaAcinetobacter 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.

Adults

IndicationsDaily dose in mgTotal duration of treatment (including switch to oral therapy as soon as possible)
Infections of the lower respiratory tract400 mg twice daily to 400 mg three times a day7 to 14 days
Infections of the upper respiratory tractAcute exacerbation of chronic sinusitis400 mg twice daily to 400 mg three times a day7 to 14 days
Chronic suppurative otitis media400 mg twice daily to 400 mg three times a day7 to 14 days
Malignant external otitis400 mg three times a day28 days up to 3 months
Urinary tract infectionsComplicated and uncomplicated pyelonephritis400 mg twice daily to 400 mg three times a day7 to 21 days, it can be continued for longer than 21 days in some specific circumstances (such as abscesses)
Prostatitis400 mg twice daily to 400 mg three times a day2 to 4 weeks (acute)
Genital tract infectionsEpididymo-orchitis and pelvic inflammatory diseases400 mg twice daily to 400 mg three times a dayat least 14 days
Infections of the gastro-intestinal tract and intra-abdominal infectionsDiarrhoea caused by bacterial pathogens including Shigella spp. other than Shigella dysenteriae type 1 and empirical treatment of severe travellers’ diarrhoea400 mg twice daily1 day
Diarrhoea caused by Shigella dysenteriae type 1400 mg twice daily5 days
Diarrhoea caused by Vibrio cholerae400 mg twice daily3 days
Typhoid fever400 mg twice daily7 days
Intra-abdominal infections due to Gram-negative bacteria400 mg twice daily to 400 mg three times a day5 to 14 days
Infections of the skin and soft tissue400 mg twice daily to 400 mg three times a day7 to 14 days
Bone and joint infections400 mg twice daily to 400 mg three times a daymax. 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 dayTherapy 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 daily60 days from the confirmation of Bacillus anthracis exposure

Children and adolescents

IndicationDaily dose in mgTotal duration of treatment (including switch to oral therapy as soon as possible)
Cystic fibrosis10 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 pyelonephritis6 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 infections10 mg/kg body weight three times a day with a maximum of 400 mg per dose.According to the type of infections

Geriatric patients

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

Renal and hepatic impairment

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

Creatinine Clearance

[mL/min/1.73 m2]

Serum Creatinine

[µmol/L]

Intravenous Dose

[mg]

> 60< 124See Usual Dosage.
30-60124 to 168200-400 mg every 12 h
< 30> 169200-400 mg every 24 h
Patients on haemodialysis> 169200-400 mg every 24 h (after dialysis)
Patients on peritoneal dialysis> 169200-400 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 200mg/100ml 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 of Ciprofloxacin 200mg/100ml solution for infusion and 30 minutes for 200 mg of Ciprofloxacin 200mg/100ml 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 6.2).

4.3 Contraindications

  • Hypersensitivity to the active substance, to other quinolones or to any of the excipients (see section 6.1).
  • Concomitant administration of ciprofloxacin and tizanidine (see section 4.5).

4.4 Special warnings and precautions for use

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population.

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic 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.

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. 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

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

Musculoskeletal System

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

Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may occur with ciprofloxacin, even within the first 48 hours of treatment. Inflammation and ruptures of tendon may occur even up to several months after discontinuation of ciprofloxacin therapy The risk of tendinopathy may be increased in elderly patients or in patients concomitantly treated with corticosteroids (see section 4.8).

At any sign of tendinitis (e.g. painful swelling, inflammation), ciprofloxacin treatment should be discontinued. Care should be taken to keep the affected limb at rest.

Ciprofloxacin should be used with caution in patients with myasthenia gravis (see section 4.8).

Photosensitivity

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

Central Nervous System

Ciprofloxacin like other quinolones are known to trigger seizures or lower the seizure threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders which may be predisposed to seizure. If seizures occur ciprofloxacin should be discontinued (see section 4.8). Psychiatric reactions may occur even after the first administration of ciprofloxacin. In rare cases, depression or psychosis can progress to suicidal ideations/thoughts culminating in attempted suicide or completed suicide. In the occurrence of such cases, ciprofloxacin should be discontinued.

Cases of polyneuropathy (based on neurological symptoms such as pain, burning, sensory disturbances or muscle weakness, alone or in combination) have been reported in patients receiving ciprofloxacin. Ciprofloxacin should be discontinued in patients experiencing symptoms of neuropathy, including pain, burning, tingling, numbness, and/or weakness in order to prevent the development of an irreversible condition (see section 4.8).

Cardiac disorders

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

– congenital long QT syndrome

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

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

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

Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ciprofloxacin, in these populations.

(See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).

Gastrointestinal System

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

Vision disorders

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

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.

Resistance

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

Cytochrome P450

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

Methotrexate

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

Interaction with tests

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

Injection Site Reaction

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

Hypoglycaemia

As with other quinolones, hypoglycaemia has been reported most often in diabetic patients, predominantly in the elderly population. In all diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

Dysglycaemia

As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported (see section 4.8), usually in 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.

NaCl Load

This medicinal product contains 354.1 mg sodium per 100 ml, equivalent to 18 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interaction with other medicinal products and other forms of interaction

Effects of other medicinal products on ciprofloxacin:

Drugs known to prolong QT interval

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

Probenecid

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

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.

Omeprazole

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

Effects of ciprofloxacin on other medicinal products:

Tizanidine

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

Methotrexate

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

Theophylline

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

Other xanthine derivatives

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

Phenytoin

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

Cyclosporin

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

Vitamin K antagonists

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

Glibenclamide

In particular cases, concurrent administration of ciprofloxacin and glibenclamide containing medicinal products can intensify the action of glibenclamide (hypoglycaemia).

Duloxetine

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

Ropinirole

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

Lidocaine

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

Clozapine

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

Sildenafil

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

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 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 (‘Cytochrome P450’ in section ‘Special warnings and precautions for use).

Zolpidem

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

4.6 Fertility, pregnancy and lactation

Pregnancy

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

Lactation

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 ClassCommon

≥ 1/100 to < 1/10

Uncommon

≥ 1/1 000 to < 1/100

Rare

≥ 1/10 000 to < 1/1 000

Very Rare

< 1/10 000

Frequency not known

(cannot be estimated from available data)

Infections and InfestationsMycotic superinfections
Blood and Lymphatic System DisordersEosinophiliaLeukopenia

Anaemia

Neutropenia

Leukocytosis

Thrombocytopenia

Thrombocytaemia

Haemolytic anaemia

Agranulocytosis

Pancytopenia (life-threatening)

Bone marrow depression (life-threatening)

Immune System DisordersAllergic reaction

Allergic oedema / angio-oedema

Anaphylactic reaction

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

Serum sickness-like reaction

Metabolism and Nutrition DisordersDecreased appetiteHyperglycaemia

Hypoglycaemia (see section 4.4)

Psychiatric DisordersPsychomotor hyperactivity / agitationConfusion and disorientation

Anxiety reaction

Abnormal dreams

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

Hallucinations

Psychotic reactions (potentially culminating in suicidal ideations/thoughts or suicide attempts and completed suicide) (see section 4.4)Mania, hypomania
Nervous System DisordersHeadache

Dizziness

Sleep disorders

Taste disorders

Par- and Dysaesthesia

Hypoaesthesia

Tremor

Seizures (incl. status epilepticus see section 4.4)

Vertigo

Migraine

Disturbed coordination

Gait disturbance

Olfactory nerve disorders

Intracranial hypertension and pseudomotor cerebri

Peripheral neuropathy and polyneuropathy (see section 4.4)
Eye DisordersVisual disturbances e.g. diplopiaVisual colour distortions
Ear and Labyrinth DisordersTinnitus

Hearing loss / Hearing impaired

Cardiac DisordersTachycardiaVentricular arrhythmia and torsades de pointes * (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolongation (see section 4.4 and 4.9).
Vascular DisordersVasodilatation

Hypotension

Syncope

Vasculitis
Respiratory, Thoracic and Mediastinal DisordersDyspnoea (including asthmatic condition)
Gastrointestinal DisordersNausea

Diarrhoea

Vomiting

Gastrointestinal and abdominal pains

Dyspepsia

Flatulence

Antibiotic associated diarrhoea including pseudomembraneous colitisPancreatitis
Hepatobiliary DisordersIncrease in transaminases

Increased bilirubin

Hepatic impairment

Cholestatic icterus

Hepatitis

Liver necrosis (very rarely progressing to life-threatening hepatic failure) (see section 4.4)
Skin and Subcutaneous Tissue DisordersRash

Pruritus

Urticaria

Photosensitivity reactions (see section 4.4)Petechiae

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, Connective Tissue and Bone DisordersMusculoskeletal pain (e.g. extremity pain, back pain, chest pain)

Arthralgia

Myalgia

Arthritis

Increased muscle tone and cramping

Muscular weakness

Tendinitis

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

Exacerbation of symptoms of myasthenia gravis (see section 4.4)

Renal and Urinary DisordersRenal impairmentRenal failure Haematuria

Crystalluria (see section 4.4)

Tubulointerstitial nephritis

General Disorders and Administration Site ConditionsInjection and infusion site reactions (only intravenous administration)Asthenia

Fever

Oedema

Sweating (hyperhidrosis)

Endocrine disordersSyndrome of inappropriate secretion of antidiuretic hormone (SIADH)
InvestigationsIncrease in blood alkaline phosphataseProthrombin level abnormal

Increased amylase

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

* These events were reported during the postmarketing period and were observed predominantly among patients with further risk factors for QT prolongation (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:

CommonVomiting, Transient increase in transaminases, Rash
UncommonThrombocytopenia, 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
RarePancytopenia, Bone marrow depression, Anaphylactic shock, Psychotic reactions, Migraine, Olfactory nerve disorders, Hearing impaired, Vasculitis, Pancreatitis, Liver necrosis, Petechiae, Tendon rupture

Paediatric patients

The incidence of arthropathy, mentioned above, is referring to data collected in studies with adults. In children, arthropathy is reported to occur commonly (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

An overdose of 12 g has been reported to lead to mild symptoms of toxicity. An acute overdose of 16 g has been reported to cause acute renal failure. Symptoms in overdose consist of dizziness, tremor, headache, tiredness, seizures, hallucinations, confusion, abdominal discomfort, renal and hepatic impairment as well as crystalluria and haematuria. Reversible renal toxicity has been reported.

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. 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.

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

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Fluoroquinolones,

Mechanism of action:

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

PK/PD relationship:

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

Mechanism of resistance:

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

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

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

Spectrum of antibacterial activity:

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

EUCAST Recommendations

MicroorganismsSusceptibleResistant
EnterobacteriaS ≤ 0.5 mg/LR > 1 mg/L
PseudomonasS ≤ 0.5 mg/LR > 1 mg/L
AcinetobacterS ≤ 1 mg/LR > 1 mg/L
Staphylococcus spp.1S ≤ 1 mg/LR > 1 mg/L
Haemophilus influenzae and Moraxella catarrhalisS ≤ 0.5 mg/LR > 0.5 mg/L
Neisseria gonorrhoeaeS ≤ 0.03 mg/LR > 0.06 mg/L
Neisseria meningitidisS ≤ 0.03 mg/LR > 0.06 mg/L
Non-species-related breakpoints*S ≤ 0.5 mg/LR > 1 mg/L
Staphylococcus spp. – breakpoints for ciprofloxacin relate to high dose therapy.

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

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

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

COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive micro-organisms

Bacillus anthracis (1)

Aerobic Gram-negative micro-organisms

Aeromonas spp.

Brucella spp.

Citrobacter koseri

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae*

Legionella spp.

Moraxella catarrhalis*

Neisseria meningitidis

Pasteurella spp.

Salmonella spp.*

Shigella spp. *

Vibrio spp.

Yersinia pestis

Anaerobic micro-organisms

Mobiluncus

Other micro-organisms

Chlamydia trachomatis ($)

Chlamydia pneumoniae ($)

Mycoplasma hominis ($)

Mycoplasma pneumoniae ($)

SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM
Aerobic Gram-positive micro-organisms

Enterococcus faecalis ($)

Staphylococcus spp. *(2)

Aerobic Gram-negative micro-organisms

Acinetobacter baumannii+

Burkholderia cepacia +*

Campylobacter spp.+*

Citrobacter freundii*

Enterobacter aerogenes

Enterobacter cloacae *

Escherichia coli*

Klebsiella oxytoca

Klebsiella pneumoniae*

Morganella morganii*

Neisseria gonorrhoeae*

Proteus mirabilis*

Proteus vulgaris*

Providencia spp.

Pseudomonas aeruginosa*

Pseudomonas fluorescens

Serratia marcescens*

Anaerobic micro-organisms

Peptostreptococcus spp.

Propionibacterium acnes

INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive micro-organisms

Actinomyces

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

Absorption

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

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

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

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

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

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

Distribution

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

Metabolism

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

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

Elimination

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

Excretion of ciprofloxacin (% of dose)
Intravenous Administration
UrineFaeces
Ciprofloxacin61.515.2
Metabolites (M1-M4)9.52.6

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

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

Paediatric patients

The pharmacokinetic data in paediatric patients are limited.

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

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

These values are within the range reported for adults at therapeutic doses. Based on population pharmacokinetic analysis of paediatric patients with various infections, the predicted mean 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.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactic acid solution, Sodium chloride, Water for Injection

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

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

Two years.

6.4 Special precautions for storage

Do not refrigerate or freeze.

Store in the original package.

6.5 Nature and contents of container

100ml PVC bag contained in a polypropylene/polyester- aluminium/polyester pouch. Pack sizes of 5 or 10 bags

6.6 Special precautions for disposal and other handling

Since the infusion solution is photosensitive, the infusion bags should be removed from the box only immediately before use. In daylight conditions complete efficacy is guaranteed for a period of three days.

Any unused solution should be disposed of.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

PACKAGE LEAFLET: INFORMATION FOR THE USER

CIPROFLOXACIN
INTRAVENOUS INFUSION BP
200MG/100ML
TAJ PHARMA

Ciprofloxacin

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

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

    1. WHAT CIPROFLOXACIN IS AND WHAT IT IS USED FOR

Ciprofloxacin contains the active substance ciprofloxacin. Ciprofloxacin is an antibiotic belonging to the fluoroquinolone family. Ciprofloxacin works by killing bacteria that cause infections. It only works with specific strains of bacteria.

Adults

Ciprofloxacin is used in adults to treat the following bacterial infections:

  • respiratory tract infections
  • long lasting or recurring ear or sinus infections
  • urinary tract infections
  • genital tract infections in men and women
  • gastro-intestinal tract infections and intra-abdominal infections
  • skin and soft tissue infections
  • bone and joint infections
  • anthrax inhalation exposure

Ciprofloxacin may be used in the management of patients with low white blood cell counts (neutropenia) who have a fever that is suspected to be due to a bacterial infection.

If you have a severe infection or one that is caused by more than one type of bacterium, you may be given additional antibiotic treatment in addition to Ciprofloxacin.

Children and adolescents

Ciprofloxacin is used in children and adolescents, under specialist medical supervision, to treat the following bacterial infections:

  • lung and bronchial infections in children and adolescents suffering from cystic fibrosis
  • complicated urinary tract infections, including infections that have reached the kidneys (pyelonephritis)
  • anthrax inhalation exposure

Ciprofloxacin may also be used to treat other specific severe infections in children and adolescents when your doctor considered this necessary.

  1. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN CIPROFLOXACIN YOU MUST NOT BE GIVEN CIPROFLOXACIN:
  • if you are allergic to the active substance, to other quinolone drugs or to any of the other ingredients of this medicine (listed in Section 6)
  • if you are taking tizanidine (see section 2: Other medicines and Ciprofloxacin)

Warnings and precautions:

Before taking this medicine

You should not take fluoroquinolone/quinolone antibacterial medicines, including Ciprofloxacin, if you have experienced any serious adverse reaction in the past when taking a quinolone or fluoroquinolone. In this situation, you should inform your doctor as soon as possible.

Talk to your doctor before you are given Ciprofloxacin:

  • if you have ever had kidney problems because your treatment may need to be adjusted.
  • if you suffer from epilepsy or other neurological conditions.
  • if you have a history of tendon problems during previous treatment with antibiotics such as Ciprofloxacin.
  • if you are diabetic because you may experience a risk of hypoglycaemia with ciprofloxacin.
  • if you have myasthenia gravis (a type of muscle weakness) because symptoms can be exacerbated.

if you have heart problems. Caution should be taken when using Ciprofloxacin, if you were born with or have family history of prolonged QT interval (seen on ECG, electrical recording of the heart), have salt imbalance in the blood (especially low level of potassium or magnesium in the blood), have a very slow heart rhythm (called ‘bradycardia’), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), you are female or elderly or you are taking other medicines that result in abnormal ECG changes (see section 2: Other medicines and Ciprofloxacin).

  • if you have been diagnosed with an enlargement or “bulge” of a large blood vessel (aortic aneurysm or large vessel peripheral aneurysm).
  • if you have experienced a previous episode of aortic dissection (a tear in the aorta wall).
  • if you have a family history of aortic aneurysm or aortic dissection or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome, or vascular Ehlers-Danlos syndrome, or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet’s disease, high blood pressure, or known atherosclerosis).
  • if you or a member of your family is known to have a deficiency in glucose-6- phosphate dehydrogenase (G6PD), since you may experience a risk of anaemia with ciprofloxacin.

For the treatment of some genital tract infections, your doctor can prescribe another antibiotic in addition to ciprofloxacin. If there is no improvement in symptoms after 3 days of treatment, please consult your doctor.

While under treatment with Ciprofloxacin

Tell your doctor immediately, if any of the following occurs during treatment with Ciprofloxacin. Your doctor will decide whether treatment with Ciprofloxacin needs to be stopped.

Prolonged, disabling and potentially irreversible serious side effects. Fluoroquinolone/quinolone antibacterial medicines, including Ciprofloxacin, have been associated with very rare but serious side effects, some of them being long lasting (continuing months or years), disabling or potentially irreversible. This includes tendon, muscle and joint pain of the upper and lower limbs, difficulty in walking, abnormal sensations such as pins and needles, tingling, tickling, numbness or burning (paraesthesia), sensory disorders including impairment of vision, taste and smell, and hearing, depression, memory impairment, severe fatigue, and severe sleep disorders.

If you experience any of these side effects after taking Ciprofloxacin, contact your doctor immediately prior to continuing treatment. You and your doctor will decide on continuing the treatment considering also an antibiotic from another class.

If you feel sudden, severe pain in your abdomen, chest or back, go immediately to an emergency room.

Severe, sudden allergic reaction (an anaphylactic reaction/shock, angiooedema). Even with the first dose, there is a rare chance that you may experience a severe allergic reaction with the following symptoms: tightness in the chest, feeling dizzy, feeling sick or faint, or experience dizziness on standing. If this happens, tell your doctor immediately since the administration of Ciprofloxacin will have to be stopped.

  • Pain and swelling in the joints and inflammation or rupture of tendons may occur rarely. Your risk is increased if you are elderly (above 60 years of age), have received an organ transplant, have kidney problems or if you are being treated with corticosteroids. Inflammation and ruptures of tendons may occur within the first 48 hours of treatment and even up to several months after stopping of Ciprofloxacin therapy. At the first sign of pain or inflammation of a tendon (for example in your ankle, wrist, elbow, shoulder or knee), stop taking Ciprofloxacin, contact your doctor and rest the painful area. Avoid any unnecessary exercise as this might increase the risk of a tendon rupture.
  • If you suffer from epilepsy or other neurological conditions such as cerebral ischemia or stroke, you may experience side effects associated with the central nervous system. If seizure happens, stop taking Ciprofloxacin and contact your doctor immediately.
  • You may rarely experience symptoms of nerve damage (neuropathy) such as pain, burning, tingling, numbness and/or weakness especially in the feet and legs or hands and arms. If this happens, stop taking Ciprofloxacin and inform your doctor immediately in order to prevent the development of potentially irreversible condition.
  • You may experience psychiatric reactions after first administration of ciprofloxacin. If you suffer from depression or psychosis, your symptoms may become worse under treatment with Ciprofloxacin. In rare cases, depression or psychosis can progress to thoughts of suicide, suicide attempts, or completed suicide. If this happens, contact your doctor immediately.
  • Hypoglycaemia has been reported most often in diabetic patients, predominantly in elderly population. If this happens, contact your doctor immediately.
  • Diarrhoea may develop while you are on antibiotics, including Ciprofloxacin, or even several weeks after you have stopped using them. If it becomes severe or persistent or you notice that your stool contains blood or mucus, stop taking Ciprofloxacin and contact your doctor immediately, as this can be life-threatening. Do not take medicines that stop or slow down bowel movements.
  • If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately.
  • Your skin becomes more sensitive to sunlight or ultraviolet (UV) light under treatment with Ciprofloxacin. Avoid exposure to strong sunlight or artificial UV light such as sunbeds.
  • Tell the doctor or laboratory staff that you are taking Ciprofloxacin if you have to provide a blood or urine sample.
  • If you suffer from kidney problems, tell the doctor because your dose may need to be adjusted.
  • Ciprofloxacin may cause liver damage. If you notice any symptoms such as loss of appetite, jaundice (yellowing of the skin), dark urine, itching, or tenderness of the stomach, Ciprofloxacin must be stopped immediately.

Ciprofloxacin may cause a reduction in the number of white blood cells and your resistance to infection may be decreased. If you experience an infection with symptoms such as fever and serious deterioration of your general condition, or fever with local infection symptoms such as sore throat/pharynx/mouth or urinary problems you should see your doctor immediately. A blood test will be taken to check possible reduction of white blood cells (agranulocytosis). It is important to inform your doctor about your medicine.

Other medicines and Ciprofloxacin

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not use Ciprofloxacin together with tizanidine, because this may cause side effects such as low blood pressure and sleepiness (see section 2: You must not be given Ciprofloxacin).

The following medicines are known to interact with Ciprofloxacin in your body. Using Ciprofloxacin together with these medicines can influence the therapeutic effect of these medicines. It can also increase the probability of experiencing side effects.

Tell your doctor if you are taking:

  • Vitamin K antagonists (e.g. warfarin, acenocoumarol, phenprocoumon or fluindione) or other oral anti-coagulants (to thin the blood)
  • probenecid (for gout)
  • methotrexate (for certain types of cancer, psoriasis, rheumatoid arthritis)
  • theophylline (for breathing problems)
  • tizanidine (for muscle spasticity in multiple sclerosis)
  • olanzapine (an antipsychotic)
  • clozapine (an antipsychotic)
  • ropinirole (for Parkinson’s disease)
  • phenytoin (for epilepsy)
  • cyclosporin (for skin conditions, rheumatoid arthritis and in organ transplantation)
  • other medicines that can alter your heart rhythm: medicines that belong to the group of antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (that belong to the group of macrolides), some antipsychotics
  • zolpidem (for sleep disorders)

Ciprofloxacin may increase the levels of the following medicines in your blood:

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

Ciprofloxacin with food and drink
Food and drink does not affect your treatment with Ciprofloxacin.
Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

It is preferable to avoid the use of Ciprofloxacin during pregnancy.

Do not take Ciprofloxacin during breast-feeding because ciprofloxacin is excreted in breast milk and can be harmful for your child.

Driving and using machines

Ciprofloxacin may make you feel less alert. Some neurological adverse events can occur. Therefore, make sure you know how you react to Ciprofloxacin before driving a vehicle or operating machinery. If in doubt, talk to your doctor.

Ciprofloxacin contains glucose

Contains 9 g glucose in 200 ml solution for infusion. This should be taken into account in patients with diabetes mellitus.

  1. How to use Ciprofloxacin

Your doctor will explain to you exactly how much Ciprofloxacin you will be given as well as how often and for how long. This will depend on the type of infection you have and how bad it is.

Tell your doctor if you suffer from kidney problems because your dose may need to be adjusted.

Treatment usually lasts between 5 and 21 days, but may be longer for severe infections.

Your doctor will give you each dose by slow infusion through a vein into your bloodstream. For children, the infusion duration is 60 minutes. In adult patients, infusion time is 60 minutes for 400 mg Ciprofloxacin and 30 minutes for 200 mg Ciprofloxacin.

Administering the infusion slowly helps prevent immediate side effects occurring. Remember to drink plenty of fluids while you are taking this medicine.

If you stop your course of Ciprofloxacin, it is important that you finish the course of treatment even if you begin to feel better after a few days. If you stop using this medicine too soon your infection may not be completely cured and the symptoms of the infection may return or get worse. You might also develop resistance to the antibiotic.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following section contains the most serious side effects that you can recognise yourself:

Stop taking Ciprofloxacin and contact your doctor immediately in order to consider another antibiotic treatment if you notice any of the following serious side effects:

Uncommon (may affect up to 1 in 100 people)

  • seizure (see section 2: Warnings and precautions)

Rare (may affect up to 1 in 1,000 people)

  • severe, sudden allergic reaction with symptoms such as tightness in the chest, feeling dizzy, sick or faint, or experience dizziness when standing up (anaphylactic shock) (see section 2: Warnings and precautions)
  • tendon rupture, particularly affecting the large tendon at the back of the ankle (Achilles tendon) (see section 2: Warnings and precautions)

Very rare (may affect up to 1 in 10,000 people)

  • severe, sudden allergic reaction with symptoms such as tightness in the chest, feeling dizzy, sick or faint, or experience dizziness when standing up (anaphylactic reaction) (see section 2: Warnings and precautions)
  • muscle weakness, inflammation of the tendons which could lead to rupture of the tendon, particularly affecting the large tendon at the back of the ankle (Achilles tendon) (see section 2: Warnings and precautions)
  • a serious life-threatening skin rash, usually in the form of blisters or ulcers in the mouth, throat, nose, eyes and other mucous membranes such as genitals which may progress to widespread blistering or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Not known (frequency cannot be estimated from the available data)

  • unusual feelings of pain, burning tingling, numbness or muscle weakness in the extremities (neuropathy) (see section 2: Warnings and precautions)
  • a drug reaction that causes rash, fever, inflammation of internal organs, hematologic abnormalities and systemic illness (DRESS Drug Reaction with Eosinophilia and Systemic Symptoms, AGEP Acute Generalised Exanthematous Pustulosis).

Very rare cases of long lasting ( up to months or years) or permanent adverse drug reactions, such as tendon inflammations, tendon rupture, joint pain, pain in the limbs, difficulty in walking, abnormal sensations such as pins and needles, tingling, tickling, burning, numbness or pain (neuropathy), depression, fatigue, sleep disorders, memory impairment, as well as impairment of hearing, vision, and taste and smell have been associated with administration of quinolone and fluoroquinolone antibiotics, in some cases irrespective of pre-existing risk factors.

Other side effects which have been observed during treatment with Ciprofloxacin are listed below by how likely they are:

Common (may affect up to 1 in 10 people)

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

Uncommon (may affect up to 1 in 100 people)

  • joint pain in adults
  • fungal superinfections
  • a high concentration of eosinophils, a type of white blood cell,
  • increased or decreased amounts of a blood clotting factor (thrombocytes)
  • decreased appetite
  • hyperactivity, agitation, confusion, disorientation, hallucinations
  • headache, dizziness, sleeping problems, taste disorders, pins and needles, unusual sensitivity to stimuli of the senses, giddiness
  • eyesight problems including double vision
  • loss of hearing
  • rapid heartbeat (tachycardia)
  • expansion of the blood vessels (vasodilation), low blood pressure
  • abdominal pain, digestive problems such as stomach upset (indigestion/heartburn), wind
  • liver disorders, increased amounts of one substance in the blood (bilirubin), jaundice (cholestatic icterus)
  • itching, hives
  • poor kidney function, kidney failure
  • pains in your muscles and bones, feeling unwell (asthenia), fever, fluid retention
  • increase in blood alkaline phosphatase (a certain substance in the blood)

Rare (may affect up to 1 in 1,000 people)

  • muscle pain, inflammation of the joints, increased muscle tone and cramping
  • inflammation of the bowel (colitis) linked to antibiotic use (can be fatal in very rare cases) (see section 2: Warnings and precautions)
  • changes to the blood count (leukopenia, leukocytosis, neutropenia, anaemia), a drop in the number of red and white blood cells and platelets (pancytopenia), which may be fatal, bone-marrow depression which may also be fatal
  • allergic reaction, allergic swelling (oedema), rapid swelling of the skin and mucous membranes (angiooedema) (see section 2: Warnings and precautions)
  • increased blood sugar (hyperglycemia)
  • decreased blood sugar (hypoglycaemia) (see section 2: Warnings and precautions)
  • anxiety reaction, strange dreams, depression (potentially leading to thoughts of suicide, suicide attempts, or completed suicide), mental disturbances (psychotic reactions potentially leading to thoughts of suicide, suicide attempts, or completed suicide) (see section 2: Warnings and precautions)
  • decreased skin sensitivity, tremor, migraine, disorder of sense of smell (olfactory disorders)

tinnitus, impaired hearing

  • fainting, inflammation of the blood vessel (vasculitis)
  • shortness of breath including asthmatic symptoms
  • pancreatitis
  • hepatitis, death of liver cells (liver necrosis) very rarely leading to life-threatening liver failure (see section 2: Warnings and precautions)
  • sensitivity to light (see section 2: Warnings and precautions), small, pin-point bleeding under the skin (petechiae)
  • blood or crystals in the urine, urinary tract inflammation
  • excessive sweating
  • increased levels of the enzyme amylase

Very rare (may affect up to 1 in 10,000 people)

  • a special type of reduced red blood cell count (haemolytic anaemia); a dangerous drop in a type of white blood cells (agranulocytosis) (see section 2: Warnings and precautions)
  • allergic reaction called serum sickness-like reaction (see section 2: Warnings and precautions)
  • disturbed coordination, unsteady walk (gait disturbance), pressure on the brain (intracranial pressure and pseudotumor cerebri)
  • visual colour distortions
  • various skin eruptions or rashes
  • worsening of the symptoms of myasthenia gravis (see section 2: Warnings and precautions)
  • fatigue
  • memory impairment

Not known (frequency cannot be estimated from the available data)

  • feeling highly excited (mania) or feeling great optimism and overactivity (hypomania)
  • abnormal fast heart rhythm, life-threatening irregular heart rhythm, alteration of the heart rhythm (called ‘prolongation of QT interval’, seen on ECG, electrical activity of the heart)
  • influence on blood clotting (in patients treated with Vitamin K antagonists)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Ciprofloxacin

Your medicine will be stored and administered by healthcare professionals, who will follow this guidance:

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after “EXP”. The expiry date refers to the last day of that month.

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

For single use only. Use immediately after first opening the infusion bag. Do not store above 25C. Do not refrigerate or freeze.

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

From a microbiological point of view, unless the method of opening and mixing with co- infusion solutions precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information What Ciprofloxacin contains

Each ml of Infusion contains:
Ciprofloxacin BP………………….2mg

The other ingredients are: glucose monohydrate, 50% lactic acid, hydrochloric acid, water for injections.

What Ciprofloxacin looks like and the contents of the pack

Solution for infusion.

Clear, nearly colourless to slightly yellowish solution.
It is available in transparent infusion (PVC or polyolefin) bags that contain 50 ml, 100 ml or 200 ml sterile solution of ciprofloxacin 2 mg/ml. The bags are sealed 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.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com