Ciprofloxacin Fresenius 2 mg/50 ml/100 ml/200 ml Solution

CIPROFLOXACIN FRESENIUS is indicated for the treatment of severe and/or complicated infections caused by ciprofloxacin-sensitive bacteria where other antimicrobials, approved for a similar indication and to which the causative bacteria are sensitive, were considered not to be an appropriate treatment option, have failed, are contraindicated, or not tolerated. CIPROFLOXACIN FRESENIUS in not indicated/approved for the initiation of treatment (first-line treatment) of infections described as mild/moderate/acute and uncomplicated, caused by bacteria sensitive to ciprofloxacin, unless treatment with other appropriate antimicrobials, approved for a similar indication and to which the causative bacteria are sensitive, have failed, are contraindicated, or not tolerated. CIPROFLOXACIN FRESENIUS is indicated for the treatment of the following bacterial infections where these infections are compliant with the indication context.

• Severe and /or complicated lower respiratory tract infections caused by Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.
• Severe and /or complicated urinary tract infections caused by Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Providencia rettgeri, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus epidermis, Streptococcus faecalis.
• Severe and /or complicated skin and soft tissue infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pyogenes.
• Severe and /or complicated gastrointestinal infections: Infective diarrhoea caused by Campylobacter jejuni, Escherichia coli, Shigella flexneri and Shigella sonnei.
• Severe and /or complicated bone infections: Osteomyelitis due to susceptible Gram-negative organisms.

In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly. Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to CIPROFLOXACIN FRESENIUS. Therapy with CIPROFLOXACIN FRESENIUS may be initiated in severe and/or complicated infections before results of these tests are known; once results become available, appropriate therapy should be continued.

Posology The dosage of CIPROFLOXACIN FRESENIUS is determined by the severity and type of infections, the sensitivity of the causative organism(s) and the age, mass and renal function of the patient.

Adults: The usual dose is 100 - 200 mg IV every 12 hours. For severe and/or complicated infections 400 mg may be administered every 12 hours. Intravenous therapy should be discontinued as soon as oral CIPROFLOXACIN FRESENIUS therapy can be substituted. The normal duration of intravenous therapy is up to 7 days.

Cystic fibrosis In cystic fibrosis patients, the normal dose is 200 mg IV every 12 hours. The low body mass of these patients should, however, be taken into consideration when determining dosage (5 -10 mg/kg/day).

Special Populations Geriatric patients (> 65 years) Elderly patients should receive as low a dose as possible; this will depend on the severity of the illness and on the creatinine clearance (see section 4.2 for dose adjustment). Patients with impaired renal or liver function: In patients with reduced renal function, the half-life of CIPROFLOXACIN FRESENIUS may be prolonged.

The dosage needs to be adjusted as shown below. For patients with renal impaired and hepatic insufficiency, monitoring of medicine serum levels provides the most reliable basis for dose adjustment.

Dose adjustment of CIPROFLOXACIN FRESENIUS for patients with renal or hepatic impairment:

1. Renal impairment
1. CL CR > 31 ml/min/1,73m2; <60 ml/min/1,73 m2 (moderate renal impairment) Max 800 mg/day intravenously
2. CL CR < 30 ml/min/1,73 m2 (severe renal impairment) Max 400 mg/day intravenously
3. Impaired renal function and haemodialysis As in 1.2 above; on dialysis days after dialysis
2. Renal impairment and CAPD (chronic ambulatory peritoneal dialysis): 2.1 Addition of CIPROFLOXACIN FRESENIUS solution to the dialysate (intraperitoneal): 50 mg ciprofloxacin per litre of dialysate administered 4 times a day.
3. Hepatic impairment No dose adjustment.

Method of administration CIPROFLOXACIN FRESENIUS should be administered by intravenous infusion over a period of 60 minutes. Slow infusion into a large vein will minimise patient discomfort and reduce the risk of venous irritation. The infusion solution can be infused either directly or after mixing with other compatible infusion solutions (see section 6.6).

CIPROFLOXACIN FRESENIUS is contraindicated:

• in patients with a history of hypersensitivity to ciprofloxacin, any other quinolones, or any of the inactive ingredients.
• when used concomitantly with other medicines known to prolong the QT interval, or in patients with disorders that prolong the QT interval to such an extent that it leads to prolonged QTcF interval known to associated with serious and potentially fatal dysrhythmias or if symptomatic dysrhythmias occur with concomitant use at time intervals shorter than QT intervals usually associated with dysrhythmias.
• in pregnancy and lactation (see section 4.6).
• in myasthenia gravis where alternative appropriate antibiotic choices are available to treat these patients.
• with concomitant use with tizanidine (see section 4.5).
• if you have a history of tendon, muscle, joint, central nervous system, epilepsy or psychotic disorders especially those related to previous quinolone/fluoroquinolone use where alternative, appropriate antibiotic choices are available for treatment.
• in aortic aneurysm and/or dissection or in patients with risk factors or conditions predisposing for aortic aneurysm and/or dissection if alternative appropriate antibiotic choices are available.
• in patients with confirmed mitral valve and/or aortic valve regurgitation unless no safer appropriate alternative antibiotic is available, has failed, or is not well tolerated.
• with concomitant use of fluoroquinolones with ACE inhibitors/ angiotensin-receptor blockers in patients with moderate to severe renal impairment (creatinine clearance u2264 30 ml/min) and in the elderly.
• CIPROFLOXACIN FRESENIUS is contraindicated in children under the age of 18 years. There is evidence of damage to the cartilage of weight-bearing joints in immature animals.

Crystalluria related to the use of ciprofloxacin has been observed. Patients receiving CIPROFLOXACIN FRESENIUS should be well hydrated and excessive alkalinity of the urine should be avoided. Pancytopenia and marrow depression are side effects that may be potentially life-threatening (See section 4.8). Concurrent administration with methotrexate may increase the concentration of methotrexate to toxic levels. Tendinitis may occur. It most frequently involves the Achilles tendon and may lead to tendon rupture. The risk of tendinitis and tendon rupture is increased in the elderly and in patients using corticosteroids and in patients with a kidney or lung transplant. Close monitoring of these patients is therefore necessary if CIPROFLOXACIN FRESENIUS is prescribed. All patients should consult their medical practitioner if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with CIPROFLOXACIN FRESENIUS must be discontinued immediately, and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon. Tendinitis and/or tendon rupture may still occur for several months after completion of treatment. The recovery process may be prolonged (weeks to months) and full recovery to the pre-treatment status may not occur.

Streptococcus pneumoniae infections CIPROFLOXACIN FRESENIUS should not be used for treatment of pneumococcal infections due to limited efficacy against Streptococcus pneumoniae. Severe infections and/or infections due to Gram-positive or anaerobic bacteria For the treatment of severe infections, CIPROFLOXACIN FRESENIUS should be used in combination with another appropriate antibacterial medicine. CIPROFLOXACIN FRESENIUS should not be used in staphylococcal infections and infections involving anaerobic bacteria.

Cardiac disorders Prolongation of the QT interval, sometimes progressing to torsade de pointes, has been associated with CIPROFLOXACIN FRESENIUS (See sections 4.3 and 4.8). Women tend to have a longer baseline QTc interval compared with men. Elderly patients and women may be more sensitive to QTc-prolonging medicines. Therefore, caution should be taken when using CIPROFLOXACIN FRESENIUS in these populations. Concomitant use of CIPROFLOXACIN FRESENIUS with medicines or in patients with disorders that can result in prolongation of the QT interval is contraindicated if:

• concomitant use leads to prolongation of QTc interval associated with serious or potentially fatal dysrhythmias or
• symptomatic dysrhythmias occur at QTc intervals less than usually associated with dysrhythmias (e.g. class IA or III antidysrhythmics, tricyclic antidepressants, macrolides, antipsychotics), (see section 4.5) or
• congenital long QT syndrome,
• risk of Torsades de Pointes,
• uncorrected electrolyte imbalance such as hypokalaemia or hypomagnesaemia and cardiac disease such as heart failure, myocardial infarction, or bradycardia.

A pre-treatment ECG and frequent follow up ECG monitoring is mandatory with concomitant use to determine whether concomitant use is contraindicated.

Vascular disorders There is some evidence of an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the elderly 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 aneurysmal disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissections, or in the presence of other risk factors or conditions predisposing aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcetu2019s disease, hypertension, known arthrosclerosis) (see section 4.3). In case of sudden abdominal, chest, or back pain, patients should be advised to immediately consult a medical practitioner in an emergency department of a hospital.

ACE inhibitors and angiotensin-receptor blockers Concomitant use of fluoroquinolones and ACE inhibitors/ angiotensin-receptor blockers may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients (see section 4.3). Renal function should be assessed before initiating treatment, and monitored during treatment, with fluoroquinolone and ACE inhibitors/ angiotensin receptor blockers.

There is some evidence, although inconclusive, of a possible association between fluoroquinolone use and mitral valve and/or aortic valve regurgitation. A thorough cardiovascular examination including an echocardiogram should be performed before oral fluoroquinolones are prescribed. Fluoroquinolones should not be prescribed to patients with mitral valve and/or aortic valve regurgitation (see section 4.3).

Children and adolescents CIPROFLOXACIN FRESENIUS is contraindicated in children below the age of 18 years (see section 4.3). In children, arthropathy is reported to occur commonly (see additional information on special populations in section 4.2).

Hypersensitivity Hypersensitivity and allergic reactions including anaphylactic/ anaphylactoid shock may occur with the first exposure to CIPROFLOXACIN FRESENIUS. Anaphylactic/Anaphylactoid reactions in instances can progress to a life-threatening shock. In these cases CIPROFLOXACIN FRESENIUS must be discontinued and supportive medical treatment e.g. for shock is required.

Gastrointestinal System The occurrence of severe and persistent diarrhoea during or after treatment with CIPROFLOXACIN FRESENIUS may indicate pseudomembranous colitis which may be fatal if not treated. In such cases CIPROFLOXACIN FRESENIUS must be discontinued and appropriate antimicrobial and supportive therapy should be initiated. Anti-peristaltic medicines are contraindicated in this situation.

Hepatobilliary system Cases of hepatic necrosis and life-threatening hepatic failure have been reported with CIPROFLOXACIN FRESENIUS. In the event of any signs and symptoms of hepatic disease (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), treatment should be discontinued (see section 4.8). There may be a temporary increase in transaminases, alkaline phosphatase or cholestatic jaundice, especially in patients with previous liver damage (see section 4.8).

Musculoskeletal System The use of CIPROFLOXACIN FRESENIUS in patients with myasthenia gravis is contraindicated if alternative appropriate antibiotic choices are available (see section 4.3). CIPROFLOXACIN FRESENIUS may exacerbate the symptoms of myasthenia gravis. Tendinitis and tendon rupture (predominantly Achilles tendon), sometimes bilateral, may occur with CIPROFLOXACIN FRESENIUS, even within the first 48 hours of treatment. Inflammation and ruptures of tendon may occur even up to several months after discontinuation of CIPROFLOXACIN FRESENIUS therapy (see section 4.3). At any sign of tendinitis (e.g. painful swelling, inflammation) the administration of CIPROFLOXACIN FRESENIUS should be discontinued and physical exercise be avoided. CIPROFLOXACIN FRESENIUS should not be used in patients with a history of tendon disorders, especially those related to previous exposure to quinolone or fluoroquinolone use (see section 4.3). CIPROFLOXACIN FRESENIUS should only be used in these patients if appropriate alternative antibiotic choices are not available, have failed, are contraindicated, or not tolerated.

Nervous System CIPROFLOXACIN FRESENIUS is known to trigger seizures or lower the seizure threshold. In patients with epilepsy and in patients who have suffered from previous central nervous system (CNS) disorders (e.g. lowered convulsion threshold, previous history of convulsions, reduced cerebral blood flow, altered brain structure or stroke). CIPROFLOXACIN FRESENIUS should only be used where alternative appropriate therapies have failed, are contraindicated, or not tolerated, since these patients are endangered due to possible central nervous system side effects. Cases of status epilepticus have been reported (see sections 4.3 and 4.8). If seizures occur, CIPROFLOXACIN FRESENIUS should be discontinued. Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving fluoroquinolones including CIPROFLOXACIN FRESENIUS. Patients on treatment with CIPROFLOXACIN FRESENIUS should be advised to inform their medical practitioner prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop (see section 4.8). The recovery process of neuropathy may be prolonged (weeks or months) and full recovery to the pretreatment status may not occur.

Psychiatric side effects Psychiatric reactions may occur after the first administration of fluoroquinolones, including CIPROFLOXACIN FRESENIUS. Cases of depression or psychotic reactions may progress to suicidal ideations/thoughts and self-injury, such as attempted or completed suicide (see sections 4.3 and 4.8). Should a patient develop any of these reactions, CIPROFLOXACIN FRESENIUS should be discontinued and appropriate measures instituted.

Skin and Appendages Ciprofloxacin has been shown to produce photosensitivity reactions. Patients taking CIPROFLOXACIN FRESENIUS should avoid direct exposure to excessive sunlight or UV- light. Therapy should be discontinued if photosensitisation (i.e. sunburn-like skin reactions) occurs (see section 4.8).

Cytochrome P450 Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 enzymes. Care should be taken when other medicines which are metabolised via the same enzymatic pathway (e.g. tizanidine, theophylline, methylxanthines, caffeine, duloxetine, ropinirole, clozapine, olanzapine) are administered concomitantly. Increased plasma concentrations associated with specific side effects may be observed due to inhibition of their metabolic clearance by ciprofloxacin (see section 4.5).

Medicines known to prolong QT interval CIPROFLOXACIN FRESENIUS should be used with caution in patients receiving medicines known to prolong QT interval (e.g. Class IA and III anti-dysrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see sections 4.3 and 4.4).

Chelation Complex Formation The simultaneous administration of ciprofloxacin (oral) and multivalent cation-containing medicines and mineral supplements (e.g. calcium, magnesium, aluminium, iron), polymeric phosphate binders (e.g. sevelamer, lanthanum carbonate), sucralfate or antacids and highly buffered medicines (e.g. anti-retrovirals) containing magnesium, aluminium or calcium reduce the absorption of CIPROFLOXACIN FRESENIUS. Consequently, CIPROFLOXACIN FRESENIUS should be administered either 1 - 2 hours before, or at least 4 hours after these preparations. The restriction does not apply to antacids belonging to the class of H2 receptor blockers.

Food and Dairy Products The concurrent administration of dairy products or mineral fortified drinks alone (e.g. milk, yoghurt, calcium fortified orange juice) and CIPROFLOXACIN FRESENIUS should be avoided because the absorption of CIPROFLOXACIN FRESENIUS is reduced. Dietary calcium as part of a meal, however, does not significantly affect absorption.

Metoclopramide Metoclopramide accelerates the absorption of CIPROFLOXACIN FRESENIUS, resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of CIPROFLOXACIN FRESENIUS.

Omeprazole Concomitant administration of CIPROFLOXACIN FRESENIUS and omeprazole containing medicines results in a 20 % reduction of the Cmax and AUC of CIPROFLOXACIN FRESENIUS.

Tizanidine In a clinical study in healthy subjects, there was an increase in tizanidine serum concentrations (C max increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given concomitantly with ciprofloxacin. Associated with the increased serum concentrations was a potentiated hypotensive and sedative effect (see section 4.4). Tizanidine-containing medicines must not be administered together with CIPROFLOXACIN FRESENIUS (see section 4.5).

Theophylline Concurrent administration of CIPROFLOXACIN FRESENIUS with theophylline may lead to elevated plasma concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related toxicity. If concomitant use cannot be avoided, plasma levels of theophylline should be monitored and dosage adjustments made as appropriate (see Cytochrome P450 in section 4.4).

Other xanthine derivatives Concurrent administration of CIPROFLOXACIN FRESENIUS with caffeine or pentoxifylline- (oxpentifylline)-containing products, may lead to raised serum concentrations of these xanthine derivatives.

Phenytoin Altered (decreased or increased) serum levels of phenytoin were observed in patients receiving CIPROFLOXACIN FRESENIUS and phenytoin simultaneously. To avoid the loss of seizure control associated with decreased phenytoin levels, and to prevent phenytoin overdose-related side effects when CIPROFLOXACIN FRESENIUS is discontinued in patients receiving both agents, monitoring of phenytoin therapy, including phenytoin serum-concentration measurements, is recommended during and shortly after co-administration of CIPROFLOXACIN FRESENIUS with phenytoin.

Methotrexate Renal tubular transport of methotrexate may be inhibited by concomitant administration of CIPROFLOXACIN FRESENIUS potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate-associated toxic reactions. Therefore, patients on methotrexate therapy should be carefully monitored when concomitant CIPROFLOXACIN FRESENIUS therapy is indicated.

NSAIDu2019s Concomitant administration of the non-steroidal anti-inflammatory medicines with quinolones such as CIPROFLOXACIN FRESENIUS may increase the risk of central nervous system stimulation and seizures.

Ciclosporin Monitoring of serum creatinine concentrations is advised in patients with concomitant ciclosporin therapy, as transient increases in serum creatinine concentrations have been observed.

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

Oral antidiabetic agents Hypoglycaemia has been reported when CIPROFLOXACIN FRESENIUS and oral antidiabetic agents, mainly sulfonylureas (e.g. glibenclamide, glimepiride), were co-administered (see section 4.8). Concurrent administration of CIPROFLOXACIN FRESENIUS and glibenclamide-containing medicines may intensify the action of glibenclamide, leading to hypoglycaemia.

Duloxetine An increase of duloxetine blood concentrations can be expected with concomitant administration with CIPROFLOXACIN FRESENIUS (see Cytochrome P450 in section 4.4).

Ropinirole Concomitant use of ropinirole with ciprofloxacin as in CIPROFLOXACIN FRESENIUS, a moderate inhibitor of the CYP450 1A2 isozyme, resulted in an increase of Cmax and AUC of ropinirole by 60 % and 84 %, respectively. Monitoring ropinirole-related side effects and/or dose adjustment as appropriate is recommended during and shortly after co-administration with CIPROFLOXACIN FRESENIUS (see Cytochrome P450 in section 4.4).

Lidocaine (Lignocaine) Concomitant use of lidocaine-(lignocaine)-containing medicines with a moderate inhibitor of CYP450 1A2 isozyme such as CIPROFLOXACIN FRESENIUS, reduces the clearance of intravenous lidocaine by 22 % and may increase the risk for lidocaine side effects.

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 FRESENIUS are advised (see Cytochrome P450 in 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. Caution is advised when prescribing CIPROFLOXACIN FRESENIUS concomitantly with sildenafil.

ACE inhibitors and angiotensin-receptor blockers Concomitant use of fluoroquinolones and ACE inhibitors/angiotensin-receptor blockers may precipitate acute kidney injury. The mechanism of the possible interaction between the different classes of medicines, over and above different mechanisms of kidney damage, is unknown (see section 4.3).

Probenecid Probenecid interferes with renal secretion of CIPROFLOXACIN FRESENIUS. Co-administration of probenecid and CIPROFLOXACIN FRESENIUS increases the CIPROFLOXACIN FRESENIUS serum concentrations.

Safety in pregnancy and lactation has not been established (see section 4.3).

Pregnancy The safety of CIPROFLOXACIN FRESENIUS in pregnant women has not been established (see section 4.3). CIPROFLOXACIN FRESENIUS must not be prescribed to pregnant women. Animal studies have demonstrated that CIPROFLOXACIN FRESENIUS may damage the articular cartilage in the foetus.

Lactation Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, mothers on CIPROFLOXACIN FRESENIUS should not breastfeed their infants.

CIPROFLOXACIN FRESENIUS can affect the speed of reaction, due to musculoskeletal and/or CNS reactions to such an extent that the ability to drive or to operate machinery is impaired (see section 4.8).

Tabulated list of adverse effects The frequencies of side effects reported with CIPROFLOXACIN FRESENIUS are summarised in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class Frequent Less frequent Infections and Infestations Candida and other fungal infections, antibiotic associated colitis (with possible fatal outcome) Blood and Lymphatic System Disorders Eosinophilia, leukopenia, anaemia, neutropenia, leucocytosis, thrombocytopenia, thrombocytaemia, haemolytic anaemia, agranulocytosis, life-threatening pancytopenia, life-threatening bone marrow depression Immune System Disorders allergic reaction, allergic oedema / angioedema, anaphylactic reaction, life-threatening anaphylactic shock, serum sickness- like reaction Metabolism and Nutrition Disorders Decreased appetite and food intake, hyperglycaemia, hypoglycaemia, particularly in diabetic patients Psychiatric Disorders Psychomotor hyperactivity/agitation, confusion and disorientation, anxiety reaction, abnormal dreams, depression (potentially culminating in self-injurious behaviour such as suicidal ideation /thoughts and attempted or completed suicide). Hallucinations, psychotic reactions (potentially culminating in self-injurious behaviour such as suicidal ideation / thoughts and attempted or completed suicide) Nervous System Disorders Headache, dizziness, sleep disorders, taste disorders, paraesthesia, dysaesthesia, hypoaesthesia. tremor, seizures (including status epilepticus), vertigo, migraine, disturbed coordination, smell disorders, hyperaesthesia, intracranial hypertension, pseudotumour cerebri Eye Disorders Visual disturbances, visual colour distortions Ear and Labyrinth Disorders Tinnitus, hearing loss, impaired hearing Cardiac Disorders Tachycardia Vascular Disorders Vasodilation, hypotension, syncope, vasculitis, phlebitis or thrombophlebitis Respiratory, Thoracic and Mediastinal Disorders Dyspnoea (including asthma) Gastro - intestinal Disorders Nausea, diarrhoea Vomiting, abdominal pains, dyspepsia flatulence, pancreatitis Hepatobiliary Disorders Increase in transaminases, increased bilirubin, hepatic impairment, jaundice, non-infective hepatitis, liver necrosis which may progress to life-threatening hepatic failure) Skin and Sub-cutaneous Tissue Disorders Rash, pruritus, urticarial, photo - sensitivity reactions, blistering, petechiae erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), toxic epidermal necrolysis (potentially life-threatening), punctate skin haemorrhages (petechiae), haemorrhage bullae and papules with signs of vascular involvement (vasculitis) Musculo - skeletal, Connective Tissue and Bone Disorders Arthralgia, myalgia, arthritis, increased muscle tone and cramping, muscular weakness, tendonitis, tendon rupture (pre-dominantly Achilles tendon), exacerbation of symptoms of myasthenia gravis Renal and Urinary Disorders Renal impairment, renal failure, haematuria, crystalluria, tubulointerstitial nephritis General Disorders and Administration Site Conditions Injection site reaction Unspecific pain, feeling unwell, fever, oedema, sweating (hyperhidrosis), gait disturbance Investigations Increase in blood alkaline phosphatase, abnormal prothrombin level (increased INR), increased amylase

The side effects identified only during post-marketing surveillance, and for which a frequency could not be estimated. Metabolism and nutrition disorders: Hyperglycaemia, hypoglycaemic coma. Nervous system disorders: Peripheral neuropathy and polyneuropathy, Guillain-Barre syndrome. Cardiac disorders: QT prolongation, ventricular dysrhythmia, Torsades de Pointes*, aortic aneurysm and dissection. Skin and subcutaneous tissue disorders: Acute generalized exanthematous pustulosis (AGEP). Investigations: Increased International Normalised Ratio (INR) (in patients treated with Vitamin K antagonist). *These events were reported during the post-marketing period and were observed predominantly among patients with further risk factors for QT prolongation (see section 4.4). Cases of mitral valve and/or aortic valve regurgitation were reported in patients treated with oral fluoroquinolones. Due to insufficient post-marketing information in the reported cases, it is unknown whether fluoroquinolone use was the causative factor, or a contributory factor, or played no role in the reported cases where mitral valve and/or aortic valve regurgitation was diagnosed.

Additional information on special populations Paediatric population 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).

In overdose, side effects may be exaggerated or exacerbated (see section 4.8). In the event of acute overdosage, the patient should be carefully observed and given supportive treatment, including monitoring of renal function, urinary pH and acidify if required to prevent crystalluria. Calcium or magnesium containing antacids may reduce the absorption of CIPROFLOXACIN FRESENIUS in overdose. Only a small amount of ciprofloxacin (< 10 %) is removed from the body after haemodialysis or peritoneal dialysis. Treatment is symptomatic and supportive and adequate hydration must be maintained.