4.1. Therapeutic indications

Because of the risk of prolonged, disabling and potentially irreversible serious adverse drug reactions (see section 4.4 and section 4.8) this product must only be prescribed when other antibiotics that are commonly recommended for the infection are inappropriate. This applies to all indications listed below. Situations where other antibiotics are considered to be inappropriate are where:

• there is resistance to other first-line antibiotics recommended for the infection;

• other first-line antibiotics are contraindicated in an individual patient;

• other first-line antibiotics have caused side effects requiring treatment to be stopped;

• treatment with other first-line antibiotics has failed.

Quinsair is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in adult patients with cystic fibrosis (CF, see section 5.1).

4.2. Posology and method of administration

Posology

The recommended dosage is 240 mg (one ampoule) administered by inhalation twice daily (see section 5.2). The doses should be inhaled as close as possible to 12 hours apart.

Quinsair is taken in alternating cycles of 28 days on treatment followed by 28 days off treatment. Cyclical therapy may be continued for as long as the physician considers that the patient is obtaining clinical benefit.

If a dose is missed, it should be taken as soon as the patient remembers providing that at least an 8-hour interval is allowed before inhaling the next dose. Patients should not inhale the contents of more than one ampoule to compensate for the missed dose.

If acute symptomatic bronchospasm occurs after receiving Quinsair, patients may benefit from the use of a short-acting inhaled bronchodilator at least 15 minutes to 4 hours prior to subsequent doses (see sections 4.4 and 4.8).

Elderly patients (≥ 65 years old)

The safety and efficacy of Quinsair in elderly patients with CF have not been established.

Renal impairment

Doses do not need to be adjusted in patients with mild to moderate renal impairment. Quinsair is not recommended for use in patients with severe renal impairment.

Hepatic impairment

No dose adjustment is required (see section 5.2).

Paediatric population

The safety and efficacy of Quinsair in children aged < 18 years old have not yet been established. Currently available data are described in sections 4.8, 5.1, 5.2 and 5.3 but no recommendation on a posology can be made.

Method of administration

Inhalation use.

Once an ampoule is opened, the contents should be used immediately (see section 6.6).

For patients taking multiple inhaled therapies, the recommended order of administration is as follows:

1. Bronchodilators;

2. Dornase alfa;

3. Airway clearance techniques;

4. Quinsair;

5. Inhaled steroids.

Quinsair should only be used with the Zirela Nebuliser Handset (including a Zirela Aerosol Head) provided in the pack connected to an eBase Controller or an eFlow rapid Control Unit (see section 6.6). The Manufacturer's Instructions for Use of the Zirela Nebuliser System should be reviewed prior to the first use of Quinsair.

4.3. Contraindications

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

• History of tendon disorders related to fluoroquinolone administration;

• Epilepsy;

• Pregnancy;

• Breast-feeding.

4.4. Special warnings and precautions for use

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

Prolonged, disabling and potentially irreversible serious adverse drug reactions

Cases of prolonged (continuing for months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (including musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. There are no pharmacological treatments established to be effective treatments of the symptoms of long lasting or disabling side effects associated with fluoroquinolones. Levofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice, so that symptoms can be appropriately investigated and to avoid further exposure which could potentially worsen adverse reactions.

Hypersensitivity reactions

Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. including angioedema and anaphylactic shock).

Severe bullous reactions

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with systemic administration of levofloxacin (see section 4.8).

Hepatobiliary disorders

Cases of hepatic necrosis up to fatal hepatic failure have been reported with systemically administered levofloxacin, primarily in patients with severe underlying diseases (e.g. sepsis, see section 4.8). Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen.

QT interval prolongation

Caution should be taken when using fluoroquinolones, including levofloxacin, in patients with known risk factors for prolongation of the QT interval (see sections 4.5, 4.8 and 4.9) such as, for example:

• Congenital long QT syndrome.

• Concomitant use of active substances that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, 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 medicinal products. Therefore, caution should be taken when using fluoroquinolones, including levofloxacin, in these populations.

Patients predisposed to seizures

Quinolones may lower the seizure threshold and may trigger seizures (see section 4.8). Levofloxacin is contraindicated in patients with a history of epilepsy (see section 4.3) and, as with other quinolones, should be used with extreme caution in patients predisposed to seizures or on concomitant treatment with active substances that lower the cerebral seizure threshold, such as theophylline (see section 4.5).

Psychotic reactions

Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In very rare cases, these have progressed to suicidal thoughts and self-endangering behaviour - sometimes after only a single dose of levofloxacin (see section 4.8). Caution is recommended if levofloxacin is used in psychotic patients or in patients with a history of psychiatric disease.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with levofloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition (see section 4.8).

Exacerbation of myasthenia gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Post-marketing serious adverse reactions, including deaths and the requirements for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Levofloxacin is not recommended in patients with a known history of myasthenia gravis.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (especially, but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, patients receiving daily doses of 1,000 mg levofloxacin, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

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

Tendinitis was reported in patients with CF receiving Quinsair as an uncommon adverse reaction during clinical trials (see section 4.8).

Bronchospasm

Bronchospasm is a complication associated with inhaled therapies including Quinsair (see section 4.8). If acute, symptomatic bronchospasm occurs after receiving treatment, patients may benefit from the use of a short-acting inhaled bronchodilator prior to subsequent doses (see section 4.2).

Haemoptysis

The use of inhaled medicinal products may induce a cough reflex. Administration of Quinsair in patients with clinically significant haemoptysis should be undertaken only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone medicinal products. Therefore, if levofloxacin has to be used in these patients, potential occurrence of haemolysis should be monitored.

Patients treated with vitamin K antagonists

Due to possible increases in coagulation tests (PT/INR) and/or bleeding in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these active substances are given concomitantly (see section 4.5).

Dysglycaemia

Disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic medicinal product (e.g. glibenclamide) or with insulin. In diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

Clostridium difficile-associated disease

Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with levofloxacin (including several weeks after treatment), may be symptomatic of Clostridium difficile-associated disease (CDAD). CDAD may range in severity from mild to life-threatening, the most severe form of which is pseudomembranous colitis.

Resistance to levofloxacin, other antibacterial medicinal products and treatment-emergent microorganisms

The development of fluoroquinolone-resistant P. aeruginosa and superinfection with fluoroquinolone-insusceptible microorganisms represent potential risks associated with the use of Quinsair. If superinfection occurs during therapy, appropriate measures should be taken.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8).

Prevention of photosensitisation

Photosensitisation has been reported with levofloxacin (see section 4.8). It is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium) during treatment and for 48 hours following treatment discontinuation in order to prevent photosensitisation.

Interference with laboratory tests

In patients treated with levofloxacin, determination of opiates in urine may give false-positive results. It may be necessary to confirm positive opiate screens by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and, therefore, may give false-negative results in the bacteriological diagnosis of tuberculosis.

Aortic aneurysm and dissection, and heart valve regurgitation/incompetence

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

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease or congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection or heart valve disease, or in presence of other risk factors or conditions predisposing

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

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

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

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

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

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

4.5. Interaction with other medicinal products and other forms of interaction

Effect of other medicinal products on levofloxacin

Levofloxacin is primarily excreted unchanged in the urine and metabolism is minimal (see section 5.2). Interactions with CYP inhibitors or inducers are thus not expected.

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs

No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study. However, a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, non-steroidal anti-inflammatory drugs, or other substances which lower the seizure threshold. Levofloxacin concentrations were about 13% higher in the presence of fenbufen than when administered alone.

Probenecid and cimetidine

The renal clearance of levofloxacin was reduced by cimetidine (24%) and probenecid (34%). This is because both active substances are capable of blocking the renal tubular secretion of levofloxacin. However, at the tested doses in the study, the statistically significant kinetic differences are unlikely to be of clinical relevance. Caution should be exercised when levofloxacin is coadministered with active substances that affect the tubular renal secretion such as probenecid and cimetidine, especially in patients with renal impairment.

Other relevant information

Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not affected to any clinically relevant extent when levofloxacin was administered together with the following active substances: calcium carbonate, digoxin, glibenclamide and ranitidine.

Effect of levofloxacin on other medicinal products

CYP1A2 substrates

In a pharmacokinetic interaction study, levofloxacin did not affect the pharmacokinetics of theophylline (which is a probe substrate for CYP1A2) indicating that levofloxacin is not a CYP1A2 inhibitor.

CYP2C9 substrates

An in vitro study indicated a low potential for interaction between levofloxacin and CYP2C9 substrates.

Interactions mediated by effects on transporters

In vitro studies demonstrated that inhibition of the key transporters associated with drug disposition in the kidney (organic anion-transporting polypeptide-1B1 (OATP1B1), OATP1B3, organic anion transporter-1 (OAT1), OAT3 and organic cationic transporter-2 (OCT2)) at exposures following inhalation of 240 mg levofloxacin twice daily is low.

Furthermore, clinical data do not suggest interaction with P-glycoprotein (P-gp) substrates such as digoxin.

Ciclosporin

The half-life of ciclosporin was increased by 33% when coadministered with levofloxacin.

Vitamin K antagonists

Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists (see section 4.4).

Active substances known to prolong the QT interval

Levofloxacin should be used with caution in patients receiving active substances known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

4.6. Fertility, pregnancy and lactation

Pregnancy

There is a limited amount of data from the use of levofloxacin in pregnant women. Animal studies with levofloxacin do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

However, in the absence of human data and findings in non-clinical studies suggesting a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, use of Quinsair is contraindicated during pregnancy (see sections 4.3 and 5.3).

Breast-feeding

There is insufficient information on the excretion of levofloxacin/metabolites in human milk; however, other fluoroquinolones are excreted in breast milk.

In the absence of human data and findings in non-clinical studies suggesting a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, use of Quinsair is contraindicated in breast-feeding women (see sections 4.3 and 5.3).

Fertility

Levofloxacin caused no impairment of fertility or reproductive performance in rats (see section 5.3).

4.7. Effects on ability to drive and use machines

Quinsair has minor influence on the ability to drive and use machines. Some adverse reactions (e.g. fatigue, asthenia, visual disturbances, dizziness) may impair patient's ability to concentrate and react. Patients who experience such symptoms should be advised not to drive or use machines.

4.8. Undesirable effects

Summary of the safety profile

The most frequently reported adverse reactions were cough/productive cough (54%), dysgeusia (30%) and fatigue/asthenia (25%).

Tabulated list of adverse reactions reported with Quinsair

The adverse reactions with at least a reasonable possibility of a causal relationship with Quinsair are presented according to the MedDRA System Organ Classification. The adverse drug reactions are ranked by frequency with the most frequent reactions first. The frequency categories are defined using the following convention: very common (≥ 1/10); common (≥ 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); and not known (cannot be estimated from the available data).

System organ class

Very common

Common

Uncommon

Infections and infestations

Vulvovaginal mycotic infection

Oral fungal infection

Blood and lymphatic system disorders

Anaemia*,

Neutropenia*

Immune system disorders

Hypersensitivity*

Metabolism and nutrition disorders

Anorexia*

Psychiatric disorders1

Insomnia*

Anxiety*,

Depression*

Nervous system disorders1

Dysgeusia

Headache,

Dizziness*

Hyposmia*,

Somnolence*,

Peripheral neuropathy

Eye disorders1

Visual disturbance*

Ear and labyrinth disorders1

Tinnitus*

Hearing loss*

Cardiac disorders**

Tachycardia*

Respiratory, thoracic and mediastinal disorders

Cough/productive cough,

Dyspnoea,

Changes in bronchial secretions (volume and viscosity)*,

Haemoptysis

Dysphonia

Bronchospasm***,

Bronchial hyper-reactivity,

Obstructive airways disorder

Gastrointestinal disorders

Nausea,

Vomiting,

Abdominal pain*,

Diarrhoea*,

Constipation*

Retching,

Dyspepsia*,

Flatulence*

Hepatobiliary disorders

Hepatitis*,

Hyperbilirubinaemia*

Skin and subcutaneous tissue disorders

Rash

Urticaria*,

Pruritus*

Musculoskeletal and connective tissue disorders1

Arthralgia,

Myalgia*

Tendinitis,

Costochondritis,

Joint stiffness

Renal and urinary disorders

Renal failure*

General disorders and administration site conditions1

Fatigue/asthenia,

Exercise tolerance decreased

Pyrexia

Investigations

Forced expiratory volume decreased*

Alanine aminotransferase increased,

Aspartate aminotransferase increased,

Pulmonary function test decreased*,

Blood glucose increased and decreased*,

Blood creatinine increased*,

Breath sounds abnormal*

Liver function test abnormal,

Blood alkaline phosphatase increased*,

Electrocardiogram QT prolonged*,

Eosinophil count increased*,

Platelet count decreased*

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

* Adverse events with uncertain relatedness to Quinsair but which are known to be associated with systemic administration of levofloxacin and/or are plausibly associated with Quinsair and were reported more frequently than with placebo in clinical studies.

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

*** See paragraph below for further details.

Tabulated list of additional adverse reactions reported following systemic administration of levofloxacin

The adverse reactions with at least a reasonable possibility of a causal relationship with levofloxacin are presented according to the MedDRA System Organ Classification. The adverse drug reactions are ranked by frequency with the most serious reactions first. The frequency categories are defined using the following convention: very common (≥ 1/10); common (≥ 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); and not known (cannot be estimated from the available data).

System organ class

Uncommon

Rare

Not known

Blood and lymphatic system disorders

Pancytopenia*,

Agranulocytosis*,

Haemolytic anaemia*

Immune system disorders

Angioedema

Anaphylactic shock,

Anaphylactoid shock

Endocrine disorders

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Metabolism and nutrition disorders

Hypoglycaemia

Hyperglycaemia

Hypoglycaemic coma

Psychiatric disorders1

Confusional state,

Nervousness

Psychotic reactions (e.g. hallucination, paranoia),

Agitation,

Abnormal dreams,

Nightmares

Psychotic disorders with self-endangering behaviour including suicidal ideation or suicide attempt

Nervous system disorders1

Tremor

Convulsion,

Paraesthesia

Peripheral sensory neuropathy,

Peripheral sensory motor neuropathy,

Dyskinesia,

Extrapyramidal disorder,

Syncope,

Benign intracranial hypertension

Eye disorders1

Transient vision loss

Ear and labyrinth disorders1

Vertigo

Cardiac disorders**

Palpitation

Ventricular tachycardia,

Ventricular arrhythmia and torsade de pointes

Vascular disorders**

Hypotension

Respiratory, thoracic and mediastinal disorders

Pneumonitis allergic

Hepatobiliary disorders

Jaundice and severe liver injury, including cases with fatal acute liver failure

Skin and subcutaneous tissue disorders

Hyperhidrosis

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS),

Fixed drug eruption

Toxic epidermal necrolysis,

Stevens-Johnson syndrome,

Erythema multiforme,

Photosensitivity reaction,

Leukocytoclastic vasculitis,

Stomatitis

Musculoskeletal and connective tissue disorders1

Muscular weakness,

Tendon rupture,

Tendinitis

Rhabdomyolysis,

Ligament rupture,

Muscle rupture,

Arthritis

General disorders and administration site conditions1

Pain (including pain in back, chest and extremities)

* See paragraph below for further details.

1 Cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, fatigue, psychiatric symptoms, memory impairment, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see section 4.4). A range of psychiatric symptoms may occur as part of these side effects, which may include, but are not necessarily limited to, sleep disorders, anxiety, panic attacks, confusion, or depression. There are no pharmacological treatments established to be effective treatments of the symptoms of long lasting or disabling side effects associated with fluoroquinolones. The frequency of these prolonged, disabling and potentially irreversible serious drug reactions cannot be estimated with precision using available data, but the reporting incidence from adverse drug reaction reports indicates the frequency is at minimum between 1/1,000 and 1/10,000 (corresponding to the Rare frequency category

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

Description of selected adverse reactions

If acute, symptomatic bronchoconstriction occurs after receiving Quinsair, patients may benefit from the use of a short-acting inhaled bronchodilator prior to subsequent doses (see sections 4.2 and 4.4).

Serious haematological adverse reactions such as pancytopenia, agranulocytosis and haemolytic anaemia have been reported following systemic administration of levofloxacin. Their frequency cannot be estimated from available data.

Paediatric population

In clinical trials, 51 adolescents with CF (≥ 12 to < 18 years old) received Quinsair 240 mg twice daily and 6 adolescents with CF received Quinsair 120 mg (n = 3) or 240 mg (n = 3) once daily. In addition, 14 children with CF (≥ 6 to < 12 years old) and 13 adolescents with CF (≥ 12 to < 17 years old) received Quinsair 180 mg or 240 mg once daily for 14 days. Based on these limited data, there does not appear to be any clinically relevant difference in the safety profile of Quinsair in these subsets of the paediatric population compared to adults. However, two cases of arthralgia have been observed in children in clinical studies with Quinsair and long-term safety data are missing especially considering the effects on cartilage observed in animals (see sections 4.2 and 5.3).

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:

Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

In the event of overdose, symptomatic treatment should be implemented. The patient should be observed and appropriate hydration maintained. ECG monitoring should be undertaken because of the possibility of QT interval prolongation. Haemodialysis, including peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD), are not effective in removing levofloxacin from the body. No specific antidote exists.