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Home , Quinolone antibiotic

SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET

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SUMMARY OF PRODUCT CHARACTERISTICS

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1. NAME OF THE MEDICINAL PRODUCT

Ofloxacin 200 mg film-coated tablets

Ofloxacin 400 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 200 mg of ofloxacin.

Each film-coated tablet contains 400 mg of ofloxacin.

Excipient with known effect Each film-coated tablet also contains 96.00 mg of lactose. Each film-coated tablet also contains 228.00 mg of lactose

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

White biconvex capsule-shaped, film-coated tablet marked ‘OF’ breakline ‘200’on one side and ‘G’ on the reverse. Yellow biconvex capsule shaped, film-coated tablet marked ‘OF’ breakline ‘400’on one side and ‘G’ on the reverse.

The tablets can be divided into equal doses.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

The following indications are restricted to adults.

Ofloxacin is suitable for treatment of the following bacterial if these are caused by sensitive to ofloxacin (see sections 4.4 and 5.1):

 Acute and complicated urinary tract infections  Non-gonococcal urethritis and cervicitis  Gonococcal urethritis and cervicitis due to susceptible Neisseria gonorrhoeae

In the following indications, ofloxacin should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections:

 Acute exacerbation of chronic obstructive pulmonary disease including bronchitis  Community-acquired  Uncomplicated cystitis  Urethritis

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

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4.2 Posology and method of administration

Posology

The of ofloxacin is determined by the type and severity of the . The dosage range for adults is 200 mg to 800 mg daily.

Up to 400 mg may be given as a single dose, preferably in the morning. Generally, individual doses should be given at approximately equal intervals.

In individual cases it may be necessary to increase the dose to a maximum total dose of 800 mg daily, which should be given as 400 mg twice daily, at approximately equal intervals. This may be appropriate in infections due to pathogens known to have reduced or variable susceptibility to ofloxacin, in severe and/or complicated infections (e.g. of the respiratory or urinary tracts) or if the patient does not respond adequately.

The following doses are recommended:

Indications Single and Daily Doses Gonococcal urethritis and cervicitis due to 400 mg susceptible Neisseria gonorrhoeae Uncomplicated cystitis 200 mg-400 mg daily Acute pyelonephritis and complicated urinary 400 mg daily, increasing if necessary, to tract infections 400 mg twice a day

Community-acquired pneumonia. 400 mg daily, increasing, if necessary, to Acute exacerbations of chronic obstructive 400 mg twice a day pulmonary disease including bronchitis. Non-gonococcal urethritis and cervicitis 400 mg daily

A single dose of 400 mg of ofloxacin is sufficient for the treatment of gonococcal urethritis and cervicitis due to susceptible Neisseria gonorrhoeae.

Special patient populations

Impaired renal function

Following a normal initial dose, dosage should be reduced in patients with impairment of renal function as determined by creatinine clearance or plasma creatinine level.

Creatinine Clearance Plasma Creatinine Maintenance Dose* 100 mg - 200 mg ofloxacin per 20 to50 ml/min 1.5 to 5 mg/dl day <20ml/min** 100 mg ofloxacin per day >5 mg/dl

* According to indication or dose interval **The serum concentration of ofloxacin should be monitored in patients with severe renal impairment and dialysis patients.

Patients undergoing haemodialysis or peritoneal dialysis should be given 100 mg ofloxacin per day.

When creatinine clearance cannot be measured, it can be estimated with reference to the serum

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creatinine level using the following Cockcroft's formula for adults:

weight(kg) x (140 -age in years) Men: ClCr (ml/min) = ------72 x serum creatinine (mg/dl) or weight(kg) x (140 -age in years) ClCr (ml/min) = ------0.814 x serum creatinine (µmol/l)

Women: ClCr (ml/min) = 0.85 x (above value)

Impaired liver function

The excretion of ofloxacin may be reduced in patients with severe hepatic dysfunction (e.g. cirrhosis of the liver with ascites). In such cases, it is recommended that the dose should not exceed 400 mg ofloxacin daily, because of possible reduction of excretion.

Elderly

No adjustment of dosage is required in the elderly. other than that imposed by consideration of renal or hepatic function see section 4.4 QT interval prolongation).

Paediatric population

Ofloxacin is contraindicated for use in children or growing adolescents (see section 4.3).

Duration

Treatment should not exceed 2 months duration.

A daily dose of up to 400 mg ofloxacin may be given as a single dose. In this case, it is preferable to administer ofloxacin in the morning.

Daily doses of more than 400 mg must be divided into two separate doses and be given at approximately equal intervals.

Method of administration

For oral use.

Ofloxacin tablets should be swallowed whole with sufficient liquid before or during meal times. They should not be taken within two hours of mineral , or metal ion preparations (aluminium, iron, magnesium or zinc), didanosine chewable or buffered tablets (for HIV), since reduction of absorption of ofloxacin can occur (see section 4.5).

4.3 Contraindications

The use of ofloxacin is contraindicated as follows:

 Hypersensitivity to the active substance, to any other fluoroquinolone antibacterials, or to any of the excipients listed in section 6.1.

 In patients with a history of or an existing central nervous system disorder with a lowered seizure threshold. Page 5 of 39

 In patients with a history of tendon disorders related to fluoroquinolone administration

 In children or growing adolescents, and in pregnant or breastfeeding women, since animal experiments do not entirely exclude the risk of damage to the growth-plate cartilage in the growing organism cannot be entirely excluded.

 In patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity because they may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

4.4 Special warnings and precautions for use

The use of ofloxacin 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 ofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3).

Ofloxacin is not the of first choice in pneumonia caused by pneumoniae or Chlamydia pneumoniae.

Methicillin-resistant S. aureus

Methicillin-resistant S. aureus is very likely to possess co-resistance to fluoroquinolones, including ofloxacin. Therefore, ofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratory results have confirmed susceptibility of the organism to ofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA-infections are considered inappropriate).

Resistance to fluoroquinolones of E. coli

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

Streptococcus pneumoniae, β-haemolytic Streptococci and Mycoplasma Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplasma or infection caused by β-haemolytic Streptococci.

Neisseria gonorhoeae infections

Due to increase in resistance to N. gonorrhoeae, ofloxacin should not be used as empirical treatment option in suspected gonococcal infection unless the pathogen has been identified and confirmed as susceptible to ofloxacin. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.

Hypersensitivity and allergic reactions

Hypersensitivity and allergic reactions have been reported for fluoroquinolones after first administration. Anaphylactic and anaphylactoid reactions can progress to life-threatening shock, even after the first administration. In these cases ofloxacin should be discontinued and suitable treatment (e.g. treatment for shock) should be initiated.

Prolonged, disabling and potentially irreversible serious adverse drug reactions

Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible Page 6 of 39

serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Ofloxacin 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.

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 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.

Severe bullous reactions

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with ofloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

Diseases caused by Clostridioides difficile

Diarrhoea, especially if severe, persistent and/or bloody, occurring during or after treatment with ofloxacin (including several weeks after treatment), may indicate a condition caused by Clostridioides difficile, the most severe form of which is pseudomembranous colitis (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with ofloxacin. If pseudomembraneous colitis is suspected, treatment should be discontinued immediately.

Appropriate specific therapy must be started without delay (e.g. oral , oral teicoplanin or ). Medicinal products that inhibit peristalsis are contraindicated in such cases.

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Patients predisposed to seizures

Quinolones may lower the seizure threshold and may trigger seizures. Ofloxacin is contraindicated in patients with a history of epilepsy or with a known predisposition to seizures (see section 4.3) and, as with other quinolones, ofloxacin should be used with extreme caution in patients predisposed to seizures.

Patients with a known predisposition to seizures may include those with pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory (NSAIDs), or with drugs which lower the cerebral seizure threshold, such as (see section 4.5 interactions).

In case of convulsive seizures, treatment with ofloxacin should be discontinued (see section 4.5).

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, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided. The daily dose should be adjusted in elderly patients based on creatinine clearance (see section 4.2). Close monitoring of these patients is therefore necessary if they are prescribed ofloxacin.

All patients should consult their physician if they experience symptoms of tendinitis. At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with ofloxacin 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 occur.

Patients with impaired renal function

Since ofloxacin is eliminated primarily via the kidneys, the dose should be adjusted in patients with impaired renal function (see section 4.2).

Patients with history of psychotic disorder

Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases these have progressed to suicidal thoughts or self-endangering behavior including suicide attempt, sometimes after a single dose of ofloxacin (see section 4.8). In the event that a patient develops these reactions, ofloxacin should be discontinued and appropriate measures instituted.

Ofloxacin should be used with caution in patients with a history of psychotic disorder or in patients with psychiatric disease.

Patients with impaired liver function

Ofloxacin should be used with caution in patients with impaired liver function, as liver damage may occur. Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with fluoroquinolones. 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 (see section 4.8).

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Patients treated with vitamin K antagonists

Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with fluoroquinolones, including ofloxacin, in combination with a vitamin K antagonist (e.g. ), coagulation tests should be monitored when these drugs are given concomitantly (see section 4.5).

Myasthenia gravis

Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and the requirement for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Ofloxacin is not recommended in patients with a known history of myasthenia gravis.

Superinfection

As with other , the use of ofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms, especially Enterococci, resistant strains of some organisms or Candida. Repeated evaluation of the patient's condition is essential and periodic in vitro susceptibility tests may be useful. If secondary infection occurs during therapy, appropriate measures should be taken.

Prevention of photosensitisation

Photosensitisation has been reported with ofloxacin (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.

QT interval prolongation

Very rare cases of QT interval prolongation have been reported in patients taking fluoroquinolones.

Caution should be taken when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example: - elderly patients and women may be more sensitive to QTc-prolonging . Therefore, caution should be taken when using fluoroquinolones, including ofloxacin, in these populations. - uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia) - 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, , antipsychotics) - cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

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

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 these diabetic patients, careful monitoring of blood glucose is recommended.

Peripheral neuropathy

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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 ofloxacin 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).

Patients with glucose-6-phosphate-dehydrogenase deficiency

Patients with latent or diagnosed glucose-6-phosphate-dehydrogenase deficiency may be predisposed to haemolytic reactions if they are treated with quinolones. Therefore if ofloxacin has to be used in these patients, potential occurrence of haemolysis should be monitored.

Interference with laboratory tests

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

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).

Excipient with known effect

Ofloxacin contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Ofloxacin contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’.

4.5 Interaction with other medicinal products and other forms of interaction

Antacids, Sucralfate, Metal Cations

Co-administered magnesium/aluminum antacids, sucralfate, zinc or iron preparations and didanosine chewable/buffered tablets can reduce absorption of ofloxacin. Therefore, ofloxacin should be taken 2 hours before such preparations.

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

No pharmacokinetic interactions of ofloxacin 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, nonsteroidal anti-inflammatory drugs, or other agents, which lower the seizure threshold.

In case of convulsive seizures, treatment with ofloxacin should be discontinued.

Probenecid, , , and methotrexate

Probenecid decreased the total clearance of ofloxacin by 24%, and increased AUC by 16%. The proposed mechanism is a competition or inhibition for active transport at the renal tubular excretion. Caution should be exercised when ofloxacin is co-administered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.

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Drugs known to prolong QT interval

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

Vitamin K antagonists

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

Glibenclamide

Ofloxacin may cause a slight increase in plasma glibenclamide levels when administered concurrently, it is therefore recommended that patients treated concomitantly with ofloxacin and glibenclamide be monitored particularly closely. Since hypoglycaemia is then more likely to occur, close monitoring of blood sugar levels is recommended in such cases.

4.6 Fertility, pregnancy and lactation

Pregnancy

Based on a limited amount of human data, the use of fluoroquinolones in the first trimester of pregnancy has not been associated with an increased risk of major malformations or other adverse effects on pregnancy outcome. Animal studies have shown damage to the joint cartilage in immature animals but no teratogenic effects (see section 5.3). Therefore, ofloxacin must not be used during pregnancy (see section 4.3).

Breast-feeding

Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the nursing infant, breast-feeding should be discontinued during treatment with ofloxacin (see section 4.3).

4.7 Effects on ability to drive and use machines

Since there have been occasional reports of drowsiness/somnolence, impairment of skills, dizziness/vertigo and visual disturbances, which may impair the patient’s ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery), patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.

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4.8 Undesirable effects

The information given below is based on data from clinical studies and on extensive post marketing experience.

System organ Uncommon Rare Very rare Not known class (≥1/1,000 to (≥1/10,000 to (< 1/10,000) (cannot be <1/100) <1/1,000) estimated from available data)* Infections and Fungal infection, infestations Pathogen resistance Blood and Anaemia, Agranulocytosis, lymphatic system Haemolytic Bone marrow disorders anaemia, failure, Leucopenia, Pancytopenia Eosinophilia, Thrombo- cytopenia Immune system Anaphylactic Anaphylactic disorders reaction*, shock*, Anaphylactoid Anaphylactoid reaction*, shock* Angioedema* Metabolism and Anorexia Hypoglycaemia in Nutrition diabetics treated disorders with hypoglycaemic agents (see section 4.4), Hyperglycaemia, Hypoglycaemic coma Psychiatric Agitation, Psychotic Psychotic disorders** Sleep disorder, disorder (for e.g. disorder and Insomnia hallucination), depression with Anxiety, self-endangering Confusional state, behaviour Nightmares, including suicidal Depression ideation or suicide attempt (see Section 4.4), Nervousness

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System organ Uncommon Rare Very rare Not known class (≥1/1,000 to (≥1/10,000 to (< 1/10,000) (cannot be <1/100) <1/1,000) estimated from available data)* Nervous system Dizziness, Somnolence, Peripheral Tremor, disorders** Headache Paraesthesia, sensory Dykinesia, Dysgeusia, neuropathy*, Ageusia, Parosmia Peripheral Syncope, sensory motor Benign neuropathy*, intracranial Convulsion*, hypertension Extra-pyramidal (Pseudotumor symptoms or cerebri) other disorders of muscular coordination Eye disorders** Eye irritation Visual Uveitis disturbance Ear and labyrinth Vertigo Tinnitus, Hearing impaired disorders** Hearing loss Cardiac Tachycardia Ventricular disorders*** and (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9) Vascular Hypotension disorders*** Respiratory, Cough, Dyspnoea, Allergic thoracic and Nasopharyngitis Bronchospasm pneumonitis, mediastinal Severe dyspnoea disorders Gastrointestinal Abdominal pain, Enterocolitis, Pseudo- Dyspepsia, disorders Diarrhoea, sometimes membranous Flatulence, Nausea, haemorrhagic colitis* Constipation, Vomiting Pancreatitis

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System organ Uncommon Rare Very rare Not known class (≥1/1,000 to (≥1/10,000 to (< 1/10,000) (cannot be <1/100) <1/1,000) estimated from available data)* Hepatobiliary Hepatic enzymes Jaundice Hepatitis, which disorders increased (ALAT, cholestatic may be severe, * ASAT, LDH, Severe liver gamma-GT injury, including and/or alkaline cases of acute phosphatase), liver failure, Blood bilirubin sometimes fatal, increased have been reported with ofloxacin, primarily in patients with underlying liver disorders (see section 4.4).

Skin and Pruritus, Urticaria, Erythema Stevens-Johnson subcutaneous Rash Hot flushes, multiforme, syndrome, tissue disorders Hyperhidrosis, Toxic epidermal Acute generalised Pustular rash necrolysis, exanthemous Photo-sensitivity pustulosis, reaction*, Drug rash, , Stomatitis, Vascular purpura, Exfoliative Vasculitis, which dermatitis can lead in exceptional cases to skin necrosis

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System organ Uncommon Rare Very rare Not known class (≥1/1,000 to (≥1/10,000 to (< 1/10,000) (cannot be <1/100) <1/1,000) estimated from available data)* Musculoskeletal Tendonitis Arthralgia, Rhabdomyolysis and connective Myalgia, and/or Myopathy, tissue disorders** Tendon rupture Muscular (e.g. Achilles weakness, tendon) which Muscle tear, may occur within Muscle rupture, 48 hours of Ligament rupture, treatment start Arthritis and may be bilateral Renal and urinary Serum creatinine Acute renal Acute interstitial disorders increased failure nephritis Congenital, Attacks of familial and porphyria in genetic disorders patients with porphyria General disorders Asthenia, and Pyrexia, administration Pain (including site conditions** pain in back, chest and extremities) * postmarketing experience ** 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 tendinitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see section 4.4). *** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).

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[to be completed nationally]

4.9 Overdose

Symptoms

The most important signs to be expected following acute overdose are CNS symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures increases in QT interval as well as gastrointestinal reactions such as nausea and mucosal erosions.

CNS effects including confusional state, convulsion, hallucination, and tremor have been observed in post marketing experience.

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Management

In the case of overdose steps to remove any unabsorbed ofloxacin e.g. gastric lavage, administration of adsorbants and sodium sulphate, if possible during the first 30 minutes, are recommended; antacids are recommended for protection of the gastric mucosa.

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Antacids may be used for protection of gastric mucosa. A fraction of ofloxacin may be removed from the body with haemodialysis. Peritoneal dialysis and CAPD are not effective in removing ofloxacin from the body. No specific antidote exists.

Elimination of ofloxacin may be increased by forced diuresis.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Quinolone Antibacterials, Fluoroquinolones. ATC code: J01 MA 01

Mechanism of action

Ofloxacin inhibits bacterial DNA replication by inhibiting bacterial , particularly DNA gyrase and IV. It is active after oral administration. Therapeutic doses of ofloxacin are devoid of pharmacological effects on the voluntary or autonomic nervous system. The NCCLS MIC breakpoint recommendations are as follows: S ≤ 2 mg/l and R ≥ 8 mg/l Intermediate susceptibility at 4 mg/l

Haemophilus influenzae and Neisseria gonorrhoea are exceptions with breakpoints at S ≤ 0.25 mg/l and R ≥ 1 mg/l

The BSAC general recommendations are S ≤ 2 mg/l and R ≥ 4 mg/l

According to DIN 58 940, the following limits apply for ofloxacin: S ≤ 1 mg/L, I =2 mg/L, R ≥ 4 mg/L.

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance on probabilities whether micro-organisms will be susceptible to ofloxacin or not.

Only those pathogens relevant to the indications are listed.

European range of acquired bacterial resistance to ofloxacin Normally susceptible Aerobic Gram-positive micro organisms S. aureus - methicillin-sensitive 0.3-12.6% S. pyogenes 2-5% Aerobic Gram-negative micro organisms spp 0.3-7.3% Citrobacter spp. 3-15%

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Enterobacter spp. 2-13% E. coli 1-8% H. influenzae 1% Klebsiella spp. 1-10% Moraxella spp. 0-0.2% Morganella morganii 0-6.9% N. gonorrhoeae 25% Proteus spp. 1-15% Serratia marcescens 2-2.4% Others Chlamydia spp L. pneumophila

Intermediately susceptible Aerobic Gram-positive micro organisms S. pneumoniae 70% Providentia 17.1% Aerobic Gram-negative micro organisms E. faecalis 50% P. aeruginosa 20-30% Serratia spp. 20-40% Stenotrophomonas maltophilia 5.1-11% Others Mycoplasma spp. 0-5.3% Ureaplasma spp. 0-2.1%

Resistant Anaerobic bacteria S. aureus - methicillin-resistant 69.2-85.7% T. pallidum

Resistance

The main mechanism of bacterial resistance to ofloxacin involves one or more in the target enzymes, which generally confer resistance to other active substances in the class. pump and impermeability mechanisms of resistance have also been described and may confer variable resistance to active substances in other classes.

5.2 Pharmacokinetic properties

Absorption

The administration of oral doses to fasting volunteers was followed by a rapid and almost complete absorption of ofloxacin. The peak plasma concentration after a single oral dose of 200 mg averaged 2. 6 µg/ml and was reached within one hour. The plasma elimination half-life was 5.7 to 7 hours and was not dose related.

Distribution

The apparent distribution volume was 120 litres. The plasma concentration did not materially rise with repeat doses (accumulation factor for twice daily dosage: 1.5). The plasma protein binding was approx. 25%. Page 17 of 39

Biotransformation

The biotransformation of ofloxacin was below 5%. The two main metabolites found in the urine were N-desmethyl-ofloxacin and ofloxacin-N-oxide.

Elimination

Excretion is primarily renal. Between 80 and 90% of the dose were recovered from the urine as unchanged substance.

Ofloxacin was present in the bile in glucuronidised form. The pharmacokinetics of ofloxacin after intravenous infusion are very similar to those after oral doses. The plasma half-life is prolonged in persons with renal insufficiency; total and renal clearance decrease in accordance with the creatinine clearance. In renal insufficiency the dose should be reduced.

No clinically relevant interactions were seen with food and no interaction was found between ofloxacin and theophylline.

5.3 Preclinical safety data

Preclinical effects in conventional studies of safety pharmacology, acute toxicity, repeated dose toxicity, reproductive studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Joint toxicity was observed at exposure in the human therapeutic range in juvenile rats and dogs. Ofloxacin exhibits a neurotoxic potential and causes reversible testicular alterations at high doses.

Mutagenicity studies showed no evidence for mutagenicity of ofloxacin. However, like some other quinolones Ofloxacin is phototoxic in animals at exposure in the human therapeutic range. The phototoxic, photomutagenic and photocarcinogenic potential of ofloxacin is comparable with that of other gyrase inhibitors.

Preclinical data from conventional genotoxicity studies reveal no special hazard to humans, carcinogen potential has not be investigated.

Reproduction toxicity

Ofloxacin has no effect on fertility, peri- or postnatal development, and therapeutic doses did not lead to any teratogenic or other embryotoxic effects in animals. Ofloxacin crosses the placenta and levels reached in the amniotic fluid are about 30% of the maximal concentrations measured in maternal serum.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients {200 mg tablets} Tablet core Maize starch Lactose Hydroxypropylcellulose Croscarmellose sodium Magnesium stearate

Film-coating Page 18 of 39

Hypromellose Titanium dioxide (E171) Macrogol 400 Talc

{400 mg tablets} Tablet core Maize starch Lactose Hydroxypropylcellulose Sodium starch glycollate (type A) Magnesium stearate

Film-coating Hypromellose Talc Titanium dioxide (E171) Macrogol 400 Iron oxide yellow (E172) Iron oxide black (E172) Carnauba wax

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Aluminium PVC/PVDC blisters and polypropylene bottles with polyethylene tamper evident closure (with optional polyethylene ullage filler).

Obtainable in the following pack sizes: {200 mg tablets}: 3, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 30, 50, 100, 250 tablets. {400 mg tablets}: 5, 6, 7, 10, 12, 14, 16, 20, 24, 30, 50, 100, 250 tablets.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

[To be completed nationally]

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8. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10. DATE OF REVISION OF THE TEXT

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LABELLING

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Cardboard Carton

1. NAME OF THE MEDICINAL PRODUCT

Ofloxacin 200 mg film-coated tablets Ofloxacin 400 mg film-coated tablets ofloxacin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 200 mg ofloxacin Each tablet contains 400 mg ofloxacin

3. LIST OF EXCIPIENTS

Contains lactose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Film-coated tablet.

3 tablets {200 mg only} 5 tablets 6 tablets 7 tablets 8 tablets {200 mg only} 10 tablets 12 tablets 14 tablets 16 tablets 20 tablets 24 tablets 30 tablets 50 tablets 100 tablets 250 tablets.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For oral use as directed by a doctor. Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

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Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP:

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

LOT:

14. GENERAL CLASSIFICATION FOR SUPPLY

[To be completed nationally]

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE ofloxacin 200 mg tablets ofloxacin 400 mg tablets

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17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: SN: NN:

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

Bottle Label

1. NAME OF THE MEDICINAL PRODUCT

Ofloxacin 200 mg film-coated tablets Ofloxacin 400 mg film-coated tablets ofloxacin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 200 mg ofloxacin Each tablet contains 400 mg ofloxacin

3. LIST OF EXCIPIENTS

Contains lactose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Film-coated tablet.

3 tablets {200 mg only} 5 tablets 6 tablets 7 tablets 8 tablets {200 mg only} 10 tablets 12 tablets 14 tablets 16 tablets 20 tablets 24 tablets 30 tablets 50 tablets 100 tablets 250 tablets.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For oral use as directed by a doctor. Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

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Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP:

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

LOT:

14. GENERAL CLASSIFICATION FOR SUPPLY

[To be completed nationally]

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

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18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Aluminium Blister Strips

1. NAME OF THE MEDICINAL PRODUCT

Ofloxacin 200 mg film-coated tablets Ofloxacin 400 mg film-coated tablets ofloxacin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

3. EXPIRY DATE

EXP:

4. BATCH NUMBER

LOT:

5. OTHER

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PACKAGE LEAFLET

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Package leaflet: information for the patient

Ofloxacin 200 mg Film-coated Tablets Ofloxacin 400 mg Film-coated Tablets ofloxacin

Read all of this leaflet carefully before you start taking 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 Ofloxacin is and what it is used for 2. What you need to know before you take Ofloxacin 3. How to take Ofloxacin 4. Possible side effects 5. How to store Ofloxacin 6. Contents of the pack and other information

1. What Ofloxacin is and what it is used for

Ofloxacin belongs to a group of medicines called quinolone antibiotics. Ofloxacin is an antibiotic that can be used to treat a variety of different infections. These include infections of:  the chest (respiratory system) such as pneumonia and bronchitis.  the bladder and kidneys (urinary tract).  the male and female genital organs when the infections involve the cervix (neck of the womb in women) and the lower genital organs in men. Ofloxacin can be used to treat both gonorrhoea and some other genital infections of both the male and female genital organs.

2. What you need to know before you take Ofloxacin

Do not take Ofloxacin - If you are allergic to ofloxacin or any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. - If you have previously had an allergic reaction to another quinolone antibiotic e.g. or . - If you suffer from epilepsy or are at risk of fits. - If you have a history of inflammation and swelling of the tendons (tendonitis) which can affect areas such as the wrist or the achilles tendon after treatment with a quinolone antibiotic e.g. ciprofloxacin, norfloxacin, or . - If you suffer from or there is a family history of glucose-6-phosphate dehydrogenase deficiency (an inherited disorder that affects the red blood cells) - If you are pregnant, think you may be pregnant or are planning to have a baby. - If you are breastfeeding. - If you are under the age of 18 years, or are still growing.

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Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Ofloxacin.

Warnings and precautions

Before taking this medicine You should not take fluoroquinolone/quinolone antibacterial medicines, including Ofloxacin, 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 or pharmacist before taking Ofloxacin if any of the following apply: - 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 been diagnosed with leaking heart valves (heart valve regurgitation) - if you have a family history of aortic aneurysm or aortic dissection or congenital heart valve disease, or other risk factors or predisposing conditions (e.g. connective tissue disorders such as Marfan syndrome or Ehlers- Danlos syndrome, Turner syndrome, Sjögren’s syndrome (an inflammatory autoimmune disease), or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behcet’s disease, high blood pressure, or known atherosclerosis, rheumatoid arthritis (a disease of the joints) or endocarditis (an infection of the heart)). - you have or have ever had a history of mental illness. - you have problems with your liver or kidneys. - you have heart disease or problems with your heartbeat. - 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. - you are taking other medicines that result in abnormal ECG changes (see section Other medicines and Ofloxacin). - you have an illness of the nervous system called ‘myasthenia gravis’ (muscle weakness). - if you are diabetic or suffer from low blood sugar.

During treatment

When taking this medicine

If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately.

If you:  experience a severe skin rash or allergic reaction, or  develop severe diarrhoea, (which may be bloody) with stomach pain and fever, or  notice pain, tenderness, or restricted movement of the tendons, or  notice numbness or tingling in the hands and feet stop taking this medicine and talk to your doctor straight away. If you feel sudden, severe pain in your abdomen, chest or back, which can be symptoms of aortic aneurysm and dissection, go immediately to an emergency room. Your risk may be increased if you are being treated with systemic corticosteroids.

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If you feel sudden, severe pain in your abdomen, chest or back, which can be symptoms of aortic aneurysm and dissection, go immediately to an emergency room. Your risk may be increased if you are being treated with systemic corticosteroids.

If you start experiencing a rapid onset of shortness of breath, especially when you lie down flat in your bed, or you notice swelling of your ankles, feet or abdomen, or a new onset of heart palpitations (sensation of rapid or irregular heartbeat), you should inform a doctor immediately.

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 Ofloxacin therapy. At the first sign of pain or inflammation of a tendon (for example in your ankle, wrist, elbow, shoulder or knee), stop taking Ofloxacin, contact your doctor and rest the painful area. Avoid any unnecessary exercise as this might increase the risk of a tendon rupture.

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 Ofloxacin and inform your doctor immediately in order to prevent the development of potentially irreversible condition.

Prolonged, disabling and potentially irreversible serious side effects Fluoroquinolone/quinolone antibacterial medicines, including Ofloxacin, 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 Ofloxacin, 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 are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Ofloxacin.

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

You must tell your doctor if you are taking other medicines that can alter your heart rhythm: - medicines that belong to the group of anti-arrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), - tricyclic antidepressants, (e.g. clomipramine, amitriptyline), - some (that belong to the group of macrolides e.g. erythromycin, clarithromycin, ), - some antipsychotics used to treat mental health conditions such as schizophrenia and bipolar disorder.

Tell your doctor if you are taking any of the following medicines: - medicines or dietary supplements that contain iron (for anaemia) or zinc. - sucralfate used for stomach ulcers. - antacids used for indigestion that contain magnesium or aluminium. - corticosteroids, used for treatment of inflammation and swelling or over-active immune system. These may increase the risk of you developing a tendon rupture. Page 32 of 39

- painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibuprofen or diclofenac, or theophylline, used to treat asthma or chronic obstructive pulmonary disease as these could make you more prone to fits if taken with ofloxacin. - glibenclamide, a medicine to control your blood sugar, as the amount of these medicines in the blood may increase and have a greater effect. - drugs that may affect your kidney function e.g. cimetidine (used for stomach ulcers or indigestion), probenecid (used for gout) and methotrexate (used for rheumatism) as they can increase the level of ofloxacin in the blood. - medicines to thin your blood, e.g. warfarin. Taking these with ofloxacin can increase the time it takes for your blood to clot. - If you are taking didanosine (a medicine used to treat HIV infections), you should not take the chewable, buffered tablets until at least two hours after taking ofloxacin. - water tablets (diuretics) such as furosemide.

This medicine should not be taken within two hours of taking iron or zinc tablets, antacids, or sucralfate, as these medicines can stop Ofloxacin from working properly.

If you are due to have urine tests for porphyrin (a pigment in the blood), or for opiates (strong painkillers), tell your doctor or nurse you are taking this medicine.

Pregnancy and breast-feeding Do not take Ofloxacin if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby. If you become pregnant while taking Ofloxacin, stop taking the tablets and contact your doctor immediately.

Driving and using machines Taking Ofloxacin may make you feel sleepy, dizzy or could affect your eyesight. Do not drive or use machines until you know how this medicine affects you. Drinking alcohol may make these symptoms worse.

Ofloxacin contains lactose If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

3. How to take Ofloxacin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

 For oral use. You should swallow these tablets whole with water. Do not chew them.  The tablets can be taken with or without food and can be divided into equal doses.  When taking Ofloxacin, avoid strong sunlight and do not use sun lamps or solaria as your skin may be more sensitive to light.  If you are taking iron tablets (for anaemia), antacids (for indigestion or heartburn) or sucralfate (for stomach ulcers) or didanosine chewable or buffered tablets (for HIV), it is important not to take these two hours before or after taking Ofloxacin.  If you feel the effect of your medicine is too weak or strong, do not change the dose yourself, but ask your doctor.

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 When taking Ofloxacin, if your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately

When to take your medicine

 The length of your treatment will depend on how serious your infection is.  Treatment should not be longer than 2 months.  Doses up to 400 mg are taken as a single dose in the morning.  Higher doses should be taken in two doses, one in the morning and one in the evening.

How much to take

Adults (including the elderly): The dose to be taken will depend on the location and the type of infection to be treated. For most infections the recommended dose is between 200 mg and 400 mg of Ofloxacin daily, preferably in the morning. For more severe infections your doctor may increase the dose to 400 mg of Ofloxacin twice daily (morning and evening).

The recommended doses for different infections are shown below. However, your doctor may decide you need a different dose.

To treat simple urine infections: The recommended dose is 200 mg or 400 mg of Ofloxacin daily.

To treat complicated upper urinary tract infections: The recommended dose is 400 mg of Ofloxacin daily. If necessary, your doctor may increase this to 400 mg twice a day.

To treat gonorrhoea of the lower organs only: A single dose of 400 mg of Ofloxacin in the morning is usually enough. To treat other infections of the lower genital organs for which Ofloxacin is a suitable antibiotic, the dose is usually 400 mg each day.

To treat a chest or lung infection: The recommended dose is 400 mg of Ofloxacin daily. If necessary, your doctor may increase this to 400 mg twice a day.

If you have liver problems: Your doctor may give you a lower dose of Ofloxacin. It is recommended that the dose should not exceed 400 mg Ofloxacin daily.

If you have kidney problems: Your doctor may recommend that you take an initial dose as recommended above, then the dose may be reduced. It is recommended that the dose should not exceed 200 mg of Ofloxacin daily.

Use in children and adolescents Children or adolescents under 18 years of age should not take these tablets.

If you take more Ofloxacin than you should If you take more tablets than you should you may become confused and dizzy or lose consciousness, you may have a seizure or fit, and you may feel sick. Contact your doctor or nearest hospital casualty department immediately. Take the container and any remaining tablets with you.

If you forget to take Ofloxacin If you forget to take a dose take it as soon as you remember unless it is nearly time for your next dose. Do not take a double dose to make up for a forgotten tablet.

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If you stop taking Ofloxacin Your doctor will tell you how long you need to take your tablets for. Do not suddenly stop taking this medicine without talking to your doctor first. If you stop, your infection may get worse again. If you feel the effect of your medicine is too weak or strong, do not change the dose yourself, but ask your doctor.

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

4. Possible side effects

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

Stop taking Ofloxacin, tell your doctor or go to your nearest hospital casualty department straight away if you have any of the following serious side effects because you may need medical attention:

Uncommon (may affect up to 1 in 100 people) . resistance of infection causing organisms to this treatment, (you may fail to respond to treatment)

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

. you have an allergic reaction. Such reactions may appear in the form of anaphylaxis (a severe form of allergic reaction) with symptoms such as: - severe skin rash - swelling of the face, lips, mouth, tongue or throat (angioedema) - anaphylactic shock (sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or difficulties in swallowing) . inflammation of the bowel, which may cause severe watery diarrhoea, which may have blood in it, possibly with stomach cramps and a high temperature . swelling of the tendons with the following symptoms; pain, tenderness, sometimes restricted movement (tendonitis). This can lead to tendon rupture, especially of the large tendon at the back of the ankle (Achilles tendon). The risk of this occurring is increased if you are also taking corticosteroids e.g. prednisolone . numbness or tingling in the hands and feet or being very sensitive to touch, numbness or weakness of the arms and legs . blurred, double or altered colour vision. If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately.

Very rare (may affect up to 1 in 10,000 people) . a condition in which the amount of oxygen-carrying pigment (haemoglobin) in the blood is below normal or an illness resulting from the destruction of red blood cells with the following symptoms; feeling tired, faint, dizzy, being short of breath when exercising and having pale skin. These may be signs of anaemia or haemolytic anaemia. . other blood disorders when the numbers of different types of cells in the blood may fall, which may cause fever, chills, sore throat, ulcers in the mouth and throat (leucopenia, agranulocytosis) . fits (seizures) . skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with dark ring around the edge) (erythema multiforme) . a widespread rash with blisters and skin peeling on much of the body surface (toxic epidermal necrolysis).

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. narrowing, blockage or leakage of blood vessels, in exceptional cases leading to severe skin reactions and death of areas of the skin . severe kidney problems, which may result in your kidneys stopping working. Signs may include a rash, high temperature, general aches and pains, or blood in the urine . hearing problems or hearing loss . liver problems, such as inflammation of the liver (hepatitis) or blockage in the bile duct, that may cause your eyes or skin to go yellow (jaundice) or you may notice the following symptoms; nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, light coloured bowel motions, dark coloured urine

Not known (frequency cannot be estimated from the available data) . 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) . severe depression or mental illness. Some people who are depressed think of harming or killing themselves. . a serious reduction in all types of blood cells (pancytopenia), which may result from a failure of the bone marrow to produce these . a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens Johnson syndrome). . swelling of the lungs with the following symptoms; coughing, difficulty breathing, wheezing . temporary paralysis or weakness of the muscles (rhabdomyolysis), disease of the muscles with the following symptoms; aching muscles, muscle tenderness or weakness, not caused by exercise . an attack of porphyria (a rare blood pigment disorder) in patients with this disease . muscle or ligament rupture . inflammation of the pancreas (pancreatitis) – you may have severe pain in the stomach and back . loss of consciousness (coma), due to a severe reduction in blood sugar levels . inflammation of the eye (uveitis) . skin redness with excessive scaling (exfoliative dermatitis) . loss of appetite, skin and eyes becoming yellow in colour, dark-coloured urine, itching, or tender stomach (abdomen). These may be signs of liver problems which may include a fatal failure of the liver.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

Uncommon (may affect up to 1 in 100 people) . feeling sick (nausea) or being sick (vomiting), diarrhoea or stomach pains . irritated or burning eyes . headaches, sleep disturbances including difficulty sleeping (insomnia) . feeling dizzy, having spinning sensations . agitation, feeling restless . cough and inflamed sore nose or throat (nasopharyngitis) . fungal infection . skin rash or itching

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Rare (may affect up to 1 in 1,000 people) . loss of appetite . fast heart beat . drowsiness . feeling confused or anxious, nightmares, seeing, feeling or hearing things that are not there, depression and mental illness . changes in or loss of your sense of taste or smell . shortness of breath or wheezing . changes in levels of liver enzymes or bilirubin, which may be seen in blood tests . excessive sweating and hot flushes . changes in kidney function shown in blood tests . feeling faint, lightheaded or dizzy, which may be due to low blood pressure . hives (urticaria) . rash with pimples

Very rare (may affect up to 1 in 10,000 people) . uncontrolled movements, unsteadiness and shaking . unusual bleeding or bruising more easily than normal (thrombocytopenia) . increase in some white blood cells (eosinophilia) . ringing in the ears (tinnitus) . joint and muscle pains . skin rashes or eruptions, which may be caused by strong sunlight . unusual purple discolouration under the skin, which may be due to bleeding or bruising due to leaky or damaged blood vessels

Not known (frequency cannot be estimated from the available data) . a red, scaly rash with bumps under the skin and blisters (exanthemous pustolosis) . muscular weakness, muscle tear . feeling weak or irritable, sweating and/or trembling. This could be due to lowering of blood sugar (glucose) levels especially in patients with diabetes or existing low blood sugar . an increase in blood sugar levels . feeling of nervousness, tremor, unusual (involuntary) muscle movements, . fainting . digestive problems such as stomach upset (indigestion/heartburn), constipation, or wind . general pain, pains in your muscles and stiffness in the bones/joints (arthritis), feeling unwell (asthenia), or fever . persistent headache with or without blurred vision (benign intracranial hypertension)

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.

Cases of an enlargement and weakening of the aortic wall or a tear in the aortic wall (aneurysms and dissections), which may rupture and may be fatal, and of leaking heart valves have been reported in patients receiving fluoroquinolones. See also section 2.

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.

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You can also report side effects directly via [to be completed nationally]. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Ofloxacin

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

Do not take this medicine after the expiry date shown on the pack. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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.

6. Contents of the pack and other information

What Ofloxacin contains - The active substance is ofloxacin. Each film-coated tablet contains 200 mg or 400 mg ofloxacin. - The other ingredients are: 200 mg tablets: maize starch, lactose, hydroxypropyl cellulose, croscarmellose sodium magnesium stearate, hypromellose, titanium dioxide (E171), talc and macrogol 400. 400 mg tablets: maize starch, lactose, hydroxypropylcellulose, sodium starch glycollate (type A), magnesium stearate, hypromellose, talc, titanium dioxide (E171), macrogol 400, iron oxide yellow (E172), iron oxide black (E172) and carnauba wax.

What Ofloxacin looks like and contents of the pack The 200 mg tablets are white capsule-shaped film-coated tablets marked ‘OF’ breakline ‘200’ on one side and ‘G’ on the other. The tablet can be divided into equal doses.

The 400 mg tablets are yellow capsule-shaped film-coated tablets marked ‘OF’ breakline ‘400’ on one side and ‘G’ on the other. The tablet can be divided into equal doses.

Ofloxacin is available in blisters or plastic bottles of 3*, 5, 6, 7, 8*, 10, 12, 14, 16, 20, 24, 30, 50, 100 and 250 tablets. *200 mg strength only

Not all pack sizes may be marketed.

Marketing Authorisation Holder: [To be completed nationally]

Manufacturer: McDermott Laboratories Ltd trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland.

This medicinal product is authorised in the Member States of the EEA under the following names:

Belgium Ofloxacine Mylan 200 mg and 400mg filmomhulde tabletten Netherlands Ofloxacine Mylan 200 mg and 400mg, filmomhulde tabletten Luxembourg Ofloxacine Mylan 200 mg and 400 mg comprimés pelliculés Page 38 of 39

Portugal Ofloxacina Mylan 200 mg comprimidos revestidos United Kingdom Ofloxacin 200 mg and 400 mg Tablets

This leaflet was last revised in

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