Levofloxacin Trinity 250 mg / 500 mg FC tablets

LEVOFLOXACIN TRINITY can be used in adults, in the treatment of the following bacterial infections:

• Acute exacerbations of chronic bronchitis: caused by H. influenzae, K. pneumoniae, M. catarrhalis, H. parainfluenzae or S. pneumoniae.
• Pneumonia (community acquired): caused by H. influenzae, S. pneumoniae, M.catarrhalis, H. parainfluenzae, K. pneumonia, Mycoplasma pneumoniae, Chlamydia pneumoniae or Legionella pneumophila.
• Sinusitis: caused by H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis or H. parainfluenzae.
• Urinary tract infections (complicated) and acute pyelonephritis: caused by K. pneumoniae, S. faecalis, P. mirabilis, and P. aeruginosa.
• Uncomplicated urinary tract infections in women: caused by K. pneumoniae.
• Skin and soft tissue infections (uncomplicated): caused by S. pyogenes, Acinetobacter calcoaceticus, P. mirabilis, K. pneumoniae or S. faecalis.
• Skin and soft tissue infections (complicated): caused by S. pyogenes, P. mirabilis, K. pneumoniae, S. faecalis, K. oxytoca.
• Intra-abdominal infections: caused by anaerobic micro-organisms.

Posology

LEVOFLOXACIN TRINITY tablets: LEVOFLOXACIN TRINITY tablets should be swallowed whole, without crushing. LEVOFLOXACIN TRINITY tablets may be taken on an empty stomach or with meals. LEVOFLOXACIN TRINITY is to be taken once or twice daily in a usual dose of 250 or 500 mg. The dosage will depend on the type of pathogen and the severity of the infection. The use of LEVOFLOXACIN TRINITY should be continued for a minimum of 48 to 72 hours after it has become evident that the patient has a bacterial infection. The duration of therapy varies according to the course of the disease.

The following daily dose are recommended for LEVOFLOXACIN TRINITY:

• Daily dosage recommended in patients with normal renal function:
• Bronchitis, bacterial exacerbations: 500 mg once daily for 5 u2013 10 days.
• Pneumonia, community acquired: 500 mg once or twice daily for 10 u2013 14 days. (The higher dosage should be chosen in the presence of complicating factors e.g., co-morbidity, advanced age).
• Sinusitis: 500 mg once daily for 10 to 14 days.
• Urinary tract infections, (complicated) and acute pyelonephritis: 250 mg once daily for 10 days.
• Urinary tract infections (uncomplicated) in women: 250 mg once daily for 3 days.
• Uncomplicated skin and soft tissue infections: 250 to 500 mg once daily for 7 u2013 10 days.
• Complicated skin and soft tissue infections: 500 mg once daily for 10 u2013 14 days.
• Intra-abdominal infections: 500 mg once daily in combination with an antibiotic with anaerobic coverage for 10 u2013 14 days.
• Above infections when bacteraemia or septicaemia is present: 500 mg twice daily for 10 u2013 14 days.

Special populations

Renal impairment; Dosage must be adjusted in patients with impaired renal function according to the degree of impairment (creatinine clearance < 50 mL/min):

• Patients with a creatinine clearance between 20 and 50 mL/min:
• 250 or 500 mg once daily: a normal single dose should be given initially and then reduced by half this dose once daily.
• 500 mg twice daily: the initial dose should be 500 mg and then 250 mg should be taken twelve hourly.

• Patients with a creatinine clearance between 10 and 19 mL/min:
• 250 mg once daily: a normal single dose should be given initially and then reduced to 125 mg every 48 hours.
• 500 mg once daily: should be given a normal single dose initially and then this dose should be reduced to 125 mg every 24 hours.
• 500 mg twice daily: should be given 500 mg initially and then this dose should be reduced to 125 mg every 12 hours.

• Patients with a creatinine clearance of less than 10 mL/min or in patients on haemodialysis or CAPD (Continuous Ambulatory Peritoneal Dialysis):
• In patients where the prescribed dosage is 250 mg once daily: a normal single dose should be given initially and then this dose should be reduced to 125 mg every 48 hours.
• 500 mg once daily: should be given a normal single dose initially and then this dose should be reduced to 125 mg every 24 hours.
• 500 mg twice daily: should be given 500 mg initially and then this dose should be reduced to 125 mg every 24 hours.

Elderly population: No adjustment of dosage is required in the elderly in patients.

Hepatic impairment: No adjustment of dosage is required in patients with impaired liver function.

Method of administration

For oral administration.

The use of LEVOFLOXACIN TRINITY is contraindicated in:

• Previous hypersensitivity reaction to levofloxacin, other quinolones, or to any of the ingredients of LEVOFLOXACIN TRINITY listed in section 6.1.
• Epilepsy.
• Patients with history of tendon disorders associated with previous fluoroquinolone administration.
• Children or adolescents (under 18 years of age).
• Pregnancy and lactation (see section 4.6).

Caution should be exercised when using LEVOFLOXACIN TRINITY in patients:

• prone to seizures, such as patients with pre-existing central nervous system lesions,
• being treated with nonsteroidal anti-inflammatory medicines or using medicines which lower the cerebral seizure threshold, such as theophylline,
• being tested for tuberculosis as LEVOFLOXACIN TRINITY inhibit the growth of Mycobacterium tuberculosis and therefore may give false-negative results in the bacteriological diagnosis of tuberculosis,
• exposed to ultraviolet (UVA) from sun beds, in order to prevent photosensitisation,
• with diabetes mellitus, as hypoglycaemia may occur.

Fluoroquinolones, such as LEVOFLOXACIN TRINITY, have been known to trigger porphyria attacks. Suspicion of pseudomembranous colitis requires immediate cessation of treatment with appropriate specific antibiotic therapy. Psychotic reactions have been reported to occur already after the first dose. In the event of psychotic side-effects, LEVOFLOXACIN TRINITY must be discontinued immediately and the doctor informed. LEVOFLOXACIN TRINITY should be used with caution in patients who are psychotic or have a history of psychotic illness. In the event of allergic manifestations, LEVOFLOXACIN TRINITY must be discontinued immediately. Medical treatment (therapy for shock) is imperative. If tendonitis is suspected, treatment with LEVOFLOXACIN TRINITY must be discontinued immediately and appropriate treatment (e.g., immobilisation) must be initiated for the affected tendon. The risk of tendon rupture is higher in the elderly and in patients on corticosteroids. Tendon rupture may occur within 48 hours after starting treatment with LEVOFLOXACIN TRINITY and may be bilateral. It may still occur weeks after stopping treatment with LEVOFLOXACIN TRINITY. Patients with glucose-6-phosphate dehydrogenase deficiency may be prone to haemolytic reactions when treated with quinolone antibacterial agents. Therefore, if LEVOFLOXACIN TRINITY has to be used in these patients, patients should be monitored for potential occurrence of haemolysis. For patients with known risk factors for prolongation of the QT interval such as, for example:

• congenital long QT syndrome
• concomitant use of medicines that are known to prolong the QT interval (e.g., Class IA and III antidysrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
• uncorrected electrolyte imbalance (e.g., hypokalaemia, hypomagnesaemia)
• cardiac disease (e.g., heart failure, myocardial infarction, bradycardia)

Caution should be exercised when taking LEVOFLOXACIN TRINITY. In addition, elderly patients and women may be more sensitive to QTc-prolonging medicines. Therefore, caution should be taken when using fluoroquinolones, including LEVOFLOXACIN TRINITY, in these populations. LEVOFLOXACIN TRINITY may have neuromuscular blocking activity and may therefore exacerbate muscle weakness in patients with myasthenia gravis. LEVOFLOXACIN TRINITY is not recommended in patients with a known history of myasthenia gravis as postmarketing serious adverse reactions, including deaths and the requirement for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Methicillin-resistant S. aureus are likely to possess co-resistance to fluoroquinolones, including levofloxacin. Therefore, for the treatment of known or suspected MRSA infections, LEVOFLOXACIN TRINITY is not recommended. LEVOFLOXACIN TRINITY can be considered if the laboratory results have confirmed susceptibility of the organism to levofloxacin and commonly recommended antibacterial agents for the treatment of MRSA-infections are considered inappropriate.

The absorption of LEVOFLOXACIN TRINITY is significantly reduced when administered with iron salts antacids and sucralfate. It is recommended that preparations containing iron salts, sucralfate, magnesium- or aluminium-containing antacids should not be taken 2 hours before or after LEVOFLOXACIN TRINITY tablet administration. LEVOFLOXACIN TRINITY is known to inhibit metabolism of some medicines and may interfere with the clearance of medicines, such as theophylline, or non u2013 steroidal anti-inflammatory medicines that lower the seizure threshold. LEVOFLOXACIN TRINITY may increase plasma warfarin levels. Close monitoring of INR is therefore required. LEVOFLOXACIN TRINITY may disturb blood glucose levels, both hypoglycaemia and hyperglycaemia have been reported in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glibenclamide) or with insulin. Careful monitoring of blood glucose is recommended.

The use of LEVOFLOXACIN TRINITY during pregnancy and lactation is contra-indicated (see section 4.3). Animal studies have shown that joint development in growing organisms has been adversely affected.

On the basis of the reported adverse reactions, such as dizziness, visual and auditory disturbances and muscular incoordination LEVOFLOXACIN TRINITY may have a minor or moderate influence on driving or operating machinery, therefore caution is advised.

a. Summary of the safety profile

Not applicable

b. Tabulated summary of adverse reactions

MedDRA system organ class Frequency Adverse reactions

Infections and infestations Less Frequent Fungal overgrowth, proliferation of other resistant organisms

Blood and lymphatic system disorders Less Frequent Eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis

Frequency unknown Haemolytic anaemia, pancytopenia

Immune system disorders Less Frequent Pruritus, rash , urticaria, vasculitis , angio-edema, hypotension, anaphylactic-like shock, allergic pneumonitis

Frequency unknown Severe bullous eruptions such as Stevens Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, hypersensitivity vasculitis

Metabolism and nutrition disorders Less Frequent Hypoglycaemia (especially in patients with diabetes mellitus)

Psychiatric disorders Less Frequent Anxiety, depression, psychotic reactions, agitation, confusion, hallucinations

Nervous system disorders Frequent Tremor, disturbances of taste and smell

Less Frequent Headache, dizziness, restlessness, drowsiness, insomnia, paraesthesia, convulsions, visual and auditory disturbances

Gastrointestinal disorders Frequent Nausea, diarrhoea, abdominal or stomach pain or discomfort, loss of appetite, vomiting

Less Frequent Bloody diarrhoea, which in some cases may be indicative of pseudomembranous colitis

Hepatobiliary disorders Less Frequent Increase in liver enzymes, increase in bilirubin, hepatitis, jaundice

Skin and subcutaneous tissue disorders Less Frequent Photosensitivity reactions, rash

Musculoskeletal and connective tissue disorders Less Frequent Arthralgia, myalgia, tendon disorders e.g., tendonitis of the Achilles tendon, tendon rupture, muscle weakness (especially relevant in patients with myasthenia gravis)

Frequency unknown Rhabdomyolysis

Renal and urinary disorders Less Frequent Interstitial nephritis, crystalluria, acute renal failure

General disorders and administration site conditions Less Frequent Asthenia, fever

Frequency unknown Local pain

Investigations Frequency unknown Increase in serum creatinine

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c 6.04 Adverse Drug Reactions Reporting Form u201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

The symptoms that can be expected from an acute overdosage of LEVOFLOXACIN TRINITY are central nervous system symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures. The treatment of an overdosage is only symptomatic and supportive. LEVOFLOXACIN TRINITY is not effectively removed by haemodialysis or peritoneal dialysis.