Ofloxacin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Lower respiratory tract infections caused by Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa
• Infections of the urinary tract
• Sexually transmitted diseases, such as acute uncomplicated urethral and cervical gonorrhoea, urethritis and cervicitis due to Chlamydia trachomatis. Mixed infections of the urethra and cervix due to Chlamydia trachomatis and Neisseria gonorrhoea 
• Prevention of colonisation by Gram-negative organisms as part of a multi-antimicrobial regimen in patients with neutropenia, secondary to cytostatic therapy

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other fluoroquinolones
• Pregnancy
• Breastfeeding
• Children or growing adolescents
• History of epilepsy or an existing central nervous system disorder with a lowered seizure threshold
• History of tendon disorders related to fluoroquinolone administration
• Pre-existing aortic aneurysm and/or aortic dissection
• Pre-existing tendinitis and tendon rupture
• Pre-existing severe valvular heart disease
• Latent or actual defects in glucose-6-phosphate dehydrogenase activity

Cautions

• Renal impairment
• Hepatic impairment
• Elderly
• Porphyria
• Pneumonia caused by Streptococcus pneumoniae or Chlamydia pneumoniae
• Known or suspected Methicillin-resistant S. aureus (MRSA) infections
• Infections caused by E. coli (depending on local prevalence of resistance to fluoroquinolones)
• Pneumonia caused by Pneumococci or Mycoplasma
• Infection caused by β-haemolytic Streptococci
• Use as empirical treatment in suspected gonococcal infection (unless the pathogen has been identified and confirmed as susceptible to ofloxacin)
• Monotherapy in pelvic inflammatory disease
• Positive family history of aneurysm disease
• Risk or predisposing factors of  for aortic aneurysm and dissection:
  - Marfan syndrome
  - Vascular Ehlers-Danlos syndrome
  - Takayasu arteritis
  - Giant cell arteritis
  - Behcet's disease
  - Hypertension
  - Known atherosclerosis
• Patients with solid organ transplants
• Risk of fluoroquinolone-induced tendinitis and tendon rupture
• History of psychotic disorder
• Psychiatric disease
• Known history of myasthenia gravis
• Unnecessary exposure to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium)
• Diabetes mellitus
• Mitral valve and/or aortic valve regurgitation
• Patients with known risk factors for prolongation of the QT interval such as, for example:
  - Elderly and women (who may be more sensitive to QTc-prolonging medications)
  - Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
  - Congenital long QT syndrome
  - Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
  - Coadministration of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
• Patients predisposed to seizures
  - Pre-existing central nervous system lesions
  - Coadministration with fenbufen and similar non-steroidal anti-inflammatory drugs, or with drugs which lower the cerebral seizure threshold, such as theophylline
• Coadministration with corticosteroids
• Coadministration with vitamin K antagonists (e.g. warfarin)
• Latent or diagnosed glucose-6-phosphate-dehydrogenase deficiency
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab, inj

Dosages below include:

• General dosing range
• International manufacturer recommendations
• South African manufacturer recommendations

Infections caused by: Some Gram-positive aerobes, such as Bacillus anthracis, Bordetella pertussis, Corynebacteria, Streptococci, S. aureus - methicillin-sensitive, S. pyogenes; Some Gram-negative aerobes, such as Campylobacter, Enterobacter, Haemophilus influenzae, Legionella sp., Legionella pneumophila, Moraxella catarrhalis, Morganella morganii, Proteus vulgaris, Salmonella, Shigella, Yersinia, Acinetobacter spp, Citrobacter spp, E coli, Klebsiella spp., N. gonorrhoeae, Serratia marcescens; Other organisms, such as Chlamydophila pneumonia, Chlamydia (Chlamydia trachomatis), Mycoplasma hominis, Mycoplasma pneumoniae and Ureaplasma urealyticum 

General dosing range

• Oral (tab): 200-400mg, 12hrly

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

International manufacturer recommendations

Acute exacerbation of chronic bronchitis

• IV: 200mg, 12hrly, as a slow infusion over ≥30min

Community-acquired pneumonia

• IV: 200mg, 12hrly, as a slow infusion over ≥30min
• Oral (tab): 400mg, 12-24hrly

Acute exacerbation of chronic obstructive pulmonary disease including bronchitis

• Oral (tab): 400mg, 12-24hrly

Complicated urinary tract infection

• IV: 200-400mg, 12hrly, as a slow infusion over ≥30min; Treatment duration: 7-21 days
• Oral (tab): 400mg, 12-24hrly

Pyelonephritis

• IV: 200-400mg, 12hrly, as a slow infusion over ≥30min; Treatment duration: 7-10 days (can be extended to 14 days)

Acute pyelonephritis

• Oral (tab): 400mg, 12-24hrly

Uncomplicated cystitis

• Oral (tab): 200-400mg, dly

Acute prostatitis

• IV: 200-400mg, 12hrly, as a slow infusion over ≥30min; Treatment duration: 2-4 weeks

Chronic prostatitis

• IV: 200-400mg, 12hrly, as a slow infusion over ≥30min; Treatment duration: 4-8 weeks

Epididymo-orchitis

• IV: 200-400mg, 12hrly, as a slow infusion over ≥30min; Treatment duration: 14 days

Gonococcal urethritis and cervicitis due to susceptible Neisseria gonorrhoeae 

• Oral (tab): 400mg, as a single dose

Non-gonococcal urethritis and cervicitis

• Oral (tab): 400mg, dly

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Where stated for the above indications, the higher end of the dosing range (i.e. 400mg, 12hrly) may be used in severe infections

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For prostatitis, longer duration of treatment may be considered after careful re-examination of the patient

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The dose of ofloxacin is determined by the type and severity of the infection. The dosage range for adults is 200mg to 800mg daily. Up to 400mg may be given as a single dose, preferably in the morning. Daily doses of more than 400mg must be divided into two separate doses and be given at approximately equal intervals

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In individual cases, it may be necessary to increase the dose to a Max. total dose of 800mg daily, which should be given as 400mg 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

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Complicated skin and soft tissue infections

• IV: 400mg, 12hrly, as a slow infusion over ≥60min

Pelvic inflammatory disease

• IV: 400mg, 12hrly, as a slow infusion over ≥60min; Treatment duration: 14 days

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Ofloxacin tablets may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with IV ofloxacin

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The duration of treatment is determined according to the response of the causative organisms and the clinical picture. As with all antibacterial agents, treatment should be continued for at least 3 days after the body temperature has returned to normal and the symptoms have subsided

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In most cases of acute infection, a course of treatment lasting 7-10 days is sufficient. Once the patient's condition has improved, the mode of administration should be changed from parenteral to oral, normally at the same total daily dose. Treatment should not exceed 2 months duration

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See additional prescribing points for administration directions

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South African manufacturer recommendations

Uncomplicated cystitis

• Oral (tab): 100mg, 12hrly; Treatment duration: 3-7 days
• IV: 100-200mg, 12hrly, as a slow infusion over 30-60min; Max: 400mg, 12hrly; Treatment duration: Until oral therapy can be substituted

Pyelonephritis

• Oral (tab): 200mg, 12hrly; Treatment duration: 5-7 days
• IV: 100-200mg, 12hrly, as a slow infusion over 30-60min; Max: 400mg, 12hrly; Treatment duration: Until oral therapy can be substituted

Lower respiratory tract infections

• Oral (tab): 400mg, 12hrly; Treatment duration: 7-10 days(The daily dose may be altered depending on the severity of the infection.)
• IV: 100-200mg, 12hrly, as a slow infusion over 30-60min; Max: 400mg, 12hrly; Treatment duration: Until oral therapy can be substituted

Uncomplicated urethral and cervical gonorrhoea

• Oral (tab): 400mg, as a single dose

Urethritis and cervicitis due to Chlamydia trachomatis

• Oral (tab): 600mg/day, in divided doses; Treatment duration: Up to 7 days
• IV: 100-200mg, 12hrly, as a slow infusion over 30-60min; Max: 400mg, 12hrly; Treatment duration: Until oral therapy can be substituted

Prevention of infections in patients with neutropenia

• Oral (tab): 400-600mg/day, in divided doses
• IV: 100-200mg, 12hrly, as a slow infusion over 30-60min; Max: 400mg, 12hrly; Treatment duration: Until oral therapy can be substituted

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In patients with neutropenia: It may be necessary to increase the dose to 600mg or 800mg daily in the presence of pathogens of varying sensitivity in severe infections

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If the treatment has been initiated via IV route, it is usually possible to switch to oral route at the same dosage after a few days, when the patient’s condition improves

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The dosage should be determined according to the sensitivity of the causative organism and severity of the infection

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See additional prescribing points for administration directions

Contraindicated

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Use of ofloxacin is contraindicated according to International and South African manufacturer recommendations in children or adolescents in the growth phase

Pregnancy

• Contraindicated
• 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; therefore, ofloxacin must not be used during pregnancy

Breastfeeding

• Contraindicated
• Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the breastfeeding infant, breastfeeding should be discontinued during treatment with ofloxacin

Renal Impairment

• Caution; dose adjustment recommended
  The serum concentration of ofloxacin should be monitored in patients with severe renal impairment and dialysis patients

Creatinine clearance (ml/min)	Dose
>50	No adjustment recommended
20-50	Oral (tab): Following a normal initial dose, the maintenance dose should be reduced to 100-200mg/24hrs  IV: 100-200mg/24hrs
<20  or Haemodialysis or Peritoneal dialysis	Oral (tab): Following a normal initial dose, the maintenance dose should be reduced to 100mg/24hrs  IV: 100mg/24hrs or 200mg/48hrs

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended (tab)  
• Mild to moderate (including cirrhosis of the liver with ascites): Caution; dose adjustment recommended (IV) 
  Max: 400mg/24hrs
• Severe (including cirrhosis of the liver with ascites): Caution; dose adjustment recommended (tab and IV)
  Max: 400mg/24hrs

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Agitation
• Sleep disorder
• Insomnia
• Psychotic disorder
• Hallucination
• Anxiety
• Confusional state
• Nightmares
• Psychotic disorder
• Depression, including self-endangering behaviour
• Suicidal ideation
• Suicide attempt
• Nervousness
• Dizziness
• Headache
• Drowsiness/ somnolence
• Paraesthesia, including associated neuropathies
• Peripheral sensory neuropathy
• Peripheral sensory motor neuropathy
• Seizures
• Extra-pyramidal symptoms
• Disorders of muscular coordination
• Tremor
• Dyskinesia
• Syncope
• Benign intracranial hypertension (Pseudotumor cerebri)
• Impairment of skills
• Asthenia
• Gait disturbance
• Memory impairment

Cardiovascular Disorders

• Tachycardia
• Ventricular arrhythmias
• Torsades de pointes
• ECG QT prolongation
• Mitral valve and/or aortic valve regurgitation
• Phlebitis (inj)
• Hypotension

Respiratory Disorders

• Cough
• Nasopharyngitis
• Dyspnoea
• Bronchospasm
• Allergic pneumonitis
• Severe dyspnoea

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Nausea and vomiting
• Enterocolitis, sometimes haemorrhagic
• Pseudomembranous colitis
• Dyspepsia
• Flatulence
• Constipation
• Pancreatitis

Hepatobiliary Disorders

• Cholestatic jaundice
• Increased hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase and/or alkaline phosphatase)
• Increased blood bilirubin
• Hepatitis
• Severe hepatic injury, including cases of acute liver failure, sometimes fatal

Genitourinary Disorders

• Increased serum creatinine
• Acute renal failure
• Acute interstitial nephritis

Endocrine and Metabolic Disorders

• Anorexia
• Hypoglycaemia (in diabetics treated with hypoglycaemic agents)
• Hyperglycaemia
• Hypoglycaemic coma
• Attacks of porphyria (in patients with porphyria)

Musculoskeletal Disorders

• Tendonitis
• Arthralgia
• Myalgia
• Tendon rupture
  - Achilles tendon
• Rhabdomyolysis
• Myopathy
• Muscular weakness
• Muscle tear
• Muscle rupture
• Ligament rupture
• Arthritis

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Urticaria
• Hot flushes
• Hyperhidrosis
• Pustular rash
• Erythema multiforme
• Toxic epidermal necrolysis
• Photosensitivity reaction
• Drug eruption
• Vascular purpura
• Vasculitis, which may lead to skin necrosis
• Stevens-Johnson syndrome
• Acute generalised exanthemous pustulosis
• Drug rash
• Stomatitis
• Exfoliative dermatitis
• Infusion site reaction (inj)
  - Pain
  - Reddening

Immune, Blood and Lymphatic System Disorders

• Fungal infection
• Pathogen resistance
• Fever
• Anaemia
• Haemolytic anaemia
• Leucopenia
• Eosinophilia
• Thrombocytopenia
• Agranulocytosis
• Bone marrow failure
• Pancytopenia
• Anaphylactic reaction
• Anaphylactoid reaction
• Angioedema
• Anaphylactic shock
• Anaphylactoid shock

Sensory Disorders

• Eye irritation
• Visual disturbance
• Uveitis
• Vertigo
• Tinnitus
• Hearing loss
• Impaired hearing
• Impaired vision
• Dysgeusia
• Parosmia
• Ageusia  

Others

• Pain, including in back, chest and extremities

• Corticosteroids
• QT-prolonging agents
• Class IA and III antiarrhythmics
• Tricyclic antidepressants
• Macrolides
• Antipsychotics
• Magnesium/ aluminum antacids
• Sucralfate
• Zinc preparations
• Iron preparations
• Didanosine
• Theophylline
• Non-steroidal anti-inflammatory drugs
• Fenbufen
• Agents that lower the seizure threshold
• Glibenclamide
• Probenecid
• Cimetidine
• Furosemide
• Methotrexate
• Anticoagulants
• Vitamin K antagonists
• Coumarin derivatives
• Warfarin

Other interactions

• Opiates or porphyrin level tests (See additional prescribing points)

None routine. Specific cases may require

• Full blood count
• Renal function
• Hepatic function
• Blood glucose
• Electrocardiogram

Additional observations

• Signs and symptoms of tendon rupture

Administration instructions

Oral (tab)

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

IV

• Ofloxacin solution is only intended for slow IV infusion and it is administered once or twice daily. The infusion time for should not be less than 30 minutes for 200mg
• This is of particular importance when ofloxacin is administered concomitantly with drugs that can lead to a reduction in blood pressure or with barbiturate-containing anaesthetics
• Generally, individual doses are to be given at approximately equal intervals
• Compatible infusion solutions include isotonic sodium chloride, Ringer's solution and 5% glucose solution. Heparin and ofloxacin are incompatible

Risk of mitral and aortic regurgitation

• There is a possible increased risk for patients to develop mitral valve and/or aortic valve regurgitation (left sided heart valves) while on treatment with oral and injectable fluoroquinolones. The increased risk continues until about 60 days after completion of treatment
• A thorough cardiovascular examination, including an echocardiogram (ECG), should be performed, before oral or injectable fluoroquinolones are prescribed
• Fluoroquinolones should not be prescribed to patients with mitral valve and/or aortic valve regurgitation, unless no safer alternative antibiotic is available, has failed or is not well tolerated

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
• 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 be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives

Ofloxacin is a quinolone-carboxylic acid derivative with a wide range of antibacterial activity. The primary mode of action of the quinolones is the specific inhibition of bacterial DNA gyrase. This enzyme is required for DNA replication, transcription, repair and recombination. Its inhibition leads to expansion and destabilisation of the bacterial DNA and hence to cell death. It appears that certain quinolones, including ofloxacin, have a second non RNA dependent action on bacterial cells, which enhances bactericidal effectiveness. The nature of this second action has not yet been clarified.

Spectrum of activity: Some Gram-positive aerobes, such as Bacillus anthracis, Bordetella pertussis, Corynebacteria, Streptococci, S. aureus - methicillin-sensitive, S. pyogenes; Some Gram-negative aerobes, such as Campylobacter, Enterobacter, Haemophilus influenzae, Legionella sp., Legionella pneumophila, Moraxella catarrhalis, Morganella morganii, Proteus vulgaris, Salmonella, Shigella, Yersinia, Acinetobacter spp, Citrobacter spp, E coli, Klebsiella spp., N. gonorrhoeae, Serratia marcescens; Other organisms, such as Chlamydophila pneumonia, Chlamydia (Chlamydia trachomatis), Mycoplasma hominis, Mycoplasma pneumoniae and Ureaplasma urealyticum 

Tablet 200mg

• Austell Ofloxacin (Camox)
• Tafloc (Pharmacare)
• Tarivid (Sanofi) originator
• Zanocin (Ranbaxy)

Tablet 400mg

• Austell Ofloxacin (Camox)
• Tafloc (Pharmacare)
• Zanocin (Ranbaxy)

Injection (per 100ml) 200mg

• Tarivid (Sanofi) originator