Tarivid film-coated tablets are suitable for the treatment of the following bacterial infections, if they have been caused by pathogens sensitive to ofloxacin:
− acute, chronic and recurrent respiratory tract infections (bronchitis), caused by Haemophilus influenzae or other Gram-negative and multi-resistant pathogens and by Staphylococcus aureus.
− pneumonia, particularly if caused by problem micro-organisms such as Escherichia coli, Klebsiella, Enterobacter, Proteus, Pseudomonas, Legionella and Staphylococcus. As pneumonia in non-hospitalised patients is mainly caused by pneumococci, Tarivid film-coated tablets are not recommended as first-line therapy in such cases.
− chronic and recurrent ear, nose and throat infections, particularly if caused by Gram-negative micro-organisms, including Pseudomonas, or caused by Staphylococcus. Tarivid film-coated tablets are thus not indicated in the treatment of acute angina tonsillaris caused by beta-haemolytic streptococci (see also section 4.2).
− skin and soft-tissue infections.
− bone infections (osteitis, osteomyelitis).
− infections of the abdominal cavity, including the lesser pelvis, and bacterial diarrhoea requiring antibiotic treatment.
− renal and genitourinary infections, gonorrhoea.
Tarivid film-coated tablets are also indicated for the prophylaxis of infection (including selective intestinal decontamination) in severely immunocompromised patients (e.g. neutropenic patients).
Ofloxacin has no activity against Treponema pallidum.
The usual and generally recognised guidelines for the appropriate use of antibiotics should be adhered to during administration of Tarivid.

The dosage, method and duration of administration depend on the nature and severity of the infection.
Dosage in patients with normal renal function
Therapeutic indications
Single and daily doses
Uncomplicated lower urinary tract infections
2 x ½ film-coated tablet of Tarivid 200 mg daily
Uncomplicated gonorrhoea
1 x 400 mg ofloxacin as a single dose, equivalent to
1 x 1 film-coated tablet of Tarivid 400 mg or
1 x 2 film-coated tablets of Tarivid 200 mg
Renal and genitourinary infections
2 x 200 mg ofloxacin daily, equivalent to
2 x 1 film-coated tablet of Tarivid 200 mg or
2 x ½ film-coated tablet of Tarivid 400 mg
Respiratory tract infections and ear, nose and throat infections
2 x 200 mg ofloxacin daily, equivalent to
2 x 1 film-coated tablet of Tarivid 200 mg or
2 x ½ film-coated tablet of Tarivid 400 mg
Skin and soft-tissue infections
2 x 200 mg ofloxacin daily, equivalent to
2 x 1 film-coated tablet of Tarivid 200 mg or
2 x ½ film-coated tablet of Tarivid 400 mg
Bone infections
2 x 200 mg ofloxacin daily, equivalent to
2 x 1 film-coated tablet of Tarivid 200 mg or
2 x ½ film-coated tablet of Tarivid 400 mg
Infections of the abdominal cavity (including bacterial diarrhoea)
2 x 200 mg ofloxacin daily, equivalent to
2 x 1 film-coated tablet of Tarivid 200 mg or
2 x ½ film-coated tablet of Tarivid 400 mg
In individual cases, it may be necessary to increase the dose when treating pathogens with varying sensitivity, in severe infections (e.g. of the respiratory tract or bones) or if the patient response is insufficient. In such cases, the dose can be increased to 400 mg ofloxacin twice daily. The same applies in infections with confounding co-factors.
For the prophylaxis of infection in severely immunocompromised patients, 400 to 600 mg ofloxacin daily are recommended.
Children and adolescents
Ofloxacin must not be used in children and adolescents (see section 4.3).
Elderly patients
Apart from the need to consider possible impaired renal function, no dose adjustment is required for elderly patients.
Dosage in patients with impaired renal function
In patients with moderately and severely impaired renal function, determined as creatinine clearance or as serum creatinine, Tarivid 400 mg film-coated tablets are not particularly suitable, due to the necessary dose reduction. In such cases, Tarivid 200 mg film-coated tablets are recommended, as they can be divided into 2 half tablets, each containing 100 mg ofloxacin. As in patients with normal renal function, the first dose is administered according to the nature and severity of the disease.
The maintenance dose should be reduced as follows:
Creatinine clearance
Serum creatinine
Maintenance dose
50 to 20 ml/min
1.5 to 5 mg/dl
100 mg to 200 mg ofloxacin daily
≤ 20 ml/min
≥ 5 mg/dl
100 mg ofloxacin daily
Haemodialysis or peritoneal dialysis
100 mg ofloxacin daily
In individual cases (see above), however, it may be necessary to increase the above dose.
Dosage in patients with impaired hepatic function
In patients with severely impaired hepatic function (e.g. cirrhosis of the liver with ascites), elimination of ofloxacin may be reduced. In such cases, it is therefore recommended that a maximum daily dose of 400 mg ofloxacin should not be exceeded.
Method of administration
Tarivid film-coated tablets should be swallowed whole, not chewed, with sufficient liquid (½ – 1 glass). They can be taken on an empty stomach or during meals.
Up to 400 mg ofloxacin can be given as a single dose. The daily dose is generally administered in two equal doses (morning and evening). It is important to maintain approximately equal dosing intervals. Single doses of up to 1 film-coated tablet with 400 mg ofloxacin daily should preferably be taken in the morning.
Duration of treatment
Duration of treatment depends upon the pathogenic response and the clinical picture. In general, treatment should be continued for at least 2 to 3 days after fever and other symptoms have subsided.
In acute infections, a treatment period of 7 to 10 days is usually sufficient. The usual duration of treatment in cases of salmonellosis is 7 to 8 days, in cases of shigellosis 3 to 5 days and in cases of intestinal infections with Escherichia coli, 3 days.
For uncomplicated lower urinary tract infections, treatment with 200 mg ofloxacin daily for 3 days is usually sufficient. For the treatment of uncomplicated gonorrhoea, a single dose of 400 mg ofloxacin is sufficient.
For infections of the bones, duration of treatment is 3 to 4 weeks and may be longer in individual cases.
If sensitivity is confirmed and infections with beta-haemolytic streptococci (e.g. erysipelas) are being treated, the treatment must be continued for at least 10 days, in order to prevent sequelae such as rheumatic fever or glomerulonephritis. As beta-haemolytic streptococci vary in their sensitivity to ofloxacin, however, treatment of such infections requires confirmation of sensitivity in individual cases.
Until further data are available, a treatment period of 2 months should not be exceeded.

 

Tarivid must not be administered: − in patients who are hypersensitive to ofloxacin, other quinolones or any of the excipients of Tarivid film-coated tablets, − in patients with epilepsy or a lowered CNS seizure threshold, − in patients with tendon disease/damage associated with previous quinolone therapy, − in children and adolescents up to 18 years of age, as the risk of articular cartilage damage cannot be safely excluded, − during pregnancy, − during lactation.

Ofloxacin is not the antibiotic of first choice in the treatment of pneumonia caused by pneumococci or Mycoplasma spp. Particularly in severe forms of pneumococcal pneumonia, ofloxacin may not guarantee optimal antibiotic therapy.
Nosocomial and other severe infections caused by P. aeruginosa may require combination therapy. In cases of specific infections caused by P. aeruginosa in particular, resistance levels must be tested in order to ensure targeted therapy.
Tarivid is not indicated for the treatment of acute angina tonsillaris caused by beta-haemolytic streptococci.
Hypersensitivity reactions
Hypersensitivity reactions following the initial administration of fluoroquinolones have been reported. Anaphylactic and anaphylactoid reactions may progress to life-threatening shock, even after the initial administration. In this case, ofloxacin must be discontinued and appropriate emergency procedures (e.g. shock treatment, including administration of antihistamines, corticosteroids, sympathomimetics and, if required, ventilation) must be initiated.
Diseases caused by Clostridium difficile
The occurrence of diarrhoea, particularly if it is severe, persistent and/or contains blood, during or after treatment with Tarivid, may indicate a disease triggered by Clostridium difficile, of which pseudomembranous colitis is the most severe form. If pseudomembranous colitis is suspected, treatment with Tarivid must be discontinued immediately and an appropriate therapy initiated without delay (e.g. oral treatment with specific antibiotics/chemotherapeutic agents with proven clinical efficacy). Medicines that inhibit intestinal peristalsis must not be taken.
Patients with a tendency for seizures
Tarivid is contraindicated in patients with known epilepsy or a known lowered CNS seizure threshold. As with other quinolones, Tarivid should be used only with extreme caution in patients otherwise predisposed to epileptic seizures, e.g. patients with existing CNS lesions, during concurrent treatment with fenbufen or comparable non-steroidal anti-inflammatory drugs, or with medicines that lower the seizure threshold, such as theophylline (see also section 4.5).
Treatment with Tarivid must be discontinued at the onset of seizures. Appropriate standard emergency procedures are indicated (e.g. maintenance of airway patency and administration of anticonvulsants such as diazepam or barbiturates).
Tendinitis
Rarely, tendinitis has been observed during quinolone therapy, which may lead to tendon rupture in some cases, particularly of the Achilles tendon. This undesirable effect can occur within 48 hours after initiation of therapy and may be bilateral. Elderly patients are more prone to tendinitis. The risk of tendon rupture may possibly be increased during corticosteroid treatment. If tendinitis is suspected, treatment with Tarivid must be immediately discontinued and the affected tendon treated appropriately (e.g. by immobilisation).
Patients with impaired renal function
Ofloxacin is mainly excreted via the kidneys. In patients with impaired renal function, Tarivid should therefore only be administered after a dose adjustment (see section 4.2), together with medical monitoring of the renal function.
Psychotic reactions
During treatment with quinolones including ofloxacin, depression and psychotic reactions have been reported in patients. Very rarely, these have developed into suicidal ideation and self-endangering behaviour (see section 4.8) – sometimes already after a single dose of ofloxacin. If the patient should develop such reactions, ofloxacin must be discontinued immediately and appropriate measures initiated. Caution should be exercised if ofloxacin is used in patients with psychotic disorders or a medical history of psychiatric disorders.
Patients with impaired hepatic function
Hepatic damage may occur during treatment with Tarivid (see section 4.8). In patients with impaired hepatic function, Tarivid should be administered only if hepatic function is medically monitored. Cases of fulminant hepatitis, which may lead to liver failure (sometimes fatal), have been reported with fluoroquinolones. Patients should be instructed to suspend treatment and seek advice from their doctor if signs of hepatic disease develop, e.g. loss of appetite, jaundice, dark discolouration of the urine, pruritus or abdominal tenderness.
Patients on treatment with vitamin K antagonists
Due to a possible increase in coagulation values (PT/INR) and/or bleeding in patients on concomitant treatment with fluoroquinolones, including ofloxacin, and a vitamin K antagonist (e.g. warfarin), coagulation values should be monitored (see section 4.5).
Myasthenia gravis
In patients with known myasthenia gravis, ofloxacin should be used only with caution.
Prevention of photosensitisation
Although photosensitisation occurs only very rarely during administration of Tarivid, patients are recommended to avoid unnecessary exposure to strong sunlight or artificial UV rays (e.g. sun lamps, solarium), in order to prevent photosensitisation.

Secondary infection
In particular, the prolonged use of antibiotics can lead to an increase in resistant bacteria and fungi. The patient’s condition should therefore be monitored at regular intervals. Appropriate measures must be taken if a secondary infection occurs.
Heart disorders
When using fluoroquinolones, including ofloxacin, caution should be taken in patients with known risk factors for QT interval prolongation, for example:
− congenital long QT syndrome,
− concomitant administration of other medicines that are known to prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic and tetracyclic antidepressants, macrolides, imidazole antifungal agents and antimalarial agents, some non-sedative antihistamines [e.g. astemizole, terfenadine, ebastine], antipsychotics).
− uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia),
− elderly patients,
− cardiac disease (heart failure, myocardial infarction, bradycardia),
(See also sections 4.2 “Elderly patients”, 4.5, 4.8 and 4.9).
Hypoglycaemia
As with all quinolones, cases of hypoglycaemia have been reported (see section 4.8), usually in patients with diabetes who have received concomitant treatment with an oral antidiabetic agent (e.g. glibenclamide) or insulin. Careful monitoring of blood glucose levels is recommended in such patients with diabetes.
Peripheral neuropathy
During treatment with fluoroquinolones, including ofloxacin, sensory or sensorimotor peripheral neuropathies of varying axonal types have been reported, the onset of which may be rapid (see section 4.8). If patients develop symptoms of neuropathy, ofloxacin should be discontinued, in order to prevent the development of irreversible damage.
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency may be predisposed to haemolytic reactions if they are treated with quinolones. Tarivid should therefore be administered with caution.
Other notes
Patients who have reacted to other quinolones with severe undesirable effects (e.g. severe neurological reactions) are at greater risk of experiencing similar reactions to ofloxacin.
Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Tarivid film-coated tablets.

 

Concurrent intake of mineral antacids or sucralfate can attenuate the effects of Tarivid film-coated tablets. The same applies to other preparations that contain metal ions (aluminium, iron, magnesium or zinc). Tarivid film-coated tablets must therefore be taken approximately 2 hours before such preparations.
There are indications that seizures are more likely to occur if quinolones are administered concurrently with other medicinal products that lower the seizure threshold. These include some non-steroidal anti-inflammatory agents (e.g. fenbufen) and theophylline, although serum theophylline concentrations are not significantly altered by ofloxacin.
Medicinal products that prolong the QT-interval
Ofloxacin, like other quinolones, should be used with caution in patients taking medicines known to prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic and tetracyclic antidepressants, macrolides, imidazole antifungal agents and antimalarial agents, some non-sedative antihistamines [e.g. astemizole, terfenadine, ebastine], antipsychotics) (see section 4.4).
Quinolones, possibly also ofloxacin, can enhance the effect of coumarin derivatives. Close monitoring of the coagulation status of patients undergoing concurrent treatment with coumarin derivatives is thus recommended.
Ofloxacin can cause a slight increase in serum glibenclamide levels. As hypoglycaemia is then more likely to occur, close monitoring of blood glucose levels is thus recommended in such cases.
In the case of high-dose treatment in particular, it must be borne in mind that mutual prevention of elimination may occur between quinolones and other medicines which are secreted in the renal tubules (e.g. probenecid, cimetidine, furosemide, methotrexate). This can cause elevated serum levels and increased undesirable effects.
Effect on laboratory tests
Determination of opiates or porphyrin in the urine may give false-positive results during treatment with ofloxacin. It may be necessary to confirm positive results by more specific screening methods.

Pregnancy
There are no sufficient data on the administration of ofloxacin to pregnant women. Animal studies have shown no teratogenic effects. In juvenile and unborn animals with quinolone exposition effects on the immature cartilage have been observed. Therefore, it can not be excluded that the medicinal product causes damage to joint cartilage of the childlike or juvenile organism/fetus.
Therefore, Tarivid is contra-indicated in the pregnancy (see section 4.3 and 5.3).
Lactation
Small amounts of ofloxacin are excreted in breast milk. Due to possible risk of arthropathy, Tarivid is contra-indicated in the lactation period (see section 4.3 and 5.3).

Some undesirable effects (e.g. vertigo/dizziness, drowsiness, visual disturbances) can impair the patient’s ability to concentrate and responsiveness and, as a result, can present a risk in situations in which these abilities are of particular importance (e.g. driving a vehicle, operating machinery). This is enhanced in association with alcohol. Patients should therefore observe their reactions to treatment before driving a vehicle or operating machinery.

The following data are based on clinical studies and extensive post-marketing experience.
See table on pages 4 and 5.
Notes
Apart from very rare cases (e.g. isolated cases of disorders of smell, taste and hearing), observed undesirable effects have resolved after the discontinuation of Tarivid.
Patients should be instructed to inform their physician or pharmacist if any of the undesirable effects listed here or any other undesirable effects occur.
Some undesirable effects (e.g. pseudomembranous colitis, hypersensitivity reactions, seizures) may be acutely life-threatening in some cases and require immediate countermeasures (see also section 4.4).

a) Symptoms of intoxication
The main symptoms of acute overdose can include (amongst others) central nervous symptoms, such as confusion, dizziness, clouding of consciousness and seizures, as well as gastrointestinal complaints, such as nausea and erosions of the gastrointestinal mucosa.
b) Treatment of intoxication
In case of overdose a symptomatic treatment should be initiated. ECG monitoring should be performed due to the possibility of QT interval prolongation. It may be necessary to monitor and secure also other organ and vital functions in an intensive care unit.

bacteria and fungi (see section 4.4)
Blood and lymphatic system disorders
Anaemia, haemolytic anaemia, leukopenia, eosinophilia, thrombocytopenia, pancytopenia
Agranulocytosis, bone marrow depression
Immune system disorders
Anaphylactic / anaphylactoid hypersensitivity reactions, angioedema of the skin and mucosa (e.g. of the tongue and larynx)
Vasculitis which may also affect inner organs, anaphylactic / anaphylactoid shock
Metabolism and nutrition disorders
Loss of appetite
Hyper- or hypoglycaemia, particularly in patients treated with antidiabetics (see section 4.4)
Psychiatric disorders
Agitation, sleep disorders, insomnia
Psychotic reactions (e.g. with hallucinations), anxiety, confusion, intensive dreaming (and even nightmares), depression
Psychotic reactions and depression with self-harm to the point of suicidal ideation or acts (see section 4.4)
Nervous system disorders
Agitation, nervousness, headache,
dizziness
Somnolence, sensory disorders such as paraesthesias (e.g. hypoaesthesia or hyperaesthesia), disturbances of taste and smell (including ageusia or anosmia),
Sensory or sensorimotor peripheral neuropathy, seizures, extrapyramidal symptoms or muscular co-ordination disorders (e.g. trembling, unsteady gait) (see section 4.4)
Eye disorders
Burning sensation in the eyes, conjunctivitis
Visual disturbances (e.g. blurred vision, diplopia and chromatopsia)
Ear and labyrinth disorders
Vertigo
Imbalance
Hearing disorders such as tinnitus, loss of hearing
Cardiac disorders
Palpitations
Tachycardia
Ventricular arrhythmias and torsade de pointes (especially reported in patients at risk of QT prolongation), ECG QT interval prolongation (see sections 4.4 and 4.9), syncope
Vascular disorders
Hypotension, hypertension
Severe hypotension to the point of collapse with loss of consciousness
Respiratory, thoracic and mediastinal disorders
Dry cough, runny nose
Dyspnoea / bronchospasm
Allergic pneumonitis, severe dyspnoea
Gastrointestinal disorders
Gastric upset, abdominal pain, dyspepsia, diarrhoea, nausea, vomiting
Enterocolitis (in isolated cases with haemorrhage)
Pseudomembranous colitis (see section 4.4)
Hepatobiliary disorders
Impairment of hepatic function with elevation of liver enzymes (ALAT, ASAT, LDH, gamma-GT, alkaline phosphatase) and/or bilirubin
Cholestatic jaundice
Hepatitis, severe hepatic damage

System organ class
Uncommon (≥ 1/1,000 to < 1/100)
Rare
(≥ 1/10,000 to < 1/1,000)
Very rare
(< 1/10,000)
Frequency not known (cannot be estimated from the available data)
Skin and subcutaneous tissue disorders
Cutaneous reactions such as rash and pruritus
Hot flushes, sweating, urticaria, vesicular or pustular rash
Serious mucocutaneous reactions (erythema multiforme, toxic epidermal necrolysis), photosensitivity (sunburn-like symptoms, discolouration or detachment of the nails), vascular purpura, vasculitis with petechiae, blisters or nodules, which may lead to skin necrosis in isolated cases.
Stevens-Johnson syndrome, acute generalised exanthematous pustulosis, fixed drug exanthema
Musculoskeletal and connective tissue disorders
Tendinitis
Articular and muscular complaints (e.g. pain), tendon rupture (e.g. of the Achilles tendon), see also section 4.4.
Rhabdomyolysis and/or myopathy, muscle weakness (of particular significance in patients with myasthenia gravis), muscle tear, muscle rupture
Renal and urinary disorders
Impairment of renal function (e.g. with a rise in serum creatinine)
Acute renal failure
Acute interstitial nephritis
Congenital, familial and genetic disorders
Porphyria attacks in patients with porphyria
General disorders and administration site conditions
Fever
No specific antidote is known. If seizures occur, sedation with diazepam is recommended.
The following measures are recommended in the event of a massive overdose: To eliminate any non-absorbed ofloxacin, measures such as gastric lavage, administration of absorbing agents and sodium sulphate (if possible within the first 30 minutes) are recommended, as well as antacids to protect the gastric mucosa; furthermore, therapy by diuresis to promote the elimination of any absorbed substance.

Pharmacotherapeutic group
Ofloxacin is a bactericidal antibiotic from the fluoroquinolone group
ATC code: J01MA01
Mechanism of action
The mechanism of action of ofloxacin is based on impairment of DNA synthesis, by inhibiting bacterial topoisomerase II (gyrase) and topoisomerase IV, resulting in a bactericidal effect.
Pharmacokinetic/pharmacodynamic relationship
Efficacy is primarily dependent on the ratio between the peak serum level (Cmax) and the minimum inhibitory concentration (MIC) of the pathogen concerned, or the ratio between AUC (area under the curve) and the MIC of the pathogen concerned.
Resistance mechanisms
Resistance to ofloxacin can be based on the following mechanisms:
− Target structure changes: The most common mechanism of resistance to ofloxacin and other fluoroquinolones consists of changes to topoisomerase II or IV as a result of mutation.
− Other resistance mechanisms lead to a decrease in fluoroquinolone concentration at the site of action. This is due to reduced cell penetration as a result of decreased porin formation, or increased secretion from the cell by efflux pumps.
− Transferable, plasmid-coded resistance has been demonstrated for Escherichia coli and Klebsiella spp.
With ofloxacin, there is partial or complete cross-resistance with other fluoroquinolones.
Breakpoints
Ofloxacin is tested using the standard dilution series. Minimum inhibitory concentrations for sensitive and resistant microbes have been established as follows:
EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints:
sensitive
resistant
Enterobacteriaceae
≤ 0.5 mg/l
> 1 mg/l
Staphylococcus spp.
≤ 1 mg/l
> 1 mg/l
Streptococcus pneumoniae
≤ 0.125 mg/l
> 4 mg/l
Haemophilus influenzae
≤ 0.5 mg/l
> 0.5 mg/l
Moraxella catarrhalis
≤ 0.5 mg/l
> 0.5 mg/l
Neisseria gonorrhoeae
≤ 0.12 mg/l
> 0.25 mg/l
non-species-specific breakpoints*
≤ 0.5 mg/l
> 1 mg/l
* mainly based on serum pharmacokinetics
Prevalence of acquired resistance
The prevalence of acquired resistance may vary geographically and over time for individual species. Local information on resistance is therefore required, particularly for the adequate treatment of severe infections. Expert therapeutic advice should be sought if the local resistance situation is such that the efficacy of ofloxacin is questionable. Particularly in the case of serious infections or treatment failure, a microbiological diagnosis – with detection of the pathogen and its susceptibility to ofloxacin – should be sought.

Prevalence of acquired resistance in Germany - based on data obtained over the past 5 years from national resistance monitoring projects and studies (status as of December 2010)
Normally susceptible species
Aerobic Gram-positive micro-organisms
Staphylococcus saprophyticus°
Streptococcus pyogenes°
Aerobic Gram-negative micro-organisms
Enterobacter aerogenes
Enterobacter cloacae
Haemophilus influenzae
Moraxella catarrhalis
Proteus vulgaris
Salmonella enterica (enteritis salmonellae only)
Serratia marcescens
Other micro-organisms
Chlamydophila pneumoniae°$
Chlamydia trachomatis°$
Legionella pneumophila°
Mycoplasma hominis°$
Mycoplasma pneumoniae°$
Ureaplasma urealyticum°$
Species in which acquired resistance may pose a problem during use
Aerobic Gram-positive micro-organisms
Enterococcus faecalis°
Staphylococcus aureus (methicillin-sensitive)
Staphylococcus aureus (methicillin-resistant)+
Staphylococcus epidermidis+
Staphylococcus haemolyticus+
Staphylococcus hominis+
Streptococcus pneumoniae$
Aerobic Gram-negative micro-organisms
Acinetobacter baumannii°$
Campylobacter jejuni$
Citrobacter freundii
Escherichia coli&
Klebsiella oxytoca
Klebsiella pneumoniae
Morganella morganii
Neisseria gonorrhoeae
Proteus mirabilis
Pseudomonas aeruginosa$
Stenotrophomonas maltophilia$
Naturally resistant species
Aerobic Gram-positive micro-organisms
Enterococcus faecium
Anaerobic micro-organisms
Bacteroides spp.
Clostridium difficile
The above categories are almost exclusively based on data on ciprofloxacin and levofloxacin.
° At the time this table was published, no updated data were available. Sensitivity is assumed in the primary literature, standard works and therapeutic guidelines.
$ The natural susceptibility of most isolates is in the intermediate range.
+ The resistance rate is more than 50% in at least one region.
& In isolates of female patients with uncomplicated cystitis, the rate of resistance is < 10%, otherwise ≥ 10%.

Following oral administration in fasting volunteers, ofloxacin is rapidly and almost completely absorbed. The mean peak serum concentration following a single oral dose of 200 mg is 2.6 μg/ml and is reached within 1 hour. The serum elimination half-life is 5.7 to 7.0 hours and is dose-independent. The apparent volume of distribution is 120 litres. Following multiple administration of ofloxacin, the serum concentration does not increase significantly (accumulation factor following twice-daily administration: 1.5). Plasma protein binding is approximately 25%. Less than 5% of ofloxacin undergoes biotransformation.
The two major metabolites which are recovered in the urine are N-desmethyl-ofloxacin and ofloxacin-N-oxide. Elimination is mainly renal. 80 to 90% of the dose is recovered in the urine as unchanged substance. Ofloxacin is recovered in the bile in glucuronidated form. The pharmacokinetics of ofloxacin following intravenous infusion closely resembles that observed following oral administration. In patients with renal insufficiency, the serum half-life is prolonged; total and renal clearance decrease according to the creatinine clearance.

Ofloxacin has a neurotoxic potential and causes reversible testicular changes at high doses. Furthermore, preclinical studies with single and repeated administration in adult animals and pharmacological safety studies have shown no indications of any further specific risks associated with ofloxacin administration.
In common with other gyrase inhibitors, ofloxacin can precipitate damage to the large, weight-bearing joints of juvenile animals during the growth phase. The extent of cartilage damage is age-, species- and dose-dependent and can be considerably reduced by relieving pressure on the joints.
Ofloxacin has no effect on fertility or perinatal and postnatal development and causes no teratogenic or other embryotoxic effects in animal studies at therapeutic doses.
No conventional long-term carcinogenicity studies have been performed for ofloxacin. In in vitro and in vivo studies, ofloxacin was shown to be non-mutagenic. Data on the phototoxicity, photomutagenicity and photocarcinogenicity of ofloxacin show only a weak photomutagenic or phototumorigenic effect in vitro or in vivo compared with other fluoroquinolones.
There are no indications of any cataractogenic or cocataractogenic effect following ofloxacin exposure. Some gyrase inhibitors are known to possess a potential for prolongation of the QT interval. Preclinical studies to date showed that ofloxacin has only a weak potential for prolongation of the QT interval compared with the aforementioned gyrase inhibitors.

Tarivid 200 mg film-coated tablets
Lactose monohydrate, magnesium stearate (Ph.Eur.) [plant-based], macrogol 8000, titanium dioxide (E171), talc, maize starch, hyprolose, carmellose sodium, hypromellose.
Tarivid 400 mg film-coated tablets
Lactose; magnesium stearate (Ph.Eur.) [plant-based], macrogol 8000, titanium dioxide (E171), iron oxide hydrate (E172), talc, maize starch, hyprolose, sodium starch glycolate, hypromellose.

Not applicable.

Tarivid 200 mg film-coated tablets: 3 years. Tarivid 400 mg film-coated tablets: 3 years.

These medicinal products do not require any special storage conditions.

Tarivid 200 mg film-coated tablets: Blister made from bluish clear PVC/aluminium foil. Pack sizes: 10, 20, 50, 300 (hospital pack) film-coated tablets.
Tarivid 400 mg film-coated tablets: Blister made from bluish clear PVC/aluminium foil. Pack sizes: 10, 20 film-coated tablets.

No special requirements.