OFLOXACIN
PROPERTIES :
Ofloxacin, the active ingredient of EVAFLOX is a bactericidal quinolone antibiotic.
Antibacterial spectrum
/ Highly susceptible organisms
Enterobacteriaceae - Escherichia coH, Enterobacter. Klebsiella, Proteus, Salmonella, Shigella, Serratia, Citrobacter
Staphylococci β’β’ Staphylococcus aureus (including methicillin-resistant Staph.l, Staphylococcus epidermidis
Neisserias : Neisseria gonorrhoeae (including ampicillin resistant strains), Neisseria meningitidis
// Susceptible organisms
campylobacter, Aerornonas, Vibrio cholerae, Yersinia enterocolitica, Helicobacter pylori. Gardnerella vaginalis, Haemophilus influenzae
/// Organisms with variabfe susceptibility
Pseudomonas aeruginosa, Enterococci
Streptococci (Strept. pyogenes, Strept. pneumoniae, Strept. viridans)
Mycoplasma (Mycoplasma hominis, Mycoplasma pneumoniae)
Mycobacteria (Mycobacterium tuberculosis, Mycobacterium fortuitumi
IV Usually resistant organisms
Urcaplasma urealyticum. Nocardia asteroides, and anaerobes (e.g.: Bacteroides, Peptococcus. Peptostreptococcus, Fusobacterium, Clostridiunn difficile)
V Resist ant organisms
Treponerna pallidum
INDICATIONS:
A. Therapeutic
Infections due to susceptible organisms: -
] Gynaecological infections (vaginitis, pelvic inflammatory disease)
2. Gonorrhoea
3. Infections of the kidney, urinary tract and genital organs
4. Lower respiratory tract infections :
a) Acute , chronic or recurrent bronchitis (esp : Staphylococcus aureus ,Haemophilus influenzae, other gram negative organisms, multi-drug-
resistant pathogens)
b) Non-pneumococcal pneumonia caused by Staphylococcus, Escherichia coli, Klebsiella, Proteus, Enterobacter, Pseudomonas, Legionella
5. Skin and soft tissue infections (e.g. : Staphylococcus aureus, Staphylococcus epidermidis) including post surgical infections
6. Abdominal infections including peritonitis and bacterial enteritis
7. E.N.T infections '. chronic and recurrent infections of the ear, nose and throat caused by grain-negative pathogens (e.g.: Staphylococcus, Pseudomonas)
8. Bone and joint infections
b. Pfophylaxia
Prevention of infections due to ofloxacin-susceptible pathogens (prophylaxis of infections also by selective decontamination of the intestines) in patients
with a significant reduction in resistance to infections (e.g. in neutropenic state).
CONTRAINDICATIONS :
EVAFLOX must not be used in
1 . Pregnancy and lactation
2. Children and adolescents in the growth phase (risk of damage to the joint cartilage in the growing organism cannot be entirely ruled out based on
animal studies)
3. Epileptics as well as in patients with a lowered cerebral seizure threshold due to pre existing central nervous system lesions
4 Patients hypersensitive to ofloxacin, other quinolones or any of the excipients
DRUG INTERACTIONS:
* With some medicines, taken concurrently, an attenuation of the effect of EVAPLOX tablets must be taken into account e.g. mineral aii~cicr. β’β’ ~~
.ilumiruum or magnesium), sucralfate, or iron preparations and calcium.
For this reason, EVAFLOX tablets must be taken about 2 hours before taking such preparations.
* With drugs that lower the seizure threshold, there are indications of a pronounced lowering of the cerebral seizure threshold e.g. theophylline.
β’ EVAFLOX may cause a slight increase in serum concentrations of glibenclamide administered concurrently. Therefore, patients should be closely
monitored.
* Concurrent administration of chloroquine with quinolones should be undertaken with care as both drugs are neurotoxic.
* Mutual impairment of excretion and an increase in serum levels must be considered when quinolones are administered together with other drugs that
also undergo renal tubular secretion particularly when administered in high doses eg : probenecid, cimetidine, furosemide or methotrexate.
* In patients who are treated with quinolones, an increase in the effect of coumarin derivatives cannot be ruled oOt. Therefore, patients undergoing
concurrent treatment with coumarin derivatives like warfarin should be closely monitored.
* Tendiniris and tendon rupture has been observed in patients treated concurrently with corticosteroids.
interference with laboratory tests
Determination of opiates or porphyrins in urine may give false-positive results during treatment with EVAFLOX.
ADVERSE EFFECTS :
Cciicral
* Hypersensitivity to light may develop in very rare cases. This may resemble severe sunburn and in some cases also involve the nails (discolouration,
loosening).
* Fever, eosinophilia and allergic inflammation of the lungs (allergic pneumonitis) may develop in very rare cases.
* Anaphylactic or anaphylactoid reactions (rapidly developing allergy or allergy-like hypersensitivity reactions) may occur in very rare instances, but
sometimes even after the first dose. These may manifest themselves in a rise in blood pressure, sweating, burning sensation in the eyes, dry cough and
nasal catarrh. These may also be accompanied by swelling of the skin and mucous membranes (angio-oedema) involving the face, tongue and larynx
(symptoms: hoarseness, difficulty in breathing). In the most serious cases, severe respiratory distress (also caused by bronchial spasm) or circulatory
collapse (shock) may develop. In the event of such reactions, treatment with EVAFLOX must be halted immediately and medical treatment initiated.
* In very rare cases, muscular complaints such as pain or weakness (of special significance in, e.g. patients with myasthenia gravis) may occur. In
isolated cases, these may be symptoms of muscle disease (rhabdomyolysis) entailing destruction of muscle tissue, which, in some cases, can lead to
muscular atrophy and acute renal failure. Very rarely, Joint and tendon discomfort (e.g. pain) may occur.
* Inflammation of tendons (tendinitis) and rupture (e.g. Achilles tendon) may occur in isolated instances during treatment with quinolones. If tendinitis
is suspected, treatment with EVAFLOX must be halted immediately and appropriate treatment must be initiated for the affected tendon.
* EVAFLOX may trigger an attack of porphyria in predisposed patients.
* Hyper or hypoglycaemia may occur in isolated cases.
* Administration of antibiotics, especially if prolonged, may lead to the proliferation of resistant microorganisms.
* Except in very rare instances (e.g. isolated cases of smell, taste and hearing disorders), the adverse effects observed subsided after discontinuation of EVAFLOX.
Systemic
' Gasiroinfestinal tract .' During treatment with EVAFLOX, stomach upsets, abdominal pain, loss of appetite, nausea, vomiiing, or diarrhoea may oc.cul
.a) Diarrhoea may sometimes be a symptom of enterocolitis, which may. be accompanied by blood in stools.
b) Pseudomembranous colitis (in most cases is due to Clostridiurn difficile). This possibility must be considered in patients in whom severe, persistent
diarrhoea occurs during treatment or in the initial weeks thereafter. If suspected, administration of EVAFLOX must be halted immediately. Drugs that
inhibit intslinal motility must not be taken in such cases.
(c) Liver : Rarely, impairment of liver function with jaundice may occur. Very rarely, cholestatic jaundice, hepatitis or severe liver damage may develop.
2. Nervous system:
* Headache, dizziness, sleep disorders, agitation and confusion may occur.
in rare cases, drowsiness, unsteadiness of gait and tremor (due to disorders of muscular co-ordination), extrapyramidai symptoms lincreased or
decreased muscle tone, involuntary movements of the face and body. tremor at rest, a decrease in spontaneous movements or slowness in initiatinc]
movements) are also seen.
* Convulsions, numbness and tingling (paraesthesia or hyperaesthesia) may rarely occur.
* Rdfely. visual disorders such as blurred vision, double vision, and abnormal colour vision have been reported.
* Disorders of taste and smell (including loss of taste and smell) may develop.
* Disorders of hearing (in exceptional cases even loss of hearing) and tinnitus are rare with EVAFLOX.
* In very rare cases, hallucinations, anxiety, depression and psychotic reactions may occur. Ceitain psychotic reactions may, in some cases, lead to self
endangering behavior. In the event of such reactions, even after the first dose, EVAPLOX must be discontinued immediately.
3. Curdiovascular system : Ingestion of EVAFLOX may be followed by tachycardia and temporary hypotension. In rare cases, as a consequence uf
pronounced hypotension, circulatory collapse is possible.
4. Blood : Very rarely, a reduction in the numbers of both red and white blood cells [this can include the absence of certain white blood cells) and/or of
platelets (anaemia, leucopenia including agranuiocytosis, thrombocytopenia, pancytopenia) may occur. In some cases, these changes result from bone
marrow depression. Very rarely, haemolytic anaemia may develop.
5. Kidney: rarely, impairment of renal functions, like an increase in serum creatinine may develop. Isolated cases of kidney inflammation have been
spen. This interstitial nephritis may progress to acute renal failure.
6. Skin, mucous nnernbranes and other reactions .' Cutaneous and mucosal reactions such as itching and skin rashes (in exceptional cases, with blisters or small pus filled pus-filled vesicles may develop. In very rare cases reddening of the skin accompanied by burning, severe skin reactions (erythema multiforme,Stpvens Johnson syndrome and Lyell's syndrome) and inflammation of the vessels (vasculitis) can occur and may manifest ilself in the form of bleeding under the skin looking like tiny red dots (petechiae). or blood filled blisters (haernorrhagic bullae) or small nodules with crust formation. It can also lead to skin lesions including irreversible damage (necrosis) in exceptional cases. Vasculitis may also invulve internal organs.
Please consult a physician if you notice any of the adverse effects listed in this package insert or any other undesired affects or unexpected chanqes.
SPECIAL WARNINGS AND PRECAUTIONS : ____
β’ Patients with a history of severe adverse reactions e.g., anaphylaxis, tendinitis with rupture of the affected tendon, severe neurological reactions to other quinolones may be at increased risk of similar reactions to EVAFLOX.
*Administration of antibiotics, especicilly if prolonged,may lead lo The proliferation of resistant microorganisms. The patient's condition must there fore be checked at regular intervals. If a secondary infection occurs, appropriate measures must be taken.
*patients undergoing treatment with EVAFLOX are advised not to expose themselves unnecessarily to strong sunlight and to avoid UV rays (sunray lamp,solarium)otherwise skin and nail reactions may occur due lo photosensilivily.
*Some adverse effects may impair the ability to concentrate and read, and therefOrc, constitute a risk in situations where these abilities are of particular importance ie driving a car or operating machinery.
DOSAGE :
A daily dose of upto 400 mq EVAFLOX may be taken as a single dose, preferably in the morning. Larger doses must be divided into two separate doses at equal intervals.
depending on the severity of the infection and on the presence of complicating factors or pathogens of moderate susceptibility, it may he recessary to increase the dose to upto 2 x 400 mg tablets daily.
Dose in patients with impaired renal function: In patients with imp;iired renal function, the following dosages are recommended.
The initial dose is the same as for normal individual with normal renal function, whereas the maintenance dose should he reduced as follows :
Creatinine clearance Maintenance dose
50-20 ml/min 100-200 mg EVAFLOX every 24 hours
< 20 ml/min 100 mg EVAFLOX every 24 hours
Hdemodialysis or uentoneal dialysis 100 mo EVAFLOX everv 24 hours
Dosage in patients with impaired liver function: The excretion of ofloxacin inay be reduced in patients with severe impairment of liver function (e.gchirrosis wilh ascites). A maximum daily dose of 400 mg ofloxacin should, therefore not be exceeded.
Until further experience is available, the duration of treatment should not exceed 2 months.
ADMINISTRATION:
EVAFLOX tablets should be swallowed without chewing with sufficient amounts of liquid approx. 1/2 glass). They may be taken on dii empty stomaL
in with meals.
STORAGE: Store in a cool, dry & dark place. Keep medicines out of the reach of children.