INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ZANOCIN 200 Tablets
ZANOCIN 400 Tablets

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ZANOCIN 200 Tablets
ZANOCIN 400 Tablets

COMPOSITION:
Zanocin 200 Tablets
Each tablet contains
Ofloxacin 200 mg

Zanocin 400 Tablets
Each tablet contains
Ofloxacin 400 mg

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum antibiotics

Mechanism of Action
Ofloxacin is a quinolone carboxylic acid derivative which has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative bacteria. Ofloxacin exerts its effect by inhibiting the bacterial DNA gyrase, which is responsible for coiling the genetic material as a prerequisite for bacterial multiplication.
The mode of action, range of activities, duration of action and MIC levels have been established mainly by means of in vitro studies using bacterial isolates.
Antibacterial Spectrum
Ofloxacin has a bactericidal effect. In vitro tests show that strains in which the sensitivity varies include pneumococci andureaplasma urealyticum. Strains that are normally resistant are:
Peptococcus, Peptostreptococcus, Eubacterium spp., Fusobacterium spp. and Treponema pallidum.
Pharmacokinetics
Ofloxacin is readily absorbed and excreted mainly unchanged in the urine. The serum elimination half-life is approximately 6 to 8 hours. Following oral administration, ofloxacin peak serum concentrations are reached within one to two hours. The plasma level usually achieved by the recommended dosage regimes (3 to 4 micrograms/mL) is in excess of the average MIC which is 1 to 2 micrograms/mL for susceptible organisms.
Ofloxacin has a low (9.4%) plasma protein binding.

INDICATIONS
Ofloxacin is indicated for the treatment of the following bacterial infections if these are due to ofloxacin-sensitive pathogens:

i)	Lower respiratory tract infections caused by Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa.
ii)	Infections of the urinary tract.
iii)	Sexually transmitted diseases; 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.

CONTRA-INDICATIONS
Hypersensitivity to ofloxacin or related chemotherapeutic agents of the quinolone-derivative group.
Ofloxacin should not be administered to pregnant or lactating women.
Ofloxacin should not be administered to patients with cerebral convulsive disorders.

WARNINGS
This medicine may lead to drowsiness and impaired concentration which may be aggravated by simultaneous intake of alcohol or other central nervous system depressants. Patients should be warned against taking charge of vehicles or performing potentially hazardous tasks where loss of concentration may lead to accidents.

Animal studies have shown that ofloxacin may affect joint development in immature animals. Ofloxacin should therefore not be given to patients under 18 years of age.

If severe and persistent diarrhoea occurs during or after therapy, the doctor should be informed because in few cases this may point to a serious intestinal disorder (pseudomembranous colitis) which requires immediate treatment. In such cases ofloxacin must be discontinued immediately and suitable therapy initiated. Products inhibiting peristalsis are contraindicated

DOSAGE AND DIRECTIONS FOR USE
Ofloxacin tablets should be swallowed with a little liquid. It may be taken on an empty stomach or with meals. The dosage should be determined according to the sensitivity of the causative organism and the severity of the infection.
The following dosages are recommended:
Pyelonephritis: 200 mg twice daily for 5-7 days.
Infections of the lower respiratory tract: 400 mg twice daily for 7-10 days. The daily dose may be altered depending on the severity of the infection.
Uncomplicated urethral and cervical gonorrhoea: A single dose of 400 mg
Urethritis and cervicitis due to chlamydia trachomatis: 600 mg daily in divided doses for up to 7 days.
For patients with impaired renal function and elderly patients the dosage of ofloxacin should be adjusted according to the degree of impairment. With a creatinine clearance of less than 30 mL to 10 mL/min, an oral single dose should be administered every 24 hours, e.g. 200 mg once daily. With a creatinine clearance of less than 10 mL/min, the normal single dose should be given initially. This dose should then be reduced to half and administered every 24 hours, e.g. 200 mg initially, thereafter 100 mg once daily.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side effects
Allergic manifestations may occur, in particular hypersensitivity reactions of the skin. There have been fleabite-like haemorrhages (petechiae), the formation of blood blisters (haemorrhagic bullae) and small nodules (papules) with crust formation indicating vessel involvement (vasculitis).
There have been symptoms such as facial oedema, swollen tongue, glottal oedema, tachycardia, dyspnoea and signs of imminent shock and acute anaphylaxis. In the event of such reactions, ofloxacin should be discontinued immediately. Medical treatment (therapy for shock) is imperative.
Erythema multiforme, Stevens Johnsons Syndrome, toxic epidermal necrolysis.
Skin reactions on exposure to strong sunlight have been reported.
Steady state theophylline levels may increase when ofloxacin and theophylline are given concurrently. Concomitant administration of ofloxacin with theophylline may prolong the half-life of theophylline, elevate serum theophylline levels and may increase the risk of theophylline-related adverse reactions.
Seizure and less frequently extrapyramidal symptoms, disturbances of the nervous system, e.g. weakness, headaches, dizziness, sleep disturbances, insomnia, nightmares, unsteady gait and tremor (disturbance of muscular co-ordination), numbness and tingling in the limbs (paraesthesiae), visual disturbances such as double vision and abnormal colour vision, disturbances of the senses of taste and smell, hallucinations, convulsions and psychotic reactions such as restlessness, agitation, anxiety, drowsiness, depression and confusion. These reactions have occurred mainly in elderly patients and patients with impaired renal function, but not exclusively. In some cases these reactions have occurred already after the first dose. In the event of such adverse reactions, ofloxacin should be discontinued immediately and the doctor informed. Paraesthesia and peripheral neuropathy have occurred.
There have been reports of pain in joints and muscles.
There have been cases of changes in the blood picture (leucopenia, eosinophilia, agranulocytosis, thrombocytopenia, anaemia),transient increases in liver enzymes and/or bilirubin and in serum creatinine.
Myalgia, gynaecomastia, cardiovascular effects including tachycardia.
Crystalluria as well as interstitial nephritis may also occur.
Gastro-intestinal symptoms may occur (gastric or abdominal symptoms and pain, loss of appetite, nausea, vomiting, dyspepsia, diarrhoea).
Experience to date shows that the adverse reaction to ofloxacin treatment resolves on discontinuation of the preparation. The doctor should always be informed of side-effects that have occurred.
Precautions
Ofloxacin should be used with caution in patients with epilepsy or a history of CNS disorders.
In patients receiving ofloxacin, myalgia and arthralgia (pain) can occur. Inflammation and rupture of tendons (e.g. the Achilles tendon) may occur within 48 hours after starting the treatment and may be bilateral. This has occurred particularly in patients treated concurrently with corticosteroids. In the event of signs of inflammation of a tendon, treatment with ofloxacin must be discontinued immediately and appropriate treatment for the affected tendon, initiated. Less frequently cases of myopathy and/or rhabdomyolysis may occur.
Since fluoroquinolones can cause degenerative changes in weight-bearing joints of young animals, it has been suggested that these compounds should not be used in children, adolescents, pregnant women, or breast feeding mothers.
Careful monitoring is required in patients with impaired hepatic or renal function, glucose-6-phosphate dehydrogenase deficiency and myasthenia gravis.
An adequate fluid intake should be maintained during treatment and excessive alkalinity of urine avoided because of risk of crystalluria.
Interactions
If mineral-containing antacids are taken at the same time, absorption of ofloxacin may be impaired.
Antacids and metal ions: The absorption of the medicine is reduced by antacids containing aluminium or magnesium and also by calcium, iron and zinc salts. Sucralfate releases aluminium ions in the stomach and thereby reduces absorption of ofloxacin. In such cases, ofloxacin should be taken about two hours before taking such preparations. High calcium content in dairy products might also interfere with the absorption of medicine.
Analgesics: Concurrent administration of fenbufen with quinolones may increase the incidence of CNS adverse effects.
Theophylline: Fluoroquinolones are known to inhibit hepatic drug metabolism and may interfere with the clearance of medicine metabolised by the liver such as theophylline. There are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with medicines that lower the seizure threshold, eg. theophylline.
Glibenclamide: Ofloxacin may cause a slight increase in serum concentrations of glibenclamide if administered concurrently. Excessive rises or falls in blood-sugar level may occur in isolated cases, especially in patients with diabetes mellitus. It is therefore recommended that patients treated concomitantly with ofloxacin and glibenclamide be monitored particularly closely.
Coumarin derivatives: As with other quinolones the effect of coumarin derivatives may be intensified when coadministered with ofloxacin. Patients undergoing concomitant treatment with coumarin derivatives should therefore be monitored carefully.
Others: Mutual impairment of excretion and an increase in serum levels must be considered when quinolones are administered together with other medicines (particularly in case of high dose therapy) that also undergo renal tubular secretion such as probenecid, cimetidine, furosemide or methotrexate.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See “Side-effects and special precautions”. Treatment is symptomatic and supportive.

IDENTIFICATION:
Zanocin 200 Tablets
White to off white, round, biconvex, film coated tablets debossed with '200' on one side and scored on the other with intact coating.
Zanocin 400 Tablets
White to off white, film coated caplets debossed with '400' on one side and scored on both sides with intact coating.

PRESENTATION:

Zanocin 200 Tablets:	Carton containing blister strip of 6 tablets.
	Carton containing blister strip of 10 tablets or ten strips of 10 tablets.
Zanocin 400 Tablets:	Carton containing blister strip of 10 tablets or ten strips of 10 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C, protected from light and moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
Zanocin 200 Tablets: 34/20.1.1/0209
Zanocin 400 Tablets: 34/20.1.1/0210

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
RANBAXY (SA) (PTY) LTD
Third Floor, Outspan House
1006, Lenchen Avenue North
Centurion

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
August 2002

Updated on this site: March 2003
Source: Pharmaceutical Industry
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