TARIVID (OFLOXACIN)

TARIVID 200 mg Tablets
TARIVID 400 mg Tablets
TARIVID I.V. 200 mg

COMPOSITION :
TARIVID 200 mg Tablets:
Each tablet contains 200 mg Ofloxacin.
TARIVID 400 mg Tablets:
Each tablet contains 400 mg Ofloxacin.
TARIVID I.V. 200 mg:
Each 100 mL infusion solution contains 220 mg ofloxacin hydrochloride, equivalent to 200 mg Ofloxacin.

PHARMACOLOGICAL CLASSIFICATION:
A: 20.1.1 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
TARIVID is a quinolone carboxylic acid derivative which has a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative bacteria.
TARIVID 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.
TARIVID is readily absorbed and excreted mainly unchanged in the urine.
The serum elimination half life is approximately 6-8 hours.
Following oral administration, TARIVID peak serum concentrations are reached within one to two hours.
The plasma level usually achieved by the recommended dosage regimen (3-4 micrograms/mL) is in excess of the average MIC which is 1-2 micrograms/mL, for susceptible organisms.
TARIVID has a low (9,4%) plasma protein binding.
TARIVID has a bactericidal effect.
In vitro tests show that strains in which the sensitivity varies include pneumococci and ureaplasma urealyticum.
Strains that are normally resistant are:
Peptococcus, Peptostreptococcus, Eubacterium spp., Fusobacterium spp. and Treponema pallidum.

INDICATIONS:
TARIVID is indicated for the treatment of the following bacterial infections if these are due to ofloxacin-sensitive pathogens:
Lower respiratory tract infections caused byHaemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Pseudomonas aeruginosa.
Infections of the urinary tract.
Sexually transmitted diseases: Acute uncomplicated urethral and cervical gonorrhoea, urethritis and cervicitis due toChlamydia trachomatis. Mixed infections of the urethra and cervix due toChlamydia 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.

CONTRA-INDICATIONS:
Hypersensitivity to ofloxacin or related chemotherapeutic agents of the quinolone-derivative group, or any of the excipients.
TARIVID should not be administered to pregnant or lactating women.
TARIVID should not be administered to patients with cerebral convulsive disorders.
TARIVID is contra-indicated in epileptics. TARIVID must not be used in patients with pre-existing central nervous system (CNS) lesions involving a lowered convulsant threshold, e.g. after cerebrocranial injuries, inflammations in the region of the CNS, or stroke.
In children or adolescents in the growth phase.
In patients with a history of tendon disorders related to fluoroquinolone administration.

WARNINGS:
Even when used as instructed, TARIVID may alter reactivity to such an extent that the ability to drive vehicles or operate machinery may be impaired.
Animal studies have shown that TARIVID may affect joint development in immature animals.
Tarivid should not be given to patients under 18 years of age.
Clostridium difficile - associated disease:
Diarrhoea, particularly if severe and/or persistent, occurring during treatment or in the initial weeks following treatment with ofloxacin or with various other antibiotics, but especially broad spectrum antibiotics, may be symptomatic of Clostridium difficile-associated disease, the most severe form of which is pseudomembranous colitis.
If a diagnosis of pseudomembranous colitis is suspected, ofloxacin should be stopped immediately and appropriate specified antibiotic therapy should be started without delay (e.g. vancomycin or metronidazole)
Tendinitis, less frequently observed, may occasionally lead to rupture, involving more particularly Achilles tendon, and occurring especially in elderly patients. Rupture seems to be favoured by treatment with corticosteroids. The onset of signs of tendinitis requires to stop the treatment, to rest both Achilles tendons by appropriate immobilization or special heel pieces, and to take orthopaedic advice.
Ofloxacin may aggravate myasthenia gravis.
Ofloxacin may inhibit the growth ofMycobacterium tuberculosis, giving false-negative results, in the bacteriological diagnosis of tuberculosis.
The serum concentration of ofloxacin should be monitored in patients with severe renal impairment and haemodialysis patients.
Although this has not been reported, the possibility cannot be ruled out that fluoroquinolones may trigger an attack of porphyria in predisposed patients.

DOSAGE AND DIRECTIONS FOR USE:
TARIVID TABLETS
TARIVID should be swallowed whole with a little liquid. It may be taken on an empty stomach or with meals.
If the treatment has been initiated via I.V. route, it is usually possible to switch to oral route at the same dosage after a few days, when the patients condition has improved.
The dosage should be determined according to the sensitivity of the causative organism and the severity of the infection.
The following dosages are recommended:
Uncomplicated Cystitis:
100 mg twice daily for 3-7 days.
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.
Prevention of infections in patients with neutropenia:
400 to 600 mg daily in divided doses.
It may be necessary to increase the dose to 600 mg or 800 mg ofloxacin daily in the presence of pathogens of varying sensitivity, in severe infections.

TARIVID I.V.
The dosage of TARIVID I.V. is determined by the severity and type of infection and the sensitivity of the causative organisms.
The usual dosage is 100-200 mg twice daily. For severe infections the dosage may be increased to 400 mg twice daily. Intravenous therapy should be discontinued as soon as oral TARIVID therapy can be substituted.
TARIVID I.V. should be infused SLOWLY over a period of 30-60 minutes.
TARIVID I.V. should be used as soon as the infusion vial has been opened. If its compatibility with other infusion solutions has not been proven, TARIVID I.V. should as a rule be administered separately.
TARIVID I.V. is compatible with the following infusion solutions:
Isotonic saline solution, Ringer’s solution, fructose solution 5%, glucose solution 5%.
Any unused portion of the I.V. solution must be discarded.
Heparin should not he administered in the same intravenous infusion fluid because of the risk of precipitation.
Impaired renal function:
For patients with impaired renal function and elderly patients the dosage of TARIVID should be adjusted according to the degree of impairment. With a creatinine clearance of less than 50 mL to 20 mL/min, a normal single dose should be administered every 24 hours, e.g. 200 mg once daily. With a creatinine clearance of less than 20 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.
Dosage in patients with impaired liver function:
The excretion of ofloxacin may be reduced in patients with severe liver function disorders (e.g. cirrhosis of the liver with ascites). A maximum daily dose of 400 mg ofloxacin should therefore not be exceeded.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Effects on the gastro-intestinal tract:
Gastro-intestinal symptoms may occur (gastric or abdominal symptoms, loss of appetite, nausea, vomiting, diarrhoea). If severe and persistent diarrhoea occurs during or after therapy, the physician should be informed because in a few cases this may point to a serious intestinal disorder (pseudomembranous colitis which is generally due to Clostridium difficile - see WARNINGS) which requires immediate treatment. In such cases TARIVID must be discontinued immediately and suitable therapy initiated. Products inhibiting peristalsis are contra-indicated.
Effects on the central nervous system:
Disturbances of the nervous system, e.g. weakness, headaches, dizziness, sleep disturbances: insomnia, nightmares, drowsiness, unsteady gait and tremor (disturbances of muscular coordination), numbness and tingling (paresthesiae), visual disturbances such as blurred vision, double vision and abnormal colour vision, disturbances of the senses of taste and smell, hearing and equilibrium, psychotic reactions such as restlessness, agitation, anxiety, depression and confusion and hallucinations, sometimes progressing to self-endangering behaviour. 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, TARIVID should be discontinued immediately and the doctor informed. Seizures, and less frequently extrapyramidal symptoms may occur.
Muco-cutaneous effects:
Allergic manifestations may occur, in particular hypersensitivity reactions of the skin such as pruritis, rash. Pustular eruption, single cases of bullous eruption (erythema multiforme, Stevens-Johnson syndrome or exceptionally, toxic epidermal necrolysis). Vascular purpura and systemic necrotising angeitis may occur in less frequent cases. 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), allergic inflammation of the lungs (pneumonitis), and fever.
Skin reactions on exposure to strong sunlight, have been reported (photosensitisation). Therefore exposure to sunlight and UV radiation should be avoided during treatment with TARIVID.
With the administration of TARIVID I.V. local irritation, pain at the site of injection, phlebitis or thrombo-phlebitis have been observed.
Anaphylactoid or anaphylactic reactions:
Acute anaphylactic or anaphylactoid reactions may occur, sometimes even after the first dose. It may manifest as hypotension, (a fall in blood pressure), burning sensation in the eyes, tickling cough and nasal catarrh, swelling of the skin and mucous membranes involving the face, tongue and larynx (hoarseness, difficulty in breathing) respiratory distress (also caused by bronchial spasm) or circulatory collapse (shock) may develop. In the event of such reactions, treatment with TARIVID should be discontinued immediately. Medical treatment (therapy for shock) is imperative.
Effects on the blood:
There have been cases of changes in the blood picture (eosinophilia, neutropenia, leukopenia, agranulocytosis, thrombocytopenia, anaemia, pancytopenia, haemolytic anaemia, bone marrow depression)
Effects on the kidneys and liver:
Transient increases in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) and/or bilirubin or hepatitis may occur. Crystalluria may also occur, as well as increases in serum creatinine, interstitial nephritis sometimes progressing to acute renal failure.
Effects on the musculoskeletal system:
Myalgia and arthralgia (pain). Inflammation and rupture of tendons (e.g. the Achilles tendon may occur within 48 hours after starting the treatment and may be bilateral (see WARNINGS). This has occurred particularly in patients treated concurrently with corticosteroids. In the event of signs of inflammation of a tendon, treatment with TARIVID must be discontinued immediately and appropriate treatment for the affected tendon, initiated. Less frequently cases of myopathy and/or rhabdomyolysis may occur.
Others:
Less frequently, hypoglycaemia in diabetics treated with hypoglycaemic agents may occur.
Treatment with ofloxacin may enhance development of resistant micro organisms and fungal growth.
TARIVID may result in an acceleration of the heart beat as well as a decrease in blood pressure which may be severe particularly after infusions and especially when given too rapidly. In the event of a serious decrease in blood pressure TARIVID I.V. should be discontinued. In less frequent cases, as a consequence of a pronounced drop in blood pressure, circulatory collapse may occur. Blood pressure should be monitored frequently during the infusion.
Experience to date shows that the adverse reaction to TARIVID treatment resolves on discontinuation of the preparation. The physician should always be informed of side-effects that have occurred.

Interactions:
Antacids containing aluminium, including sucralfate, and magnesium hydroxides, aluminium phosphate or calcium, zinc, iron are liable to reduce the absorption of TARIVID. In such cases TARIVID should be taken about 2 hours before taking such preparations.
There are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with other medicines that lower the seizure threshold, e.g. theophylline. The possibility cannot be ruled out with certainty that during treatment with TARIVID, as with other quinolones, the effect of coumarin derivatives may be intensified. Patients undergoing concomitant treatment with coumarin derivatives should therefore be monitored carefully.
Excessive rises or falls in blood-sugar level may occur in isolated cases, especially in patients with diabetes mellitus. Ofloxacin may cause a slight increase in serum concentrations of glibenclamide if administered concurrently, it is therefore recommended that patients treated concomitantly with TARIVID and glibenclamide be monitored particularly closely.
The concomitant use of TARIVID I.V. and hypotensive medicines and barbiturates may cause a fall in blood pressure.
Particularly in case of high dose therapy, mutual impairment of excretion and an increase in serum levels must be considered when quinolones are administered together with other medicines 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. The most important signs to be expected following acute overdosage are CNS symptoms such as confusion, dizziness, impairment of consciousness and seizures as well as gastro-intestinal reactions such as nausea and mucosal erosions. In the event of overdose, gastric lavage and symptomatic treatment should be implemented. No specific antidote exists.

IDENTIFICATION:
TARIVID 200 mg Tablet: A pale, yellowish-white, oblong, biconvex, film-coated tablet, scored on both sides with MXI imprinted on one side of the score and the company logo on the other side. On the other side of the tablet the imprint is reversed.
TARIVID 400 mg Tablet: A pale, yellowish-white, oblong, biconvex, film-coated tablet, scored on both sides. Both sides imprinted MXL and the company logo.
TARIVID I.V. 200 mg: A clear, slightly yellow solution in a 100 mL infusion vial.

PRESENTATION:
TARIVID 200 mg Tablets: Cardboard containers with opaque blister packs containing 6, 10 or 100 tablets each.
TARIVID 400 mg Tablets: Cardboard containers with one or more opaque blister packs of 10 tablets each.
TARIVID I.V. 200 mg: 5 Infusion vials of 100 mL.

STORAGE INSTRUCTIONS:
Store below 25°C in a dry place.
Protect from light. Keep in the pack until required.
Once the infusion vial has been opened, the infusion solution must be used without delay.
Do not use later than the date of expiry.
Keep out of reach of children.