Ofloxacin Tablets USP 400mg Taj Pharma

  1. NAME OF THE MEDICINAL PRODUCT

Ofloxacin Tablets USP 200mg Taj Pharma
Ofloxacin Tablets USP 400mg Taj Pharma

  1. Qualitative and quantitative composition
    a) Each film-coated tablet contains:
    Ofloxacin USP……………………..200mg
    Excipients………………………………q.s.

    b) Each film-coated tablet contains:
    Ofloxacin USP……………………..400mg
    Excipients………………………………q.s.

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Film-coated tablet

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

The following indications are restricted to adults.

Ofloxacin is suitable for treatment of the following bacterial infections if these are caused by pathogens sensitive to ofloxacin (see section 5.1):

  • Lower respiratory tract infections including pneumonia, bronchitits and acute exacerbations of chronic bronchitis caused by gram negative aerobic bacteria. (Ofloxacin tablets are not the drug of first choice in pneumonia caused by Streptococcus pneumoniae, Mycoplasma pneumoniae or Chlamydia pneumoniae);
  • Upper and lower urinary tract infections, including uncomplicated (cystitis) and complicated urinary tract infections.
  • Uncomplicated urethral and cervical gonorrhoea, non-gonococcal urethritis and cervicitis.

Consideration should be given to official guidance on the appropriate use of anti-bacterial agents.

4.2 Posology and method of administration

Posology

The dose of ofloxacin is determined by the type and severity of the infection. The dosage range for adults is 200 mg to 800 mg daily.

Up to 400 mg may be given as a single dose, preferably in the morning. Generally, individual doses should be given at approximately equal intervals.

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

The following doses are recommended:

Indications Single and Daily Doses
Uncomplicated urethral/ cervical gonorrhoea 400 mg
Uncomplicated lower urinary tract infections 200 mg-400 mg daily
Complicated infections of the upper urinary tract 400 mg daily, increasing if necessary, to 400 mg twice a day
Lower respiratory tract infections 400 mg daily, increasing, if necessary, to 400 mg twice a day
Non-gonococcal urethritis and cervicitis 400 mg daily

A single dose of 400 mg of ofloxacin is sufficient for the treatment of uncomplicated gonorrhoea.

Special patient populations

Impaired renal function

Following a normal initial dose, dosage should be reduced in patients with impairment of renal function as determined by creatinine clearance or plasma creatinine level.

Creatinine Clearance Plasma Creatinine Maintenance Dose*
20 to 50 ml/min* 1.5 to 5 mg/dl 100 mg – 200 mg ofloxacin per day)
<20ml/min** >5 mg/dl 100 mg ofloxacin per day

* According to indication or dose interval

** The serum concentration of ofloxacin should be monitored in patients with severe renal impairment and dialysis patients.

Patients undergoing haemodialysis or peritoneal dialysis should be given 100 mg ofloxacin per day.

When creatinine clearance cannot be measured, it can be estimated with reference to the serum creatinine level using the following Cockcroft’s formula for adults:

Impaired liver function

The excretion of ofloxacin may be reduced in patients with severe hepatic dysfunction.

(e.g. cirrhosis of the liver with ascites). In such cases, it is recommended that the dose should not exceed 400 mg ofloxacin daily, because of possible reduction of excretion.

Paediatric population

Ofloxacin is contraindicated for use in children or growing adolescents (see section 4.3).

Elderly

No adjustment of dosage is required in the elderly, other than that imposed by consideration of renal or hepatic function. (See section 4.4 QT interval prolongation).

Duration

Treatment should not exceed 2 months duration.

A daily dose of up to 400 mg ofloxacin may be given as a single dose. In this case, it is preferable to administer ofloxacin in the morning.

Daily doses of more than 400 mg must be divided into two separate doses and be given at approximately equal intervals.

Method of administration

For oral use.

Ofloxacin tablets should be swallowed whole with sufficient liquid before or during meal times. They 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 (see section 4.5).

4.3 Contraindications

The use of ofloxacin is contraindicated as follows:

  • Hypersensitivity to the active substance, to any other fluoroquinolone antibacterials, or to any of the excipients listed in section 6.1.
  • In patients with a history of epilepsy or an existing central nervous system disorder with a lowered seizure threshold.
  • In patients with a history of tendon disorders related to fluoroquinolone administration
  • In children or growing adolescents, and in pregnant or breastfeeding women, since animal experiments do not entirely exclude the risk of damage to the growth-plate cartilage in the growing organism cannot be entirely excluded.
  • In patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity because they may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

4.4 Special warnings and precautions for use

Ofloxacin tablets are not the drug of first choice in pneumonia caused by Streptococcus pneumoniae or Chlamydia pneumoniae.

Methicillin-resistant S. aureus

Are very likely to possess co-resistance to fluoroquinolones, including ofloxacin. Therefore ofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratory results have confirmed susceptibility of the organism to ofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA-infections are considered inappropriate).

Resistance to fluoroquinolones of E. coli

The most common pathogen involved in urinary tract infections – varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in E. coli to fluoroquinolones.

Severe bullous reactions

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with ofloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

Tendonitis

Tendonitis, rarely observed with quinolones, may occasionally lead to rupture involving Achilles tendon in particular. Tendinitis and tendon rupture, sometimes bilateral, may occur within 48 hours of starting treatment with ofloxacin and have been reported up to several months after discontinuation of ofloxacin. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years and in patients using corticosteroids. The daily dose should be adjusted in elderly patients based on creatinine clearance (see section 4.2). Close monitoring of these patients is therefore necessary if they are prescribed ofloxacin. All patients should consult their physician if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with ofloxacin must be halted immediately, and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon (see sections 4.3 and 4.8).

Hypersensitivity

Hypersensitivity and allergic reactions have been reported for fluoroquinolones after first administration. Anaphylactic and anaphylactoid reactions can progress to life-threatening shock, even after the first administration. In these cases ofloxacin should be discontinued and suitable treatment (e.g. treatment for shock) should be initiated.

Diseases caused by Clostridium difficile

Diarrhoea, especially if severe, persistent and/or bloody, occurring during or after treatment with ofloxacin (including several weeks after treatment), may indicate a condition caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis (CDAD) CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with ofloxacin. If pseudo-membraneous colitis is suspected, treatment should be discontinued immediately.

Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin, oral teicoplanin or metronidazole). Medicinal products that inhibit peristalsis are contraindicated in such cases.

Patients predisposed to seizures

Quinolones may lower the seizure threshold and may trigger seizures. Ofloxacin is contraindicated in patients with a history epilepsy or with a known predisposition to seizures (see section 4.3).

Patients with a known predisposition to seizures may include those with pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs (NSAIDs), or with drugs which lower the cerebral seizure threshold, such as theophylline (see section 4.5 interactions).

In case of convulsive seizures, treatment with ofloxacin should be discontinued (see section 4.5).

Patients with impaired renal function

Since ofloxacin is eliminated primarily via the kidneys, the dose should be adjusted in patients with impaired renal function (see section 4.2).

Patients with history of psychotic disorder

Psychotic reactions have been reported in patients receiving fluoroquinolones including ofloxacin. In some cases these have progressed to suicidal thoughts or self-endangering behavior including suicide attempt, sometimes after a single dose of ofloxacin (see section 4.8). In the event that a patient develops these reactions, ofloxacin should be discontinued and appropriate measures instituted.

Ofloxacin should be used with caution in patients with a history of psychotic disorder or in patients with psychiatric disease.

Patients with impaired liver function

Ofloxacin should be used with caution in patients with impaired liver function, as liver damage may occur. Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with fluoroquinolones. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen (see section 4.8).

Patients treated with vitamin K antagonists

Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with fluoroquinolones, including ofloxacin, in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs are given concomitantly (see section 4.5).

Myasthenia gravis

Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and the requirement for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Ofloxacin is not recommended in patients with a known history of myasthenia gravis.

Superinfection

As with other antibiotics, the use of ofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms, especially Enteracci, resistant strains of some organisms or Candida. Repeated evaluation of the patient’s condition is essential and periodic in vitro susceptibility tests may be useful. If secondary infection occurs during therapy, appropriate measures should be taken.

Prevention of photosensitisation

Photosensitisation has been reported with ofloxacin (see section 4.8). It is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), during treatment and for 48 hours following treatment discontinuation in order to prevent photosensitisation.

QT interval prolongation

Very rare cases of QT interval proplongation have been reported in patients taking fluoroquinolones.

Caution should be taken when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:

– elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ofloxacin, in these populations.

– uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia) – congenital long QT syndrome

– concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)

– – cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

(See section 4.2 Elderly, section 4.5, section 4.8 and section 4.9).

Dysglycaemia

As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In these diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

Peripheral neuropathy

Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving fluoroquinolones, including ofloxacin, which can be rapid in its onset. Ofloxacin should be discontinued if the patient experiences symptoms of neuropathy. This would minimise the possible risk of developing an irreversible condition (see section 4.8).

Patients with glucose-6-phosphate-dehydrogenase deficiency

Patients with latent or diagnosed glucose-6-phosphate-dehydrogenase deficiency may be predisposed to haemolytic reactions if they are treated with quinolones. Therefore if ofloxacin has to be used in these patients, potential occurrence of haemolysis should be monitored.

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.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8).

Excipient with known effect

Ofloxacin contains lactose anhydrous. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

For treatment of severe and/or life-threatening infections parenteral therapy is indicated.

4.5 Interaction with other medicinal products and other forms of interaction

Antacids, Sucralfate, Metal Cations

Co-administered magnesium/aluminum antacids, sucralfate, zinc or iron preparations and didanosine chewable/buffered tablets can reduce absorption of ofloxacin tablets. Therefore, ofloxacin should be taken 2 hours before such preparations.

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs

No pharmacokinetic interactions of ofloxacin were found with theophylline in a clinical study. However, a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, nonsteroidal antiinflammatory drugs, or other agents, which lower the seizure threshold.

Probenecid, cimetidine, furosemide, and methotrexate

Probenecid decreased the total clearance of ofloxacin by 24%, and increased AUC by 16%. The proposed mechanism is a competition or inhibition for active transport at the renal tubular excretion. Caution should be exercised when ofloxacin is coadministered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.

Drugs known to prolong QT interval

Ofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) (see section 4.4 QT interval prolongation).

Vitamin K antagonists

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, therefore, be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives (see section 4.4).

Glibenclamide

Ofloxacin may cause a slight increase in plasma glibenclamide levels when administered concurrently, it is therefore recommended that patients treated concomitantly with ofloxacin and glibenclamide be monitored particularly closely. Since hypoglycaemia is then more likely to occur, close monitoring of blood sugar levels is recommended in such cases.

4.6 Fertility, pregnancy and lactation

Pregnancy

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 (see section 5.3). Therefore ofloxacin must not be used during pregnancy (see section 4.3).

Breast-feeding

Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the nursing infant, breast-feeding should be discontinued during treatment with ofloxacin (see section 4.3).

4.7 Effects on ability to drive and use machines

Since there have been occasional reports of drowsiness/somnolence, impairment of skills, dizziness/vertigo and visual disturbances, which may impair the patient’s ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery), patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.

4.8 Undesirable effects

The information given below is based on data from clinical studies and on extensive post marketing experience.

System organ class Uncommon

(≥1/1,000 to <1/100)

Rare

(≥1/10,000 to <1/1,000)

Very rare

(< 1/10,000)

Not known (cannot be estimated from available data)*
Infections and infestations Fungal infection,

Pathogen resistance

Blood and lymphatic system disorders Anaemia,

Haemolytic anaemia,

Leucopenia,

Eosinophilia,

Thrombocytopenia

Agranulocytosis,

Bone marrow failure,

Pancytopenia

Immune system disorders Anaphylactic reaction*,

Anaphylactoid reaction*,

Angioedema*

Anaphylactic shock*,

Anaphylactoid shock*

Metabolism and Nutrition disorders Anorexia Hypoglycaemia in diabetics treated with hypoglycaemic agents (see section 4.4),

Hyperglycaemia,

Hypoglycaemic coma

Psychiatric disorders Agitation,

Sleep disorder,

Insomnia

Psychotic disorder (for e.g. hallucination),

Anxiety,

Confusional state,

Nightmares,

Depression

Psychotic disorder and depression with self-endangering behaviour including suicidal ideation or suicide attempt (see Section 4.4),

Nervousness

Nervous system disorders Dizziness,

Headache

Somnolence,

Paraesthesia,

Dysgeusia,

Parosmia

Peripheral sensory neuropathy*,

Peripheral sensory motor neuropathy* ,

Convulsion*,

Extra-pyramidal symptoms or other disorders of muscular coordination

Tremor,

Dykinesia,

Ageusia,

Syncope

Eye disorders Eye irritation Visual disturbance Uveitis
Ear and labyrinth disorders Vertigo Tinnitus,

Hearing loss

Hearing impaired
Cardiac disorders Tachycardia Ventricular arrhythmias and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9)
Vascular disorders Hypotension
Respiratory, thoracic and mediastinal disorders Cough,

Nasopharyngitis

Dyspnoea,

Bronchospasm

Allergic pneumonitis,

Severe dyspnoea

Gastrointestinal disorders Abdominal pain,

Diarrhoea,

Nausea,

Vomiting

Enterocolitis, sometimes haemorrhagic Pseudomembranous colitis* Dyspepsia,

Flatulence,

Constipation,

Pancreatitis

Hepatobiliary disorders Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase),

Blood bilirubin increased

Jaundice cholestatic Hepatitis, which may be severe*

Severe liver injury, including cases with acute liver failure, sometimes fatal, have been reported with ofloxacin, primarily in patients with underlying liver disorders (see section 4.4).

Skin and subcutaneous tissue disorders Pruritus,

Rash

Urticaria,

Hot flushes,

Hyperhidrosis

Pustular rash

Erythema multiforme,

Toxic epidermal necrolysis,

Photo-sensitivity reaction*,

Drug eruption ,

Vascular purpura,

Vasculitis, which can lead in exceptional cases to skin necrosis

Stevens-Johnson syndrome,

Acute generalised exanthemous pustulosis,

Drug rash,

Stomatitis

Exfoliative dermatitis

Musculoskeletal and connective tissue disorders Tendonitis Arthralgia,

Myalgia,

Tendon rupture (e.g. Achilles tendon) which may occur within 48 hours of treatment start and may be bilateral

Rhabdomyolysis and/or Myopathy,

Muscular weakness,

Muscle tear, Muscle rupture,

Ligament rupture,

Arthritis

Renal and urinary disorders Serum creatinine increased Acute renal failure Acute interstitial nephritis
Congenital, familial and genetic disorders Attacks of porphyria in patients with porphyria
General disorders and administration site conditions Asthenia,

Pyrexia,

Pain (including pain in back, chest and extremities)

* postmarketing experience

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms

The most important signs to be expected following acute overdose are CNS symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures increases in QT interval as well as gastrointestinal reactions such as nausea and mucosal erosions.

CNS effects including confusional state, convulsion, hallucination, and tremor have been observed in post marketing experience.

Management

In the case of overdose steps to remove any unabsorbed ofloxacin e.g. gastric lavage, administration of adsorbants and sodium sulphate, if possible during the first 30 minutes, are recommended; antacids are recommended for protection of the gastric mucosa.

In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Antacids may be used for protection of gastric mucosa. A fraction of ofloxacin may be removed from the body with haemodialysis. Peritoneal dialysis and CAPD are not effective in removing ofloxacin from the body. No specific antidote exists.

Elimination of ofloxacin may be increased by forced diuresis.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Quinolone Antibacterials, Fluoroquinolones

Mechanism of action

Ofloxacin inhibits bacterial DNA replication by inhibiting bacterial topoisomerases, particularly DNA gyrase and topoisomerase IV. It is active after oral administration.

Therapeutic doses of ofloxacin are devoid of pharmacological effects on the voluntary or autonomic nervous system.

The NCCLS MIC breakpoint recommendations are as follows:

S ≤ 2 mg/l and R ≥ 1 mg/l

Haemophilus influenzae and Neisseria gonorrhoea are exceptions with breakpoints at S ≤ 0.25 mg/l and R ≥ 1 mg/l

The BSAC general recommendations are S ≤ 2 mg/l and R ≥ 4 mg/l

According to DIN 58 940, the following limits apply for ofloxacin:

S ≤ 1 mg/L, I = 2 mg/L, R ≥ 4 mg/L.

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance on probabilities whether micro-organisms will be susceptible to ofloxacin or not.

Only those pathogens relevant to the indications are listed.

European range of acquired bacterial resistance to ofloxacin
Normally susceptible
Aerobic Gram-positive micro organisms
S. aureus – methicillin-sensitive 0.3-12.6%
S. pyogenes 2-5%
Aerobic Gram-negative micro organisms
Acinetobacter spp 0.3-7.3%
Citrobacter spp. 3-15%
Enterobacter spp. 2-13%
E. coli 1-8%
H. influenzae 1%
Klebsiella spp. 1-10%
Moraxella spp. 0-0.2%
Morganella morganii 0-6.9%
N. gonorrhoeae 25%
Proteus spp. 1-15%
Serratia marcescens 2-2.4%
Others
Chlamydia spp
L. pneumophila
Intermediately susceptible
Aerobic Gram-positive micro organisms
S. pneumoniae 70%
Providentia 17.1%
Aerobic Gram-negative micro organisms
E. faecalis 50%
P. aeruginosa 20-30%
Serratia spp. 20-40%
Stenotrophomonas maltophilia 5.1-11%
Others
Mycoplasma spp. 0-5.3%
Ureaplasma spp. 0-2.1%
Resistant
Anaerobic bacteria
S. aureus – methicillin-resistant 69.2-85.7%
T. pallidum

Resistance

The main mechanism of bacterial resistance to ofloxacin involves one or more mutations in the target enzymes, which generally confer resistance to other active substances in the class. Efflux pump and impermeability mechanisms of resistance have also been described and may confer variable resistance to active substances in other classes.

5.2 Pharmacokinetic properties

Absorption

The administration of oral doses to fasting volunteers was followed by a rapid and almost complete absorption of ofloxacin. The peak plasma concentration after a single oral dose of 200mg averaged 2.6 µg/ml and was reached within one hour. The plasma elimination half-life was 5.7 to 7.0 hours and was not dose related.

Distribution

The apparent distribution volume was 120 litres. The plasma concentration did not materially rise with repeat doses (accumulation factor for twice daily dosage: 1.5). The plasma protein binding was approx. 25%.

Biotransformation

The biotransformation of ofloxacin was below 5%. The two main metabolites found in the urine were N-desmethyl-ofloxacin and ofloxacin-N-oxide.

Elimination

Excretion is primarily renal. Between 80 and 90% of the dose were recovered from the urine as unchanged substance.

Ofloxacin was present in the bile in glucuronidised form. The pharmacokinetics of ofloxacin after intravenous infusion are very similar to those after oral doses. The plasma half-life is prolonged in persons with renal insufficiency; total and renal clearance decrease in accordance with the creatinine clearance. In renal insufficiency the dose should be reduced.

No clinically relevant interactions were seen with food and no interaction was found between ofloxacin and theophylline.

5.3 Preclinical safety data

Preclinical effects in conventional studies of safety pharmacology, acute toxicity, repeated dose toxicity, reproductive studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. Joint toxicity was observed at exposure in the human therapeutic range in juvenile rats and dogs. Ofloxacin exhibits a neurotoxic potential and causes reversible testicular alterations at high doses.

Mutagenicity studies showed no evidence for mutagenicity of ofloxacin. However, like some other quinolones Ofloxacin is phototoxic in animals at exposure in the human therapeutic range. The phototoxic, photomutagenic and photocarcinogenic potential of ofloxacin is comparable with that of other gyrase inhibitors.

Preclinical data from conventional genotoxicity studies reveal no special hazard to humans, carcinogen potential has not be investigated.

Reproduction toxicity

Ofloxacin has no effect on fertility, peri- or postnatal development, and therapeutic doses did not lead to any teratogenic or other embryotoxic effects in animals. Ofloxacin crosses the placenta and levels reached in the amniotic fluid are about 30% of the maximal concentrations measured in maternal serum.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core Maize starch, Lactose, anhydrous Hydroxypropylcellulose, Croscarmellose sodium, Magnesium stearate

Film-coating: Hypromellose, Titanium dioxide, Macrogol, Talc

6.2 Incompatibilities

Not applicable

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Aluminium PVC/PVDC blisters and polypropylene bottles with polyethylene tamper evident closure (with optional polyethylene ullage filler).

Obtainable in the following pack sizes: 3, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 30, 50, 100, 250 tablets.

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

No special requirements.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

OFLOXACINE TABLETS USP
200MG / 400mg
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Ofloxacin

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).

WHAT IS IN THIS LEAFLET

  1. What Ofloxacin is and what it is used for
  2. What you need to know before you take Ofloxacin
  3. How to take Ofloxacin
  4. Possible side effects
  5. How to store Ofloxacin
  6. Contents of the pack and other information1. WHAT OFLOXACIN IS AND WHAT IT IS USED FOR

Ofloxacin belongs to a group of medicines called quinolone antibiotics. Ofloxacin is an antibiotic that can be used to treat a variety of different infections. These include infections of:

  • the chest (respiratory system) such as pneumonia and bronchitis.
    · the bladder and kidneys (urinary tract).
    · the male and female genital organs when the infections involve the cervix (neck of the womb in women) and the lower genital organs in men. Ofloxacin can be used to treat both gonorrhoea and some other genital infections of both the male and female genital organs.
  1. WHAT YOU NEED TO KNOW BEFORE YOU
    TAKE OFLOXACIN


Do not take Ofloxacin
– If you are allergic to ofloxacin or any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.
– If you have previously had an allergic reaction to another quinolone antibiotic e.g. ciprofloxacin or norfloxacin
– If you suffer from epilepsy or are at risk of fits
– If you have a history of inflammation and swelling of the tendons (tendonitis) after treatment with a quinolone antibiotic e.g. ciprofloxacin, norfloxacin, or nadifloxacin
– If you suffer from or there is a family history of glucose-6-phosphate dehydrogenase deficiency (an inherited disorder that affects red blood cells).
– If you are pregnant, think you may be pregnant or are planning to have a baby
– If you are breastfeeding
– If you are under the age of 18 years, or you are over 18 years but think you are still growing
Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Ofloxacin.

Warnings and precautions

Talk to your doctor or pharmacist before taking Ofloxacin if any of the following apply:

– you have or have ever had a history of mental illness
– you have problems with your liver or kidneys
– you have an illness of the nervous system called ‘myasthenia gravis’ (muscle weakness)
– if you are diabetic or suffer from low blood sugar

Heart problems

Caution should be taken when using this kind of medicine, if you were born with or have family history of prolonged QT interval (seen on ECG, electrical recording of the heart), have salt imbalance in the blood (especially low level of potassium or magnesium in the blood), have a very slow heart rhythm (called ‘bradycardia’), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), you are female or elderly or you are taking other medicines that result in abnormal ECG changes (see section Other medicines and Ofloxacin).

During treatment

When taking this medicine:

If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult aneye specialist immediately.

If you:

  • experience a severe skin rash or allergic reaction, or
    · develop severe diarrhoea, (which may be bloody) with stomach pain and fever, or
    · notice pain, tenderness, or restricted movement of the tendons, or
    · notice numbness or tingling in the hands and feet stop taking this medicine and talk to your doctor straight away.
    When taking Ofloxacin, avoid strong sunlight and do not use sun lamps or solaria.
    If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Ofloxacin tablets.

Other medicines and Ofloxacin
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
– You must tell your doctor if you are taking other medicines that can alter your heart rhythm: medicines that belong to the group of anti-arrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, (e.g. clomipramine, amitriptyline), some antimicrobials (that belong to the group of macrolides e.g. erythromycin, clarithromycin, azithromycin), some antipsychotics used to treat mental health conditions such as schizophrenia and bipolar disorder.

Tell your doctor if you are taking any of the following medicines:
– medicines or dietary supplements that contain iron (for anaemia) or zinc
– sucralfate used for stomach ulcers
– antacids used for indigestion that contain magnesium or aluminium
This medicine should not be taken within two hours of taking iron or zinc tablets, antacids, or sucralfate, as these medicines can stop Ofloxacin from working properly
– corticosteroids, used for treatment of inflammation and swelling or over-active immune system. These may increase the risk of you developing a tendon rupture
– painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibruprofen or diclofenac, or theophylline, used to treat asthma or chronic obstructive pulmonary disease as these could make you more prone to fits if taken with Ofloxacin
– glibenclamide, a medicine to control your blood sugar as the amount of these medicines in the blood may increase and have greater effect
– drugs that may affect your kidney function e.g. cimentidine, probenicid and methotrexate as they can increase the level of ofloxacin in the blood
– medicines to thin your blood, e.g. warfarin. Taking these with ofloxacin can increase the time it takes for your blood to clot
– if you are taking didanose (a medicine used to treat HIV infections), you should not take the chewable, buffered tablets until at least two hours after taking ofloxacin
– water tablets (diuretics) such as furosemide

If you are due to have urine tests for porphyrin (a pigment in the blood), or for opiates (strong painkillers), tell your doctor or nurse you are taking this medicine.

Pregnancy and breast-feeding

Do not take Ofloxacin if you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby. If you become pregnant while taking Ofloxacin, stop taking the tablets and contact your doctor immediately.

Driving and using machines

Taking Ofloxacin may make you feel sleepy, dizzy or could affect your eyesight. Do not drive or use machines until you know how this medicine affects you. Drinking alcohol may make these symptoms worse.

Ofloxacin contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

  1. HOW TO TAKE OFLOXACIN
    For oral use. You should swallow these tablets whole with water. Do not chew them.
    · The tablets can be taken with or without food and can be divided into equal doses.
    · If you are taking iron tablets (for anaemia), antacids (for indigestion or heartburn) or sucralfate (for stomach ulcers) or didanosine chewable or buffered tablets (for HIV), it is important not to take these two hours before or after taking Ofloxacin tablets.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The length of your treatment will depend on how serious your infection is.

Treatment should not be longer than 2 months.

Doses up to 400 mg are taken as a single dose in the morning. Higher doses should be taken in two doses, one in the morning and one in the evening.

The recommended doses of Ofloxacin are as follows:

Adults (including the elderly): The dose to be taken will depend on the location and the type of infection to be treated. For most infections the recommended dose is between 200 mg and 400 mg of Ofloxacin daily, preferably in the morning. For more severe infections your doctor may increase the dose to 400 mg of Ofloxacin twice daily (morning and evening).

The recommended doses for different infections are shown below. However, your doctor may decide you need a different dose.

To treat simple urine infections: The recommended dose is 200 mg or 400 mg of Ofloxacin daily.

To treat complicated upper urinary tract infections: The recommended dose is 400 mg of Ofloxacin daily. If necessary, your doctor may increase this to 400 mg twice a day.

To treat gonorrhoea of the lower genital organs only: A single dose of 400 mg of Ofloxacin in the morning is usually enough. To treat other infections of the lower genital organs for which Ofloxacin is a suitable antibiotic, the dose is usually 400 mg each day.

To treat a chest or lung infection: The recommended dose is 400 mg of Ofloxacin daily. If necessary, your doctor may increase this to 400 mg twice a day.

If you have liver problems: Your doctor may give you a lower dose of Ofloxacin. It is recommended that the dose should not exceed 400 mg Ofloxacin daily.

If you have kidney problems: Your doctor mayrecommend that you take an initial dose as recommended above, then the dose may be reduced. It is recommended that the dose should not exceed 200 mg of ofloxacin daily.

Use in children and adolescents

Children or adolescents under 18 years of age should not take these tablets.

If you take more Ofloxacin than you should

If you take more tablets than you should you may become confused and dizzy or lose consciousness, you may have a seizure or fit, and you may feel sick. Contact your doctor or nearest hospital casualty department immediately. Take the container and any remaining tablets with you.

If you forget to take Ofloxacin

If you forget to take a dose take it as soon as you remember unless it is nearly time for your next dose. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Ofloxacin

Your doctor will tell you how long you need to take your tablets for. Do not suddenly stop taking this medicine without talking to your doctor first. If you stop, your infection may get worse again. If you feel the effect of your medicine is too weak or strong, do not change the dose yourself, but ask your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. POSSIBLE SIDE EFFECT

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Ofloxacin, tell your doctor or go to your nearest hospital casualty department straight away if you have any of the following serious side effects because you may need medical attention:

Uncommon (may affect up to 1 in 100 people)
§ resistance of infection causing organisms to this treatment, (you may fail to respond to treatment)

Rare (may affect up to 1 in 1,000 people)
§ you have an allergic reaction. Such reactions may appear in the form of anaphylaxis (a severe form of allergic reaction) with symptoms such as:
– severe skin rash
– swelling of the face, lips, mouth, tongue or throat (angioedema)
– anaphylactic shock (sudden wheezing, swelling of your lips, tongue and throat or body, rash, fainting or difficulties in swallowing)
§ inflammation of the bowel, which may cause severe watery diarrhoea, which may have blood in it, possibly with stomach cramps and a high temperature
§ swelling of the tendons with the following symptoms; pain, tenderness, sometimes restricted movement (tendonitis). This can lead to tendon rupture, especially of the large tendon at the back of the ankle (Achilles tendon). The risk of this occurring is increased if you are also taking corticosteroids e.g. prednisolone
§ numbness or tingling in the hands and feet or being very sensitive to touch, numbness or weakness of the arms and legs
§ blurred, double or altered colour vision. If your eyesight becomes impaired or if your eyes seem to be otherwise affected, consult an eye specialist immediately.

Very rare (may affect up to 1 in 10,000 people)
§ a condition in which the amount of oxygen-carrying pigment (haemoglobin) in the blood is below normal or an illness resulting from the destruction of red blood cells with the following symptoms; feeling tired, faint, dizzy, being short of breath when exercising and having pale skin. These may be signs of anaemia or haemolytic anaemia.
§ other blood disorders when the numbers of different types of cells in the blood may fall, which may cause fever, chills, sore throat, ulcers in the mouth and throat (leucopenia, agranulocytosis)
§ fits (seizures)
§  skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with dark ring around the edge) (erythema multiforme)
§ a widespread rash with blisters and skin peeling on much of the body surface (toxic epidermal necrolysis).
§ narrowing, blockage or leakage of blood vessels, in exceptional cases leading to severe skin reactions and death of areas of the skin
§ severe kidney problems, which may result in your kidneys stopping working. Signs may include a rash, high temperature, general aches and pains, or blood in the urine
§ hearing problems or hearing loss
§ liver problems, such as inflammation of the liver (hepatitis) or blockage in the bile duct, that may cause your eyes or skin to go yellow (jaundice) or you may notice the following symptoms; nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, light coloured bowel motions, dark coloured urine

Not known (frequency cannot be estimated from the available data)
§ abnormal fast heart rhythm, life-threatening irregular heart rhythm, alteration of the heart rhythm (called ‘prolongation of QT interval’, seen on ECG, electrical activity of the heart)
§ severe depression or mental illness. Some people who are depressed think of harming or killing themselves.
§ a serious reduction in all types of blood cells (pancytopenia), which may result from a failure of the bone marrow to produce these
§ a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens Johnson syndrome).
§ swelling of the lungs with the following symptoms; coughing, difficulty breathing, wheezing
§ temporary paralysis or weakness of the muscles (rhabdomyolysis), disease of the muscles with the following symptoms; aching muscles, muscle tenderness or weakness, not caused by exercise
§ an attack of porphyria (a rare blood pigment disorder) in patients with this disease
§ muscle or ligament rupture
§ inflammation of the pancreas (pancreatitis) – you may have severe pain in the stomach and back
§ loss of consciousness (coma), due to severe reduction in blood sugar levels
§ inflammation of the eye (uveitis)
§ skin redness with excessive scaling (exfoliative dermatitis)
§ loss of appetite, skin and eyes becoming yellow in colour, dark-coloured urine, itching, or tender stomach (abdomen). These may be signs of liver problems which may include a fatal failure of the liver.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

Uncommon (may affect up to 1 in 100 people)
§ feeling sick (nausea) or being sick (vomiting), diarrhoea or stomach pains
§ irritated or burning eyes
§ headaches, sleep disturbances including difficulty sleeping (insomnia)
§ feeling dizzy, having spinning sensations
§ agitation, feeling restless
§ cough and inflamed sore nose or throat (nasopharyngitis)
§ fungal infection
§ skin rash or itching

Rare (may affect up to 1 in 1,000 people)
§ loss of appetite
§ fast heart beat
§ drowsiness
§ feeling confused or anxious, nightmares, seeing, feeling or hearing things that are not there,
§depression and mental illness  changes in or loss of your sense of taste or smell
§ shortness of breath or wheezing
§ changes in levels of liver enzymes or bilirubin, which may be seen in blood tests
§ excessive sweating and hot flushes
§ changes in kidney function shown in blood tests
§ feeling faint, lightheaded or dizzy, which may be due to low blood pressure
§ hives (urticaria)
§ rash with pimples

Very rare (may affect up to 1 in 10,000 people)
§ uncontrolled movements, unsteadiness and shaking
§ unusual bleeding or bruise more easily than normal (thrombocytopenia)
§ increase in some white blood cells (eosinophilia)
§ ringing in the ears (tinnitus)
§ joint and muscle pains
§ skin rashes or eruptions, which may be caused by strong sunlight
§ unusual purple discolouration under the skin, which may be due to bleeding or bruising due to leaky or damaged blood vessels

Not known (frequency cannot be estimated from the available data)
§ a red, scaly rash with bumps under the skin and blisters (exanthemous pustolosis)
§ muscular weakness
§ feeling weak or irritable, sweating and/or trembling. This could be due to lowering of blood sugar (glucose) levels especially in patients with diabetes or existing low blood sugar
§ an increase in blood sugar levels
§ feeling of nervousness, tremor, unusual (involuntary) muscle movements
§ fainting
§ digestive problems such as stomach upset (indigestion/heartburn), constipation, or wind
§ general pain, pains in your muscles and stiffness in the bones/joints (arthritis), feeling unwell (asthenia), or fever.

Reporting of side effects
If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

  1. HOW TO STORE OFLOXACIN

Keep this medicine out of the sight and reach of children.
Do not take this medicine after the expiry date shown on the pack. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. CONTENTS OF THE PACK AND FURTHER INFORMATION

What Ofloxacin contain
a) Each film-coated tablet contains:
Ofloxacin USP……………………..200mg
Excipients………………………………q.s.

b) Each film-coated tablet contains:
Ofloxacin USP……………………..400mg
Excipients………………………………q.s.

The other ingredients are: maize starch, lactose anhydrous, hydroxypropyl cellulose, magnesium stearate, hypromellose, titanium dioxide (E171), talc and macrogol 400. The 200 mg tablets also contain croscarmellose sodium and the 400 mg tablets also contain sodium starch glycollate, yellow and black iron oxides and carnauba wax.

What Ofloxacin look like and contents of the pack
The 200 mg tablets are white capsule-shaped film-coated tablets. The tablet can be divided into equal doses.
The 400 mg tablets are yellow capsule-shaped film-coated tablets The tablet can be divided into equal doses.

Ofloxacin Tablets are available in blisters or plastic bottles of 3*, 5, 6, 7, 10, 12, 14, 16, 20, 24, 30, 50, 100 and 250 tablets. The 200 mg tablets are also available in blisters of 8 tablets. *200 mg strength only
Not all pack sizes may be marketed

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

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Taj Generics (Taj Pharma) provides a wide range of products to the Indian market, including an extensive range of generics and specialty products; Our products cover a vast array of therapeutic categories, and we offer an extensive range of dosage forms and delivery systems including oral solids, controlled-release, steriles, injectables, topicals, liquids, transdermals, semi-solids and high-potency products. Our Generics portfolio offers over 1500 products in the major therapeutic areas of gastro-intestinal, cardiovascular, pain management, oncology, anti-infectives, paediatrics and dermatology.