INSTRUCTION

for medical use of the medicinal product

 

OFLOXACIN

 

Composition:

active substance: ofloxacin;

100 ml of solution contain ofloxacin 200 mg;

exipients: sodium chloride, disodium edetate, concentrated hydrochloric acid, sodium hydroxide, water for injections.

 

Pharmaceutical form. Solution for infusion.

Basic physical and chemical properties: a clear, colourless to yellowish solution.

 

Pharmacotherapeutic group. Antibacterial agents for systemic use. Quinolones. Ofloxacin. ATC code J01M A01.

 

Pharmacological properties.

Pharmacodynamics.

Ofloxacin is a synthetic antibacterial agent for fluoride chinolone of a wide range of products.

In concentrations identical to the minimum inhibitory concentration (МІС), or slightly higher, ofloxacin has a bactericidal effect (by inhibiting DNA gyrase – an enzyme required for replication and transcription of bacterial DNA).

The antimicrobial spectrum includes: gram-negative and gram-positive bacteria sensitive to ofloxacin: Enterobacteriaceae (Escherichia coli, Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia species), Pseudomonas spp., including Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus ducreyi, Branhamella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Acinetobacter spp., Campylobacter spp., Gardnerella vaginalis, Helicobacter pylori, Pasteurella multocida, Vibrio spp., Brucella melitens; staphylococci, including penicillinase-producing strains and some methicillin-resistant strains; it is also active against Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Ureaplasma urealyticum (at MIC limits), Mycobacterium tuberculosis, Mycobacterium leprae and some other mycobacteria.

The susceptibility of streptococci group A, B and C is extreme.

Most anaerobes, excluding Clostridium perfringens, are resistant.

Ofloxacin is inactive against Treponema pallidum.

Pharmacokinetics.

Ofloxacin penetrates tissues. It is also well distributed in body fluids, including the cerebrospinal fluid. Its concentrations in bile are relatively high. The distribution volume is 1.5–2.5 l/kg. Plasma protein binding is 25%.

Ofloxacin is partially converted to desmethyl-ofloxacin and ofloxacin-N-oxide. Desmethyl-ofloxacin has weak antimicrobial activity.

The plasma half-life of ofloxacin is approximately 5-8 hours. It is prolonged depending on the degree of insufficiency to 15-20 hours when renal insufficiency. Ofloxacin is mainly excreted by the kidneys with tubular secretion and glomerular filtration. 75–80% of the administrated dose is excreted unchanged in the urine within 24–48 hours, and less than 5% is excreted as metabolites. 4-8% of the administrated dose is excreted in the feces. Ofloxacin excretion may be delayed in patients with severe liver damage (e.g. cirrhosis). Regardless of the dose, renal excretion of ofloxacin is 173 ml/min, total excretion – up to 214 ml/min. Only a small amount can be eliminated by hemodialysis (15-25%). The biological half-life when hemodialysis is approximately 8-12 hours. At peritoneal dialysis the biological half-life is 22 hours.

Ofloxacin has a postantibiotic effect.

 

Clinical particulars.

Indications.

Infectious and inflammatory diseases caused by pathogens sensitive to ofloxacin:

- exacerbation of chronic obstructive pulmonary disease (including chronic bronchitis)*, community-acquired pneumonia*;

- uncomplicated acute cystitis*, urethritis*, acute pyelonephritis and complicated urinary tract infections;

- complicated skin and soft tissue infections*.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

*only if the use of other antibacterial agents commonly prescribed for the treatment of this infection is considered as ineffective or inappropriate.

 

Contraindications.

- Hypersensitivity to ofloxacin and to other components of the drug or other fluoroquinolones;

- epilepsy;

- disorders of the central nervous system with a reduced convulsive threshold (after traumatic brain injury, stroke, the brain’s inflammatory processes and meninges);

- history of tendinitis;

- glucose-6-phosphate dehydrogenase deficiency;

- 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.

Ofloxacin is contraindicated for patients with QT prolongation, patients with uncompensated hypokalaemia, or those patients taking class IA (quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmics.

 

Interaction with other medicinal products and other forms of interaction. 

As with other fluoroquinolones, ofloxacin should be used with caution in patients taking medicinal products with a known ability to prolong the QT interval (e.g. class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see paragraph "QT prolongation" in the section “Precautions for use”).

Increased bleeding time has been reported with co-administration of ofloxacin and anticoagulants.

When ofloxacin is used with nonsteroidal anti-inflammatory drugs derived from nitroimidazole and methylxanthines, the risk of neurotoxic effects increases.

Co-administration of ofloxacin with glucocorticosteroids increases the risk of tendon rupture, especially in elderly patients.

Co-administration of ofloxacin with procainamide may cause an increase in procainamide levels in patients. Careful monitoring of procainamide levels in blood plasma, ECG and dosage adjustment are carried out if necessary.

In some cases a sudden decrease in pressure may be observed when ofloxacin is co-administrated with antihypertensive drugs or anaesthetic barbiturates.

If quinolones are taken concomitantly with other drugs that lower the seizure threshold, such as theophylline, an additional reduction in the seizure threshold of the brain may occur. However, it is believed that ofloxacin, unlike some other fluoroquinolones, does not interact with theophylline.

An additional reduction in the seizure threshold of the brain may also occur when ofloxacin is co-administered with certain nonsteroidal anti-inflammatory drugs and drugs that lower the seizure threshold activity as well.

If seizures occur, ofloxacin should be discontinued.

Ofloxacin may cause a slight increase in serum glibenclamide concentrations; patients receiving this combination should be closely monitored.

Quinolone excretion may be impaired, and serum levels may be increased when ofloxacin is co-administered with other drugs secreted into the renal tubules (e.g. probenecid, cimetidine, furosemide and methotrexate).

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.

Mycobacterium tuberculosis is moderately sensitive to ofloxacin. This can lead to false-negative results in the bacteriological diagnosis of tuberculosis.

Continuous monitoring is required with concomitant administration of insulin, caffeine, theophylline, cimetidine, cyclosporine, nonsteroidal anti-inflammatory drugs, anticonvulsants and drugs metabolized by cytochrome P450.

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.

 

Precautions for use.

The use of ofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone (see section “Adverse reactions”). Treatment of these patients with ofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see section “Contraindications”).

If the patient's condition allows, it is recommended to switch to treatment with appropriate doses of ofloxacin tablets.

If allergic reactions or severe adverse reactions occurred in the central nervous system (CNS), the drug should be discontinued immediately.

Caution should be exercised when prescribing the drug to impaired renal function patients having CNS diseases (severe cerebrovascular atherosclerosis, acute cerebrovascular accident).

A dose of 400 mg per day should not be exceeded in patients with acute hepatic insufficiency.

Patients should drink enough water to avoid crystalluria.

Ofloxacin should only be administered by slow intravenous infusion over 60 minutes. Rapid or bolus injections can lead to hypotension.

Ofloxacin is not the drug of choice for the treatment of pneumococcal or mycoplasma pneumonia or acute tonsillitis caused by β-hemolytic streptococci.

If ofloxacin is intravenously co-administrated with antihypertensive drugs, a sudden decrease in blood pressure may occur. In such cases, or if the drug is co-administrated with barbiturate anesthetics, it is necessary to monitor the functions of the cardiovascular system.

Methicillin-resistant S. aureus is 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.

Neisseria gonorhoeae infections

Due to increase in resistance to N. gonorrhoeae, ofloxacin should not be used as empirical antibiotic treatment option in suspected gonococcal infection (gonococcal urethritis, inflammation of the pelvic organs and epididymoorchitis) unless the pathogen has been identified and confirmed as susceptible to ofloxacin. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.

Inflammatory diseases of the pelvic organs

For the treatment of pelvic inflammatory disease ofloxacin should be used only in combination with drugs active against anaerobic microorganisms.

Hypersensitivity and allergic reactions

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.

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 “Adverse reactions”). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

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 be a symptom of pseudomembranous colitis. Clostridium difficile may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis (see section “Adverse reactions”). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with ofloxacin. If pseudomembraneous 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 of epilepsy (see section “Contraindications”). As with other quinolones, ofloxacin should be used with extreme caution in patients predisposed to seizures and those co-administrated with active substances which lower the cerebral seizure threshold, such as theophylline (see section "Interaction with other medicinal products and other forms of interaction"). In case of convulsive seizures, treatment with ofloxacin should be discontinued.

Prolonged, disabling and potentially irreversible serious drug reactions

Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Ofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with ofloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.

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 “Method of administration and dosage”).

QT interval prolongation

Very rare cases of QT interval prolongation 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:

- uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia);

- congenital long QT syndrome;

- acquired QT interval prolongation;

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

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

- 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.

Aortic aneurysm and dissection

Epidemiologic studies report an increased risk of aortic aneurysm and dissection, especially in the elderly, and regurgitation of the aortic and mitral valves after taking fluoroquinolones as well. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatalities), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section “Adverse reactions”).

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with a history of aneurysm or congenital heart valve disease, and for patients diagnosed with aortic aneurysm and/or aortic dissection or heart valve disease, or in the presence of other risk factors:

- risk factors for aortic aneurysm and dissection and regurgitation/heart valve insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis);

- risk factors for aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, or Sjogren's syndrome;

- risk factors for regurgitation/heart valve insufficiency: infectious endocarditis.

The risk of aortic aneurysm and dissection and rupture is also increased in patients receiving concomitant systemic corticosteroids.

In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients should be advised to seek medical attention immediately in the event of acute shortness of breath, a new attack of rapid heartbeat, edema of the abdomen or lower extremities.

Patients with history of psychotic disorder

Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases these reactions have progressed to suicidal thoughts or self-endangering behavior including suicide attempt, sometimes after a single dose of ofloxacin. If a patient develops these reactions, ofloxacin should be discontinued and appropriate measures must be initiated. 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 “Adverse reactions”)

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 “Interaction with other drugs and other types of interactions”).

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.

Prevention of photosensitisation

Photosensitisation has been reported with ofloxacin (see section “Adverse reactions”). 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.

Superinfection

As with other antibiotics, the use of ofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential and periodic. If secondary infection occurs during therapy, appropriate measures should be taken.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy causing paresthesia, hypoaesthesia, dysesthesia or weakness have been reported in patients receiving quinolones and fluoroquinolones (including ofloxacin). If symptoms of neuropathy, such as pain, burning, tingling, numbness or weakness, occur in patients treated with the drug, the patients should inform their physician about such syptoms to prevent the development of a potentially irreversible condition (see section “Adverse reactions”).

Dysglycaemia

As with all quinolones, including ofloxacin, 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 “Adverse reactions”).

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, ofloxacin should be used with caution in these patients and potential occurrence of haemolysis should be monitored.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections (see sections “Effects on ability to drive and use machines” and “Adverse reactions”).

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.

Patients with rare hereditary disorders

Patients with rare hereditary disorders, such as galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

The drug contains 365.47 mg/dose of sodium, so caution should be exercised when using in patients on a sodium-controlled diet.

 

Pregnancy and lactation.

Animal studies have shown damage to the joint cartilage in immature animals, but no teratogenic effects. Therefore, ofloxacin is contraindicated during pregnancy.

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.

 

Effects on ability to drive and use machines.

The speed of psychomotor reactions can be disturbed. Therefore, it is necessary to refrain from driving vehicles and mechanisms.

Since there have been occasional reports of drowsiness, impaired ability to operate machinery, vertigo and visual disturbances after drug’s administration, patients should be aware of how they react to ofloxacin before they drive or operate machinery.

 

Method of administration and dosage.

Apply to adults. Drop-by-drop administration. A skin allergy test should be performed before administration.

The dose of Ofloxacin is adjusted by the doctor individually, depending on the sensitivity of microorganisms, the type and severity of the infectious process.

Exacerbation of chronic obstructive pulmonary disease (including chronic bronchitis), community-acquired pneumonia: 200 mg twice a day.

Uncomplicated acute cystitis, urethritis, acute pyelonephritis and complicated urinary tract infections: 200 mg twice a day.

Complicated skin and soft tissue infections: 400 mg twice a day.

The infusion time should be at least 30 minutes for every 200 mg. In general, individual doses should be administered at regular intervals. The dose of 400 mg twice a day can be used for severe or complicated infections.

Dosage for patients with impaired renal function.

Patients with impaired renal function may require a dose reduction depending on creatinine clearance. If the creatinine clearance is 20-50 ml/min, the dose should be reduced to 100-200 mg every 24 hours. At creatinine clearance <20 ml/min, the dose should be 100 mg every 24 hours. For patients on hemodialysis or peritoneal dialysis, the dose of ofloxacin should be 100 mg every 24 hours.

The duration of use of ofloxacin depends on the type of infectious process and clinical parameters. After normalization of body temperature and improvement of the general condition of the patient, the drug’s treatment should be continued for another 3 days.

In most cases of acute process, the duration of treatment is 7-10 days. The physician may switch the patient from parenteral to oral administration without changing the dose.

The duration of treatment should not exceed 2 months.

 

Children.

This medicinal product is contraindicated for children.

 

Overdose.

The most important signs to be expected following acute overdose are CNS symptoms, such as dizziness, disorientation, drowsiness, confusion, inhibition, convulsions, QT prolongation, and gastrointestinal reactions, such as nausea, vomiting and mucosal erosions.

There is no antidote. The treatment is symptomatic. Ofloxacin is mainly excreted by the kidneys (75-80% of the administered dose is excreted unchanged in the urine within 24-48 hours), and its elimination can be accelerated by forced volume diuresis. Only a limited amount of ofloxacin can be removed from the body by haemodialysis (average 15–25%) or peritoneal dialysis (less than 2%).

ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

It is recommended to use antacids to protect the gastric mucosa.

 

Adverse reactions.

The adverse reactions listed below are classified by organ system and frequency. Frequency is classified as follows: common (≥ 1/100 – <1/10), uncommon (≥ 1/1000 – <1/100), rare (≥ 1/10000 – <1/1000), very rare (<1 / 10000), not known (cannot be determined from the available data).

Infections and infestations: uncommon – mycosis; pathogen resistance.

Blood and lymphatic system disorders: very rare – anaemia, haemolytic anaemia, leukopenia, eosinophilia, thrombocytosis; not known – agranulocytosis, inhibition of bone marrow haematopoiesis.

Immune system disorders: rare – hypersensitivity reactions including anaphylactic/anaphylactoid reactions**, angioneurotic oedema** (including swelling of the tongue, larynx, pharynx, oedema/swelling of the face); very rarely – anaphylactic/anaphylactoid shock**.

Metabolism and nutrition disorders: rare – anorexia; not known – hypoglycemia in patients with diabetes taking antihyperglycemic drugs, hyperglycemia, hypoglycemic coma.

Psychiatric disorders*: uncommon – agitation, sleep disorders, insomnia; rare – psychotic disorders (e.g., hallucinations), anxiety, confusion, nightmares, depression; not known – psychotic disorders and depression with self-destructive behaviors, including suicidal ideation or suicide attempts, nervousness.

Nervous system disorders*: uncommon – dizziness, headache; rare – drowsiness, paresthesia, dysgeusia, parosmia; very rare – peripheral sensory neuropathy**, peripheral sensorimotor neuropathy**, muscle cramps**, extrapyramidal symptoms or other disorders of muscle coordination; not known – tremor, dyskinesia, ageusia (loss of taste sensations), syncope, benign intracranial hypertension.

Eye disorders*: uncommon – irritation of eyes mucousa; rare – visual disorders;  not known – uveitis.

Ear and labyrinth disorders*: uncommon – vertigo; very rare – tinnitus, hearing loss;  not known – mild hearing loss.

Cardiac disorders***: rare – tachycardia; not known – ventricular arrhythmias; torsades de pointes (these reactions has been reported mainly in patients with risk factors for QT prolongation); QT prolongation on ECG.

Vascular disorders***: common – phlebitis; rare – hypotension; not known – tachycardia and hypotension may hypotension occur during ofloxacin infusion. In very rare cases, such decrease in blood pressure can be severe.

Respiratory, thoracic and mediastinal disorders: uncommon – cough, nasopharyngitis; rare – shortness of breath, bronchospasm; not known – allergic pneumonitis, severe shortness of breath.

Gastrointestinal disorders: uncommon – abdominal pain, diarrhea, nausea, vomiting; rare – enterocolitis, sometimes hemorrhagic; very rare – pseudomembranous colitis*; not known – dyspepsia, flatulence, constipation, pancreatitis.

Hepatobiliary disorders: rare – hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase), blood bilirubin increased; very rare – jaundice cholestatic; not known – hepatitis, which can be severe**. Severe hepatic impairment, including cases of fatal acute liver failure, primarily in patients with severe underlying liver disease has been reported (see section ‘Special precautions’).

Skin and subcutaneous tissue disorders: uncommon – itching, rash; rare – urticaria, hot flushes, sweating, pustular rash, vasculitis; very rare – erythema multiforme, toxic epidermal necrolysis, photosensitivity reactions**, drug eruption, vascular purpura, vasculitis, which can lead to skin necrosis in exceptional cases; not known – Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, drug rash, stomatitis, exfoliative dermatitis.

Musculoskeletal and connective tissue disorders*: rare – tendinitis; very rare – arthralgia, myalgia, tendon ruptures (including Achilles tendon), which may occur within 48 hours of treatment start and may be bilateral; not known – rhabdomyolysis and/or myopathy, muscle weakness, muscle strain, muscle rupture, ligament rupture, arthritis..

Renal and urinary disorders: rare – serum creatinine increased; very rare – acute renal failure; not known – acute interstitial nephritis.

Congenital, familial and genetic disorders: not known – attacks of porphyria in patients with porphyria.

General disorders and administration site conditions*: common – reaction at the infusion site (pain, redness); not known – asthenia, pyrexia, pain (including pain in the back, chest and extremities).

 

* Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesiae, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see section "Precautions for use").

** Postmarketing experience.

*** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatalities), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section "Precautions for use").

 

Reporting of suspected adverse reactions

Reporting of 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 national pharmacovigilance system.

 

Shelf life. 3 years.

 

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °С.

Keep out of reach of children.

Any unused medicinal product must be disposed.

 

Incompatibility.

Ofloxacin solution must not be mixed with heparin and other infusion solutions, except those of which compatibility with ofloxacin has been studied.

When prescribed with drugs that alkalize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

The drug is compatible with the following infusion solutions: 0.9% sodium chloride solution, Ringer's solution and 5% glucose solution.

 

Packaging.

100 ml in a container. 1 container in polyvinyl chloride film along with the instruction for medical use in a box

 

Terms of dispensing. On prescription.

 

Manufacturer.

Eurolife Healthcare Pvt. Ltd.

 

Manufacturer’s registered address.

Khasra No. 520, Bhagwanpur, Roorkee, Haridwar, India.

 

Applicant.

Ananta Medicare Ltd.

 

Applicant’s registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

 

Date of last update.

05.03.2021