Product Index

Black Box Warning: 

Serious Adverse Reactions, Including Tendinitis, Tendon Rupture, Peripheral Neuropathy, Central Nervous System (CNS) Effects And Exacerbation Of Myasthenia Gravis

Composition

OFLOX IV

Each 100 mL contains:

Ofloxacin IP......200 mg

Sodium Chloride IP .....0.9%w/v

Water for Injection IP q.s...100 mL

Dosage Form

Intravenous (IV) infusion

Pharmacology

Pharmacodynamics

Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of ofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases) enzymes required for DNA replication, transcription, repair and recombination.

Ofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms. Ofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Fluoroquinolones, including ofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and beta-lactam antibiotics, including penicillins.  Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.

Resistance to ofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10–9 to 10–11). Although cross-resistance has been observed between ofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to ofloxacin.

Ofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections:

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus (methicillin-susceptible strains)

Streptococcus pneumoniae (penicillin-susceptible strains)

Streptococcus pyogenes

Aerobic Gram-Negative Microorganisms

Citrobacter (diversus) koseri

Enterobacter aerogenes

Escherichia coli

Haemophilus influenzae

Klebsiella pneumoniae

Neisseria gonorrhoeae

Proteus mirabilis

Pseudomonas aeruginosa

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ofloxacin.

Other Microorganisms

Chlamydia trachomatis

The following in vitro data are available, but their clinical significance is unknown. Ofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥90%) strains of the following microorganisms; however, the safety and effectiveness of ofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms

Staphylococcus epidermidis (methicillin-susceptible strains)

Staphylococcus saprophyticus

Streptococcus pneumoniae (penicillin-resistant strains)

Aerobic Gram-Negative Microorganisms

Acinetobacter calcoaceticus

Bordetella pertussis

Citrobacter freundii

Enterobacter cloacae

Haemophilus ducreyi

Klebsiella oxytoca

Moraxella catarrhalis

Morganellamorganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic Microorganisms

Clostridium perfringes

Other Microorganisms

Chlamydia pneumoniae

Gardnerella vaginalis

Legionella pneumophila

Mycoplasma hominis

Mycoplasma pneumoniae

Ureaplasma urealyticum

Ofloxacin is not active against Treponema pallidum.

Many strains of other streptococcal species, Enterococcus species, and anaerobes are resistant to ofloxacin.

Pharmacokinetics

Maximum plasma concentrations occur within 5 minutes of the end of the infusion. The peak serum concentration, after a single oral dose of 200 mg, averages 2.5–3 µg/mL within 1 hour. The serum elimination half-life is 6–7 hours and is linear. The apparent volume of distribution is 120 litres. Following multiple dosing, the serum concentration is not significantly increased (multiplication factor approximately 1.5). Ofloxacin concentrations in the urine and at the site of urinary tract infections (UTIs) exceed those measured in serum by 5- to 100-fold. Ofloxacin is primarily excreted unchanged in the urine.

Urinary clearance is reduced in renal impairment.

Indications

Ofloxacin is indicated in adults for the treatment of the following bacterial infections:

• Pyelonephritis and complicated UTIs
• Prostatitis, epididymo-orchitis
• Pelvic inflammatory disease, in combination treatment
• Sepsis due to the above-mentioned genito-urinary infections

For the infections mentioned below, ofloxacin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections:

• Complicated skin and soft tissue infections
• Acute exacerbation of chronic bronchitis
• Community-acquired pneumonia

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

Dosage and Administration

General Dosage Recommendations

The dose of ofloxacin is determined by the type and severity of the infection. 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

Adults: The usual IV dosages in adults are as follows:

Acute Exacerbation of Chronic Bronchitis, Community-acquired Pneumonia: 200 mg twice daily.

Complicated Skin and Soft Tissue Infections: 400 mg twice daily.

The dose may be increased to 400 mg twice daily in severe or complicated infections.

Indication	Daily Dose Regimen (according to severity)	Duration of Treatment (according to severity)
Complicated UTIs	200 mg twice daily (can be increased to 400 mg twice daily)	7–21 days
Pyelonephritis	200 mg twice daily (can be increased to 400 mg twice daily)	7–10 days (can be extended to 14 days)
Acute prostatitis Chronic prostatitis	200 mg twice daily (can be increased to 400 mg twice daily)	2–4 weeks* 4–8 weeks*
Epididymo-orchitis	200 mg twice daily (can be increased to 400 mg twice daily)	14 days
Pelvic inflammatory disease	400mg twice daily	14 days

* For prostatitis, longer duration of treatment may be considered after careful re-examination of the patient.

Ofloxacin tablets may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with IV ofloxacin.

Ofloxacin solution is only intended for SLOW IV infusion; it is to be administered once or twice daily. The infusion time for ofloxacin IV should not be less than 30 minutes for 200 mg. This is of particular importance when ofloxacin is administered concomitantly with drugs that can lead to a reduction in blood pressure or with barbiturate-containing anaesthetics. Generally, individual doses are to be given at approximately equal intervals.

Posology in Patients with Renal Impairment

In patients with impaired renal function, the following oral or I.V. dosages are recommended:

Creatinine Clearance	Unit Dose mg*	Number/24 hours	Intervals (hours)
50–20 mL/min	100–200	1	24
<20 mL/min** or haemodialysis or peritoneal dialysis	100 or 200	1 1	24 48

* According to indication or dose interval.

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

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:

Posology in Hepatic Impairment (e.g. cirrhosis with ascites)

It is recommended that a maximum daily dose of 400 mg of ofloxacin be not exceeded, because of possible reduction of excretion.

Children: Ofloxacin is not indicated for use in children or growing adolescents.

Elderly: Age in itself does not impose to adapt the dosage of ofloxacin. However, special attention to renal function should be paid in elderly patients and the dosage should be adapted accordingly.

Duration of Treatment: The duration of treatment is determined according to the response of the causative organisms and the clinical picture. As with all antibacterial agents, treatment with ofloxacin should be continued for at least 3 days after the body temperature has returned to normal and the symptoms have subsided.

In most cases of acute infection, a course of treatment lasting 7–10 days is sufficient. Once the patient's condition has improved, the mode of administration should be changed from parenteral to oral, normally at the same total daily dose.

Treatment should not exceed 2 months’ duration.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients.
• Ofloxacin should not be used in patients with a past history of tendinitis.
• Ofloxacin, like other 4-quinolones, is contraindicated in patients with a history of epilepsy or with a lowered seizure threshold.
• Ofloxacin is contraindicated in children or growing adolescents, and in pregnant or breastfeeding women, since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject.
• Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

Warnings and Precautions

Disabling and Potentially Irreversible Serious Adverse Reactions, Including Tendinitis and Tendon Rupture, Peripheral Neuropathy and CNS Effects

Fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and CNS effects (hallucinations, anxiety, depression, insomnia, severe headaches and confusion). These reactions can occur within hours to weeks after starting ofloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions.

Discontinue ofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including ofloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

Tendinitis and Tendon Rupture

Fluoroquinolones, including ofloxacin, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon and rupture of the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting ofloxacin, or as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally.

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Discontinue ofloxacin immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including ofloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

Peripheral Neuropathy

Fluoroquinolones, including ofloxacin, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons, resulting in paraesthesias, hypoesthesias, dysaesthesias and weakness, have been reported in patients receiving fluoroquinolones, including ofloxacin. Symptoms may occur soon after initiation of ofloxacin and may be irreversible in some patients.

Discontinue ofloxacin immediately if the patient experiences symptoms of peripheral neuropathy, including pain, burning, tingling, numbness, and/or weakness or other alterations in sensations, including light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength in order to minimise the development of an irreversible condition. Avoid fluoroquinolones, including ofloxacin, in patients who have previously experienced peripheral neuropathy.

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including ofloxacin, have neuromuscular-blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid ofloxacin in patients with a known history of myasthenia gravis.

CNS Effects

Fluoroquinolones, including ofloxacin, have been associated with an increased risk of CNS effects, including convulsions, increased intracranial pressure (including pseudotumour cerebri), and toxic psychoses. Quinolones may also cause CNS stimulation, which may lead to tremors, restlessness, lightheadedness, confusion, and hallucinations. If these reactions occur in patients receiving ofloxacin, the drug should be discontinued and appropriate measures instituted.

The effects of ofloxacin on brain function or on the electrical activity of the brain have not been tested. Therefore, until more information becomes available, ofloxacin, like all other quinolones, should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, and other factors that predispose to seizures

Methicillin-resistant S. aureus (MRSA) strains 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).

Ofloxacin is not the drug of first choice for pneumonia caused by pneumococci or mycoplasma or infection caused by beta-haemolytic streptococci.

Escherichia coli Infection

E. coli is the most common pathogen involved in UTIs. Prescribers are advised to take into account the local prevalence of resistance in E. coli to fluoroquinolones.

Neisseria gonorrhoeae Infections

Due to increase in resistance to N. gonorhoeae, ofloxacin should not be used as empirical treatment option in suspected gonococcal infection (urethral gonococcal infection, pelvic inflammatory disease and epididymo-orchitis), unless the pathogen has been identified and confirmed as susceptible to ofloxacin. If clinical improvement is not achieved in 3 days of treatment, the therapy should be reconsidered.

Pelvic Inflammatory Disease

For pelvic inflammatory disease, ofloxacin should only be considered in combination with anaerobe coverage.

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

Clostridium difficile-associated Disease (CDAD)

Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with ofloxacin (including several weeks after treatment), may be symptomatic of pseudo- membranous colitis (CDAD). CDAD may range in severity from mild to life-threatening, the most severe form of which is pseudomembranous colitis. It is, therefore, important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with ofloxacin. If pseudomembranous colitis is suspected, ofloxacin must be stopped immediately.

Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin, oral teicoplanin or metronidazole). Products inhibiting the peristalsis are contraindicated in this clinical situation

Patients Predisposed to Seizures

Quinolones may lower the seizure threshold and may trigger seizures. Ofloxacin is contraindicated in patients with a history of epilepsy and, as with other quinolones, ofloxacin should be used with extreme caution in patients predisposed to seizures.

Such patients may be patients with pre-existing CNS lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs or with drugs that lower the cerebral seizure threshold, such as theophylline.

In case of convulsive seizures, treatment with ofloxacin should be discontinued

Tendinitis

Tendinitis, 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. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years and in patients using corticosteroids. Furthermore, as transplanted patients are at increased risk of tendinitis, caution is recommended when fluoroquinolones are used in this population. The daily dose should be adjusted in elderly patients based on creatinine clearance. 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.

Patients with Renal Impairment

Since ofloxacin is mainly excreted by the kidneys, the dose of ofloxacin should be adjusted in patients with renal impairment.

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 mentioned below:

• 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)
• Uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
• Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
• 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.

Patients with a History of Psychotic Disorder

Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases, these have progressed to suicidal thoughts or self-endangering behaviour, including suicide attempt, sometimes after a single dose. 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.

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.

Prevention of Photosensitisation

Photosensitisation has been reported with ofloxacin. 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. If secondary infection occurs during therapy, appropriate measures should be taken.

Dysglycaemia

As with all quinolones, disturbances in blood glucose, including both hyperglycaemia and hypoglycaemia 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.

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.

Vision Disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.

Interference with Laboratory Tests

In patients treated with ofloxacin, determination of opiates in urine may give false-positive results. It may be necessary to confirm positive opiate screens by more specific method.

Patients with Rare Hereditary Disorders

Patients with rare hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Drug Interactions

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 anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Prolongation of bleeding time has been reported during concomitant administration of ofloxacin and anticoagulants.

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 anti-inflammatory drugs or other agents that lower the seizure threshold.

In case of convulsive seizures, treatment with ofloxacin should be discontinued.

Glibenclamide

Ofloxacin may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.

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 co-administered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.

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 be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives.

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. Therefore, ofloxacin should not be used during pregnancy.

Lactation

Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the nursing infant, breastfeeding should be discontinued during treatment with ofloxacin.

Effects on the Ability to Drive and Use Machines

Since there have been occasional reports of somnolence, impairment of skills, dizziness and visual disturbances, patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.

Undesirable Effects

System Organ Class	Common (≥1/100 to <1/10 )	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 infectionPathogen resistance
Blood and the Lymphatic System Disorders					Anaemia Haemolytic anaemiaLeucopaeniaEosinophilia Thrombocytopaenia	Agranulocytosis Bone marrow failure
Immune System Disorders			Anaphylactic reaction*, anaphylactoid reaction*, angio-oedema*		Anaphylactic shock*, anaphylactoid shock*
Metabolism and Nutrition Disorders				Anorexia		Hypoglycaemia in diabetics treated with hypoglycaemic agents
Psychiatric Disorders		Agitation, sleep disorder, insomnia		Psychotic disorder (e.g. hallucination) Anxiety Confusional state NightmaresDepression		Psychotic disorder and depression with self-endangering behaviour, including suicidal ideation or suicide attempt
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
Eye Disorders		Eye irritation		Visual disturbance
Ear and Labyrinth Disorders		Vertigo			Tinnitus, hearing loss
Cardiac Disorders				Tachycardia		Ventricular arrhythmias, torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged
Vascular Disorders	Applies only to the solution for infusion: Phlebitis			Hypotension		Applies only to the solution for infusion: During infusion of ofloxacin, tachycardia and hypotension may occur. Such a decrease in blood pressure may, in very rare cases, be severe.
Respiratory, Thoracic and Mediastinal Disorders		CoughNasopharyngitis		DyspnoeaBronchospasm		Allergic pneumonitisSevere dyspnoea
Gastro-intestinal Disorders		Abdominal pain, diarrhoea, nausea, vomiting		Enterocolitis, sometimes haemorrhagic	Pseudo-membranous colitis*
Hepato-biliary Disorders				Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) Blood bilirubin increased	Jaundice cholestatic	Hepatitis, which may be severe*
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
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
Renal and Urinary Disorders				Serum creatinine increased	Acute renal failure	Acute interstitial nephritis
Congenital and Familial/Genetic Disorders						Attacks of porphyria in patients with porphyria
General Disorders and Administration Site Conditions	Applies only to the solution for infusion: Infusion-site reaction (pain, reddening)

* Postmarketing experience

The drug may cause low blood sugar and mental health-related side effects. Low blood sugar levels, also called hypoglycaemia, can lead to coma. The mental health side effects that are more prominent and more consistent across the systemic fluoroquinolone drug class are as mentioned below:

• Disturbances in attention
• Disorientation
• Agitation
• Nervousness
• Memory impairment
• Delirium (serious disturbances in mental abilities)

Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) have been reported with ofloxacin.

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 18002677779 (Cipla Number) or you can report to PvPI on 1800 180 3024.

By reporting side-effects, you can help provide more information on the safety of this product.

Overdosage

The most important signs to be expected following acute overdosage are CNS symptoms such as confusion, dizziness, impairment of consciousness and seizures, increased 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 postmarketing experience.

Elimination of ofloxacin may be increased by forced diuresis.

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.

Storage and Handling Instructions

Protect from heat and light. Do not freeze.

Packaging Information

OFLOX IV: Vial of 100 mL

Last Updated: Jan 2019

Last Reviewed: Jan 2019