Ofloxacin Zentiva (Tablets, Solution) Instructions for Use

ATC Code

J01MA01 (Ofloxacin)

Active Substance

Ofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

Ofloxacin is a synthetic broad-spectrum antibacterial drug from the fluoroquinolone group, which has a bactericidal effect. The main mechanism of action of quinolones is the specific inhibition of bacterial DNA gyrase. DNA gyrase is necessary for the replication, transcription, repair, and recombination of bacterial DNA. Its inhibition leads to the unwinding and destabilization of bacterial DNA and, as a result, to the death of the microbial cell.

Fluoroquinolones have concentration-dependent bactericidal activity and a moderate post-antibacterial effect. The ratio of AUC to MIC or the ratio of C_max in plasma to MIC is a predictive factor for successful therapy.

Susceptible microorganisms

Microorganisms of variable susceptibility (possibly due to acquired resistance): Citrobacter freundii, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Neisseria gonorrhoeae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia spp., Staphylococcus spp. (coagulase-negative strains), Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pneumoniae.

Resistant microorganisms

Acinetobacter baumannii, Bacteroides spp., Clostridium difficile, Enterococci, Listeria monocytogenes, Staphylococcus spp. (methicillin-resistant strains), Nocardia spp.

Resistance

Resistance to ofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA gyrase and topoisomerase IV. Other resistance mechanisms, for example, affecting the permeability of the external structures of the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa), the efflux mechanism (active removal of the antimicrobial agent from the microbial cell), can also affect the sensitivity of microorganisms to ofloxacin.

MIC breakpoints

MIC breakpoints (mg/L) for ofloxacin, approved by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Pharmacokinetics

Absorption

Absorption after oral administration is rapid and complete. Bioavailability is almost 100%. C_max after oral administration of a 200 mg dose averages 2.5-3 µg/ml and is achieved within 1 hour.

Distribution

Plasma protein binding is 25%. The apparent V_d is 120 L. Ofloxacin concentrations in urine and in infected urinary tracts exceed plasma concentrations of ofloxacin by 5 to 100 times.

After repeated administration, serum concentrations increase slightly (accumulation factor is about 1.5).

Metabolism

It is metabolized in the liver (about 5%) to form ofloxacin N-oxide and N-desmethylofloxacin.

Elimination

T_1/2 is 6-7 hours. It is excreted mainly by the kidneys – 80-90% (unchanged), about 4% is excreted in bile as a glucuronide.

Pharmacokinetics in special patient groups

In elderly patients, an increase in T_1/2 is noted, but C_max does not change.

In patients with renal failure, T_1/2 is longer, while renal clearance values decrease depending on creatinine clearance values.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to ofloxacin

• Pyelonephritis;
• Prostatitis, epididymitis, orchitis;
• Pelvic infections;
• Cystitis, urinary tract infections (as an alternative to other antimicrobial drugs).

As an alternative to other antimicrobial drugs, Ofloxacin can be used to treat the following infectious and inflammatory diseases

• Bone and joint infections;
• Skin and soft tissue infections;
• Acute sinusitis;
• Exacerbation of chronic bronchitis, community-acquired pneumonia;
• Prevention of infections caused by microorganisms sensitive to ofloxacin in patients with a significant decrease in immune status (for example, with neutropenia).

When using the drug Ofloxacin Zentiva, official national recommendations for the appropriate use of antibacterial drugs, as well as the sensitivity of pathogenic microorganisms in a particular country, should be taken into account.

ICD codes

Dosage Regimen

Tablets

The drug is taken orally, regardless of meals. The tablets should be taken with a sufficient amount of liquid. Simultaneous administration with antacids (drugs containing aluminum, calcium, iron or zinc) should be avoided.

The dose of ofloxacin and the duration of treatment depend on the severity and type of infection, the general condition of the patient and renal function.

Adult patients with normal renal function (creatinine clearance greater than 50 ml/min)

Ofloxacin Zentiva is prescribed at a daily dose of 400 mg, divided into 2 doses (every 12 hours).

The daily dose can be increased to 600-800 mg for severe infections or when treating patients with excess body weight. A dose of up to 400 mg/day can be prescribed as a single dose, preferably in the morning. Doses above 400 mg/day should be divided into 2 doses at equal time intervals.

For uncomplicated lower urinary tract infections, the drug is prescribed at a dose of 200 mg/day for 3-5 days.

For gonorrhea, 400 mg is prescribed as a single dose.

Patients with impaired renal function

The following dosage regimen is recommended for patients with impaired renal function

*According to indications.

**Serum concentrations of ofloxacin should be monitored in patients with severe renal impairment and in patients on dialysis.

***When choosing a dose of 100 mg/day, a dosage of 200 mg must be used.

If it is not possible to determine creatinine clearance, it should be calculated from the serum creatinine concentration using the Cockcroft formula for adults.

Men

Creatinine Clearance (ml/min) = body weight (kg)×(140 – age (years))/72×serum creatinine concentration (mg/dl)

Or

Creatinine Clearance (ml/min) = body weight (kg)×(140 – age (years))/0.814×serum creatinine concentration (µmol/L)

Women Creatinine Clearance (ml/min) = 0.85×(value for men).

In patients with hepatic insufficiency, it is not recommended to exceed the maximum daily dose of 400 mg.

In elderly patients with normal renal function, dose adjustment is not required. However, special attention should be paid to monitoring renal function and ECG (risk of QT interval prolongation), selecting the appropriate dose.

Duration of treatment

The duration of treatment depends on the severity of the disease. Like any treatment with antimicrobial drugs, treatment with Ofloxacin Zentiva should continue for at least 48-72 hours after normalization of body temperature or if there is confirmation of pathogen eradication.

After several days of improvement in the patient’s condition, treatment with Ofloxacin Zentiva initiated as intravenous infusion can be continued by taking the drug in tablet form at the same dose.

Solution

The drug is intended only for slow infusion. IV infusion is administered 1 or 2 times/day.

Doses are selected individually depending on the location and severity of the infection, as well as on the state of renal function.

Adults with normal renal function (creatinine clearance greater than 50 ml/min) for the treatment of infections caused by microorganisms sensitive to ofloxacin are prescribed 200 mg 2 times/day or 400 mg 1 time/day. Usually the daily dose is 400 mg. For treatment of severe infections or in patients with excess body weight, the daily dose can be increased to 600 mg.

For urinary tract infections, the drug is prescribed at a dose of 100 mg 1-2 times/day.

For kidney and genital infections – 100-200 mg 2 times/day.

For respiratory tract infections, as well as ENT infections, skin and soft tissue infections, bone and joint infections, abdominal infections, bacterial enteritis, septic infections – 200 mg 2 times/day. If necessary, the dose is increased to 400 mg 2 times/day.

For prevention of infections in patients with a pronounced decrease in immunity, 400-600 mg/day is prescribed.

The duration of treatment depends on the severity of the disease. Like any treatment with antimicrobial drugs, treatment with ofloxacin should be continued for at least 48-72 hours after normalization of body temperature or if there is confirmation of eradication of the bacterial agent.

After several days of improvement in the patient’s condition, treatment with ofloxacin initiated as intravenous infusion can be continued by administering the drug orally at the same doses.

In case of impaired renal function, the dosage regimen of the drug depends on creatinine clearance.

For creatinine clearance 50-20 ml/min, single dose in (mg)*

* According to indications.

** It is recommended to monitor serum concentrations of ofloxacin in patients with severe renal impairment or in patients on dialysis.

In case of severe liver dysfunction (for example, liver cirrhosis with ascites), it is not recommended to exceed the dose of ofloxacin 400 mg/day.

The patient’s age, as such, does not require adjustment of the ofloxacin dose. However, when using the drug in elderly patients, special attention should be paid to renal function, as in case of its decrease, appropriate adjustment of the dosage regimen may be required.

Administration of the drug

The duration of infusion should be at least 30 minutes for each 200 mg dose of ofloxacin solution. This is especially important if Ofloxacin is administered simultaneously with other drugs that may lower blood pressure or with agents for non-inhalational general anesthesia from the barbiturate group.

A daily dose of up to 400 mg of ofloxacin can be administered once a day. In this case, administration of the drug in the morning is preferable. A daily dose of more than 400 mg should be divided into two parts and administered at 12-hour intervals.

Administration of the drug Ofloxacin Zentiva after opening the vial should be carried out immediately.

Adverse Reactions

The information below is based on data from clinical studies and data from extensive post-registration experience with the drug.

Definition of the frequency of adverse reactions according to the WHO classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

Infections and infestations: uncommon – fungal infection, resistance of pathogenic microorganisms.

Blood and lymphatic system disorders: very rare – anemia, hemolytic anemia, leukopenia, eosinophilia, thrombocytopenia; frequency unknown – agranulocytosis, pancytopenia, bone marrow depression.

Immune system disorders: rare – anaphylactic reaction, anaphylactoid reaction, angioedema; very rare – anaphylactic shock, anaphylactoid shock.

Metabolism and nutrition disorders: rare – anorexia; frequency unknown – hyperglycemia, hypoglycemia, hypoglycemic coma (in diabetic patients receiving hypoglycemic drugs).

Psychiatric disorders: uncommon – agitation, sleep disorder, insomnia; rare – psychotic disorders (hallucinations), anxiety, nervousness, confusion, nightmares, depression; frequency unknown – psychotic disorders and depression with self-destructive behavior, including suicidal thoughts and suicide attempts.

Nervous system disorders: uncommon – dizziness, headache; rare – drowsiness, paresthesia, dysgeusia (taste perception disorder), parosmia (smell disorder); very rare – peripheral sensory neuropathy, peripheral sensorimotor neuropathy, convulsions, extrapyramidal symptoms including tremor and other muscle coordination disorders; frequency unknown – ageusia (loss of ability to taste), increased intracranial pressure.

From the organ of vision: infrequently – irritation of the eye mucosa, conjunctivitis; rarely – visual impairment (diplopia, impaired color perception); frequency unknown – uveitis.

From the hearing organ and labyrinthine disorders: infrequently – vertigo; very rarely – ringing or noise in the ears, hearing loss.

Cardiac disorders: rarely – tachycardia; infrequently – palpitations; frequency unknown – torsades de pointes ventricular arrhythmia (observed mainly in patients with risk factors for QT interval prolongation), QT interval prolongation on ECG.

Vascular disorders: rarely – increased BP, decreased BP.

From the respiratory system: infrequently – cough, nasopharyngitis; rarely – dyspnea, bronchospasm; frequency unknown – allergic pneumonitis, severe dyspnea.

From the digestive system: infrequently – abdominal pain, diarrhea, nausea, vomiting, decreased appetite; rarely – enterocolitis (sometimes hemorrhagic); very rarely – pseudomembranous colitis; frequency unknown – dyspepsia, flatulence, constipation, pancreatitis, stomatitis.

From the liver and biliary tract: rarely – increased activity of hepatic transaminases (AST, ALT, LDH, GGT and/or ALP) and/or bilirubin concentration; very rarely – cholestatic jaundice; frequency unknown – hepatitis (may be severe) with ofloxacin use (mainly in patients with impaired liver function). Cases of severe hepatic failure, including acute hepatic failure, sometimes fatal, have been reported.

From the skin and subcutaneous tissues: infrequently – rash, itching; rarely – urticaria, flushing, increased sweating, pustular rash; very rarely – erythema multiforme, toxic epidermal necrolysis, photosensitivity reaction, drug rash, vascular purpura, vasculitis (which in some cases may lead to skin necrosis); frequency unknown – Stevens-Johnson syndrome; acute generalized exanthematous pustulosis, exfoliative dermatitis.

From the musculoskeletal system and connective tissue: rarely – tendonitis; very rarely – arthralgia, myalgia, tendon rupture (Achilles tendon, as with other fluoroquinolones this adverse effect may occur within 48 hours after starting treatment and may be bilateral); frequency unknown – rhabdomyolysis and/or myopathy, muscle weakness (which may be particularly important in patients with myasthenia gravis), muscle strain, muscle rupture, ligament rupture, arthritis.

From the urinary system: rarely – increased serum creatinine concentration; very rarely – acute renal failure; frequency unknown – acute interstitial nephritis, increased blood urea concentration.

General disorders: frequency unknown – asthenia, increased body temperature, back pain, chest pain, limb pain.

Congenital, hereditary and genetic disorders: frequency unknown – exacerbation of porphyria in patients with porphyria.

Contraindications

• Hypersensitivity to ofloxacin, other quinolones, or excipients of the drug;
• Epilepsy;
• Myasthenia gravis;
• Tendon damage during previous treatment with quinolones;
• Age under 18 years (the risk of damage to the cartilage growth zones in a child cannot be completely excluded);
• Pregnancy (the risk of damage to the cartilage growth zones in the fetus cannot be completely excluded);
• Breastfeeding period;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution

In patients predisposed to the development of seizures (in patients with CNS lesions such as severe cerebral atherosclerosis, history of cerebrovascular accidents, organic CNS lesions, history of head trauma; in patients simultaneously receiving drugs that lower the seizure threshold of the brain, such as fenbufen or other NSAIDs, theophylline). If seizures occur, treatment with Ofloxacin Zentiva should be discontinued.

In patients with latent or manifested glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions during treatment with quinolones).

In patients with impaired renal function (mandatory monitoring of renal function parameters, as well as adjustment of the dosage regimen is required).

In patients with hepatic insufficiency (monitoring of liver function parameters).

In patients with porphyria (risk of porphyria exacerbation).

In patients with risk factors for QT interval prolongation: in elderly patients; with uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs capable of prolonging the QT interval (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics).

In patients with diabetes mellitus receiving oral hypoglycemic agents (e.g., glibenclamide) or insulin (increased risk of hypoglycemia).

In patients with severe adverse reactions to other quinolones, such as severe neurological reactions (increased risk of similar adverse reactions with ofloxacin use).

In patients with a history of psychosis and other mental disorders.

Use in Pregnancy and Lactation

The use of Ofloxacin Zentiva during pregnancy is contraindicated.

Since Ofloxacin passes into breast milk, due to the possible risk to the child, the use of Ofloxacin Zentiva is contraindicated. If its use is necessary, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

The drug should be prescribed with caution to patients with chronic hepatic insufficiency. It is not recommended to exceed the maximum daily dose of 400 mg.

Use in Renal Impairment

The drug should be prescribed with caution to patients with chronic renal insufficiency. In patients with renal insufficiency, the dose should be selected according to CC.

Pediatric Use

The use of the drug in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

In elderly patients with normal renal function, dose adjustment is not required. However, special attention should be paid to monitoring renal function and ECG (risk of QT interval prolongation), selecting the appropriate dose.

Special Precautions

Hypersensitivity and allergic reactions

The development of hypersensitivity and allergic reactions has been reported with the use of fluoroquinolones. Anaphylactic and anaphylactoid reactions can progress to life-threatening shock, even after the first use. In these cases, the use of Ofloxacin Zentiva should be discontinued and appropriate treatment initiated.

Clostridium difficile-associated disease

Diarrhea, especially severe, persistent and/or bloody, during or after treatment with ofloxacin, may be a symptom of pseudomembranous colitis. If pseudomembranous colitis is suspected, treatment with Ofloxacin Zentiva should be discontinued immediately. Appropriate supportive and specific antibacterial therapy should be initiated immediately. Drugs that inhibit peristalsis are contraindicated in this clinical situation.

Patients predisposed to seizures

Like other quinolones, Ofloxacin Zentiva should be used with caution in patients predisposed to seizures (patients with a history of CNS lesions, patients taking fenbufen or other NSAIDs, as well as other drugs that lower the seizure threshold of the brain, such as theophylline). If seizures occur, treatment with Ofloxacin Zentiva should be discontinued immediately.

Tendinitis

Tendinitis, which is rarely observed during treatment with quinolones, can sometimes lead to tendon rupture, particularly the Achilles tendon. Elderly patients are more prone to developing tendinitis. The risk of tendon rupture may increase with the concomitant use of corticosteroids. This adverse effect may develop within 48 hours after starting treatment and may be bilateral. If tendinitis is suspected, treatment with Ofloxacin Zentiva must be discontinued immediately. Appropriate treatment (e.g., immobilization) of the affected tendon should be initiated.

Severe cutaneous adverse reactions

The development of severe bullous reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, has been reported with ofloxacin use. Patients should be informed that if skin reactions and/or mucosal lesions occur, they should immediately consult a doctor before continuing treatment with Ofloxacin Zentiva.

Patients with impaired renal function

Since Ofloxacin is primarily eliminated by the kidneys, the dose of Ofloxacin Zentiva should be adjusted in patients with impaired renal function.

Patients with a history of psychotic disorders

Psychotic reactions, including suicidal thoughts/attempts, have been reported in patients receiving fluoroquinolones, including Ofloxacin. If such reactions occur, treatment with Ofloxacin Zentiva should be discontinued, and appropriate measures should be initiated. Ofloxacin Zentiva should be used with caution in patients with a history of psychotic disorders or in patients with mental illness.

Patients with impaired liver function

Ofloxacin Zentiva should be used with caution in patients with impaired liver function. Cases of fulminant hepatitis leading to acute liver failure (including fatal cases) have been observed with the use of fluoroquinolones. Patients should be advised to discontinue treatment and contact their doctor if symptoms of liver damage occur, such as anorexia, jaundice, dark urine, itching, or abdominal pain.

Myasthenia gravis

Fluoroquinolones, including Ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including respiratory failure (with mechanical ventilation) and fatal outcomes, associated with the use of fluoroquinolones in patients with myasthenia gravis have been observed in the post-marketing period. The use of Ofloxacin Zentiva in patients with a diagnosed myasthenia gravis is not recommended.

Prevention of photosensitivity

Due to the risk of photosensitivity, exposure to intense sunlight and UV radiation should be avoided during treatment with Ofloxacin Zentiva.

Secondary infection

As with the use of other antimicrobial drugs, during ofloxacin administration, especially prolonged, the development of a secondary infection associated with the growth of drug-resistant microorganisms is possible, for the exclusion and confirmation of which the patient’s condition should be re-evaluated. If a secondary infection develops during therapy, necessary measures for its treatment should be taken.

QT interval prolongation

Cases of QT interval prolongation have been observed in patients taking fluoroquinolones, including Ofloxacin.

Caution should be exercised when using Ofloxacin Zentiva in patients with known risk factors for QT interval prolongation

• Elderly age;
• Uncorrected electrolyte imbalance (e.g., hypokalemia, hypomagnesemia);
• Congenital long QT syndrome;
• Heart disease (e.g., heart failure, myocardial infarction, bradycardia);
• Concomitant use of drugs that cause QT interval prolongation (e.g., class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, antipsychotics).

Dysglycemia (hypo- and hyperglycemia)

Cases of both hypoglycemia and hyperglycemia have been reported with the use of fluoroquinolones, including Ofloxacin. Hypoglycemic coma has been reported in patients with diabetes mellitus simultaneously receiving oral hypoglycemic drugs (e.g., glibenclamide) or insulin. In such patients, careful monitoring of blood glucose levels is recommended.

Peripheral neuropathy

Sensory and sensorimotor neuropathy, which may have a rapid onset, has been reported in patients receiving fluoroquinolones, including Ofloxacin. If patients develop symptoms of neuropathy, treatment with Ofloxacin Zentiva should be discontinued to help minimize the potential risk of irreversible conditions.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or diagnosed glucose-6-phosphate dehydrogenase deficiency may be predisposed to hemolytic reactions during treatment with quinolones. Ofloxacin Zentiva should be used with caution in such patients.

Patients with rare hereditary diseases

Ofloxacin Zentiva is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption, because the tablet contains lactose monohydrate.

Patients taking vitamin K antagonists

Due to the possible increase in prothrombin time/INR and/or the development of bleeding in patients simultaneously taking Ofloxacin Zentiva and vitamin K antagonists (e.g., warfarin), careful monitoring of blood coagulation parameters is recommended.

Risk of resistance development

The prevalence of acquired resistance of microorganisms may vary geographically and over time for individual species. Therefore, local information on resistance is required; microbiological diagnostics with pathogen isolation and determination of its sensitivity should be carried out, especially in severe infections or in the absence of therapeutic effect.

Infections caused by Escherichia coli

Resistance of Escherichia coli – the most common causative agent of urinary tract infections – to fluoroquinolones varies in different geographical areas. Physicians are advised to consider the local resistance of Escherichia coli to fluoroquinolones.

Infections caused by Neisseria gonorrhoeae

Due to the increasing resistance of Neisseria gonorrhoeae, Ofloxacin Zentiva should not be used as empirical treatment for suspected gonococcal urinary tract infection. Tests for the pathogen’s sensitivity to ofloxacin should be performed to ensure targeted therapy.

Methicillin-resistant Staphylococcus aureus

It is highly likely that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including Ofloxacin. Therefore, Ofloxacin Zentiva is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus, unless laboratory tests have confirmed the sensitivity of this microorganism to ofloxacin.

Bone and joint infections

In bone and joint infections, the need for combined use of Ofloxacin Zentiva with other antibacterial drugs should be considered.

Effect on laboratory parameters and diagnostic tests

Ofloxacin may inhibit the growth of Mycobacterium tuberculosis, leading to false-negative results in the bacteriological diagnosis of tuberculosis.

When determining opiates and porphyrins in urine during treatment with Ofloxacin Zentiva, a false-positive result is possible. Confirmation of positive results using more specific methods may be necessary.

Other

During treatment, it is not recommended to consume fluids containing ethanol.

Effect on ability to drive vehicles and mechanisms

When taking Ofloxacin Zentiva, dizziness, drowsiness, and visual disturbances may occur, therefore caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms from the CNS – dizziness, confusion, disorientation, convulsions; from the digestive system – nausea, vomiting, erosive lesions of the gastrointestinal mucosa.

Treatment: gastric lavage, administration of activated charcoal and other adsorbents, symptomatic therapy. Antacids can be used to protect the gastric mucosa. ECG monitoring should be mandatory due to possible QT interval prolongation. Ofloxacin fractions can be removed from the body by hemodialysis. There is no specific antidote.

Drug Interactions

Antacids containing aluminum hydroxide, sucralfate, magnesium hydroxide, aluminum phosphate, or preparations containing zinc or iron

Antacids containing aluminum hydroxide, sucralfate, magnesium hydroxide, aluminum phosphate, or preparations containing zinc or iron reduce the absorption of ofloxacin by forming insoluble complexes. When using the above-mentioned drugs and Ofloxacin Zentiva, the interval between their administrations should be approximately 2 hours.

Theophylline, fenbufen or similar NSAIDs

Clinical studies have not revealed a pharmacokinetic interaction between ofloxacin and theophylline. Nevertheless, a pronounced decrease in the seizure threshold of the brain may be observed with the simultaneous use of quinolones with theophylline, NSAIDs or other agents that lower the seizure threshold of the brain (including fenbufen).

Drugs causing QT interval prolongation

Ofloxacin Zentiva, like other fluoroquinolones, should be used with caution in patients receiving drugs that cause QT interval prolongation on ECG (e.g., class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolide antibiotics, antipsychotics).

Vitamin K antagonists (coumarin derivatives, including warfarin)

An increase in prothrombin time/INR values and/or the development of bleeding (including severe) have been observed in patients with concomitant use of ofloxacin and vitamin K antagonists (e.g., warfarin). With simultaneous use of vitamin K antagonists and Ofloxacin Zentiva, monitoring of blood coagulation system parameters is necessary.

Glibenclamide

Ofloxacin may cause a slight increase in the serum concentration of glibenclamide, therefore, in patients simultaneously receiving Ofloxacin and glibenclamide, careful monitoring of blood glucose levels is recommended.

Other oral hypoglycemic agents and insulin

Ofloxacin increases the risk of hypoglycemia, more careful monitoring of blood glucose concentration is required.

Probenecid, cimetidine, furosemide and methotrexate

When using quinolones concomitantly with drugs eliminated from the body by renal tubular secretion (such as probenecid, cimetidine, furosemide, methotrexate), mutual slowing of elimination and an increase in serum concentrations are possible (especially in the case of high-dose use).

Corticosteroids

When using the drug Ofloxacin Zentiva concomitantly with corticosteroids, the risk of tendon rupture increases, especially in elderly patients.

Drugs that alkalinize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate)

When using the drug Ofloxacin Zentiva concomitantly with drugs that alkalinize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

Storage Conditions

The drug should be stored in a dry place, out of the reach of children, at a temperature between 10°C (50°F) and 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.