Ofloxacin Welfarm, 200 mg 10 pcs

Pharmacotherapeutic group: antimicrobial agent – fluoroquinolone

ATX code: J01MA01

Pharmacological properties

Pharmacodynamics

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

Highly active against most gram-negative and gram-positive microorganisms.

Fluoroquinolones have concentration-dependent bactericidal activity and moderate postantibacterial action. The ratio of AUC to minimum inhibitory concentration (MIC) or the ratio of maximum concentration to MIC is a predictive factor for successful clinical treatment.

Sensitive microorganisms

Non-sensitive microorganisms (possibly due to acquired resistance): Citrobacter freundii, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Neisseria gonorrhoeae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia spp, Staphylococcus spp. (coagulazonegative strains), Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis, Campylobacter jejuni, Enterococcus faecalis, Streptococcus pneumoniae. Resistant microorganisms

Acinetobacter baumannii, Bacteroides spp., Clostridium difficile, Enterococci (including Enterococcus faecium), Listeria monocytogenes, Staphylococcus aureus (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 mechanisms of resistance, such as a mechanism of influence on the permeability of the external structures of the microbial cell (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active excretion of the antimicrobial agent from the microbial cell), can also affect the sensitivity of microorganisms to ofloxacin.

MPC limit values

MPC limit values (mg/L) ofloxacin as approved by the European Committee on Antibiotic Susceptibility Testing (EUCAST).

Moraxella catarrhalis

species of microorganism

Pharmacokinetics

After oral administration, ofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is almost 100%. Maximum blood plasma concentration ofloxacin after a single dose of 200 mg is 2.5-3 mcg/ml and is reached after 1 hour. Binding with plasma proteins is 25%. The volume of distribution is about 120 l. Less than 5% of Ofloxacin undergoes biotransformation.

It is mainly excreted by the kidneys (80-90% of the dose is unchanged). Two main metabolites are detected in the urine: N-desmethylofloxacin and ofloxacin N-oxide. About 4% ofloxacin is excreted with bile as glucuronides. The elimination half-life is 6-7 hours. Concentrations of ofloxacin in urine and in infected urinary tract are 5-100 times higher than those ofloxacin in blood serum.

Special patient groups Elderly patients

Elderly patients have an increased half-life, but the maximum concentration does not change.

Renal failure

In renal failure, the half-life is prolonged; total and renal clearance decrease in proportion to the decrease in creatinine clearance.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to Ofloxacin:

– pyelonephritis;

– prostatitis, epididymitis, orchitis;

– pelvic organ infections;

– cystitis.

As an alternative to other antimicrobial agents, ofloxacin can be used to treat the following infectious and inflammatory diseases:

– uncomplicated urinary tract infections;

– skin and soft tissue infections;

– bone and joint infections;

– acute sinusitis;

– exacerbation of chronic bronchitis, community-acquired pneumonia;

– prophylaxis of infections caused by microorganisms sensitive to Ofloxacin in patients with a significant decrease in immune status (for example, in neutropenia).

The official national guidelines for the appropriate use of antibacterials, as well as the sensitivity of pathogens in a particular country, should be considered when using the drug.

Active ingredient

How to take, the dosage

Orally.

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

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

The drug is indicated in a daily dose of 400 mg divided into 2 doses (every 12 hours).

The daily dose can be increased to 600-800 mg in severe infections or when treating overweight patients.

In uncomplicated lower urinary tract infections, the drug is prescribed in a dose of 200 mg daily for 3-5 days.

In gonorrhea, 400 mg is prescribed once.

The daily dose of up to 400 mg may be prescribed at 1 time, preferably in the morning. A daily dose of more than 400 mg should be divided into 2 doses at regular intervals.

The tablets should be swallowed whole with plenty of water. The drug may be taken both before and with meals. Concomitant use with antacids should be avoided.

Patient special groups

Elderly patients

The age of patients does not require dose adjustment of Ofloxacin. However, when using the drug in elderly patients, special attention should be paid to renal function because if it declines, the dosing regimen may need to be adjusted accordingly.

Patients with hepatic impairment

In patients with hepatic impairment it is not recommended to exceed the daily dose of Ofloxacin 400 mg.

Patients with impaired renal function

The following dosing regimen is recommended with impaired renal function depending on creatinine clearance:

Creatinine clearance

Dose (mg)*

Frequency of administration

50-20 ml/min

200*

once a day (every 24 hours)

200*

1 time per day (every 24 hours)/td>

< 20 ml/min** or hemodialysis, or

peritoneal dialysis

/p>

200

Once every 2 days (every 48 h)

* except for indications in which the adjusted dose of ofloxacin is 100 mg.

** It is recommended that serum concentrations ofloxacin be monitored in patients with severe renal impairment or in patients on dialysis.

In cases where creatinine clearance (CK) cannot be determined, it can be calculated from serum creatinine concentration using the Cockroft formula for adults:

for men:

CK (ml/min) = or

Body weight (kg) x (140 – age in years) 72 x serum creatinine (mg/dL)

CK (ml/min) =

for women:

Body weight (kg) x (140 – age in years) 0.814 x serum creatinine (μmol/L)

CK (ml/min) = 0.85 x index in men.

The duration of treatment

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

Interaction

With antacids containing aluminum hydroxide, sucralfate, magnesium hydroxide, aluminum phosphate, or preparations containing zinc, iron

Antacids containing aluminum hydroxide, sucralfate, magnesium hydroxide, aluminum phosphate, or preparations containing zinc or iron reduce absorption of Ofloxacin. When the above drugs and ofloxacin are used, an interval of approximately two hours between doses should be observed.

With vitamin K antagonists

Enhancement of prothrombin time/international normalized ratio and/or bleeding (including severe bleeding) have been reported in patients with concomitant use of ofloxacin and vitamin K antagonists (such as warfarin). When concomitant use of vitamin K antagonists it is necessary to monitor the blood clotting system.

With glibenclamide

Ofloxacin may slightly increase serum concentrations of glibenclamide when used simultaneously. Careful monitoring of patients and blood glucose concentrations is recommended during concomitant use of ofloxacin and glibenclamide.

With other oral hypoglycemic agents and insulin

Ofloxacin increases the risk of hypoglycemia; closer monitoring of blood glucose concentrations is required.

With probenecid, cimetidine, furosemide or methotrexate

. When using quinolones with drugs that are excreted by renal tubular secretion (such as probenecid, cimetidine, furosemide, methotrexate), mutual retardation of excretion and increased serum concentrations (especially when using high doses) are possible.

With drugs that may decrease the threshold of cerebral seizure activity, such as theophylline, phenbufen (and other similar non-steroidal anti-inflammatory drugs)

In clinical studies no pharmacokinetic interactions of Ofloxacin with theophylline have been established. However, there may be a significant decrease in cerebral seizure threshold when using quinolones concomitantly with drugs that reduce cerebral seizure threshold (theophylline, phenbufen [and other similar non-steroidal anti-inflammatory drugs]).

With glucocorticosteroids

Concomitant use with glucocorticosteroids increases the risk of tendon rupture, especially in older patients.

With drugs that may prolong the QT interval

Ofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that may prolong the QT interval (antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides, neuroleptics).

With drugs that alkalize the urine (carboanhydrase inhibitors, citrates, sodium hydrogen carbonate)

When prescribed with drugs that alkalize the urine (carboanhydrase inhibitors, citrates, sodium hydrogen carbonate), the risk of crystalluria and nephrotoxic effects increases.

Special Instructions

Renal failure

Due to the fact that ofloxacin is mainly excreted by the kidneys, patients with renal failure require dosage adjustment of ofloxacin (see sections “Caution”, “Dosage and administration”).

Prevention of photosensitization

Exposure to bright sunlight and ultraviolet light should be avoided during treatment with Ofloxacin because of the risk of photosensitization.

Secondary infection

As with other antimicrobial agents, with the use of of ofloxacin, especially over the long term, secondary infection may develop due to growth of microorganisms resistant to the drug; the patient should be reassessed to exclude and confirm this. If secondary infection develops during therapy, necessary measures should be taken to treat it.

Peripheral neuropathy

Patients receiving fluoroquinolones, including ofloxacin, have reported the development of sensory and sensory-motor neuropathy, which may have a rapid onset. If patients develop symptoms of neuropathy, treatment with ofloxacin should be discontinued to minimize the possible risk of developing irreversible conditions (see Caution).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with diagnosed glucose-6-phosphate dehydrogenase deficiency may be predisposed to hemolytic reactions when treated with quinolones. Therefore, in these patients caution should be exercised when using ofloxacin (see section “Caution”).

Pseudomembranous colitis caused by Clostridium difficile

The appearance of diarrhea, especially in severe form, persistent and/or with blood admixture, during or after treatment with ofloxacin may be a manifestation of pseudomembranous colitis. If pseudomembranous colitis is suspected, treatment with ofloxacin should be stopped immediately and appropriate specific antibacterial therapy (oral vancomycin, oral teicoplanin or oral metronidazole) should be prescribed immediately. Drugs that inhibit intestinal peristalsis are contraindicated in this clinical situation.

Patients who are prone to developing seizures

. Like other quinolones, ofloxacin should be used with caution in patients who are predisposed to the development of seizures (patients with a history of CNS lesions, in patients simultaneously receiving drugs that reduce the threshold of cerebral seizure activity (theophylline, phenbufen [and other similar non-steroidal anti-inflammatory drugs]), (see “Caution. section “Caution”). If seizures develop, treatment with Ofloxacin should be discontinued.

Tendinitis

Tendinitis, which rarely occurs with quinolones, can sometimes lead to tendon rupture, including the Achilles tendon, especially in elderly patients and in patients taking glucocorticosteroids simultaneously. This undesirable effect may develop within 48 hours after the start of treatment and may be bilateral. In case of signs of tendinitis (inflammation of the tendon) it is recommended to stop treatment with Ofloxacin immediately. Appropriate treatment (e.g. immobilization) of the damaged tendon may be required.

QT interval prolongation

Some caution is necessary when taking fluoroquinolones, including ofloxacin, in patients with known risk factors for QT interval prolongation, such as:

– older age;

– unadjusted electrolyte imbalances (e.g., hypokalemia, hypomagnesemia);

– congenital QT interval prolongation;

– cardiovascular system disorders (heart failure, myocardial infarction, bradycardia);

– concurrent use of drugs prolonging the QT interval (classes IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, neuroleptics).

Pseudoparalytic myasthenia gravis

Fluoroquinolones, including ofloxacin, are characterized by blocking neuromuscular conduction activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. Serious adverse reactions, including pulmonary failure requiring artificial ventilation and death, associated with fluoroquinolones in patients with pseudoparalytic myasthenia gravis have been observed in the post-registration period. The use of Ofloxacin in a patient with a confirmed diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side effects”).

Serious skin reactions

The development of severe bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis has been reported while taking ofloxacin. Patients should be informed that if skin reactions and/or mucous membrane lesions develop, it is necessary to immediately consult a physician before continuing treatment with ofloxacin.

Hypersensitivity reactions and allergic reactions

The development of hypersensitivity reactions and allergic reactions (anaphylactic shock and anaphylactoid reactions, which may progress to life-threatening conditions) has been reported with fluoroquinolones. In these cases, the use of Ofloxacin should be discontinued and appropriate treatment should be initiated.

Psychotic reactions

Psychotic reactions, including suicidal thoughts/attempts, have been reported in patients taking fluoroquinolones, including ofloxacin. Ofloxacin should be administered with caution in patients with psychotic disorders (including a history) (see section

“Caution”). Psychotic adverse reactions may occur even after a single dose. If these reactions develop, treatment with ofloxacin should be discontinued immediately and appropriate treatment should be prescribed immediately and therapy with an antibiotic other than fluoroquinolones should be switched to another antibiotic, if possible.

Hepatic disorders

Ofloxacin should be used with caution in patients with hepatic impairment because liver damage may occur (see section “Caution”). Cases of fulminant hepatitis leading to liver failure (including cases with fatal outcome) have been reported when using fluoroquinolones. Patients should be advised to discontinue treatment and consult a physician if symptoms and signs of liver disease, such as anorexia, jaundice, darkened urine, itching of the skin, and abdominal pain are observed.

Dysglycemia (hypo- and hyperglycemia)

. When using fluoroquinolones, including ofloxacin, the development of both hyperglycemia and hypoglycemia, as well as severe hypoglycemia, up to development of hypoglycemic coma, especially in elderly patients, diabetic patients taking oral hypoglycemic drugs or insulin has been reported (signs of hypoglycemia: confusion, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, sweating, shivering, weakness). Plasma glucose concentration in these patients should be carefully monitored. In case of development of adverse reactions, such as decreased glucose concentration, treatment with ofloxacin should be discontinued immediately and appropriate treatment should be prescribed immediately and therapy should be switched to another antibiotic other than fluoroquinolones, if possible.

Patients taking vitamin K antagonists

Due to the possible increase in prothrombin time/international normalized ratio and/or bleeding development in patients taking simultaneously ofloxacin and vitamin K antagonists (such as warfarin), close monitoring of blood clotting is recommended.

The risk of developing resistance

The prevalence of acquired resistance can vary geographically and over time for individual species. Therefore, local information on resistance is required. Microbiological diagnosis with isolation of the pathogen and determination of its sensitivity should be performed, especially in severe infections or lack of response to treatment.

Infections caused by Escherichia coli

The resistance to fluoroquinolones of Escherichia coli, the most common pathogen of urinary tract infections, varies in different geographic areas. Physicians are advised to consider the local resistance of Escherichia coli to fluoroquinolones.

Infections caused by Neisseria gonorrhoeae

Due to the increased resistance of Neisseria gonorrhoeae, ofloxacin should not be used as an empirical treatment for suspected urinary tract gonococcal infection. Sensitivity tests for Ofloxacin should be performed to ensure targeted therapy.

Methicillin-resistant Staphylococcus aureus

There is a high probability that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including ofloxacin. Therefore, ofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus if laboratory tests have not confirmed the sensitivity of this microorganism to ofloxacin.

Bone and joint infections

Infections of bones and joints should be considered when combining ofloxacin with other antibacterial drugs.

Impact on laboratory values and diagnostic tests

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

When opiates and porphyrins are detected in urine during treatment with ofloxacin, false-positive results may occur. It may be necessary to confirm positive results with more specific methods.

Other

To avoid ethanol during treatment.

Effect on ability to drive, machinery

Some adverse reactions, such as dizziness/vertigo, drowsiness, and visual disturbances may decrease psychomotor responsiveness and ability to concentrate and therefore increase risk in situations in which these abilities are particularly important (such as driving or other machinery).

Synopsis

Round biconvex film-coated white or almost white tablets. Cross-section shows a white or white with a yellowish tint.

Contraindications

– hypersensitivity to ofloxacin, other quinolones or excipients of the drug;

– epilepsy;

Pseudoparalytic myasthenia gravis (see sections “Side Effects” and “Special Precautions”). Side effects, special indications);

– tendon lesions when taking fluoroquinolones in the anamnesis;

– childhood and adolescence before 18 years of age (the risk of damage of cartilaginous bone growth zones in a child cannot be completely excluded);

Pregnancy (the risk of fetal cartilage cannot be completely ruled out);

Breastfeeding (we cannot completely rule out the risk of cartilage damage in the baby).

With caution

– in patients predisposed to the development of seizures (in patients with previous central nervous system (CNS) lesions, such as marked atherosclerosis of cerebral vessels, cerebral blood circulation disorders in the history, organic CNS lesions, brain injuries in the history; patients concomitantly receiving medications that lower the cerebral seizure threshold, such as phenbufen or other non-steroidal anti-inflammatory drugs, theophylline;)

– in patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions when treated with quinolones);

– in patients with impaired renal function (mandatory renal function monitoring is required, as well as dosing regimen correction, see “Dosage method.

– in patients with hepatic impairment (monitoring of liver function parameters);

– in patients with porphyria (risk of exacerbation of porphyria);

– in patients with risk factors for QT interval prolongation: in elderly patients; in uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); in congenital QT interval prolongation syndrome; in heart disease (heart failure, myocardial infarction, bradycardia); concomitant use of medications that may prolong the QT (class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, neuroleptics). – In patients with diabetes 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);

– In patients with a history of psychosis and other psychiatric disorders.

Side effects

The information below is based on data obtained from clinical trials and data from extensive post-registration experience with Ofloxacin. The side effects listed below are presented according to the following frequency gradations: Very common (>1/10); common (>1/100, <1/10); infrequent (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000) (including individual reports); frequency unknown (the incidence cannot be determined from available data).

Chronic disorders: rare – tachycardia; infrequent – palpitations; frequency unknown – QT interval prolongation, ventricular pirouette arrhythmia (especially in patients with risk factors for QT interval prolongation).

Vascular disorders: rarely – increased blood pressure, decreased blood pressure.

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

Nervous system disorders: infrequent – dizziness, headache; rare – somnolence, paresthesia, dysgeusia (taste perception disorder), parosmia (odor perception disorder); very rare – peripheral sensory neuropathy, peripheral sensory-motor neuropathy, seizures, extrapyramidal symptoms, including tremor, and other disorders of muscle coordination; frequency unknown – aguesia, increased intracranial pressure.

Psychiatric disorders: infrequent – agitation, sleep disorders, insomnia; rare – psychotic disorders (e.g., hallucinations), anxiety, nervousness, confusion, nightmares, depression; frequency unknown – psychotic disorders and depression with self-harm, in rare cases, up to suicidal thoughts or attempts, attention disorders, disorientation, memory disorders, delirium.

Visual organ disorders: infrequent – irritation of the mucous membrane of the eye, conjunctivitis; rare – visual disturbances (diplopia, color perception disorders); frequency is unknown – uveitis.

Hearing and labyrinth disorders: infrequent – vertigo; very rare – hearing disorders (tinnitus), hearing loss.

Respiratory system, chest and mediastinum disorders: infrequent – cough, nasopharyngitis; rare – shortness of breath, bronchospasm; frequency unknown – allergic pneumonitis, severe shortness of breath.

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

Liver and biliary tract disorders: rare – increased activity of “liver” enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (ACT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT) and/or alkaline phosphatase (ALP) and/or blood bilirubin concentrations; very rare – cholestatic jaundice; frequency is unknown – hepatitis, which may be severe; when using ofloxacin (mainly in patients with liver dysfunction) there were reported cases of severe liver failure, including acute liver failure, sometimes with fatal outcome.

Repnal and urinary tract disorders: rare – increased serum creatinine concentration; very rare – acute renal failure; frequency unknown – acute interstitial nephritis, increased blood urea concentration.

Skin and subcutaneous tissue disorders: infrequent – itching, rash; rare – urticaria, hyperhidrosis, pustular rash, “flushes” of blood to the skin; very rare – erythema multiforme exudative, toxic epidermal necrolysis, photosensitization reactions, drug rash, vascular purpura, vasculitis, which in exceptional cases can lead to cutaneous necrosis; frequency unknown – Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, exfoliative dermatitis.

Muscular and connective tissue disorders: rare – tendinitis; very rare – arthralgia, myalgia, tendon rupture (such as Achilles tendon) (as with other fluoroquinolones, this side effect may develop within 48 h after treatment initiation and may be bilateral); frequency unknown – rhabdomyolysis and/or myopathy, muscle weakness, especially important in patients with pseudoparalytic myasthenia gravis, muscle tears, muscle tears, ligament tears, arthritis.

Metabolic and nutritional disorders: rare – anorexia; frequency unknown – hyperglycemia, hypoglycemia, severe hypoglycemia, up to hypoglycemic coma, especially in elderly patients, diabetic patients taking oral hypoglycemic agents or insulin.

Infectious and parasitic diseases: infrequent fungal infections, resistance of pathogenic microorganisms.

Immune system disorders: rarely – anaphylactic reactions, anaphylactoid reactions, angioedema; very rarely – anaphylactic shock, anaphylactoid shock.

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

General disorders and disorders at the site of administration: frequency unknown – asthenia, increased body temperature, pain in the back, chest, extremities.

Overdose

Symptoms

The most important symptoms of overdose are CNS symptoms (such as dizziness, confusion, loss of consciousness, seizures), prolonged QT interval, and gastrointestinal reactions (such as nausea and erosions of the gastrointestinal mucosa).

Treatment

Pregnancy use

Pregnancy

Ofloxacin should not be used during pregnancy (see section “Contraindications”).

Breastfeeding

Since Ofloxacin is excreted into the breast milk, due to the risks to the baby, women breastfeeding should not take Ofloxacin or, if necessary, stop breastfeeding.

Similarities