Levofloxacin-Teva, 500 mg 14 pcs.

Indications

The treatment of infection and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

Active ingredient

Composition

How to take, the dosage

To use

Tablets Levofloxacin-Teva 500 mg are taken orally once or twice a day. The tablets should be swallowed without chewing and with plenty of fluid (0.5 to 1 cup). If necessary, the tablets may be crushed into a separating groove.

The drug may be taken before meals or at any time between meals, since eating has no effect on absorption of the drug (see section “Pharmacokinetics”).

The drug should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and/or aluminum, iron, zinc, or sucralfate (see section “Interaction with other medicinal products”).

Given that the bioavailability of levofloxacin when receiving Levofloxacin-Teva in tablets is 99-100%, if the patient is transferred from intravenous infusion of Levofloxacin-Teva to tablets, treatment should be continued in the same dose that was used for intravenous infusion (see section “Pharmacological properties”, subsection “Pharmacokinetics”).

Missing one or more doses of the drug

If the drug is accidentally missed, the next dose must be taken as soon as possible and Levofloxacin-Teva must be continued according to the recommended dosing regimen.

Doses and duration of treatment

The dosing regimen is determined by the nature and severity of the infection and the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

Recommended dosing regimen and duration of treatment in patients with normal renal function (CKR greater than 50 ml/min)

Dosing regimen in patients with impaired renal function (CK ≤ 50 ml/min)

Levofloxacin is mainly excreted by the kidneys; therefore, when treating patients with impaired renal function the drug dose must be reduced (see table below).

Creatinine Clerance (CK)

Dosing regimen

Over 50 ml/min

500 mg/24 h

500 mg/12 h

50-20 mL/min

first dose: 500 mg

then 250 mg/24 h

first dose: 500 mg

then 250 mg/12 h

Due to the lack of risk and the inability to provide a dosing regimen of 125 mg/24 h, Levofloxacin-Teva is contraindicated in patients with a CK of less than 50 mL/min when dosing with an initial dosing regimen of 250 mg/24 h; Patients with a CKR of less than 20 ml/min when dosing with the original dosage of 500 mg/24 h and 500 mg/12 h; patients with a CKR of less than 10 ml/min (including hemodialysis).including in hemodialysis and continuous ambulatory peritoneal dialysis) for all dosing regimens (see section “Contraindications”). If it is necessary to use levofloxacin in the form of infusion solution or tablets 250 mg with a separating ridge.

Dosing regimen in patients with hepatic impairment

The dosing regimen does not need to be adjusted if hepatic function is impaired because levofloxacin is only slightly metabolized in the liver.

Dosing regimen in elderly patients

The dosing regimen does not need to be adjusted in elderly patients unless the CK falls to 50 ml/min or lower.

Interaction

Interactions requiring caution

With drugs containing magnesium, aluminum, iron and zinc, didanosine

Drugs containing bivalent or trivalent cations, such as zinc or iron salts (drugs for the treatment of anemia), magnesium and/or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer) are recommended at least 2 hours before or 2 hours after taking Levofloxacin-Teva tablets.

Calcium salts have minimal effect on the absorption of levofloxacin when taken orally.

With sucralfate

The effect of Levofloxacin-Teva is significantly impaired when sucralfate (gastric mucosal protection agent) is used simultaneously.

Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after taking levofloxacin.

With theophylline, phenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs that lower the cerebral seizure threshold

The pharmacokinetic interaction of levofloxacin with theophylline has not been identified. However, with concomitant use of quinolones and theophylline, nonsteroidal anti-inflammatory drugs and other drugs that reduce cerebral seizure threshold, there may be a marked decrease in cerebral seizure threshold.

The concentration of levofloxacin is increased by only 13% when concomitant administration of phenbufen.

With indirect anticoagulants (vitamin K antagonists)

. In patients treated with levofloxacin in combination with indirect anticoagulants (e.g., warfarin), increased prothrombin time/international normalized ratio and/or bleeding have been observed, including severe bleeding. Therefore, when concomitant use of indirect anticoagulants and levofloxacin, regular monitoring of blood clotting parameters is necessary.

With probenecid and cimetidine

When concomitant use of drugs that impair renal tubular secretion, such as probenecid and cimetidine, and levofloxacin, caution should be exercised, especially in patients with renal insufficiency.

Elevation (renal clearance) of levofloxacin is slowed by 24% by cimetidine and 34% by probenecid. This is unlikely to be clinically relevant in normal renal function.

With cyclosporine

Levofloxacin increased T1/2 cyclosporine by 33%. Since this increase is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

With glucocorticosteroids

The simultaneous use of glucocorticosteroids increases the risk of tendon rupture.

With drugs that prolong the QT interval

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medications that prolong the QT interval (e.g., antiarrhythmic drugs of class IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

Clinical and pharmacological studies have been conducted to examine possible pharmacokinetic interactions of levofloxacin

Special Instructions

Hospital infections caused by Pseudomonas aeruginosa may require combination treatment.

Risk of developing resistance

The prevalence of acquired resistance of the microbial strains being isolated may vary by geographic region and over time. This requires information about resistance to the drug in a particular country. For therapy of severe infections or in case of ineffective treatment it is necessary to establish microbiological diagnosis with pathogen isolation and determination of its sensitivity to levofloxacin.

Methicillin-resistant Staphylococcus aureus

There is a high probability that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin 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 levofloxacin.

Loss of function (disability) and potentially irreversible serious adverse reactions due to fluoroquinolones

. The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems that may develop simultaneously in the same patient. Fluoroquinolone-induced adverse reactions include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may occur within a few hours to a few weeks after the start of therapy with levofloxacin. The development of these adverse reactions has been noted in patients of any age or without previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, the use of levofloxacin should be stopped immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have had any of these serious adverse reactions.

Patients susceptible to seizures

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include those with previous lesions of the central nervous system, such as stroke, severe craniocerebral trauma; patients simultaneously taking drugs that lower the seizure threshold of the brain, such as phenbufen and other similar non-steroidal anti-inflammatory drugs or other drugs that lower the seizure threshold, such as theophylline (see section “Interaction with other medicinal products”). If seizures develop, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis

. Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or with blood, may be a symptom of pseudomembranous colitis caused by Clostridium difficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (oral vancomycin, teicoplanin or metronidazole) started immediately. Drugs that inhibit intestinal peristalsis are contraindicated.

Tendinitis and tendon rupture

Tendinitis is rarely seen with quinolones, including levofloxacin, which can sometimes lead to tendon rupture, including the Achilles tendon, and may be bilateral. This side effect may develop within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to develop tendonitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant use of glucocorticosteroids. In addition, patients after transplantation have an increased risk of tendinitis, so caution is recommended when prescribing fluoroquinolones for this category of patients. In patients with impaired renal function the daily dose should be adjusted based on creatinine clearance. Patients should be advised to remain at rest at the first signs of tendinitis or tendon rupture, and to consult the attending physician. If tendinitis or tendon rupture is suspected, treatment with Levofloxacin-Teva should be stopped immediately and appropriate treatment of the affected tendon should be initiated, e.g. sufficient immobilization (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock), even when initial doses are used (see section “Side effects”). Patients should immediately stop taking the drug and consult a physician.

Serious bullous reactions

When using levofloxacin there have been cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see section “Adverse effects”). If any skin or mucous membrane reactions develop, the patient should immediately consult a physician and not continue treatment until he or she has been consulted.

Hepatic and biliary tract disorders

Hepatic necrosis, including development of hepatic failure with fatal outcome, has been reported when using levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see section “Adverse effects. See section “Side effects”). Patients should be warned to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage, such as anorexia, jaundice, darkened urine, itching of the skin and abdominal pain appear.

Patients with impaired renal function

As levofloxacin is mainly excreted through the kidneys, mandatory renal function monitoring is required in patients with impaired renal function as well as dosing regimen adjustment. When treating elderly patients it should be taken into account that patients of this group often have impaired renal function (see section “Dosage and administration”).

Preventing photosensitization reactions

. Although photosensitization by using levofloxacin is very rare, to prevent its development the patients are not recommended during the treatment and within 48 hours after the treatment with levofloxacin to be exposed to strong sunlight or artificial ultraviolet radiation without any special need (e.g. to visit a solarium).

Superinfection

. As with other antibiotics, use of levofloxacin, especially for a long time, may lead to increased proliferation of microorganisms which are not sensitive to it (bacteria and fungi) which may cause changes in the microflora which are normally present in humans. As a result, superinfection may develop. Therefore, it is imperative that the patient is reassessed during treatment, and if superinfection develops during treatment, appropriate measures should be taken.

QT interval prolongation

Very rare cases of QT interval prolongation have been reported in patients taking fluoroquinolones, including levofloxacin.

When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for QT interval prolongation: In patients with uncorrected electrolyte abnormalities (with hypokalemia, hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with concurrent use of drugs that can prolong the QT interval, such as: class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, neuroleptics.

The elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore fluoroquinolones including levofloxacin should be used with caution in these patients (see sections Caution, Dosage and administration, Side effects and Overdose, Interaction with other medicinal products).

Patients with glucose-6-phosphate dehydrogenase deficiency

. Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to develop hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with other quinolones, cases of hyperglycemia and hypoglycemia have been observed with levofloxacin. During therapy with levofloxacin dysglycemia occurred more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (e.g., glibenclamide) or insulin. When using levofloxacin in such patients the risk of hypoglycemia increases, up to hypoglycemic coma. Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, sweating, trembling, weakness). If the patient develops hypoglycemia, treatment with levofloxacin should be stopped immediately and appropriate therapy should be started. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. When treating with levofloxacin in elderly patients, in patients with diabetes mellitus, close monitoring of blood glucose concentration is recommended.

Peripheral neuropathy

In patients taking fluoroquinolones, including levofloxacin, cases of sensory and sensory-motor peripheral neuropathy have been reported, which may have a rapid onset. If the patient develops symptoms of neuropathy, the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes. Patients should be informed of the need to report any symptoms of neuropathy to their physician. Fluoroquinolones should not be prescribed in patients with a history of peripheral neuropathy.

Exacerbation of pseudoparalytic myasthenia gravis

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

Application in the anthrax airborne route

The use of levofloxacin in humans for this indication is based on data on its sensitivity to Bacillus anthracis sensitivity data from in vitro studies and animal experiments, as well as limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect a consensus view on the treatment of anthrax.

Psychotic reactions

Psychotic reactions, including suicidal thoughts/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose. In case of development of any side effects on the central nervous system, including mental disorders, treatment with levofloxacin should be stopped immediately and appropriate therapy should be prescribed. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. Caution should be exercised when prescribing the drug in patients with psychosis or patients with a history of mental illness.

Visual disturbances

If any visual disturbances develop, immediate consultation with an ophthalmologist is necessary (see section on side effects).

Influence on laboratory tests

In patients taking levofloxacin, urinary opioid determination may lead to false positives that must be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and further lead to false negatives in the bacteriological diagnosis of tuberculosis.

Aortic aneurysm and/or aortic dissection

Epidemiological studies have reported an increased risk of aortic aneurysm and aortic dissection after fluoroquinolones, especially in elderly patients. Therefore, fluoroquinolones should be used only after careful assessment of the benefit-risk ratio and consideration of other therapeutic options in patients with a family history of aortic aneurysm, or in patients with diagnosed aortic aneurysm and/or aortic dissection, or in the presence of other risk factors or conditions predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu arteritis, giant cell arteritis, Behçet disease, arterial hypertension, atherosclerosis).

If patients have sudden pain in the abdomen, chest, or back, they should immediately see a physician in the emergency department.

Effects on driving and operating ability

The adverse reactions of Levofloxacin-Teva such as dizziness or vertigo, somnolence and visual disturbances (see section “Adverse effects”) may impair psychomotor responses and ability to concentrate. This may pose some risk in situations where these abilities are particularly important (e.g., driving a car, operating machinery, working in an unsteady position).

Synopsis

Contraindications

Cautions

. In patients with a family history of aortic aneurysm, or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis) (see See section “Special Indications”).

Side effects

The adverse reactions 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 (no data available to determine incidence).

Infectious and parasitic diseases: infrequent – fungal infections, growth of resistant pathogens.

Data obtained in clinical studies and post-registration use of the drug

Cardiac disorders

Rarely: Sinus tachycardia, palpitations. Frequency unknown (post-registration data): QT interval prolongation, ventricular arrhythmias, ventricular tachycardia, pirouette-type ventricular tachycardia, which may lead to cardiac arrest (see sections “Overdose”, “Special Instructions”).

Disorders of the blood and lymphatic system

Infrequent: leukopenia (decreased number of leukocytes in peripheral blood), eosinophilia (increased number of eosinophils in peripheral blood). Seldom: neutropenia (decrease in the number of neutrophils in peripheral blood), thrombocytopenia (decrease in the number of platelets in peripheral blood). Frequency unknown (post-registration data): pancytopenia (decrease in the number of all formular elements in peripheral blood), agranulocytosis (absence or dramatic decrease in the number of granulocytes in peripheral blood), hemolytic anemia.

Nervous system disorders

Frequently:headache, dizziness. Infrequent:drowsiness, tremor, dysgeusia (perversion of taste). Rarely: paresthesia, seizures (see section “Special Precautions”).

Frequency unknown (post-registration data):peripheral sensory neuropathy, peripheral sensory-motor neuropathy (see section “Special Indications. Special Indications, dyskinesia, extrapyramidal disorders, aguesia (loss of sense of taste), parosmia (disorder of sense of smell, especially subjective sense of smell objectively absent), including loss of smell; syncope, increased intracranial pressure (benign intracranial hypertension, pseudotumor brain).

Visual disturbances

Rarely:visual disturbances such as blurred visible images. Frequency unknown (post-registration data): transient visual loss, uveitis.

Hearing and labyrinth disorders

Infrequent: Vertigo (feeling of deviation or spinning, either of one’s own body or of surrounding objects). Rarely: ringing in the ears. Frequency unknown (post-registration data): hearing loss, hearing loss.

Disorders of the respiratory system, thoracic and mediastinal organs

Infrequent: dyspnea. Frequency unknown (post-registration data): bronchospasm, allergic pneumonitis.

Gastrointestinal tract disorders

Frequently: diarrhea, vomiting, nausea. Infrequent: abdominal pain, dyspepsia, flatulence, constipation. Frequency unknown (post-registration data): hemorrhagic diarrhea, which in very rare cases may be a sign of enterocolitis, including pseudomembranous colitis (see section “Special Instructions”), pancreatitis.

Renal and urinary tract disorders

Infrequent: increased serum creatinine concentration. Rarely: acute renal failure (e.g., due to the development of interstitial nephritis).

Skin and subcutaneous tissue disorders

Infrequent: rash, itching, urticaria, hyperhidrosis. Frequency unknown (post-registration data): toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme exudative, photosensitization reactions (hypersensitivity to sunlight and ultraviolet radiation) (see section “Special Indications”), leukocytoclastic vasculitis, stomatitis.

Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Musculoskeletal and connective tissue disorders

Infrequent: arthralgia, myalgia. Rarely: tendonitis, including tendonitis (e.g., Achilles tendon), muscle weakness, which may be particularly dangerous in patients with pseudoparalytic myasthenia gravis (myasthenia gravis) (see section “Special Indications”). Frequency is unknown (post-registration data): Rhabdomyolysis, tendon rupture (e.g., Achilles tendon). This adverse reaction may occur within 48 hours after the start of treatment and may be bilateral (see also section “Special Indications”), ligament tears, muscle tears, arthritis.

Metabolic and nutritional disorders

Infrequent: anorexia. Rarely: hypoglycemia, especially in patients with diabetes mellitus (possible signs of hypoglycemia: “wolfish” appetite, nervousness, sweating, trembling). Frequency unknown: hyperglycemia, severe hypoglycemia, up to the development of hypoglycemic coma, especially in elderly patients, patients with diabetes taking oral hypoglycemic drugs or insulin.

Infectious and parasitic diseases

Infrequent: fungal infections, development of resistance of pathogens.

vascular disorders

Rarely: reduction of blood pressure.

General disorders

Infrequent: asthenia. Rarely: pyrexia (increased body temperature). Frequency unknown: pain (including pain in the back, chest, and extremities).

Immune system disorders

Rarely: angioneurotic edema. Frequency unknown (post-registration data): anaphylactic shock, anaphylactoid shock.

Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Liver and biliary tract disorders

Frequently: Elevated activity of “hepatic” enzymes in the blood (e.g., alanine aminotransferase (ALT), aspartate aminotransferase (AST)), increased activity of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT). Infrequent: increase of bilirubin concentration in blood. Frequency unknown (post-registration data): severe hepatic failure, including cases of acute hepatic failure, sometimes with fatal outcome, especially in patients with severe underlying disease (e.g., patients with sepsis) (see section “Special Indications”); hepatitis, jaundice.

Mental disorders

Often: insomnia. Infrequent: sensation of restlessness, anxiety, confusion. Rarely: psychiatric disorders (e.g., hallucinations, paranoia), depression, agitation (agitation), sleep disturbances, nightmares. Frequency unknown (post-registration data): Mental disturbances with self-harm behavioral disorders, including suicidal ideation and suicide attempts, attention disorders, disorientation, nervousness, memory impairment, delirium.

Other possible adverse effects relevant to all fluoroquinolones

Very rare: Perchance of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

Symptoms

Based on the data obtained in toxicological studies conducted in animals, the most important expected symptoms of acute overdose of the drug Levofloxacin-Teva are symptoms of the central nervous system (disorders of consciousness, including confusion, dizziness and seizures).

In post-registration use of the drug, central nervous system effects including confusion, seizures, hallucinations and tremors were observed in case of overdose.

Nausea and gastrointestinal mucosal erosions may occur.

In clinical and pharmacological studies conducted with doses of levofloxacin greater than therapeutic, prolongation of the QT interval was observed.

Treatment

In case of overdose, close patient monitoring is required, including electrocardiogram monitoring. Treatment is symptomatic. In case of acute overdose of Levofloxacin-Teva tablets gastric lavage and administration of antacids for protection of gastric mucosa are indicated. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Pregnancy use

Similarities