Avelox tablets 400 mg No. 7 - Instructions

Pharmacological properties of the drug Avelox

Moxifloxacin (1-cyclopropyl-7{(S,S)-2,8-diaza-bicyclo[4.3.0]non-8-ue}-6-fluoro-8-methoxy-1,4-dihydro-4-oxo -3-quinolinecarboxylic acid hydrochloride) is a broad-spectrum fluoroquinolone antibacterial drug. The bactericidal effect of the drug is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of DNA biosynthesis of the microbial cell and its death. The activity of moxifloxacin depends on its concentration in the blood plasma: the minimum bactericidal concentrations correspond to the minimum bacteriostatic concentrations. The mechanisms of resistance of microorganisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial effectiveness of moxifloxacin. Cross-resistance between the drug Avelox and the listed antibiotics has not been observed. There were also no cases of plasmid resistance. The overall incidence of resistance is very low (10-7–10-10). Resistance to moxifloxacin develops slowly through numerous mutations. Repeated action of moxifloxacin on microorganisms at concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in the MIC. Cross-resistance is usually observed between antibacterial agents of the quinolone group. However, some gram-positive and anaerobic microorganisms that are resistant to other quinolones are sensitive to moxifloxacin. Moxifloxacin in vitro against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical forms such as Micoplasma, Chlamydia, Legionella . Moxifloxacin is effective against bacteria resistant to β-lactam and macrolide antibiotics. The following are sensitive to the drug: gram-positive microorganisms - Staphylococcus aureus (including strains sensitive to methicillin), Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A); gram-negative microorganisms - Haemophillus influenzae (including strains producing β-lactamases), Haemophillus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including strains producing β-lactamases), Escherichia coli, Enterobacter cloacae ; atypical forms - Chlamydia pneumoniae, Mycoplasma pneumoniae , Legionella pneumoniae . The following gram-positive microorganisms are relatively sensitive to moxifloxacin: Streptococcus milleri, Str. mitior, Str. agalactiae, Str. dysgalactiae, Staphylococcus cohnii, S. epidermidis (including methicillin-resistant strains), S. haemolyticus, S. hominis, S. saprophyticus, S. simulans, Corynebacterium diphtheriae ; gram-negative microorganisms - Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii ; anaerobes - Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella sp p., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum ; atypical forms - Legionella pneumophila, Caxiella burnettii. Sensitivity to moxifloxacin was confirmed by clinical data. Moxifloxacin is less active against Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia. When taken orally, moxifloxacin is absorbed quickly and almost completely. Absolute bioavailability reaches almost 91%. In the dose range from 50 to 1200 mg for a single dose and at a dose of 600 mg/day for 10 days, the pharmacokinetics are linear. Stable blood concentrations are achieved after 3 days of use. After a single dose of 400 mg of the drug, the maximum concentration in the blood plasma is reached within 0.5–4 hours and is 3.1 mg/l. When taking moxifloxacin simultaneously with food, there is a slight increase in the time to reach maximum concentration (by 2 hours) and a slight decrease in maximum concentration (by approximately 16%), while the duration of absorption does not change. However, these data are not clinically significant and the drug can be taken regardless of meals. Moxifloxacin is rapidly distributed in tissues and organs and binds to plasma proteins (mainly albumin) by approximately 45%. The volume of distribution is approximately 2 l/kg. High concentrations of the drug, exceeding the concentration in the blood plasma, are achieved in the lung tissue (alveolar macrophages), bronchial mucosa, paranasal sinuses and especially in areas of inflammation. In interstitial fluid and saliva, moxifloxacin is determined in a free state, not bound to proteins, in a higher concentration than in blood plasma. Moxifloxacin does not undergo biotransformation by the microsomal cytochrome P450 system in the liver and is excreted from the body by the kidneys both unchanged and in the form of inactive sulfo compounds and glucuronides. 45% of the unchanged drug is excreted in urine and feces. The half-life of the drug is approximately 12 hours. The average total clearance after administration of a dose of 400 mg is 179–246 ml/min. About 19% of a single dose is excreted unchanged in the urine and 25% in feces. Age (not studied in children) and sex differences in the pharmacokinetics of moxifloxacin have not been established. There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (creatinine clearance 30 ml/min•1.73 m2) and in those on continuous hemodialysis and long-term ambulatory peritoneal dialysis. In patients with minor and moderate liver dysfunction (stages A and B according to the Child-Pugh classification), the pharmacokinetics of the drug does not change. There are no data on use in cases of severe liver dysfunction (Child-Pugh stage C).

Avelox tablets 400 mg No. 7 - Instructions

Release form, packaging and composition of Avelox

Pink, film-coated tablets, matte, oblong, biconvex, beveled, engraved “BAYER” on one side and “M400” on the other.
1 tablet contains moxifloxacin hydrochloride 436.8 mg, which corresponds to the content of moxifloxacin 400 mg.

Excipients: microcrystalline cellulose - 136 mg, croscarmellose sodium - 32 mg, lactose monohydrate - 68 mg, magnesium stearate - 6 mg.

Composition of the film shell: hypromellose - 9-12.6 mg, red iron oxide dye - 300-420 mcg, macrogol 4000 - 3-4.2 mg, titanium dioxide - 2.7-3.78 mg.

Clinical and pharmacological group

Antibacterial drug of the fluoroquinolone group.

Pharmacotherapeutic group

Antimicrobial agent, fluoroquinolone.

pharmachologic effect

Broad-spectrum antibacterial bactericidal drug, 8-methoxyfluoroquinolone. The bactericidal effect of moxifloxacin is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of the processes of replication, repair and transcription of microbial cell DNA biosynthesis and, as a consequence, to the death of microbial cells.

The minimum bactericidal concentrations of the drug are generally comparable to its MIC.

Mechanisms of resistance

The mechanisms leading to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial activity of moxifloxacin. There is no cross-resistance between these groups of antibacterial drugs and moxifloxacin. So far, no cases of plasmid resistance have been observed either. The overall incidence of resistance is very low (10-7-10-10). Resistance to moxifloxacin develops slowly through multiple mutations. Repeated exposure of microorganisms to moxifloxacin at concentrations below the MIC is accompanied by only a slight increase. Cases of cross-resistance to quinolones have been reported. However, some gram-positive and anaerobic microorganisms resistant to other quinolones remain sensitive to moxifloxacin.

It has been established that the addition of a methoxy group at position C8 to the structure of the moxifloxacin molecule increases the activity of moxifloxacin and reduces the formation of resistant mutant strains of gram-positive bacteria. The addition of a bicycloamine group at position C7 prevents the development of active efflux, a mechanism of resistance to fluoroquinolones.

Moxifloxacin is active in vitro against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria, such as Mycoplasma spp., Chlamydia spp., Legionella spp., as well as bacteria resistant to beta-lactam and macrolide antibiotics.

Effect on human intestinal microflora

In two studies conducted on volunteers, the following changes in the intestinal microflora were noted after oral administration of moxifloxacin: a decrease in the concentrations of Escherichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp., Klebsiella spp., as well as the anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. No Clostridium difficile toxins were detected.

In vitro susceptibility testing

The spectrum of antibacterial activity of moxifloxacin includes the following microorganisms:

*sensitivity to moxifloxacin is confirmed by clinical data.

** the use of Avelox® is not recommended for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Suspected or confirmed MRSA infections should be treated with appropriate antibacterial drugs.

For certain strains, the distribution of acquired resistance may vary across geographic regions and over time. Therefore, it is desirable to have local information on resistance when testing strain susceptibility, especially when treating severe infections.

If in patients undergoing treatment in a hospital, the AUC/MIC90 value exceeds 125, and the Cmax/MIC90 is in the range of 8-10, then this suggests clinical improvement. In outpatients, the values ​​of these surrogate parameters are usually lower: AUC/MIC90 >30-40.

* AUIC—area under the inhibition curve (AUC/MIC90 ratio).

Pharmacokinetics

Suction

After oral administration, moxifloxacin is absorbed quickly and almost completely. Absolute bioavailability is about 91%.

The pharmacokinetics of moxifloxacin when taken at a dose of 50 to 1200 mg once, as well as 600 mg/day for 10 days, is linear.

After a single dose of moxifloxacin at a dose of 400 mg, Cmax in the blood is reached within 0.5-4 hours and is 3.1 mg/l. After oral administration of moxifloxacin at a dose of 400 mg 1 time/day, Cssmax and Cssmin are 3.2 mg/l and 0.6 mg/l, respectively.

When taking moxifloxacin with food, there is a slight increase in the time to reach Cmax (by 2 hours) and a slight decrease in Cmax (by approximately 16%), while the duration of absorption does not change. However, these data do not have clinical significance, and the drug can be used regardless of food intake.

Distribution

The equilibrium state is achieved within 3 days. Binding to blood proteins (mainly albumin) is about 45%. Moxifloxacin is rapidly distributed in organs and tissues. Vd is approximately 2 l/kg.

High concentrations of moxifloxacin, exceeding those in plasma, are created in the lung tissue (including in epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoid sinuses), in nasal polyps, foci of inflammation (in the contents of blisters in skin lesions ). In interstitial fluid and saliva, moxifloxacin is determined in a free form, not bound to proteins, in a concentration higher than in plasma. In addition, high concentrations of moxifloxacin are determined in the tissues of the abdominal organs, peritoneal fluid, as well as in the tissues of the female genital organs.

Metabolism

Moxifloxacin undergoes phase 2 biotransformation and is excreted from the body by the kidneys and also through the intestines, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the microsomal cytochrome P450 system. Metabolites M1 and M2 are present in plasma in concentrations lower than the parent compound. Based on the results of preclinical studies, it was proven that these metabolites do not have a negative effect on the body in terms of safety and tolerability.

Removal

T1/2 is approximately 12 hours. The average total clearance after taking the drug orally at a dose of 400 mg is 179-246 ml/min. Renal clearance is 24-53 ml/min. This indicates partial tubular reabsorption of the drug.

The mass balance of parent compound and phase 2 metabolites is approximately 96-98%, indicating the absence of oxidative metabolism. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% through the intestines.

Pharmacokinetics in special groups of patients

A study of the pharmacokinetics of moxifloxacin in men and women revealed differences of 33% in AUC and Cmax. The absorption of moxifloxacin did not depend on gender. Differences in AUC and Cmax were due to differences in body weight rather than gender and are not considered clinically significant.

There were no clinically significant differences in the pharmacokinetics of moxifloxacin in patients of different ethnic groups and different ages.

Pharmacokinetic studies of moxifloxacin have not been conducted in children.

There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including those with creatinine clearance <30 ml/min/1.73 m2) and in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis.

There were no significant differences in moxifloxacin concentrations in patients with hepatic impairment (Child-Pugh classes A and B) compared with healthy volunteers and patients with normal hepatic function.

Indications for the drug Avelox

Infectious and inflammatory diseases in adults caused by microorganisms sensitive to the drug:

• acute sinusitis;
• exacerbation of chronic bronchitis;
• community-acquired pneumonia (including those caused by strains of microorganisms with multiple antibiotic resistance*);
• uncomplicated skin and soft tissue infections;
• complicated infections of the skin and subcutaneous structures (including infected diabetic foot);
• complicated intra-abdominal infections, including polymicrobial infections, incl. intraperitoneal abscesses;
• uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).

* Streptococcus pneumoniae with multiple antibiotic resistance includes strains resistant to penicillin and strains resistant to two or more antibiotics from such groups as penicillins (with MIC ≥2 mg/ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Current official guidelines on the use of antibacterial agents must be taken into account.

Dosage regimen

The drug is prescribed orally at 400 mg 1 time/day. The tablets should be taken without chewing, with plenty of water, regardless of meals. Do not exceed the recommended dose.

The duration of treatment with Avelox when taken orally is determined by the severity of the infection and the clinical effect and is: for exacerbation of chronic bronchitis - 5-10 days; for community-acquired pneumonia, the total duration of stepwise therapy (IV administration followed by oral administration) is 7-14 days, first IV, then orally, or 10 days orally; for acute sinusitis and uncomplicated infections of the skin and soft tissues - 7 days; for complicated infections of the skin and subcutaneous tissues, the total duration of stepwise therapy (iv administration followed by oral administration) is 7-21 days; for complicated intra-abdominal infections, the total duration of step-down therapy (iv administration of the drug followed by oral administration) is 5-14 days; for uncomplicated inflammatory diseases of the pelvic organs - 14 days.

The duration of treatment with Avelox can be up to 21 days.

No change in dosage regimen is required in elderly patients.

The effectiveness and safety of moxifloxacin in children and adolescents has not been established.

Patients with impaired liver function do not require a change in dosage regimen.

In patients with impaired renal function (including severe renal failure with CC ≤30 ml/min/1.73 m2), as well as in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis, no change in dosage regimen is required.

In patients of different ethnic groups, no change in dosage regimen is required.

Side effect

Adverse reactions reported with moxifloxacin 400 mg (oral, step-down [IV followed by oral] and IV alone) are derived from clinical studies and post-marketing reports (shown in italics). Adverse reactions listed in the “common” group occurred with an incidence of less than 3%, with the exception of nausea and diarrhea.

In each frequency group, adverse drug reactions are listed in descending order of importance. Determination of the frequency of adverse reactions: often (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), rarely (from ≥1/10,000 to <1/1000), very rarely (<1/10,000).

Infections: often - fungal superinfections.

From the hematopoietic system: uncommon - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolongation of prothrombin time/increased INR; rarely - changes in thromboplastin concentration; very rarely - increased prothrombin concentration/decreased INR.

From the immune system: infrequently - allergic reactions, urticaria, itching, rash, eosinophilia; rarely - anaphylactic/anaphylactoid reactions, angioedema, including laryngeal edema (potentially life-threatening); very rarely - anaphylactic/anaphylactoid shock (including potentially life-threatening).

From the side of metabolism: infrequently - hyperlipidemia; rarely - hyperglycemia, hyperuricemia; very rarely - hypoglycemia.

Mental disorders: infrequently - anxiety, psychomotor hyperreactivity, agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicide attempts), hallucinations is possible; very rarely - depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts or suicide attempts).

From the nervous system: often - dizziness, headache; uncommon - paresthesia, dysesthesia, taste disturbances (including in very rare cases ageusia), confusion, disorientation, sleep disturbances, tremor, vertigo, drowsiness; rarely - hypoesthesia, olfactory disturbances (including anosmia), atypical dreams, loss of coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to injury due to a fall, especially in elderly patients), seizures with various clinical manifestations (including including “grand mal” seizures), attention disorders, speech disorders, amnesia, peripheral neuropathy, polyneuropathy; very rarely - hyperesthesia.

On the part of the organ of vision: infrequently - visual impairment (especially with reactions from the central nervous system); very rarely - transient loss of vision (especially with reactions from the central nervous system).

On the part of the hearing organ: rarely - tinnitus, hearing impairment, including deafness (usually reversible).

From the cardiovascular system: often - prolongation of the QT interval in patients with concomitant hypokalemia; uncommon - prolongation of the QT interval, palpitations, tachycardia, vasodilation; rarely - increased blood pressure, decreased blood pressure, fainting, ventricular tachyarrhythmias; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (pirouette type), cardiac arrest (mainly in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

From the respiratory system: infrequently - shortness of breath, including asthmatic conditions.

From the digestive system: often - nausea, vomiting, abdominal pain, diarrhea; uncommon - decreased appetite and reduced food consumption, constipation, dyspepsia, flatulence, gastroenteritis (except erosive gastroenteritis), increased amylase activity; rarely - dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).

From the liver and biliary tract: often - increased activity of liver transaminases; uncommon - liver dysfunction (including increased LDH activity), increased bilirubin concentration, increased GGT and alkaline phosphatase activity; rarely - jaundice, hepatitis (mainly cholestatic); very rarely - fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).

From the skin: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

From the musculoskeletal system: infrequently - arthralgia, myalgia; rarely - tendinitis, increased muscle tone and cramps, muscle weakness; very rarely - arthritis, tendon ruptures, gait disturbance due to damage to the musculoskeletal system, increased symptoms of myasthenia gravis.

From the urinary system: infrequently - dehydration (caused by diarrhea or decreased fluid intake); rarely - impaired renal function, renal failure as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impaired renal function).

From the body as a whole: often - reactions at the injection/infusion site; infrequently - general malaise, nonspecific pain, sweating.

The incidence of the following adverse reactions was higher in the group receiving stepwise therapy: often - increased GGT activity; uncommon - ventricular tachyarrhythmias, arterial hypotension, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), convulsions with various clinical manifestations (including “grand mal” seizures), hallucinations, impaired renal function, renal failure (due to dehydration, which can lead to kidney damage, especially in older patients with pre-existing renal impairment).

Contraindications for use

• a history of tendon pathology that developed as a result of treatment with quinolone antibiotics;
• in preclinical and clinical studies, after the administration of moxifloxacin, changes in electrophysiological parameters of the heart were observed, expressed in prolongation of the QT interval. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories: congenital or acquired documented prolongation of the QT interval, electrolyte disturbances, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; a history of rhythm disturbances accompanied by clinical symptoms;
• moxifloxacin should not be used with other drugs that prolong the QT interval;
• due to the presence of lactose in the drug, its use is contraindicated in cases of congenital lactose intolerance, lactase deficiency, glucose-galactose malabsorption (for tablets);
• due to the limited amount of clinical data, the use of moxifloxacin is contraindicated in patients with impaired liver function (Class C according to the Child-Pugh classification) and in patients with elevated transaminases more than 5 times the ULN;
• pregnancy;
• lactation (breastfeeding);
• age under 18 years;
• hypersensitivity to moxifloxacin, other quinolones or any other component of the drug.

The drug should be prescribed with caution for diseases of the central nervous system (including diseases suspected of involving the central nervous system), predisposing to the occurrence of convulsive seizures and reducing the threshold of convulsive readiness; in patients with a history of psychosis and/or psychiatric illness; in patients with potentially proarrhythmic conditions such as acute myocardial ischemia and cardiac arrest, especially women and elderly patients; for myasthenia gravis; with cirrhosis of the liver; when taken simultaneously with drugs that reduce potassium levels; in patients with a genetic predisposition or actual deficiency of glucose-6-phosphate dehydrogenase.

Use during pregnancy and breastfeeding

The safety of moxifloxacin during pregnancy has not been established and its use is contraindicated. Cases of reversible joint damage have been described in children receiving some quinolones, but this effect has not been reported in the fetus (when used by the mother during pregnancy).

Reproductive toxicity has been shown in animal studies. The potential risk to humans is unknown.

Like other quinolones, moxifloxacin causes cartilage damage in large joints in premature animals. Preclinical studies have shown that small amounts of moxifloxacin are excreted in breast milk. There are no data on its use in women during lactation. Therefore, the use of moxifloxacin during breastfeeding is contraindicated.

Use for liver dysfunction

Patients with impaired liver function do not require a change in dosage regimen.

The drug should be used with caution in patients with liver cirrhosis.

Use for renal impairment

Patients with impaired renal function (including those with CC <30 ml/min/1.73 m2), as well as patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis, do not require changes in the dosage regimen.

Use in children

Contraindicated: children and adolescents under 18 years of age.

Use in elderly patients

Elderly patients do not require changes in the dosage regimen.

special instructions

In some cases, after the first use of the drug, hypersensitivity and allergic reactions may develop, which should be reported to your doctor immediately. Very rarely, even after the first use of the drug, anaphylactic reactions can progress to life-threatening anaphylactic shock. In these cases, treatment with Avelox should be stopped and the necessary therapeutic measures (including anti-shock) should be started immediately.

When using the drug Avelox, some patients may experience prolongation of the QT interval.

Avelox should be used with caution in women and elderly patients. Because women have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to drugs that affect the QT interval.

The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. However, in patients with pneumonia, a correlation between moxifloxacin plasma concentrations and QT interval prolongation was noted. None of the 9,000 patients receiving Avelox experienced cardiovascular complications or deaths associated with QT prolongation.

When using Avelox, the risk of developing ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias. In this regard, Avelox is contraindicated in:

• changes in electrophysiological parameters of the heart, expressed in prolongation of the QT interval (congenital or acquired documented prolongation of the QT interval, electrolyte disturbances, especially uncorrected hypokalemia, clinically significant bradycardia, clinically significant heart failure with reduced left ventricular ejection fraction, a history of indications of rhythm disturbances accompanied by clinical symptoms);
• use with other drugs that prolong the QT interval.

Avelox should be used with caution:

• in patients with potentially proarrhythmic conditions such as acute myocardial ischemia;
• in patients with liver cirrhosis (since in this category of patients the risk of developing QT prolongation cannot be excluded).

Cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases), have been reported while taking Avelox. The patient should be informed that if symptoms of liver failure occur, it is necessary to consult a doctor before continuing treatment with Avelox.

Cases of bullous skin lesions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) have been reported while taking Avelox. The patient should be informed that if symptoms of skin or mucous membrane lesions occur, it is necessary to consult a doctor before continuing treatment with Avelox.

The use of quinolone drugs is associated with a possible risk of developing seizures. Avelox should be used with caution in patients with diseases of the central nervous system and disorders of the central nervous system that predispose to seizures or lower the threshold for seizure activity.

The use of broad-spectrum antibacterial drugs, including Avelox, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be considered in patients who develop severe diarrhea during treatment with Avelox. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in the development of severe diarrhea.

Avelox should be used with caution in patients with myasthenia gravis due to a possible exacerbation of the disease.

During therapy with quinolones, incl. moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving corticosteroids. Cases have been described that occurred within several months after completion of treatment. At the first symptoms of pain or inflammation at the site of injury, the drug should be stopped and the affected limb should be unloaded.

When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as when using the drug Avelox in practice, no photosensitivity reactions were observed. However, patients receiving Avelox should avoid exposure to direct sunlight and ultraviolet radiation.

The use of the drug in the form of tablets for oral administration is not recommended in patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses).

Moxifloxacin is not recommended for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Suspected or confirmed MRSA infections should be treated with appropriate antibacterial drugs.

The ability of Avelox to inhibit the growth of mycobacteria may cause in vitro interaction of moxifloxacin with the test for Mycobacterium spp., leading to false negative results when analyzing samples from patients who are being treated with Avelox during this period.

In patients treated with quinolones, including Avelox, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients being treated with Avelox should be advised to seek immediate medical attention before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness or weakness, occur.

Psychiatric reactions can occur even after the first prescription of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts. If patients develop such reactions, the drug Avelox should be discontinued and the necessary measures taken. Caution should be exercised when prescribing Avelox to patients with a history of psychosis and/or psychiatric illness.

Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, moxifloxacin monotherapy should not be used in the treatment of patients with pelvic inflammatory disease, unless the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If the presence of fluoroquinolone-resistant N. gonorrhoeae cannot be excluded, consideration should be given to supplementing empiric moxifloxacin therapy with an appropriate antibiotic that is active against N. gonorrhoeae (eg, a cephalosporin).

As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, were observed when using Avelox. During therapy with Avelox, dysglycemia occurred predominantly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When treating patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended.

Impact on the ability to drive vehicles and operate machinery

Fluoroquinolones, including moxifloxacin, may impair the ability of patients to drive a car and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to their effects on the central nervous system and visual impairment.

Overdose

There are limited data on overdose with moxifloxacin. There were no side effects observed when using Avelox at a dose of up to 1200 mg once and 600 mg for 10 days or more.

Treatment: in case of overdose, symptomatic and supportive therapy with ECG monitoring is carried out in accordance with the clinical situation.

The use of activated charcoal immediately after oral administration of the drug may help prevent excessive systemic exposure to moxifloxacin in cases of overdose.

Drug interactions

No dose adjustment is required when using Avelox® with atenolol, ranitidine, calcium supplements, theophylline, cyclosporine, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid (the absence of clinically significant interaction with moxifloxacin has been confirmed).

The possible additive QT interval prolonging effect of moxifloxacin and other drugs that affect QT prolongation should be considered. Due to the combined use of moxifloxacin and drugs that affect the prolongation of the QT interval, the risk of developing ventricular arrhythmia, including polymorphic ventricular tachycardia of the “pirouette” type, increases. The combined use of moxifloxacin with the following drugs that affect the prolongation of the QT interval is contraindicated: class IA antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide); neuroleptics (including phenothiazine, pimozide, sertindole, haloperidol, sultopride); tricyclic antidepressants; antimicrobials (sparfloxacin, IV erythromycin, pentamidine, antimalarials, especially halofantrine); antihistamines (terfenadine, astemizole, mizolastine); others (cisapride, IV vincamine, bepridil, difemanil).

Storage conditions for Avelox

The drug should be stored out of reach of children, in a dry place at a temperature not exceeding 25°C.

Shelf life of Avelox

Shelf life: 5 years.

Terms of sale

The drug is available with a prescription.

Indications for use of the drug Avelox

Treatment of bacterial infections caused by microorganisms sensitive to the drug. Infectious diseases of the respiratory tract:

• chronic bronchitis during exacerbation;
• community-acquired pneumonia, the causative agents of which are strains of microorganisms with multiple resistance to antibiotics;
• acute sinusitis;

Uncomplicated skin and soft tissue infections. Uncomplicated inflammatory diseases of the pelvic organs (including infectious diseases of the upper genital area in women, including salpingitis and endometritis). Complicated infectious diseases of the skin and subcutaneous structures (including infected diabetic foot). Complicated intra-abdominal infections, including polymicrobial infections (such as abscess formation). Streptococcus pneumonie with multiple resistance to antibiotics, including strains resistant to penicillin and strains resistant to two or more antibiotics of such groups as penicillins (with minimal inhibitory activity ≥2 μg/ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Use of the drug Avelox

Adults: 400 mg 1 time per day for any infections. Duration of therapy The duration of therapy is determined by the severity of the infection and the clinical effect. At the initial stages of treatment, Avelox solution can be used for infusion, and then to continue therapy, if indicated, the drug can be prescribed orally in tablets. Exacerbation of chronic bronchitis - 5 days. Community-acquired pneumonia - 10 days. Acute sinusitis - 7 days. Uncomplicated skin and soft tissue infections - 7 days. Uncomplicated inflammatory diseases of the pelvic organs - 14 days. Complicated infections of the skin and subcutaneous structures - the total duration of stepwise therapy with moxifloxacin (IV administration of the drug followed by oral administration) is 7–21 days. Complicated intra-abdominal infections - the total duration of step-down therapy (iv administration of the drug followed by oral administration) is 5-14 days. According to clinical studies, the duration of therapy with Avelox tablets and infusion solution was up to 21 days (for the treatment of complicated infections of the skin and subcutaneous structures). In elderly patients and in patients with impaired liver function, the dosage regimen does not change. In patients with impaired renal function (including those with creatinine clearance ≤30 ml/min•1.73 m2) and in those on continuous hemodialysis and long-term ambulatory peritoneal dialysis, there is no need for dose adjustment. Use for the treatment of patients of different ethnic groups - there is no need to change the dosage regimen. The tablets should be taken without chewing, with plenty of water, regardless of meals. Moxifloxacin infusion solution is used both for antibacterial monotherapy and in combination with other compatible drugs. Moxifloxacin solution remains stable for 24 hours at room temperature and when using the following solvents: water for injection, sodium chloride solutions 0.9%, sodium chloride 1M, glucose 5%, 10% and 40%, solution xylitol 20%, Ringer's solution and Ringer's lactate, drugs Aminofusin 10% and Ionosteril D5. The infusion solution should be administered intravenously slowly over 60 minutes. The maximum dose is 600 mg once or 400 mg once a day for 7–21 days. Avelox is prescribed intravenously at a dose of 400 mg once a day. The drug can be used intravenously throughout the course of treatment or at the initial stages of treatment, followed by a transition to taking moxifloxacin in tablet form.

Instructions for use AVELOX® (AVALOX)

In some cases, hypersensitivity and allergic reactions may develop after the first use of the drug. Very rarely, anaphylactic reactions can progress to life-threatening anaphylactic shock even after the first use of the drug. In these cases, moxifloxacin should be discontinued and the necessary therapeutic measures (including anti-shock) should be taken.

QT interval prolongation may occur in some patients when using moxifloxacin.

Given that women tend to prolong the QT interval compared to men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more sensitive to drugs that affect the QT interval. The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. However, in patients with pneumonia, there was no correlation between moxifloxacin plasma concentrations and QT interval prolongation. None of the 9000 patients treated with moxifloxacin experienced cardiovascular complications or deaths associated with QT prolongation. However, in patients with conditions predisposing to arrhythmias, the risk of developing ventricular arrhythmias may increase when using moxifloxacin.

In this regard, the use of moxifloxacin should be avoided in patients with QT prolongation, uncorrected hypokalemia, as well as in those receiving class IA (quinidine, procainamide) or class III antiarrhythmic drugs (amiodarone, sotalol), since experience with the use of moxifloxacin in these patients organic Moxifloxacin should be used with caution as an additive effect of moxifloxacin cannot be excluded in the following conditions:

• in patients receiving concomitant treatment with drugs that prolong the QT interval (cisapride, erythromycin, antipsychotic drugs, tricyclic antidepressants);
• in patients with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia;
• in patients with liver cirrhosis, since the presence of QT interval prolongation in them cannot be excluded;
• in women or elderly patients who may be more sensitive to drugs that prolong the QT interval.

Cases of fulminant hepatitis, potentially leading to life-threatening liver failure, including death, have been reported. If signs of liver failure appear, patients should immediately consult a doctor before continuing treatment.

Bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening) have been reported. If reactions occur on the skin and/or mucous membranes, you should also immediately consult your doctor before continuing treatment. The use of quinolone drugs is associated with a possible risk of developing a seizure. Moxifloxacin should be used with caution in patients with diseases of the central nervous system and with conditions suspected of involving the central nervous system, predisposing to the occurrence of seizures or lowering the seizure threshold.

The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with the risk of developing antibiotic-associated pseudomembranous colitis. This diagnosis should be considered in patients who experience severe diarrhea during treatment with moxifloxacin. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in patients who have severe diarrhea.

Avelox should be used with caution in patients with myasthenia gravis, as the drug may exacerbate the symptoms of this disease.

During therapy with fluoroquinolones, including moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving glucocorticosteroids. At the first symptoms of pain or inflammation at the site of injury, the drug should be stopped and the affected limb should be unloaded.

For patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses), for whom IV treatment is indicated, taking Avelox 400 mg tablets is not recommended.

When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as when using moxifloxacin in practice, no photosensitivity reactions were observed. However, patients receiving moxifloxacin should avoid direct sunlight and ultraviolet radiation.

Prolongation of the QTc interval and potentially associated clinical conditions

Moxifloxacin has been found to prolong the QTc interval in electrocardiograms of some patients. In an analysis of ECGs obtained as part of a clinical trial program, the prolongation of the QTc interval when taking moxifloxacin was 6 milliseconds ± 26 milliseconds, which is equal to 1.4% compared to baseline. Because the baseline QTc interval is longer in women than in men, women may be more susceptible to the effects of QTc prolonging drugs. Elderly people are also more susceptible to the drug's effects on the QT interval. Precautions should be taken when prescribing drugs that may decrease potassium levels to patients taking moxifloxacin.

Precautions should be taken when prescribing moxifloxacin to people with current proarrhythmogenic conditions (especially women and the elderly), such as acute myocardial ischemia or QT prolongation, which may increase the risk of developing ventricular arrhythmias (including torsades de pointes) and cardiac arrest. The degree of QT prolongation increases with increasing drug concentrations. Therefore, the recommended dose should not be exceeded.

If symptoms of cardiac arrhythmia occur during treatment with moxifloxacin, you should stop taking the drug and have an ECG.

Impact on the ability to drive vehicles and operate machinery

Fluoroquinolones, including moxifloxacin, may impair the ability to drive or operate machinery due to CNS reactions.

Side effects of the drug Avelox

Moxifloxacin is well tolerated in most patients. During clinical trials of moxifloxacin, the majority of adverse events (90%) were mild or moderate in severity. The rate of discontinuation of treatment using the Avelox infusion solution due to the development of side effects did not exceed 3.8%. With a development frequency of ≥1%≤10% From the cardiovascular system - prolongation of the QT in patients with concomitant hypokalemia. From the gastrointestinal tract - abdominal pain, nausea, diarrhea, vomiting, symptoms of dyspepsia, changes in liver tests. From the central nervous system, sensory organs - dizziness, headache. With a development frequency of ≥0.1%≤1% General reactions - asthenia, hyperhidrosis, general weakness, pain in the chest area. From the cardiovascular system - tachycardia, increased blood pressure, palpitations, prolongation of the QT interval. From the gastrointestinal tract - dry mouth, nausea, vomiting, flatulence, constipation, stomatitis, lack of appetite, oral candidiasis, glossitis, increased gamma-glutamyl transpeptidase and amylase. From the blood and lymphatic system - leukopenia, decreased prothrombin levels, eosinophilia, thrombocytopenia. From the musculoskeletal system - arthralgia, myalgia. From the nervous system - insomnia, dizziness, nervousness, drowsiness, anxiety, tremor, paresthesia. From the respiratory system - shortness of breath. On the skin - rashes, itching, sweating. From the genitourinary system - vaginal candidiasis, vaginitis. With an incidence of ≥0.01%≤0.1% General reactions - pelvic pain, facial swelling, back pain, changes in laboratory tests, allergic reactions, leg pain. From the cardiovascular system - decreased blood pressure, loss of consciousness, peripheral edema, vasodilation (flush of blood to the face). From the gastrointestinal tract - gastritis, discoloration of the tongue, dysphagia, jaundice (predominantly cholestatic), diarrhea (caused by Clostridium difficile ). From the blood and lymphatic system - decreased thromboplastin levels, increased prothrombin levels, thrombocytopenia, anemia. From the metabolic side - hyperglycemia, hyperlipidemia, hyperuricemia, increased LDH in combination with abnormal liver tests. From the musculoskeletal system - arthritis, tendon damage. From the nervous system - hallucinations, depersonalization, increased muscle tone, loss of coordination, agitation, amnesia, aphasia, emotional lability, disturbances in sleep, speech, thinking, decreased tactile sensitivity, pathological dreams, convulsions, confusion, depression. From the respiratory system - bronchospasm. On the skin - rashes (maculopapular, pustular, purpura), urticaria. From the senses - tinnitus, blurred vision, loss of taste, parosmia (including changes in the sense of smell, decrease and loss of smell), amblyopia. From the genitourinary system - impaired renal function (increased creatinine or urea levels). With a development frequency of ≤0.01% Allergic reactions - anaphylactic reactions, anaphylactic shock (including life-threatening), angioedema (including laryngeal edema, life-threatening). From the gastrointestinal tract - pseudomembranous colitis (in isolated cases life-threatening), hepatitis (mainly cholestatic). From the musculoskeletal system - tendon rupture. On the skin side - Stevens-Johnson syndrome. From the nervous system - psychotic reactions. From the cardiovascular system - ventricular tachyarrhythmia (very rare), ventricular fibrillation and flutter and cardiac arrest, mainly in people prone to arrhythmia. From the laboratory parameters - an increase or decrease in the hematocrit value and a decrease or increase in the content of red blood cells, leukocytosis, hypoglycemia, decrease in hemoglobin, increase in the level of alkaline phosphatase, ALT, AST, bilirubin, uric acid, creatinine, urea. The relationship between changes in these laboratory parameters and the use of moxifloxacin has not been established.

AVELOX

special instructions

In some cases, after the first use of the drug, hypersensitivity and allergic reactions may develop, which should be reported to your doctor immediately.
Very rarely, even after the first use of the drug, anaphylactic reactions can progress to life-threatening anaphylactic shock. In these cases, treatment with Avelox® should be stopped and the necessary therapeutic measures (including anti-shock) should be started immediately.

When using Avelox®, some patients may experience prolongation of the QT interval. Avelox® should be used with caution in women and elderly patients. Because women have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to drugs that affect the QT interval.

Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. However, in patients with pneumonia, no correlation was observed between moxifloxacin plasma concentrations and QT interval prolongation. None of the 9,000 patients receiving Avelox® experienced cardiovascular complications or deaths associated with QT prolongation. When using Avelox®, the risk of developing ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias.

In this regard, the drug Avelox® is contraindicated in:

- changes in electrophysiological parameters of the heart, expressed in prolongation of the QT interval: congenital or acquired documented prolongation of the QT interval, electrolyte disturbances, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; a history of rhythm disturbances accompanied by clinical symptoms;

- use with other drugs that prolong the QT interval (see section “Interaction with other drugs”).

Avelox® should be used with caution:

- in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest;

- in patients with liver cirrhosis (since in this category of patients the risk of developing a prolongation of the QT interval cannot be excluded).

Cases of fulminant hepatitis, potentially leading to the development of liver failure (including fatal cases) have been reported while taking Avelox® (see section "Side effects"). The patient should be informed that if symptoms of liver failure occur, it is necessary to consult a doctor before continuing treatment with Avelox®.

Cases of developing bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported while taking Avelox® (see section "Side effects"). The patient should be informed that if symptoms of damage to the skin or mucous membranes appear, it is necessary to consult a doctor before continuing treatment with Avelox®.

The use of quinolone drugs is associated with a possible risk of developing seizures. Avelox® should be used with caution in patients with diseases of the central nervous system and with disorders of the central nervous system that predispose to seizures or reduce the threshold for seizure activity.

The use of broad-spectrum antibacterial drugs, including Avelox®, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be kept in mind in patients who develop severe diarrhea during treatment with Avelox®. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in the development of severe diarrhea.

Avelox® should be used with caution in patients with myasthenia gravis

due to possible exacerbation of the disease.

During therapy with quinolones, including moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving glucocorticosteroids. Cases have been described that occurred within several months after completion of treatment. At the first symptoms of pain or inflammation at the site of injury, the drug should be stopped and the affected limb should be unloaded.

When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as when using the drug Avelox® in practice, no photosensitivity reactions were observed. However, patients receiving Avelox® should avoid exposure to direct sunlight and ultraviolet light. The use of the drug in the form of tablets for oral administration is not recommended in patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses).

The use of moxifloxacin is not recommended for the treatment of infections caused by Staphylococcus
aureus
(MRSA).
In cases of suspected or confirmed infections caused by MRSA, treatment with appropriate antibacterial drugs should be prescribed (see section "Pharmacodynamics"). The ability of Avelox® to inhibit the growth of mycobacteria may cause in vitro
of moxifloxacin with the test for
Mycobacterium spp .,
leading to false negative results when analyzing samples from patients who are being treated with Avelox® during this period.

In patients treated with quinolones, including Avelox®, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients being treated with Avelox® should be warned to seek immediate medical attention before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness or weakness, occur (see section "Side Effects").

Psychiatric reactions may occur even after the first use of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts (see section "Side effects"). If patients develop such reactions, the drug Avelox® should be discontinued and the necessary measures taken. Caution must be exercised when using Avelox® in patients with psychosis and/or a history of psychiatric illness.

Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria
gonorrhoeae
, patients with pelvic inflammatory disease should not be treated with moxifloxacin monotherapy unless the presence of fluoroquinolone-
resistant N. gonorrhoeae
excluded.
to exclude the presence of fluoroquinolone-resistant N. gonorrhoeae ,
it is necessary to decide whether to supplement empirical therapy with moxifloxacin with an appropriate antibiotic that is active against
N. Gonorrhoeae
(eg, cephalosporin).

Dysglycemia

As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, were observed when using Avelox®. During therapy with Avelox®, dysglycemia occurred predominantly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When conducting treatment in patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended (see section “Side Effects”).

Special instructions for the use of Avelox

In the case of combined use of Avelox infusion solution and other drugs for intravenous administration, each of these drugs must be administered separately. Only clear infusion solutions of moxifloxacin are allowed. Special warnings and precautions The use of quinolone drugs is associated with a possible risk of developing a seizure. Moxifloxacin should be used with caution in patients with diseases of the central nervous system that predispose to the occurrence of seizures or lower the threshold for their occurrence. The drug should not be prescribed to patients with epilepsy. In patients with moderately severe liver failure, dosage adjustment of moxifloxacin is not performed. The use of the drug in patients with severe liver dysfunction (Child-Pugh stage C) is not recommended due to the lack of sufficient clinical experience. When using moxifloxacin, as well as during therapy with other quinolones and macrolides, the QT . None of the 9000 patients receiving moxifloxacin experienced cardiovascular events or deaths QT However, moxifloxacin should be administered with caution to patients with congenital or acquired diseases accompanied by prolongation of the QT , hypokalemia, or receiving drugs that potentially slow cardiac conduction (for example, class Ia (quinidine, procainamide) or class III antiarrhythmic drugs (amiodarone, sotalol)) . The degree of prolongation of the QT may increase with increasing drug concentrations, so the recommended dose should not be exceeded. The safety of moxifloxacin during pregnancy and lactation has not been established and its use is contraindicated. A small amount of the drug is excreted in breast milk. Effect on the ability to drive vehicles and operate machinery Although moxifloxacin rarely causes adverse reactions from the central nervous system, patients should determine their individual response to the drug before driving or operating machinery. It must be taken into account that during therapy with fluoroquinolones, including moxifloxacin, especially in elderly patients and patients receiving corticosteroids, the development of tenosynovitis and tendon rupture is possible. If pain and signs of inflammation of the tendon appear at the site of injury, it is recommended to stop taking the drug and reduce the load on the affected limb. It should be taken into account that the use of broad-spectrum antibacterial drugs is associated with the risk of developing pseudomembranous colitis. Cases of pseudomembranous colitis have not been reported with the use of moxifloxacin, but caution should be exercised in prescribing the drug to patients with a history of severe diarrhea during antibiotic therapy. If severe diarrhea occurs, the drug should be discontinued and appropriate therapy should be prescribed. In some cases, hypersensitivity and allergic reactions may develop after the first dose of the drug. Very rarely, allergic reactions can progress to the development of anaphylactic shock, even after the first dose of the drug. In such cases, moxifloxacin should be discontinued and appropriate therapeutic measures (including anti-shock) should be taken. When using quinolones, photosensitivity reactions are observed, although moxifloxacin does not have phototoxic properties. Patients receiving the drug should avoid direct sunlight and ultraviolet radiation. Children The use of moxifloxacin in children and adolescents is not recommended, since the effectiveness and safety of the drug have not been reliably established.

Avelox®

In some cases, after the first use of the drug, hypersensitivity and allergic reactions may develop, which should be reported to your doctor immediately. Very rarely, even after the first use of the drug, anaphylactic reactions can progress to life-threatening anaphylactic shock. In these cases, treatment with Avelox® should be stopped and the necessary therapeutic measures (including anti-shock) should be started immediately.

When using Avelox®, some patients may experience prolongation of the QT interval.

Avelox® should be used with caution in women and elderly patients. Because women have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to drugs that affect the QT interval.

The degree of QT interval prolongation may increase with increasing drug concentrations, so the recommended dose should not be exceeded. However, in patients with pneumonia, a correlation between moxifloxacin plasma concentrations and QT interval prolongation was noted. Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. None of the 9,000 patients receiving Avelox® experienced cardiovascular complications or deaths associated with QT prolongation.

When using Avelox®, the risk of developing ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias.

In this regard, Avelox® is contraindicated:

- patients with established prolongation of the QT interval;

- patients with uncorrected hypokalemia.

Due to the risk of additive effects on the QT interval, Avelox® is contraindicated:

- patients with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia;

- patients with liver cirrhosis (since in this category of patients the risk of developing a prolongation of the QT interval cannot be excluded).

The combined use of moxicloxacin with the following drugs that affect the prolongation of the QT interval is contraindicated:

- class IA antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide);

- class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide);

- neuroleptics (including phenothiazine, pimozide, sertindole, haloperidol, sultopride);

- tricyclic antidepressants;

- antimicrobial drugs (including sparfloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine);

- antihistamines (terfenadine, astemizole, mizolastine);

- others (cisapride, IV vincamine, bepridil, difemanil).

Cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases), have been reported while taking Avelox®. The patient should be informed that if symptoms of liver failure occur, it is necessary to consult a doctor before continuing treatment with Avelox®.

Cases of bullous skin lesions (such as Stevens-Johnson syndrome or toxic epidermal necrolysis) have been reported while taking Avelox®. The patient should be informed that if symptoms of skin or mucous membrane lesions appear, it is necessary to consult a doctor before continuing treatment with Avelox®.

The use of quinolone drugs is associated with a possible risk of developing seizures. Avelox® should be used with caution in patients with diseases of the central nervous system and disorders of the central nervous system that predispose to seizures or reduce the threshold for seizure activity.

The use of broad-spectrum antibacterial drugs, including Avelox®, is associated with the risk of developing pseudomembranous colitis associated with antibiotic use. This diagnosis should be kept in mind in patients who develop severe diarrhea during treatment with Avelox®. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility are contraindicated in the development of severe diarrhea.

Avelox® should be used with caution in patients with myasthenia gravis due to a possible exacerbation of the disease.

During therapy with quinolones, incl. moxifloxacin, tendonitis and tendon rupture may develop, especially in the elderly and patients receiving corticosteroids. Cases have been described that occurred within several months after completion of treatment. At the first symptoms of pain or inflammation at the site of injury, the drug should be stopped and the affected limb should be unloaded.

When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as when using the drug Avelox® in practice, no photosensitivity reactions were observed. However, patients receiving Avelox® should avoid exposure to direct sunlight and ultraviolet light.

The use of the drug in the form of tablets for oral administration is not recommended in patients with complicated inflammatory diseases of the pelvic organs (for example, associated with tubo-ovarian or pelvic abscesses).

The use of moxifloxacin is not recommended for the treatment of infections caused by methicillin-resistant strains of Staphylococcus aureus. Suspected or confirmed MRSA infections should be treated with appropriate antibacterial drugs.

The ability of Avelox® to inhibit the growth of mycobacteria may cause in vitro interaction of moxifloxacin with the test for Mycobacterium spp., leading to false negative results when analyzing samples from patients who are being treated with Avelox® during this period. In patients treated with quinolones, including Avelox®, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients being treated with Avelox should be advised to seek immediate medical attention before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness or weakness, occur.

Psychiatric reactions can occur even after the first prescription of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts. If patients develop such reactions, the drug Avelox® should be discontinued and the necessary measures taken. Caution should be exercised when prescribing Avelox® to patients with psychosis and patients with a history of psychiatric diseases.

Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, moxifloxacin monotherapy should not be used in the treatment of patients with pelvic inflammatory diseases. Unless the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If the presence of fluoroquinolone-resistant N. gonorrhoeae cannot be excluded, consideration should be given to supplementing empiric moxifloxacin therapy with an appropriate antibiotic that is active against N. gonorrhoeae (eg, a cephalosporin).

Patients on a low-salt diet (with heart failure, renal failure, nephrotic syndrome) should take into account that the solution for infusion contains sodium chloride.

Impact on the ability to drive vehicles and operate machinery

Fluoroquinolones, including moxifloxacin, may impair the ability of patients to drive a car and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to their effects on the central nervous system and visual impairment.

Avelox drug interactions

Antacids, minerals and multivitamins. The combined use of moxifloxacin with antacids, minerals and multivitamins may cause malabsorption of the drug due to the formation of chelate complexes with polyvalent cations contained in these drugs, and this may in turn lead to a decrease in their concentration in the blood plasma. Therefore, antacids, antiretrovirals and other drugs containing calcium, magnesium, aluminum, iron should be taken at least 4 hours before or 2 hours after oral administration of moxifloxacin. Ranitidine The combined use of ranitidine and moxifloxacin slightly changes the absorption of the latter. Drugs containing calcium When moxifloxacin was combined with high doses of drugs containing calcium, no clinically significant effect on the absorption of moxifloxacin was detected, with the exception of a slight decrease in the rate of absorption. Theophylline Moxifloxacin does not affect the pharmacokinetics of theophylline (and vice versa), therefore, does not interact with isoenzymes of cytochrome P450 subtype 1A2. Warfarin When moxifloxacin is used in combination with warfarin, prothrombin time and other blood coagulation parameters do not change. But sometimes in patients receiving anticoagulants simultaneously with fluoroquinolones, cases of increased anticoagulant activity of antithrombotic drugs were noted. Risk factors are the presence of infectious diseases (and concomitant inflammatory process), age and general condition of the patient. Therefore, in the case of combined use of warfarin and moxifloxacin, it is necessary to adjust the dose of oral antithrombotic drugs. Oral contraceptives No interactions were observed between moxifloxacin and oral contraceptives. Antidiabetic agents No clinically significant interaction has been established between glibenclamide and moxifloxacin. Itraconazole When combined with moxifloxacin, the AUC of itraconazole changes slightly. There was no significant mutual influence of the drugs, so there is no need to change the dosage regimen of any of the drugs. Digoxin The pharmacokinetics of digoxin did not change under the influence of moxifloxacin and vice versa. Morphine With parenteral administration of morphine and simultaneous oral administration of moxifloxacin, a decrease in the bioavailability of the latter was not noted; The maximum concentration of moxifloxacin in blood plasma decreases slightly (17%). Atenolol The pharmacokinetics of atenolol are slightly altered by moxifloxacin. After taking a single dose, the AUC of atenolol increases by 4%, and the maximum plasma concentration decreases by 10%. Probenecid Probenecid does not affect the total and renal clearance of moxifloxacin, so there is no need for dose adjustment when used in combination. Infusion solution of moxifoloxacin is incompatible with solutions of sodium chloride 10% and 20%, sodium bicarbonate 4.2% and 8.4%. The drug should not be administered simultaneously with other antibiotics.

Overdose of the drug Avelox, symptoms and treatment

No side effects were observed when using Avelox in healthy volunteers in single doses of up to 1.2 g or at a dose of 600 mg/day for 10 days. In case of overdose, symptomatic therapy is carried out, combined with ECG monitoring, in accordance with the clinical situation. The use of activated carbon is advisable only in case of an overdose of moxifloxacin in tablet form; this will prevent systemic exposure to moxifloxacin at an early stage. After its intravenous administration, activated carbon slightly (20%) reduces the systemic exposure of the drug.