Moxifloxacin - instructions for use, dose, side effects, contraindications

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

The minimum bactericidal concentrations of the drug as a whole are comparable to its minimum inhibitory concentrations (MIC).

Mechanisms of resistance

Mechanisms that lead to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines, do not affect the antibacterial activity of moxifloxacin. Cross-resistance between these groups of antibacterial drugs and moxifloxacin is not noted. So far, no cases of plasmid resistance have been observed. The overall frequency of development of resistance is very low (10^-7-10^-10). Resistance to moxifloxacin develops slowly, through multiple mutations. Multiple effects of moxifloxacin on microorganisms at concentrations below MIC are accompanied by only a slight increase in MIC. There are cases of cross-resistance to quinolones. Nevertheless, some gram-positive and anaerobic microorganisms resistant to other quinolones retain sensitivity to moxifloxacin.

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

Moxifloxacin in vitro is active 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., and also bacteria resistant to β-lactam and macrolide antibiotics.

Influence on human intestinal microflora

In two studies conducted on volunteers, the following changes in the intestinal microflora were observed after oral administration of moxifloxacin. Decreased concentrations Escherichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp., Klebsiella spp., as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. Toxins Clostridium difficile not detected.

In Vitro Sensitivity Testing

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

Sensitive	Moderately sensitive	Resistant
Gram-positive
Gardnerella vaginalis
Streptococcus pneumoniae* (including penicillin resistant strains and strains with multiple antibiotic resistance), as well as strains resistant to 2 or more antibiotics, such as penicillin (MIC ≥2 μg / ml), second-generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, trimethoprim-sulfamethoxazole
Group Streptococcus milleri (S. anginosus , S. constellatus and S. intermedius )*
Streptococcus pyogenes (group A) *
Group Streptococcus viridans (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus, S. constellatus)
Streptococcus agalactiae
Streptococcus dysgalactiae
Staphylococcus aureus (including methicillin-sensitive strains) *		Staphylococcus aureus (methicillin / ofloxacin resistant strains)⁺
Coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), methicillin-sensitive strains		Coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), methicillin-resistant strains
	Enterococcus faecalis * (only strains sensitive to vancomycin and gentamicin)
	Enterococcus avium *
	Enterococcus faecium *
Gram-negative
Haemophilus influenzae (including strains producing and not producing β-lactamases) *
Haemophilus parainfluenzae *
Moraxella catarrhalis (including strains producing and not producing β-lactamases) *
Bordetella pertussis
Legionella pneumophila	Escherichia coli*
Acinetobacter baumanii	Klebsiella pneumoniae*
	Klebsiella oxytoca
	Citrobacter freundii*
	Enterobacter spp. (E. aerogenes, E. intermedius, E. sakazaki)
	Enterobacter cloacae*
	Pantoea agglomerans
		Pseudomonas aeruginosa
	Pseudomonas fluorescens
	Burkholderia cepacia
	Stenotrophomonas maltophilia
	Proteus mirabilis*
Proteus vulgaris
	Morganella morganii
	Neisseria gonorrhoeae *
	Providencia spp. (P. rettgeri, P. stuartii)
Anaerobes
	Bacteroides spp. (B. fragilis B. distasonis** B. thetaiotaomicron, B. ovatus*, B. uniformis** B. vulgaris )*
Fusobacterium spp.
	Peptostreptococcus spp*
Porphyromonas spp.
Prevotella spp.
Propionibacterium spp.
	Clostridium spp.*
Atypical
Chlamydia pneumoniae *
Chlamydia trachomatis *
Mycoplasma pneumoniae*
Mycoplasma hominis
Mycoplasma genitalium
Legionella pneumophila*
Coxiella burnetii

* Sensitivity to moxifloxacin is confirmed by clinical data.

⁺ The use of the drug Moxifloxacin is not recommended for the treatment of infections caused by strains S. aureus, resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, treatment should be prescribed with appropriate antibacterial drugs.

For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time. In this regard, when testing the sensitivity of a strain, it is desirable to have local information on resistance, especially when treating severe infections.

If patients undergoing treatment in the hospital, the area under the pharmacokinetic curve "concentration-time" AUC / MIK₉₀ exceeds 125, and the maximum concentration in blood plasma C_max/ MIC₉₀ is in the range of 8 to 10, then this implies a clinical improvement. In outpatients, the values of these surrogate parameters are usually less: AUC / MIK₉₀ >30-40.

Values of pharmacodynamic parameters of moxifloxacin in outpatients

Parameter (mean) MIC₉₀, mg / l	*AUIC , h**	FROM_max / MIC90 (infusion for 1 h)**
0,125	313	32,5
0,25	156	16,2
0,5	78	8,1

* Area under the inhibitory curve (ratio AUC *** / MIK₉₀).

** The maximum concentration of the drug in the blood plasma.

*** Area under the pharmacokinetic curve "concentration-time".

Pharmacokinetics:

Suction

After a single infusion of moxifloxacin at a dose of 400 mg for 1 hour C_m_Oh moxifloxacin is achieved at the end of the infusion and is approximately 4.1 mg / L, corresponding to an increase of approximately 26% compared with the value of this index when taking moxifloxacin by mouth. Exposure of moxifloxacin, determined by the indicator AUC, slightly exceeds that when taking moxifloxacin inside. Absolute bioavailability is approximately 91%.

After multiple intravenous infusions of moxifloxacin at a dose of 400 mg for 1 hour 1 time per day, the maximum value of stable concentration (Css^max) and the minimum value of stable concentration (Css^min) vary between 4.1 and 5.9 mg / L and between 0.43 and 0.84 mg / L, respectively. An average stable concentration of 4.4 mg / l is achieved at the end of the infusion.

Distribution

Moxifloxacin is rapidly distributed in tissues and organs and binds to plasma proteins (mainly albumins) by about 45%. The distribution volume is approximately 2 l / kg.

High concentrations of moxifloxacin, exceeding those in blood plasma, are created in the lung tissue (including epithelial fluid, alveolar macrophages), in bronchial mucosa, in the nasal sinuses (maxillary and etmoidal sinuses), in nasal polyps, in the foci of inflammation (in the contents blisters in case of skin lesions). In the interstitial fluid and in the saliva moxifloxacin is determined in a free, not protein-bound form in a concentration exceeding that in the blood plasma. In addition, high concentrations of moxifloxacin are determined in the tissues of the abdominal cavity, peritoneal fluid and female genital organs.

Metabolism

Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, and also through the intestine both in unchanged form and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin does not undergo biotransformation by the microsomal system of cytochrome P450. Metabolites M1 and M2 are present in blood plasma at lower concentrations than the parent compound. In preclinical studies it was shown that these metabolites do not have a negative impact on the body in terms of safety and tolerability.

Excretion

The half-life of moxifloxacin is approximately 12 hours. The average total clearance after administration in a dose of 400 mg is 179-246 ml / min. Kidney clearance is 24-53 ml / min. This indicates a partial tubular reabsorption of moxifloxacin.

The balance for the initial compound and the metabolites of the 2nd phase is approximately 96-98%, which indicates the absence of oxidative metabolism. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% - through the intestine.

Pharmacokinetics the separate patient groups

Age, gender and ethnicity

In studies of the pharmacokinetics of moxifloxacin in men and women, differences in indices AUC and C_m_Oh (33%). Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and C_m_Oh were due more to the difference in body weight than sex, and are not clinically relevant.

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

Children

The pharmacokinetics of moxifloxacin in children have not been studied.

Renal insufficiency

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

Impaired liver function

The concentrations of moxifloxacin in patients with varying degrees of impaired liver function (Child-Pugh class A and B classes) did not differ significantly from those in healthy volunteers or in patients with normal liver function (use in patients with cirrhosis of the liver - see also section "Special instructions").

Indications:

Infectious-inflammatory diseases caused by micro-organisms sensitive to moxifloxacin:

- community-acquired pneumonia, including community-acquired pneumonia, caused by strains of microorganisms with multiple resistance to antibiotics *;

- complicated skin and soft tissue infections (including infected diabetic foot);

- Complicated intra-abdominal infections, including polymicrobial infections, in including intraperitoneal abscesses.

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

It is necessary to take into account the current official guidelines on the rules for the use of antibacterial drugs.

Contraindications:

- Hypersensitivity to moxifloxacin or any other component of the drug, as well as to other quinolones.

- Pregnancy and the period of breastfeeding.

- Age to 18 years.

- The presence in the anamnesis of the pathology of the tendons, which developed as a result of the treatment with antibiotics of the quinolone series.

- Changes in the electrophysiological parameters of the heart, expressed in lengthening the interval QT: Congenital or acquired documented cases of lengthening the interval QT, electrolyte disorders, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with a reduced fraction of the left ventricular ejection; presence in the anamnesis of rhythm disturbances,accompanied by clinical symptoms.

- Simultaneous use with other drugs that extend the interval QT (see the section "Interaction with other medicinal products").

- Violations of liver function (class C according to the Child-Pugh classification) and an increase in the content of transaminases is more than 5 times higher than the upper limit of the norm due to the limited amount of clinical data.

Carefully:

Moxifloxacin should be used with caution:

- for diseases of the central nervous system (including suspicious for involvement of the central nervous system), predisposing to the appearance of seizures and reducing the threshold of convulsive activity;

- in patients with potentially proarrhythmic conditions (especially in women and elderly patients), such as acute myocardial ischemia and cardiac arrest;

- with myasthenia gravis gravis;

- with cirrhosis of the liver;

- with simultaneous administration with drugs that reduce the content of potassium;

- in patients with psychoses and / or patients with psychiatric illnesses in the anamnesis (see section "Side effect").

Patients with a genetic predisposition or an actual presence of a deficiency of glucose-6-phosphate dehydrogenase are prone to hemolytic reactions in the treatment with quinolones. As a result, in such patients moxifloxacin should be used with caution.

Pregnancy and lactation:

The safety of moxifloxacin during pregnancy is not established, and its use is contraindicated. Cases of reversible joint damage in children receiving certain quinolones are described, but there is no information on the manifestation of this effect in the fetus (if the mother used it during pregnancy). In animal studies, reproductive toxicity has been demonstrated. The potential risk to humans is unknown. Like other quinolones, moxifloxacin causes damage to the cartilage of large joints in preterm animals.

In preclinical studies it was found that a small amount of moxifloxacin is excreted in breast milk. Data on its use in women during lactation are absent, therefore the use of moxifloxacin during breastfeeding is contraindicated.

Dosing and Administration:

Adults

The recommended dosage regimen of moxifloxacin is 400 mg (250 ml solution for infusion) once a day for the infections mentioned above. Do not exceed the recommended dose.

Duration of treatment

The duration of treatment is determined by the localization and severity of the infection, and clinical effect. At the initial stages of treatment, moxifloxacin solution for infusion, and then, in the presence of indications, moxifloxacin can be appointed orally in the form of the tablets covered with a film cover.

- Community-acquired pneumonia: total duration of stepwise therapy (intravenous administration followed by oral administration) is 7-14 days.

- Complicated infections of the skin and subcutaneous structures: the total duration of the stepwise therapy (intravenous administration followed by oral administration) is 7-21 days.

- Complicated intra-abdominal infections: the total duration of the stepwise therapy (intravenous administration followed by oral administration) is 5-14 days. Do not exceed the recommended duration of treatment. According to clinical studies, the duration of treatment with moxifloxacin in the form of a solution for infusions can reach 21 days.

Elderly patients

Changes in the dosing regimen in elderly patients are not required.

Children and teens

There is no data on the efficacy and safety of moxifloxacin in children and adolescents.

Violation of the function of the liver (classes A and B according to the Child-Pugh classification)

In patients with impaired hepatic function, there is no need to change the dosage regimen (use in patients with cirrhosis of the liver - see section "Special instructions").

Renal insufficiency

In patients with impaired renal function (including severe renal failure with creatinine clearance ≤ 30 ml / min / 1.73 m²), as well as in patients on continuous hemodialysis and long-term outpatient peritoneal dialysis, changes in the dosing regimen are not required.

Patients of different ethnic groups

Dosage regimen changes are not required.

Mode of application

The drug is administered intravenously in the form of infusion lasting not less than 60 minutes both in undiluted form and in combination with the following compatible solutions (using the T-shaped adapter):

- water for injections;

- solution of sodium chloride 0.9%;

- solution of sodium chloride 1 M;

- dextrose solution 5%;

- dextrose solution 10%;

- dextrose solution 40%;

- xylitol solution 20%;

- Ringer's solution;

- Ringer's lactate solution.

If moxifloxacin the solution for infusions is prescribed together with other drugs, then each drug should be administered separately.

At a temperature below 15 ° C, a precipitate may precipitate, which dissolves at room temperature (15 to 25 ° C). Do not store the drug in the refrigerator. The preparation should be stored in a production package. Before use, visually check the solution for inclusions. Use only a clear, solution-free solution.

Side effects:

Data on adverse reactions recorded with the use of moxifloxacin at a dose of 400 mg (by mouth, with stepwise therapy [intravenous administration of the drug followed by oral administration] and only intravenously) are obtained from clinical studies and post-marketing messages (highlighted italics).

Adverse reactions listed in the column "Often", occurred with a frequency below 3%, with the exception of nausea and diarrhea.

In each frequency group, undesirable drug reactions are listed in order of decreasing significance.

The frequency is defined as follows: 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).

System-Organ Classes (MedDRA)	Often	Infrequently	Rarely	Rarely
Infectious and parasitic diseases	Fungal superinfections
On the part of the hematopoiesis system		Anemia Leukopenia Neutropenia Thrombocytopenia Thrombocytosis Prothrombin time extension / increase in the international normalized ratio (INR)	Change in the concentration of thromboplastin	Increase in prothrombin concentration / decrease in INR
From the immune system		Allergic reactions Itching Rash Hives Eosinophilia	Anaphylactic / anaphylactoid reactions Angioedema, including laryngeal edema (potentially life-threatening)	Anaphylactic / anaphylactoid shock (including potentially life-threatening)
From the side of metabolism		Hyperlipidemia	Hyperglycaemia Hyperuricemia	Hypoglycaemia
Mental disorders		Anxiety Psychomotor hyperactivity / agitation	Emotional lability Depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts) is possible. Hallucinations	Depersonalization Psychotic reactions (potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts)
From the nervous system	Headache Dizziness	Paresthesia / Dysaesthesia Disturbances of taste sensitivity (including, in very rare cases, agesia) Confusion and disorientation Sleep Disorders Tremor Vertigo Drowsiness	Hypesesia Abnormalities of smell (including anosmia) Atypical dreams Violations of coordination (including gait disturbance due to dizziness or vertigo, in very rare cases leading to injury from falling, especially in elderly patients) Seizures with various clinical manifestations (including seizures of "grand mal") Violations of attention Violations of speech Amnesia Peripheral neuropathy and polyneuropathy	Hyperesthesia
From the side of the organ of vision		Visual impairment (especially against the backdrop of CNS reactions)		Transient loss of vision (especially against the background of reactions from the central nervous system)
From the side of the hearing organ and labyrinthine disorders			Noise in the ears Impairment of hearing, deafness (usually reversible)
From the side of the cardiovascular system	Elongation of the QT interval in patients with concomitant hypokalemia	QT interval extension Heart palpitations Tachycardia Vasodilation	Ventricular tachyarrhythmias Fainting Increased blood pressure Reduction of blood pressure	Nonspecific arrhythmias Polymorphic ventricular tachycardia (torsades de pointes) Heart failure (mainly in individuals with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia)
On the part of the respiratory system, the organs of the thorax and the mediastinum		Shortness of breath (including asthmatic conditions)
From the gastrointestinal tract	Nausea Vomiting Stomach ache Diarrhea	Reduced appetite and reduced food intake Constipation Dyspepsia Flatulence Gastroenteritis (other than erosive gastroenteritis) Increase of amylase activity	Dysphagia Stomatitis Pseudomembranous colitis (in very rare cases - associated with life-threatening complications)
From the liver and biliary tract	Increased activity of "liver" transaminases	Dysfunction of the liver (including increased levels of lactate dehydrogenase) Increased bilirubin level Increase in activity of gamma-glutamyl transferase Increase in blood activity of alkaline phosphatase	Jaundice Hepatitis (predominantly cholestatic)	Fulminant hepatitis, potentially leading to life-threatening hepatic insufficiency (including fatal cases)
From the skin and soft tissues				Bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening)
From the musculoskeletal and connective tissue		Arthralgia Myalgia	Tendonitis Increased muscle tone and cramps Muscle weakness	Tendon tendons Arthritis Gait disorders due to damage to the musculoskeletal system Increased symptoms of myasthenia gravis
From the side of the kidneys and urinary tract		Dehydration (caused by diarrhea or decreased fluid intake)	Impaired renal function Renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impairment of kidney function)
General disorders and injuries at the site of administration	Local reactions at the site of administration	General malaise Pain without a clear cause Sweating Phlebitis / thrombophlebitis at the site of administration	Edema

The frequency of development of the following adverse reactions was higher in the group receiving the stepwise therapy (intravenous administration of the drug followed by oral administration).

Often: increased activity of gamma-glutamyltransferase.

Infrequently: ventricular tachyarrhythmias, hypotension, edema, pseudomembranous colitis (in very rare cases - associated with life-threatening complications), seizures with various clinical manifestations (including seizures "grand mal"), hallucinations, 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).

Overdose:

There are limited data on the overdose of moxifloxacin. No side effects were observed with moxifloxacin at a dosage up to 1200 mg once and 600 mg for 10 days or more. In case of an overdose, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

Interaction:

When combined with atenolol, ranitidine, calcium-containing additives, theophylline, cyclosporin, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid (no clinically significant interaction with moxifloxacin was confirmed), dose adjustment is not required.

Drugs that extend the interval QT

It is necessary to take into account the possible additive effect (lengthening of the interval QT) moxifloxacin and other drugs that can cause lengthening of the interval QT.

Due to the combined use of moxifloxacin and drugs that affect the lengthening of the interval QT, the risk of developing ventricular arrhythmia increases, including polymorphic ventricular tachycardia (torsades de pointes).

Contraindicated joint use of moxifloxacin with the following drugs that affect the lengthening of the interval QT:

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

- antiarrhythmic drugs of class III (amiodarone, sotalol, dofetilide, ibutilide and etc.);

- antipsychotics (phenothiazine, pimozide, sertindole, haloperidol, sultopride and etc.);

- tricyclic antidepressants;

- antimicrobial agents (sparfloxacin, erythromycin (intravenously), pentamidine), as well as anti-malarial drugs, especially halofantrine;

- antihistamines (terfenadine, astemizole, misolastine);

- preparations of other groups (cisapride (intravenously), bepridil, difemanyl).

Warfarin

When combined with warfarin prothrombin time and other parameters of blood coagulation do not change.

Change the value of INR. In patients who received anticoagulants in combination with antibiotics, including moxifloxacin, there have been cases of increased anticoagulant activity of anticoagulant drugs. Risk factors are the presence of an infectious disease (and concomitant inflammatory process), the age and general condition of the patient. Despite the fact that there is no interaction between moxifloxacin and warfarin, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the INR and the need to adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not have a significant effect on pharmacokinetic parameters of each other. When appointing repeated doses of moxifloxacin C_m_Oh digoxin increased by about 30%, while AUC and the minimum digoxin concentration did not change.

Activated carbon

With intravenous administration of moxifloxacin with simultaneous oral administration of activated charcoal, the systemic bioavailability of moxifloxacin slightly decreases (by approximately 20%) due to adsorption of moxifloxacin in the lumen of the gastrointestinal tract during enterohepatic recirculation.

Incompatibility

Do not administer the infusion solution of moxifloxacin simultaneously with other incompatible solutions, which include:

- solution of sodium chloride 10%;

- solution of sodium chloride 20%;

- solution of sodium bicarbonate 4.2%;

- solution of sodium hydrogen carbonate 8.4%.

Special instructions:

In some cases, hypersensitivity and allergic reactions may develop after the first use of moxifloxacin, which should be reported immediately to the doctor. Very rarely, even after the first use of moxifloxacin, anaphylactic reactions can progress to a life-threatening anaphylactic shock.In these cases, the treatment with moxifloxacin should be discontinued and immediately begin the necessary medical measures (including anti-shock).

With the use of moxifloxacin in some patients, lengthening of the interval QT. Because women have a longer interval than men QT, they may be more sensitive to drugs that extend the interval QT. Elderly patients are also more prone to the effects of drugs that affect the interval QT.

Interval lengthening QT is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

Degree of lengthening interval QT can increase with increasing concentration moxifloxacin, therefore, do not exceed the recommended dose and infusion rate (400 mg for 60 minutes). However, in patients with pneumonia, the correlation between the concentration of moxifloxacin in the blood plasma and the lengthening of the interval QT was not noted. None of the 9,000 patients who received moxifloxacin, there were no cardiovascular complications and lethal cases associated with lengthening the interval QT.

With the use of moxifloxacin, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase. Concerning moxifloxacin contraindicated in:

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

- application with other drugs that extend the interval QT (see the section "Interaction with other medicinal products").

Moxifloxacin should be used with caution:

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

- in patients with cirrhosis of the liver (since this category of patients can not exclude the risk of developing an extension of the interval QT).

When moxifloxacin was used, cases of fulminant hepatitis were reported,potentially leading to the development of hepatic insufficiency (including fatal cases) (see section "Side effect"). The patient should be informed that if symptoms of hepatic insufficiency occur, the doctor should be consulted before continuing with moxifloxacin therapy.

When moxifloxacin was used, cases of developing bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, were reported. The patient should be informed that in case of symptoms of skin or mucous membrane damage, the doctor should be consulted before continuing with moxifloxacin therapy.

The use of drugs quinolone series is associated with a possible risk of seizures. Moxifloxacin should be used with caution in patients with diseases of the central nervous system and with violations of the CNS, predisposing to the onset of seizures or reducing the threshold of convulsive activity.

The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with a risk of developing pseudomembranous colitis.This diagnosis should be borne in mind in patients who have developed severe diarrhea with moxifloxacin. In this case, immediate therapy should be prescribed. Drugs that inhibit the peristalsis of the intestine are contraindicated in the development of severe diarrhea.

Moxifloxacin should be used with caution in patients with myasthenia gravis gravis in connection with a possible exacerbation of the disease.

Against the background of quinolone therapy, including moxifloxacin, especially in the elderly and patients receiving glucocorticosteroids, tendonitis and tendon rupture may develop. Cases which have arisen within several months after the end of treatment are described. At the first symptoms of pain or inflammation at the site of damage, the use of moxifloxacin should be stopped and unloaded the affected limb.

When applying quinolones, photosensitivity reactions are noted. However, in pre-clinical and clinical studies, as well as with the use of moxifloxacin, no photosensitivity reactions were observed in practice. Nevertheless, patients receiving moxifloxacin, should avoid exposure to direct sunlight and ultraviolet light.

It is not recommended to use moxifloxacin for the treatment of infections caused by strains Staphylococcus aureus, resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, should be prescribed treatment with appropriate antibacterial drugs (see the section "Pharmacodynamics").

The ability of moxifloxacin to inhibit the growth of mycobacteria can cause interaction in vitro moxifloxacin with a Mycobacterium spp., leading to false-negative results in the analysis of samples of patients treated with moxifloxacin during this period.

In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy, leading to paresthesia, hypoesthesia, dysesthesia or weakness are described. Patients undergoing treatment with moxifloxacin should be warned about the need for immediate medical attention before continuing treatment in the event of symptoms Neuropathy, including pain, burning, tingling, numbness or weakness (see.section "Side effect").

Reactions from the psyche 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 suicidal attempts (see "Side effect" section). In case of development of such reactions in patients it is necessary to cancel moxifloxacin and take the necessary measures. Caution should be exercised when using moxifloxacin in patients with psychoses and / or psychiatric illnesses in the anamnesis.

Disglycemia

As in the case of other fluoroquinolones, the use of moxifloxacin showed a change in the concentration of glucose in the blood, including hypo- and hyperglycemia. Against the background of moxifloxacin therapy, disglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (eg, sulfonylureas) or insulin. When performing treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended (see section "Side effect").

Patients who follow a diet with a low salt content (with heart failure, kidney failure, with nephrotic syndrome) should take into account that the infusion solution contains sodium chloride. The daily dose of sodium in the preparation is 36.5 mmol.

Effect on the ability to drive transp. cf. and fur:

Fluoroquinolones, including moxifloxacin, can disrupt the ability of patients to drive a car and engage in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions, due to the effects on the central nervous system and visual impairment.

Form release / dosage:

Solution for infusion is 1.6 mg / ml.

Packaging:

For 50 ml of the drug in bottles of colorless glass I hydrolytic class, hermetically sealed with rubber stoppers, crimped aluminum caps. For 5 bottles together with the instructions for use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004454

Date of registration:12.09.2017

Expiration Date:12.09.2022

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

R-PHARM, JSC Russia

Information update date: & nbsp06.10.2017

Illustrated instructions

Instructions

Moxifloxacin (Moxifloxacine)