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

Excipients: sodium chloride 8.00 mg, sodium hydroxide q.s. to pH 4.1-4.6, concentrated hydrochloric acid q.s. to a pH of 4.1 to 4.6, water for injection to 1 ml.

Theoretical osmolarity: 283 mOsmol / l.

Description:Transparent solution of yellow-green color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:

Mechanism of action

Moxifloxacin - a bactericidal antibacterial broad-spectrum preparation, 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 moxifloxacin are generally comparable to its minimum inhibitory concentrations (MICs).

Mechanisms resistance

Mechanisms leading to the development of resistance to penicillin, 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 exposure of moxifloxacin to microorganisms at concentrations below the minimum inhibitory concentration (MIC) is 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., Eubactcrium spp., Peptostreptococcus spp. These changes were reversible within two weeks. Toxins Clostridium difficile not detected.

Sensitivity testing in vitro

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

Sensitive	Moderately- sensitive	Resistant
Gram-positive
Gardnerella vaginalis
Streptococcus pneumoniae (including strains resistant to penicillin and strains with multiple resistance to antibiotics), as well as strains resistant to two or more antibiotics, such as penicillin (MIC ≥ 2 μg / ml), cephalosporins II generation (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole
Streptococcus pyogenes (Group A)*
Gruppa Streptococcus milleri (S. anginosus , S. constellatus . And S. intermedius *)
Group Streptococcus viridans (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus, S. constellatus)
Streptococcus agalactiae
Streptococcus dysgalcictiae
Staphylococcus aureus (methicillin-sensitive strains) *		Staphylococcus aureus (methicillin / ofloxacin resistant strains)⁺
Coagulase-negative staphylococciS. 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 non-producing β-lactamases) *
Haemophillus parainfluenzae *
Moraxella catarrhalis (including strains producing and non-producing β-lactamases) *
Inrdetella pertussis
Legionella pneumophila	Escherichia coli *
Acinetobacter baumanii	Klebsiella pneumoniae *
	Klebsiella oxytoca
	Citrobacter freundii *
	Enterobacter spp. (E. aerogenes, E. intermedius, E. sakazakii)
	Enterobacter cloacae *
	Pantoca agglomerans
		Pseudomonas aeruginosa
	pseudomonas fluorcscens
	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 *)
fusobactcrium 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 burnettii

* sensitivity to moxifloxacin is confirmed by clinical data.

⁺ 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, should be prescribed treatment with appropriate antibacterial drugs.

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

if patients undergoing treatment in a hospital, the area under the pharmacokinetic curve "concentration-time" (auc) / mik₉₀, exceeds 125, and the maximum concentration in blood plasma (s_max) / mic₉₀ is within the range of 8-10 - this implies a clinical improvement. in ambulatory patients, the values of these surrogate parameters are usually less: auc/ mik₉₀ > 30-40.

parameter (average value)	auic * (h)	from_max/ mik₉₀
mik₉₀0,125 mg / l	313	32,5
mik₉₀ 0.25 mg / l	156	16,2
mik₉₀ 0.5 mg / l	78	8,1

*auic- area under the inhibitory curve (ratio auc/ mik₉₀).

Pharmacokinetics:

Suction

After a single infusion of moxifloxacin at a dose of 400 mg for 1 hour FROM_max 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 inside.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 400 mg for 1 hour, the maximum and minimum steady-state concentrations range from 4.1 mg / L to 5.9 mg / L and 0.43 mg / L to 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 blood 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 in epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoid sinuses), in nasal polyps, in the foci of inflammation (in the contents of blisters in the lesion of the skin). In the interstitial fluid and in the saliva moxifloxacin is determined in a free, not protein-related form, at a concentration higher than 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 kidneys, as well as intestines, both in unchanged form, and in as inactive sulfo compounds (M1) and glucuronides (M2).

Moxifloxacin is not biotransformation of microsomal system of cytochrome P450. Metabolites M1 and M2 are present in the plasma blood in concentrations lower than the original compound. According to the results of preclinical studies, it was proved 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.

Balance for the initial compound and metabolites of the 2 nd phase is approximately 96-98%, indicating that there is no oxidative metabolism.About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% by the intestine.

Pharmacokinetics in different patient groups

Age, gender and ethnicity

When studying the pharmacokinetics of moxifloxacin in men and women, differences were found in 33% of the indicators AUC and C_m_Oh. Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and C_m_Ohwere due to the difference in weight rather than sex and are not clinically significant.

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 concentration of moxifloxacin in patients with hepatic impairment (Child-Pugh class A and B classes) did not have significantdifferences in comparison with those in healthy volunteers or in patients with normal liver function (for use in patients with cirrhosis of the liver, see also "Special instructions").

Indications:

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

- Community-acquired pneumonia, including community-acquired pneumonia, whose pathogens are strains of microorganisms with multiple antibiotic resistance *;

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

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

* Streptococcus pneumoniae with multiple antibiotic resistance include penicillin resistant strains and strains resistant to two or more antibiotics from groups such as penicillins (with MIC ≥ 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, other quinolones or any other component of the drug;

- age to 18 years;

- pregnancy and the period of breastfeeding;

- the presence in the anamnesis of a pathology of tendons, developed as a result of antibiotic treatment of the quinolone series;

- changes in the electrophysiological parameters of the heart, expressed in lengthening interval QT: congenital or acquired documented lengthening interval QT, electrolyte disorders, especially uncorrected hypokalemia; clinically relevant 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;

- 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 more than five times higher than the upper limit of the norm, due to the limited amount of clinical data.

Carefully:

In diseases of the central nervous system (including suspicious of involvement CNS) predisposing to seizures, and reducing the threshold convulsive activity, in patients with potentially proarrhythmic states (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 with psychiatric illnesses in the anamnesis.

Patients with a genetic predisposition, or actual presence of deficiency of glucose-6-fosfatdegidrogeiazy prone to haemolytic reactions with quinolones therapy. As a result, in such patients moxifloxacin should be used with caution.

Pregnancy and lactation:

Safety of moxifloxacin during pregnancy is not is established and its use is contraindicated. Cases of reversible joint damage in children receiving certain quinolones are described, but no evidence of this effect was reported 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 into 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 for moxifloxacin is 400 mg (250 ml infusion solution) 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, as well as clinical effect. At the initial stages of treatment, the drug Moxifloxacin STADA, a solution for infusions can be used, and then, if there are indications, moxifloxacin can be prescribed for oral administration in the form of tablets coated with film shell.

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

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

- Complicated intra-abdominal infections: the total duration of stepwise therapy with moxifloxacin (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

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

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

Patients with hepatic dysfunction are not required to change the dosage regimen (for use in patients with cirrhosis see the 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.

Use in patients of different ethnic groups

Dosage regimen changes are not required.

Mode of application

The drug is administered intravenously in the form of infusion duration ns less than 60 minutes both undiluted and in combination with the following compatible solutions (using a T-shaped adapter):

- water for injections;

- 0.9% solution of sodium chloride;

- solution of sodium chloride 1M;

- 5% dextrose solution;

- 10% dextrose solution;

- 40% dextrose solution;

- 20% xylitol solution;

- Ringer's solution;

- Ringer's lactate solution.

If the drug Moxifloxacin STADA, a solution for infusion, is used in conjunction with other drugs, then each drug should be administered separately.

The mixture of the solution of the preparation Moxifloxacin STADA with the above infusion solutions remains stable for 24 hours at room temperature.

Because the solution can not be frozen or cooled, it can not be stored in the refrigerator. When cooling, a precipitate may form,which dissolves at room temperature. The solution should be stored in a production package. Only use a clear solution.

Side effects:

Data on adverse reactions recorded with the use of moxifloxacin 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-registration reports (in italics).

Adverse reactions listed in the "frequently" group occurred with a frequency below 3%, except for nausea and diarrhea.

In each frequency group, undesirable drug reactions are listed in order of decreasing importance. The frequency is determined 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).

Systems bodies	Often	Infrequently	Rarely	Rarely
Infectious and parasitic diseases	Fungal superinfection
From the side hematopoiesis systems		Anemia Leukopenia Neutropenia Thrombocytopenia Thrombocytosis Elongation prothrombin time / increase in the international normalized ratio (INR)	Change Thromboplastin concentration	Increase prothrombin concentration / decrease INR
From the side 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 metabolism		Hyperlipidemia	Hyperglycaemia Hyperuricemia	Hypoglycaemia
Mental disorders		Anxiety Psychomotor hyperreactivity / agitation	Emotional lability Depression (at very rare cases perhaps behavior with a tendency towards self-harm, such as suicidal thoughts or suicidal attempts) Hallucinations	Depersonalization Psychotic reactions (potentially manifested in behavior with a tendency towards self-harm, such as suicidal thoughts or suicidal attempts)
From the nervous side systems	Headache Dizziness	Paresthesia / Dysaesthesia Violation taste sensitivity (including in very rare cases, agevia) Confusion consciousness and disorientation Sleep Disorders Tremor Vertigo Drowsiness	Hypesesia Violations smell (including anosmia) Atypical dreaming Violation coordination (including gait disturbance due to dizziness or vertigo, at very rare cases leading to injuries in result fall, especially elderly patients) Seizures with various clinical manifestations (including "grand mal" seizures) Violations attention Violations speech Amnesia Peripheral neuropathy and polyneuropathy	Hypersthesia
From the side of the organ of vision		Violations (especially in reactions from the central nervous system (CNS))		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 ears Deterioration hearing, including deafness (usually reversible)
From the side of the cardiovascular system	Elongation of the QT interval in patients with concomitant hypokalemia	Elongation of the QT interval Feeling palpitation Tachycardia Vasodilation	Ventricular tachyarrhythmias Fainting Increase blood pressure Decrease blood pressure	Nonspecific arrhythmias Polymorphic ventricular tachycardia (Torsade de pointes) Stop hearts (mainly in people with 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		Dyspnea (including asthmatic conditions)
From the gastrointestinal side tract	Nausea Vomiting Stomach ache Diarrhea	Reduced appetite and reduced food intake Constipation Dyspepsia Flatulence Gastroenteritis (except erosive gastroenteritis) Increase activity of amylase	Dysphagia Stomatitis Pseudomembranous colitis (in very rare cases associated with life-threatening complications)
From the liver and biliary tract	Increase activity of "liver" transaminases	Violations liver function (including increased lactate dehydrogenase activity) Increase bilirubin concentration Increase activity of gamma-glutamyl transferase The 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 dermal reaction, eg, syndrome Stevens-Johnson or toxic epidermal necrolysis (potentially dangerous for life).
From the musculoskeletal and connective tissue		Arthralgia Myalgia	Tendonitis Increase muscle tone and cramps Muscular weakness	Breaks tendons Arthritis Violation gait due to damages musculoskeletal systems Gain symptoms myasthenia gravis gravis
From the side of the kidneys and urinary tract		Dehydration (caused by diarrhea or decrease admission liquid)	Impaired renal function Renal failure due to dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impaired renal function)
General disorders and injuries at the site of administration	Reactions at the injection / infusion site	General malaise Nonspecific pain 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:

Often:

Increase in activity of gamma-glutamyl transferase

Infrequently:

Ventricular tachyarrhythmias, hypotension, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), convulsions with various clinical manifestations (incl. "grand mal" seizures), 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 the use of moxifloxacin in a dose of 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 and supportive therapy with ECG monitoring.

Interaction:

When combined with atenolol, ranitidine, calcium-containing additives, theophylline, cyclosporine, 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 should be taken into account the possible additive effect of lengthening the interval QT moxifloxacin and other drugs that affect the 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 (Torsade 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, etc.);

Antiarrhythmic drugs of class III (amiodarone, sotalol, dofetilide, ibutilide, etc.);

Neuroleptics (phenothiazine, pimozide, sertindole, haloperidol, sultopride, etc.);

Tricyclic antidepressants;

Antimicrobials (sparfloxacin, erythromycin for intravenous administration, pentamidine, antimalarial drugs, especially halofantrine);

- Antihistamines (terfenadine, astemizole, misolastine);

- Others (cisapride, wincamine for intravenous administration, 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 antibacterial drugs, including moxifloxacin, there are cases of increased anticoagulant activity of anticoagulants. 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, if necessary, adjust the dose indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not have a significant impact on pharmacokinetic parameters of each other. When repeated doses of moxifloxacin were used, the maximum digoxin concentration increased by approximately 30%, while the area under the concentration-time curve (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 the drug is slightly reduced (approximately 20%) due to adsorption of moxifloxacin in the lumen of the gastrointestinal tract during enterohepatic recirculation.

Dairy products and food intake

Absorption of moxifloxacin does not change with simultaneous intake of food (including dairy products). Moxifloxacin can be used regardless of food intake.

Incompatibility

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

- 10% solution of sodium chloride;

- 20% solution of sodium chloride;

- 4.2% sodium bicarbonate solution;

- 8.4% solution of sodium bicarbonate.

Special instructions:

In some cases, after the first use of the drug may develop hypersensitivity and allergic reactions, which should immediately inform the doctor. Very rarely even after the first use of the drug, anaphylactic reactions can progress to a life-threatening anaphylactic shock. In these cases, treatment 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 may increase with increasing drug concentration, 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. Interval lengthening QT is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. 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 lengthening interval QT: congenital or acquired documented lengthening interval QT, electrolyte disorders, especially uncorrected hypokalemia, clinically significant bradycardia; clinically significant heart failure with a reduced fraction of the left ventricular ejection; in the presence of a history of rhythm disturbances, accompanied by clinical symptoms;

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

The drug 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 lengthening 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.

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.

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

The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with a risk of developing pseudomembranous colitis.This diagnosis should be kept in mind in patients who have 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, tendonitis and tendon rupture are possible, especially in the elderly and patients receiving glucocorticosteroids. 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 drug should be stopped and unloaded.

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. However, patients who use 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 with analysis of samples of patients who are treated during this period moxifloxacin.

In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor axonal polyneuropathy affecting small and (or) large axons, and leading to paresthesia, hypesthesia, dysesthesia and weakness are described. Symptoms may appear immediately after application and be irreversible. Patients treated with moxifloxacin, should be warned about the need to immediately seek medical attention in case of symptoms of neuropathy, including pain, burning, tingling,numbness and / or weakness or other sensitivity disorders, including tactile, pain, temperature, vibration sensitivity and a sense of position (see "Side effect"), Moxifloxacin must be immediately canceled.

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.

Because of the wide spread and growing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae in the treatment of patients with inflammatory diseases of the pelvic organs, monotherapy with moxifloxacin should not be carried out, except when the presence of a resistant to fluoroquinolones Neisseria gonorrhoeae excluded.If there is no way to exclude the presence of fluoroquinolones resistant Neisseria gonorrhoeae, it is necessary to resolve the issue of supplementing empirical therapy with moxifloxacin, an appropriate antibacterial drug that is active against Neisseria gonorrhoeae.

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 the use of moxifloxacin, disglycemia appeared mainly in elderly patients with diabetes mellitus receiving concomitant oral therapy hypoglycemic drugs (eg, drugs sulfonylureas) or insulin. When performing treatment in patients with diabetes, careful monitoring of the concentration of glucose in the blood is recommended.

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 chloride in moxifloxacin is 34 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 250 ml of the drug in a transparent glass bottle (type II), capped with chlorobutyl stopper and aluminum cap with a plastic lid. A label is attached to the vial.

For 1 bottle together with the instructions for use and the holder for the bottle in a cardboard box.

Storage conditions:

In the dark place at a temperature of 8 to 25 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003205

Date of registration:17.09.2015 / 25.11.2016

Expiration Date:17.09.2020

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

Hemomont d.o.o. Montenegro

Information update date: & nbsp12.06.2018

Illustrated instructions

Instructions

Moxifloxacin STADA (Moxifloxacine STADA)