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

Excipients: core - mannitol - 113.03 mg, silicon dioxide colloid - 28.70 mg, microcrystalline cellulose (type 102) - 114,80 mg, sodium carboxymethyl starch (type A) - 41.00 mg, giprolose - 41.00 mg, magnesium stearate - 20.50 mg, talc - 24.60 mg;

film sheath - Opapray II pink (85F240037): (partially hydrolysed polyvinyl alcohol (E1203) 40.00%, titanium dioxide (E171) 22.36%, macrogol (E1521) 20.20%, talc (E553b) - 14.80%, coloring iron oxide yellow (E172) - 1.43%, coloring iron oxide red (E172) - 1.21%) - 24.60 mg.

Description:

Oblong, biconvex tablets, covered with a film membrane, pink.

On the cross-section the nucleus is from light yellow to yellow.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:

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 moxifloxacin are generally comparable to its minimum inhibitory concentrations (MICs).

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 by multiple mutations. Multiple exposure of moxifloxacin to microorganisms at concentrations below MIC is accompanied by only a slight increase. 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., as well as bacteria resistant to beta-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: a decrease in 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

Gram-positive

Gardnerella vaginalis, Streptococcus pneumoniae* (including strains resistant to penicillin and strains with multiple antibiotic resistance), as well as strains resistant to two or more antibiotics, such as penicillin (MIC ≥ 2 μg / ml), second-generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole, Streptococcus pyogenes (group A) *, group Streptococcus milleri (S. anginosus*, S. constellatus*, S. intermedins*), Group Streptococcus viridans (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophiles, S. constellatus), Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (including methicillin-sensitive strains) *, coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), including methicillin-sensitive strains.

Gram-negative

Haemophilus influenzae (including strains producing and non-producing beta-lactamases) *, Haemophilus parainfluenzae*, Moraxella catarrhalis (including strains producing and non-producing beta-lactamases) *, Bordetella pertussis, Legionella pneumophila, Acinetobacter baumanii, Proteus vulgaris.

Anaerobes

Fusobacterium spp., Porphyromonas spp., Prevotella spp., Propionibacterium spp.

Atypical

Chlamydia pneumoniae *, Chlamydia trachomatis* Mycoplasma pneumoniae *, Mycoplasma hominis, Mycoplasma genitalium, Legionella pneumophila *, Coxiella burnetii.

Moderately sensitive

Gram-positive

Enterococcus faecalis * (strains only, sensitive to vancomycin and gentamycin), Enterococcus avium*, Enterococcus faecium*.

Gram-negative

Escherichia coli*, Klebsiella pneumoniae*, Klebsiella oxytoca, Citrobacter freundii *, Enterobacter spp. (E. aerogenes, E. intermedins, E. sakazakii), Enterobacter cloacae *, Pantoea agglomerans, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Proteus mirabilis *, 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 *), Peptostreptococcus spp. *, Clostridium spp. *.

Resistant

Gram-positive

Staphylococcus aureus (methicillin-resistant / ofloxacin-resistant strains) **, coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), resistant to methicillin strains.

Gram-negative

Pseudomonas aeruginosa.

* - sensitivity to moxifloxacin is confirmed by clinical data;

** - Use of the drug 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 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 the blood plasma (C_max) / MIC₉₀ is within the range of 8-10, this implies a clinical improvement. In outpatients, the values of these surrogate parameters are usually less: AUC / MIK₉₀ > 30-40.

Parameter (average)	*AUIC (h) for oral administration**	FROM_m_Oh/MIC₉₀
MIC₉₀0,125 mg / l	279	23,6
MIC₉₀0,25 mg / l	140	11,8
MIC₉₀ 0.5 mg / l	70	5,9

* AUIC - the area under the inhibitory curve (ratio AUC/ MIC₉₀).

Pharmacokinetics:

Suction

After oral administration moxifloxacin quickly and almost completely absorbed from the gastrointestinal tract (GIT).

Absolute bioavailability with oral administration is about 91%.

The pharmacokinetics of moxifloxacin when administered at a dose of 50 to 1200 mg once, and also at 600 mg per day for 10 days is linear. The equilibrium state is reached within 3 days.

After a single dose of moxifloxacin at a dose of 400 mg, the maximum concentration (C_mOh) in blood plasma is achieved within 0.5-4 hours and is 3.1 mg / l. After taking 400 mg of moxifloxacin once a day C_ss^maxand C_ss^min are 3.2 mg / L and 0.6 mg / L, respectively.

When moxifloxacin is taken with food, there is a slight increase in the time to reach C_mOh (at 2 h) and a slight decrease in C_mOh (approximately 16%), while the duration of absorption does not change. However, these data have no clinical significance, and the drug can be used regardless of food intake.

Distribution

The association with plasma proteins (mainly with albumins) is about 45%. Moxifloxacin quickly distributed in organs and tissues. The distribution volume is approximately 2 l / kg.

High concentrations of moxifloxacin, exceeding those in blood plasma, are reached in the lung tissue (including in the epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoid sinuses), in nasal polyps, inflammation foci (in exudate from the focus of cutaneous inflammation). In addition, high concentrations of moxifloxacin are determined in the tissues of the abdominal cavity, peritoneal fluid and female genital organs. 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 plasma.

Metabolism

After passing the 2nd phase of biotransformation moxifloxacin is excreted from the body by the kidneys, and also through the intestine, both in unmodified 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 the blood plasma at concentrations lower than the original compound.

The results of preclinical studies proved that these metabolites have no negative impact on the body in terms of safety and tolerability.

Excretion

The half-life (T_1/2) of moxifloxacin is about 12 hours.The average total clearance after taking 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 mass balance of 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 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_mOh. Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and C_mOh were due to the difference in weight rather than sex and are not considered clinically significant.

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

Children

Studies of the pharmacokinetics of moxifloxacin in children have not been conducted.

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.

Dysfunction of the liver

There were no significant differences in the concentration of moxifloxacin in patients with impaired liver function (Child-Pugh class A and B classes) compared to healthy volunteers and patients with normal liver function (for use in patients with cirrhosis, see "Contraindications ").

Indications:

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

- acute bacterial sinusitis;

- exacerbation of chronic bronchitis;

- uncomplicated infections of the skin and subcutaneous structures;

- complicated infections of the skin and subcutaneous structures (including an infected diabetic foot);

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

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

- uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).

* - Streptococcus pneumoniae with multiple antibiotic resistance include strains resistant to penicillin 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 agents.

Contraindications:

- Hypersensitivity to moxifloxacin, other quinolones or any other component of the drug;

- pregnancy and the period of breastfeeding;

- age to 18 years;

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

- use of moxifloxacin leads to lengthening of the interval QT. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories:

- 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;

- presence in the anamnesis of rhythm disturbances, accompanied by clinical symptoms;

- moxifloxacin Do not use with other drugs that extend the interval QT (see section "Interaction with other medicinal products ");

- Due to the limited number of clinical data, moxifloxacin is contraindicated in patients with impaired liver function (Child-Pugh class C) and in patients with elevated transaminases more than 5 times the upper limit of the norm (VGN).

Carefully:

- Diseases of the central nervous system (CNS) (including diseases with suspected involvement of the central nervous system in this process), predisposing to the occurrence of seizures and reducing the threshold of convulsive activity;

- psychosis and / or psychiatric illness in the anamnesis;

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

- myasthenia gravis gravis;

- cirrhosis of the liver;

- simultaneous intake of drugs that reduce the content of potassium;

- patients with a genetic predisposition or an actual deficiency of glucose-6-phosphate dehydrogenase.

Pregnancy and lactation:

Safety of moxifloxacin during pregnancy is not established, and the use of the drug Moxistar during this period is contraindicated. Cases of reversible joint damage in children taking certain quinolones have been described, but there was no reported occurrence 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 cartilaginous tissue 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 the drug Moxistar during breastfeeding is contraindicated.

Dosing and Administration:

Inside.

The drug is prescribed by mouth 1 tablet (400 mg) once a day.

Tablets should be taken without chewing, squeezed with enough water, regardless of food intake.

Duration of treatment The drug Moxistar is determined by localization, severity of infection and clinical effect:

When exacerbation of chronic bronchitis - 5-10 days.

When acute sinusitis and uncomplicated infections of the skin and subcutaneous structures - 7 days.

When community-acquired pneumonia - the total duration of stepwise therapy with moxifloxacin (intravenous (iv) administration followed by oral administration) is 7-14 days.

When 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.

When complicated intra-abdominal infections the total duration of the stepwise therapy (iv administration of the drug with subsequent ingestion) is 5-14 days.

When uncomplicated pelvic inflammatory disease - 14 days. Duration of treatment can reach 21 days.

Special patient groups

Changes in the dosing regimen the elderly patients not required.

Efficacy and safety of moxifloxacin the children and adolescents (up to 18 years) not installed.

Patients from impaired hepatic function (class A, B on the Child-Pugh scale), a change in the dosing regimen is not required.

Patients with impaired renal function (including those with severe renal insufficiency with CC <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 different ethnic groups a change in the dosage regimen is not required. Do not exceed the recommended dose and duration of treatment with Moxistar.

Side effects:

Data on adverse reactions recorded with the use of moxifloxacin 400 mg (by mouth, with stepwise therapy [iv administration of moxifloxacin followed by oral administration] and only IV) are obtained from clinical studies and post-marketing reports (highlighted 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 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).

Infectious and parasitic diseases: often - fungal superinfections.

On the part of the blood and lymphatic system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia. prolongation of prothrombin time / increase in the international normalized ratio (INR); rarely - change in the concentration of thromboplastin; very rarely - an increase in the concentration of prothrombin / decrease INR.

From the immune system: infrequently - allergic reactions, including hives, 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 and nutrition: infrequently - hyperlipidemia; rarely hyperglycemia, hyperuricemia; very rarely - hypoglycemia.

Disorders of the psyche: infrequently - a sense of anxiety, psychomotor hyperreactivity / agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts), hallucinations; very rarely - depersonalization, psychotic reactions {potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts).

From the nervous system: often - headache, dizziness; infrequent paresthesia / dysesthesia, disorders of taste sensitivity (including very rare cases of agevia), confusion and disorientation, sleep disturbances, tremor, vertigo, drowsiness: rarely - hypoesthesia, smell (including anosmia), atypical dreams, impaired coordination gait disturbances due to dizziness or vertigo, in very rare cases leading to trauma from falling, especially in elderly patients), seizures with various clinical manifestations (including "grand mal" seizures), disturbances Imanias, speech disorders, amnesia, peripheral neuropathy, polyneuropathy; very rarely hyperesthesia.

From the side of the organ of vision: infrequently - visual impairment (especially with reactions from the central nervous system); very rarely - 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: rarely - noise in the ears, hearing impairment, including deafness (usually reversible).

From the side of the cardiovascular system: often - prolongation of the QT interval in patients with concomitant hypokalemia; infrequent - prolongation of the QT interval, palpitation, tachycardia, vasodilation: rarely - ventricular tachyarrhythmias, fainting, increased blood pressure, lower blood pressure; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (torsade de pointes), cardiac arrest (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: infrequently - shortness of breath, including asthmatic condition.

From the gastrointestinal tract: often - nausea, vomiting, abdominal pain, diarrhea; infrequent - reduced appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (other than 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; infrequent liver function disorders (including increased lactate dehydrogenase activity), increased bilirubin concentration, increased activity of gamma-glutamyl transferase (GGT), and alkaline phosphatase; rarely - jaundice, hepatitis (mostly cholestatic); very rarely - fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).

From the skin and subcutaneous tissues: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening, see the section "Special instructions").

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

From the side of the kidneys and urinary tract: infrequent - dehydration (caused by diarrhea or decreased fluid intake); rarely - renal dysfunction, renal failure due to dehydration, which can lead to kidney damage,especially in elderly patients with pre-existing impaired renal function.

General disorders and disorders at the site of administration: infrequently - general malaise, nonspecific pain, sweating; rarely - swelling.

The frequency of development of the following adverse reactions was higher in the group receiving stepwise therapy: often - increased GGT activity; infrequently - ventricular tachyarrhythmias, decreased blood pressure, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including "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.

Treatment: In case of an overdose, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

In case of an overdose with the use of tablets, the use of activated charcoal at an early stage of absorption prevents further increase in the systemic effect.

Interaction:

There is no clinically significant interaction when combined with: atenolol, ranitidine, calcium-containing additives, theophylline, cyclosporine, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid. Correction of the dosing regimen when combined with these drugs 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 the drug Moxistar with the following drugs affecting the lengthening of the interval QT:

- Antiarrhythmic drugs class IA (quinidine, hydroquinidine, disopyramide, etc.);

- Antiarrhythmic drugs of class III (amiodarone, sotalol, dofetilide, ibutilide and other);

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

- Tricyclic antidepressants;

- Antimicrobials (sparfloxacin, erythromycin (intravenously), pentamidine, antimalarial drugs, especially halofantrine);

- Antihistamines (terfenadine, astemizole, misolastine);

- Others (cisapride, wincamine (intravenously), bepridil, difemanyl).

Antacids, multivitamins and minerals

The administration of the drug Moxistar simultaneously with antacids, polyvitamins and minerals can lead to impaired absorption of moxifloxacin, due to the formation of chelate complexes with polyvalent cations contained in these preparations. As a result, the concentration of moxifloxacin can be significantly reduced. In this regard, antacid, antiretroviral drugs (for example, didanosine) and other drugs containing magnesium, aluminum, sucralfate, iron or zinc, should be taken at least 4 hours before or 4 hours after ingestion of moxifloxacin.

Warfarin

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

Changing the value of the MPR

In patients who received anticoagulants in combination with antibiotics, including moxifloxacin. there are 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. that interaction between moxifloxacin and warfarin is not revealed, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the INR and. if necessary, adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not significantly affect the 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 minimal digoxin concentration did not change.

Activated carbon

With the simultaneous use of activated carbon and moxifloxacin inside at a dose of 400 mg, the systemic bioavailability of moxifloxacin is reduced by more than 80% as a result of inhibition of its absorption. In the case of an overdose, the use of activated carbon at an early stage of absorption inhibits further increase in systemic exposure.

Glucocorticosteroids

With the simultaneous use of the drug Moxistar and glucocorticosteroids, the risk of tendonitis and rupture of tendons increases.

Special instructions:

Allergic reactions

In some cases, even after the first use of fluoroquinolones, including after the use of this drug, hypersensitivity and allergic reactions may develop, which should be reported immediately to 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 with the drug Moxistar should be stopped and immediately begin to carry out the necessary medical measures (including anti-shock).

The elongation of the QT interval

With the use of the drug Moxistar in some patients may be an extension of the interval QT. The drug Moxistar should be used with caution in women and elderly patients. 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 an increase in the concentration of moxifloxacin in the blood plasma, therefore, do not exceed the recommended dose. However, in patients with pneumonia, the correlation between the concentration of moxifloxacin in the blood plasma and the lengthening of the interval QT it was noted. None of the 9,000 patients who received moxifloxacin, there were no cardiovascular complications and lethal cases associated with lengthening the interval QT. When using the drug Moxistar may increase the risk of ventricular arrhythmias in patients with predisposing to arrhythmias.

In this regard, the drug Moxistar contraindicated when:

- changes in the electrophysiological parameters of the heart, expressed in the lengthening of the 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; presence in the anamnesis of rhythm disturbances, accompanied by clinical symptoms;

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

The drug Moxistar should be used carefully:

- 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).

Severe hepatic impairment

When moxifloxacin was taken, cases of the development of fulminant hepatitis, potentially leading to the development of hepatic insufficiency (including fatal cases) were reported (see section Side effect). The patient should be informed that if symptoms of fulminant hepatitis (such as rapidly developing asthenia, accompanied by jaundice, darkening of the urine, increased bleeding, or hepatic encephalopathy) appear, consult a doctor before continuing with the drug.

A liver function test should be performed in case of signs of liver dysfunction.

Severe bullous lesions of skin

When moxifloxacin was taken, cases of developing bullous skin lesions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, were reported (see "Side effect"). The patient should be informed that in case of symptoms of skin or mucous membrane damage, the doctor should be consulted before continuing treatment with the drug.

Patients with a predisposition to develop seizures

The use of drugs quinolone series is associated with a possible risk of seizures. The drug Moxistar should be used with caution in patients with CNS diseases and with violations of the CNS,predisposing to the occurrence of seizures or reducing the threshold of convulsive activity. In case of seizures, treatment with the drug should be discontinued and appropriate treatment initiated.

Diarrhea caused by taking antibiotics, including pseudomembranous colitis

The use of broad-spectrum antibacterial drugs, including the drug Moxistar. is associated with a risk of developing antibiotic-associated diarrhea and colitis, including pseudomembranous colitis, and antibiotic-associated diarrhea of an infectious nature caused by Clostridium difficile. This diagnosis should be borne in mind in patients who are on the background of treatment with the drug Moxistar or at the end of treatment there is severe diarrhea. In case of suspicion of diarrhea caused by taking antibiotics, or colitis, and if these diagnoses are confirmed, treatment should be stopped with antibacterial drugs, including the drug Moxistar, and immediately appropriate treatment. In the case of the infectious nature of the disease, appropriate measures should be taken to prevent the spread of infection.Preparations that inhibit the intestinal peristalsis are contraindicated in the development of severe diarrhea.

Patients with myasthenia gravis

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

Inflammation and rupture of tendons

Against the background of quinolone therapy, including moxifloxacin, especially in elderly patients and patients receiving glucocorticosteroids, it is possible to develop inflammation (tendinitis) and tendon rupture (especially Achilles tendon), sometimes on both legs. The cases of the development of these phenomena 48 hours after the initiation of moxifloxacin therapy, as well as several months after the end of treatment, are described.

With the first symptoms of pain or inflammation in the tendon area, stop taking the medication, reduce the load on the affected limb and inform the treating doctor about it, so that it takes appropriate measures (for example, immobilization of the affected limb) (see "Contraindications " and "Side effect").

Prevention of photosensitivity reactions

When applying quinolones, photosensitivity reactions are noted.However, when conducting studies in moxifloxacin, a lower risk of photosensitivity reactions was noted. Nevertheless, patients taking the drug Moxistar should avoid exposure to direct sunlight and ultraviolet light.

Patients with complicated pelvic inflammatory disease

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).

Inflammatory diseases of the pelvic organs can be caused by a 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 N. gonorrhoeae excluded. If there is no way to exclude the presence of fluoroquinolones resistant N. gonorrhoeae it is necessary to resolve the issue of supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. gonorrhoeae (e.g., cephalosporin).In the absence of a clinical response to treatment with the drug Moksistar within three days of therapy should be reviewed.

Patients with infectious diseases caused by MRSA

It is not recommended to use the drug Moxistar 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 section "Pharmacodynamics ").

Impact on laboratory tests

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 who undergo drug treatment during this period.

Peripheral Neuropathy

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 the drug Moxistar should be warned about the need for immediatetreatment to the doctor before continuing treatment in case of symptoms of neuropathy, including pain, burning, tingling, numbness or weakness (see "Side effect").

Mental disorders

Even after the first use of fluoroquinolones, including moxifloxacin, the development of mental disorders was reported. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a propensity for self-harm, including suicidal attempts (see "Side effect"). When developing these reactions in a patient, the drug should be discontinued and appropriate measures taken. Caution should be exercised when using the drug Moxistar in patients with psychoses and / or with psychiatric illnesses in the anamnesis.

Disglycemia

As in the case of other fluoroquinolones. when using the drug Moxistar, there may be a change in the concentration of glucose in the blood, including hypo- and hyperglycemia. On the background of moxifloxacin therapy, disglycemia occurs mainly in elderly patients with diabetes mellitus who received concomitant therapy with oral hypoglycemic drugs (eg, sulfonylureas) or insulin.When performing treatment in patients with diabetes, careful monitoring of the concentration of glucose in the blood is recommended (see section "Side effect").

Visual impairment

If there is a visual impairment, you should immediately seek advice from an ophthalmologist (see "Side effect" and "Influence on the ability to drive vehicles and mechanisms ").

Patients with deficiency of glucose-6-phosphate dehydrogenase

In patients with a family history or suffering from a deficiency of 6-phosphate dehydrogenase, there is a predisposition to the development of hemolysis during treatment with quinolones. In this group of patients, the drug Moxistar should be used with caution.

Childhood

Due to the fact that in the preclinical studies of moxifloxacin, the effect on young cartilage tissue of animals was revealed, the use of the drug Moxistar in children and adolescents under the age of 18 is contraindicated.

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

Fluoroquinolones, including the drug Moxistar, can impair the ability of patients to drive vehicles and engage in other potentially hazardous activities,requiring increased attention and speed of psychomotor reactions, due to impaired vision and influence on the central nervous system (dizziness, fainting).

Form release / dosage:

Tablets, film-coated, 400 mg.

Packaging:

For 5, 7 or 10 tablets in Al / Al blister.

By 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003838

Date of registration:14.09.2016

Expiration Date:14.09.2021

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

PHARMATEN, SA Greece

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp11.06.2018

Illustrated instructions

Instructions

Moxistar (Moxistar)