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

Component	Amount, mg
Active substance:
Moxifloxacin hydrochloride (in terms of moxifloxacin)	436,4 (400,0)
Excipients (core):
Intragranular:
Croscarmellose sodium	13,60
Copovidone	20,40
Microcrystalline cellulose	116,80
Pregelatinized starch	35,00
Talc	6,80
Silica colloidal dioxide	6,80
Magnesium stearate	6,80
Extragranular:
Croscarmellose sodium	27,20
Talc	3,40
Silica colloidal dioxide	3,40
Magnesium stearate	3,40
Auxiliary substances (shell):
Opapray II white 85F18422 (polyvinyl alcohol (partially hydrolyzed) 7.89 mg, titanium dioxide 4.93 mg, macrogol 3.98 mg, talc 2.92 mg)	19,72
Iron Oxide Red Dye Oxide	0,28

Description:

Oblong, biconvex tablets of pink color, covered with a film shell with an engraving "400" on one side. On the cross-section the nucleus of the tablet is yellowish in color.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:

Mechanism of action

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 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., 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. 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. Toxin Clostridium difficile Not found.

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 strains resistant to penicillin and strains with multiple antibiotic resistance), as well as strains resistant to two or more antibiotics, such as penicillin (MIC2 μg / ml), second-generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole
Streptococcus pyogenes (group A) *
Group Streptococcus milleri (S. anginosus , S. constellatus , S. intermedius )*
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) *		Staphylococcus aureus (methicillin / mofloxacin 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 non-producing β-lactamases) *
Haemophilus parainfluenzae*
Moraxella catarrhalis (including strains producing and non-producing β-lactamases) *
Bordetella pertussis
Legionella pneumophila	Escherichia coli *
Acinetobacter baumanii	Klebsiella pneumoniae *
	Klebsiella oxytoca
	Citrobacter freundii *
	Enterobacter spp. (E. aero genes, E. intermedius, E. sakazaki)
	Enterobacter cloacae *
	Pantoea agglomerans
		Pseudomonas aeruginosa
	Pseudomonas fluoresce ns
	Burkholderia cepacia
	Stenotrophomonas maltophilia
	Proteus mirabilis *
Proteus vulgaris
	Morganella morganii
	Neisseria gonorrhoeae *
	Providencia spp. (P. rettgeri, P.stuartii)
Anaerobes
	Bacteroides spp. (B. fragilis , B. distasoni , 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;

⁺ - use of 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 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 a hospital, the area under the pharmacokinetic curve "concentration-time" (AUC) / MIK₉₀, exceeds 125, and the maximum concentration in the blood plasma (FROM_m_Oh) / 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 / MIC₉₀ >30-40

Parameter (average)	*AUIC (h)**	FROM_m_Oh/ MIC₉₀
MIC₉₀ 0,125 mg / l	279	23,6
MIC₉₀ 0.25 mg / l	140	11,8
MIC₉₀ 0.5 mg / l	70	5,9

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

Pharmacokinetics:

Absorption and bioavailability

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

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

After a single application of 400 mg of moxifloxacin, the maximum concentration (FROM_max) in the blood is reached 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 achieve FROM_m_Oh(on 2 hours) and a slight decrease FROM_m_Oh (approximately 16%), while the duration of suction does not change. However, these data have no clinical significance, and the drug can be used regardless of food intake.

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 the 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 skin lesions ). 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 organs of the abdominal cavity, peritoneal fluid, and the tissues of the 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 unmodified form and in the form of inactive sulfo compounds (Ml) 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 concentrations lower than the parent 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 the drug.

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 the different patient groups

Age, gender and ethnicity

In studies of the pharmacokinetics of moxifloxacin in men and women, differences in 33% by indicators AUC and FROM_m_Oh. Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and FROM_m_Oh 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

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

There was no significant difference in moxifloxacin concentration in patients with impaired hepatic 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 also "Specific guidance" ).

Indications:

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

- acute sinusitis;

- exacerbation of chronic bronchitis;

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

- uncomplicated skin and soft tissue infections;

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

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

- uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis), without concomitant tubo-ovarian or intranasal abscess.

* - 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 of ≥2 mg / ml), cephalosporins of the second generation (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;

- 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;

- in preclinical and clinical studies after administration of moxifloxacin, a change in the electrophysiological parameters of the heart was observed, expressed in the lengthening of the interval QT. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories: congenital or acquired documentary 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 can not be used with other drugs that extend the interval QT;

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

Carefully:

FROM caution use:

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

- in patients with psychoses and / or with psychiatric illnesses in the anamnesis;

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

- with myasthenia gravis gravis;

- in patients with cirrhosis;

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

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

- in patients with drug therapy, which can lower potassium levels (eg diuretics of the loop and thiazide type, laxatives and enemas (in large volumes), corticosteroids, amphotericin B), or drug therapy associated with clinically significant bradycardia.

Pregnancy and lactation:

Contraindicated the use of the drug during pregnancy and lactation.

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 no evidence of this effect was reported in the fetus (if the mother used it during pregnancy).

AT animal research reproductive toxicity was 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 appointment of moxifloxacin during breastfeeding is contraindicated.

Dosing and Administration:

For oral administration.

The recommended dosage regimen of moxifloxacin is 400 mg (1 tablet) once a day for the infections mentioned above. Do not exceed the recommended dose.

Tablets should be swallowed whole, not liquid, squeezed with enough water, regardless of food intake.

Duration of treatment

The duration of treatment is determined by the localization and severity of the infection, as well as the clinical effect:

- Exacerbation of chronic bronchitis: 5-10 days;

- acute sinusitis: 7 days;

- uncomplicated infections of the skin and subcutaneous structures: 7 days;

- Community-acquired pneumonia: the total duration of the stepwise therapy (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 the stepwise therapy (intravenous administration followed by oral administration) is 5-14 days;

- Uncomplicated pelvic inflammatory disease - 14 days.

Do not exceed the recommended duration of treatment.

According to clinical studies, the duration of treatment with moxifloxacin in tablets can reach 21 days.

Patents of the elderly

Changes in the dosing regimen elderly patients not required.

Children

Efficacy and safety of moxifloxacin children and adolescents to 18 years is not established.

Dysfunction of the liver

Insufficient data on the use of the drug in patients with impaired liver function (see section "Contraindications.") For use in patients with cirrhosis of the liver, see "Special instructions".

Renal insufficiency

In patients with impaired kidney function (including those with 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.

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-marketing messages (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 hematopoiesis system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, lengthening of prothrombin time / increase in international normalized ratio (INR); rarely - change in the concentration of thromboplastin; very rarely - an increase in the concentration of prothrombin / decrease in INR, agranulocytosis.

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

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

Mental disorders: infrequently - anxiety, psychomotor hyperactivity / agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts) is possible, 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 - dizziness, headache; infrequently - confusion and disorientation, vertigo, drowsiness, tremor, sleep disturbances, paresthesia / dysesthesia, disorders of taste sensitivity (including very rare cases of agevia); rarely - hypoesthesia, impaired sense of smell (including anosmia), atypical dreams, impaired coordination (including gait disturbance 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), attention disorders, speech disorders, amnesia, peripheral neuropathy and polyneuropathy, very rarely hyperesthesia.

From the side of the organ of vision: infrequently - visual impairment (especially with CNS reactions); 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 - lengthening the interval QT in patients with concomitant hypokalemia; infrequent - lengthening of the interval QT, palpitation, tachycardia, vasodilation, atrial fibrillation, angina pectoris; rarely - increased blood pressure, lower blood pressure, fainting, ventricular tachyarrhythmias; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (Torsade de pointes), cardiac arrest (mainly in persons with predisposing conditions to arrhythmia, 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 (LDH) activity), increased bilirubin concentration, increased activity of gamma-glutamyltransferase (GGT), increased alkaline phosphatase (AC) activity in the blood; rarely - jaundice, hepatitis (mostly cholestatic); rarely - fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).

From the skin and soft tissues: infrequent: dry skin; rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

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

From the side of the kidneys and urinary tract: infrequently - 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 renal dysfunction).

From the body as a whole: infrequently - general malaise, nonspecific pain, sweating, phlebitis / thrombophlebitis at the site of infusion; rarely - swelling.

The frequency of development of the following adverse reactions was higher in the group receiving the stepwise therapy:

often - increased activity of gamma-glutamyl transferase (GGT);

infrequently - ventricular tachyarrhythmias, lowering of arterial pressure, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), convulsions with various clinical manifestations (including "grand mal(seizures), hallucinations, impaired renal function, renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impaired renal function).

With prolonged intake of other fluoroquinolones,reported very rare cases of side effects that could also have been observed during moxifloxacin therapy: hypernatremia, hypercalcemia, hemolytic anemia, acute skeletal muscle necrosis, photosensitivity reactions.

If any of these instructions side effects are compounded, or if you notice any side effects not listed in this manual, report it the doctor.

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 maintenance therapy with ECG monitoring.

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

Interaction:

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

Preparations, extension intervals 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 joint application of moxifloxacin and drugs affecting the lengthening of the interval QT, it increases the risk of ventricular arrhythmias, 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 and others);

- antiarrhythmic drugs of class III (amiodarone, solatol, dofetilin, ibutiline and others);

- neuroleptics (phenothiazine, pimozide, sertindole, haloperidol, sultopride and others);

- 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 moxifloxacin concomitantly with antacid agents, multivitamins and minerals can lead to impaired moxifloxacin absorption due to the formation of chelate complexes with polyvalent cations contained in these preparations. As a result, the concentration of moxifloxacin in the blood plasma may be significantly lower than desired. In this regard, antacids, antiretroviral (for example, didanosine) and other preparations containing magnesium or aluminum, sucralfate and other preparations containing 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 parameters of blood coagulation do not change.

Change the value of INR. In patients who received anticoagulants in combination with antibiotics, 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 of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not significantly affect the pharmacokinetic parameters of each other. When repeated doses of moxifloxacin C_maxdigoxin increased by approximately 30%. The area under the concentration-time curve (AUC) and C_min digoxin do not change.

Activated carbon

With the simultaneous use of activated carbon and moxifloxacin inside at a dose of 400 mg, the systemic bioavailability of the drug 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.

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, 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.

Moxifloxacin 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 increasing drug concentration, 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 was not noted. In patients receiving moxifloxacin preparations, there were no cardiovascular complications and lethal cases associated with elongation of the inte- rest QT. When using moxifloxacin preparations, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase.

In connection with this, the drug Moxiflocacin-Alvogen contraindicated in:

- changes in the electrophysiological parameters of the heart, expressed in elongation of the QT interval: congenital or acquired documented lengthening of the QT interval, electrolyte disturbances, 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 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; 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 administered, cases of fulminant hepatitis potentially leading to hepatic insufficiency (including fatal cases) were reported (see "Side effects.") The patient should be informed that if symptoms of hepatic insufficiency occur, the doctor should be consulted before continuing drug treatment Moxifloxacin-Alvogen.

When receiving moxifloxacin preparations, cases of development of bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, were reported (see "Side effect" section). 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 Moxifloxacin-Alvogen.

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 with CNS disorders that predispose to seizures or reduce the threshold of seizure activity.

The use of broad-spectrum antibacterial drugs, including moxifloxacin preparations, 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, taking the drug should stop and unload 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.

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).

It is not recommended to use moxifloxacin for the treatment of infections caused by strains Staphylococcus aureus resistant to methylclyline (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 who are treated with the drug during this period Moxifloxacin-Alvogen.

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 Moxifloxacin-Alvogen should be warned about the need to immediately consult a doctor before continuing treatment in case of symptoms of 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 cases of development of such reactions in patients, it is necessary to cancel the drug Moxifloxacin-Alvogen and take the necessary measures.Care should be taken when using moxifloxacin preparations in patients with psychoses and / or psychiatric illnesses in history.

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 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).

Disglycemia

As in the case of other fluoroquinolones, the use of moxifloxacin preparations showed a change in the concentration of glucose in the blood, including hypo- and hyperglycemia. Against the background of therapy with moxifloxacin preparations, 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").

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:

Tablets, film-coated, 400 mg.

Packaging:

For 5 tablets, film-coated in a blister of Al // PA / Al / PVC.

For 1 or 2 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

In the original packaging in a place protected from light and moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003795

Date of registration:18.08.2016

Expiration Date:18.08.2021

The owner of the registration certificate:Alvogen IPKo S.A.L.Alvogen IPKo S.A.L. Luxembourg

Manufacturer: & nbsp

RIVOPHARM, S.A. Switzerland

Representation: & nbspAlvogen Pharma Trading EuropeAlvogen Pharma Trading Europe

Information update date: & nbsp12.06.2018

Illustrated instructions

Instructions

Moxifloxacin-Alvogen (Moxifloxacin-Alvogen)