Avelox - instructions for use of the drug, structure, Contraindications

Active material: Moxifloxacin
When ATH: J01MA14
CCF: Fluoroquinolone antibacterial drug
ICD-10 codes (testimony): J01, J15, J42, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, N70, N71, N72, N73.0
Manufacturer: BAYER HealthCare AG (Germany)

Avelox: dosage form, composition and packaging

Pills, coated Pink colour, matt, oblong, convex, with overprint in the form of the logo “BAYER” on the one hand and “M400” – with reverse; of presentations – homogeneous mass from white to light yellow with a greenish tint, surrounded by Pink-coated.

Excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, gipromelloza, iron oxide red, macrogol 4000, Titanium dioxide.

5 PC. – blisters (1) – packs cardboard.
5 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (1) – packs cardboard.

Solution for infusion clear, greenish yellow.

Excipients: sodium chloride, Sodium hydroxide, hydrochloric acid, water d / and.

250 ml – glass bottles (1) – cardboard boxes.
250 ml – Polyolefin bags (1) – plastic bags, laminated foil (12) – cardboard boxes.

Avelox: pharmachologic effect

Fluoroquinolone antibacterial drug. It has bactericidal activity. The mechanism of action is due to inhibition of bacterial topoizomeraz (II) and (IV), that leads to disruption of DNA synthesis of microbial cells and, Consequently, the deaths of microbial cells. Minimum bactericidal concentrations of the drug generally comparable to his MEEK.

In vitro drug active against a wide range of gramotricationah and grampolaugitionah microorganisms, anaerobes, acid-resisting bacteria and atypical forms of, such as Mycoplasma spp., Chlamidia spp., Legionella spp., as well as bacteria, resistant to β-lactam and macrolide antibiotics.

By Aveloksu^® sensitive Gram-positive aerobic bacteria: Streptococcus pneumoniae (including strains, resistant to penicillin and macrolides), Streptococcus pyogenes (Group a)*, Streptococcus milleri, Streptococcus, Streptococcus agalactiae *, Streptococcus dysgalactiae, Streptococcus anginosus *, Streptococcus constellatus *, Staphylococcus aureus (including Methicillin-sensitive strains)*, Staphylococcus cohnii, Staphylococcus epidermidis (including Methicillin-sensitive strains), Staphylococcus haemolyticus, Staphylococcus man, Staphylococcus saprophyticus, Staphylococcus simulating, Corynebacterium diphtheriae, Enterococcus faecalis (only strains, susceptible to vancomycin and gentamicin)*; Gram-negative aerobic bacteria: Haemophilus influenzae (including strains, producing and non-producing β-lactamase)*, Haemophilus parainfluenzae*, Klebsiella pneumoniae*, Moraxella catarrhalis (including strains, producing and non-producing β-lactamase)*, Escherichia coli*, Enterobacter cloacae*, Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus the wonderful*, Proteus vulgaris, Morganella morganii, Rettgeri Providence, Providence stuartii, Gardnerella vaginalis; anaerobic bacteria: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis*, Bacteroides ovatus, Bacteroides thetaiotaomicron*, Bacteroides uniform, Fusobacterium spp., Peptostreptococcus spp. *, Porphyromonas spp. (incl. Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus), Prevotella spp., Propionibacterium spp., Clostridium perfringens *, Clostridium ramosum; atypical bacteria: Chlamydia pneumoniae *, Mycoplasma pneumoniae *, Legionella pneumophila *, Coxiella burnettii, Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium.

Moxifloxacin less active against Staphylococcus aureus (strains, resistant to metitillino/ofloxacin)*, Staphylococcus epidermidis (strains, resistant to metitillino/ofloxacin)*, Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Neisseria gonorrhoea.

Machinery, leading to the development of resistance to Penicillins, cephalosporins, aminoglycosides, macrolides and tetracycline, do not violate the antibacterial activity of moxifloxacin. Cross-resistance between these groups of antibacterial drugs and no moksifloksacinom. So far there have been no cases also of plasmid stability. The overall incidence of very weak sustainability (10^-7-10^-10). Outbreaks of resistance develops slowly through multiple mutations. Repeated exposure to moxifloxacin on micro-organisms at concentrations below MICK accompanied by only a slight increase in the MICK.

There are cases of cross-resistance to hinolonam. Nonetheless, some resistant to other hinolonam Gram-positive and anaerobic microorganisms sensitive to outbreaks.
* sensitivity to outbreaks confirmed clinical data.

Avelox: pharmacokinetics

Absorption

After intake of moxifloxacin is absorbed rapidly and almost completely. After receiving a single dose of moxifloxacin 400 mg C_max Blood achieved within 0.5-4 h and is 3.1 mg / l. When receiving moxifloxacin with food noted a slight increase in time with_max (on 2 no) and a slight decrease from_max (approximately 16%), duration of absorption is not changed. However, these data do not have clinical significance, and the drug can be used regardless of the meal.

After a single infusion Aveloksa^® dose 400 mg for 1 h C_max achieved at the end of the infusion and is 4.1 mg / l, that matches her increased approximately 26% compared to the value of this indicator ingestion. When multiple in/infuziah in dose 400 mg for a period of 1 h C_max varies in the range from 4.1 mg/l to 5.9 mg / l. Middle C_ss, equal 4.4 mg / l, achieved at the end of infusion.

The absolute bioavailability of approximately 91%.

Pharmacokinetics of moxifloxacin in one-time doses from 50 mg 1200 mg, as well as a dose of 600 mg / day for 10 days is linear.

Distribution

The equilibrium is achieved within 3 days.

Linking blood protein (mainly albumin) is about 45%.

Moxifloxacin rapidly distributed in the tissues and organs. V_d approximately 2 l / kg.

High concentrations of the drug, exceeding such in plasma, created in lung tissue (incl. in alveolar macrophages), in the bronchial mucosa, in the nasal sinuses, soft tissue, skin and subcutaneous structures, hotbeds of inflammation. In the interstitial fluid and saliva drug defined freely, not associated with the protein form, at concentrations above, than in plasma. Besides, high concentrations of the drug are defined in the abdominal organs and peritoneal fluid, as well as in the tissues of the female genital organs.

Metabolism

Biotransformiroetsa to inactive glukuronidov and sul'fosoedinenij.

Moxifloxacin is biotransformation mikrosomalnami liver enzymes zitohroma r450.

Deduction

After passing 2-phase biotransformation moxifloxacin is excreted through the kidneys and intestines as unchanged, and in the form of inactive glukuronidov and sul'fosoedinenij.

Excreted in the urine, as well as feces, as unchanged, and in the form of inactive metabolites. When a single dose of 400 about mg 19% excreted unchanged in the urine, about 25% – with feces. T_1/2 is approximately 12 no. The average total clearance after admission to dose 400 mg is from 179 ml / min to 246 ml / min.

Pharmacokinetics in special clinical situations

Not found differences in the pharmacokinetic parameters of moxifloxacin depending on age, sex and race.

Research pharmacokinetics of moxifloxacin in children have not been conducted.

Not revealed significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (incl. at CC<30 ml / min / 1.73 m²) and those on continuous hemodialysis and long-term ambulatory peritoneal dialysis.

In patients with mild and moderate human liver (class a or b on a scale Child-Pugh) pharmacokinetics of moxifloxacin does not change. In patients with severe violations of the liver (class C Child-Pugh) data on the pharmacokinetics of moxifloxacin there.

Avelox: testimony

Infectious and inflammatory diseases in adults, caused by susceptible to malaria infections:

- Ostryi sinusitis;

- Community-acquired pneumonia (incl. caused by strains of microorganisms with multiple antibiotic resistance *);

- Exacerbation of chronic bronchitis;

-uncomplicated skin and soft tissue infections;

— complicated skin infections and subcutaneous structures (including the infected diabetic foot);

— acute intraabdominal infection, including polymicrobial infections, incl. intraperitoneal abscesses;

-uncomplicated pelvic inflammatory disease (incl. salpingitis and endometritis).

* – Streptococcus pneumoniae with multiple antibiotic resistance include strains, resistant to penicillin, strains and, resistant to two or more antibiotics from such groups, like Penicillins (at the lowest concentrations ≥ overwhelming 2 mg/ml), II generation cephalosporins (cefuroxime), makrolidы, tetracyclines and trimethoprim / sulfamethoxazole.

Avelox: dosing regimen

The agent shall inside and/on 400 mg 1 time / day.

Duration of treatment Aveloksom^® the ingestion and/in the introduction was determined by the seriousness of the infection and clinical effect and is: at exacerbation of chronic bronchitis – 5 days; at community-acquired pneumonia the total duration of the step therapy (in/in the introduction followed by inside) – 7-14 in the first days/, then inside, or 10 days inside; at acute sinusitis and uncomplicated skin and soft tissue infections – 7 days; at complicated infections of skin and subcutaneous tissue – the total duration of the step therapy (in/in the introduction followed by inside) is 7-21 day; at complicated intraabdominal'nyh infections – the total duration of the step therapy (in/in the introduction of the drug followed by inside) is 5-14 days; at normal inflammatory pelvic diseases -14 days.

Duration of treatment Aveloksom^® in/in can reach 14 days, inside – 21 day.

Elderly patients, patients with mild liver (class a or b on a scale Child-Pugh), patients with impaired renal function (incl. at CC <30 ml / min / 1.73 m²), and patients, in continuous hemodialysis and long-term ambulatory peritoneal dialysis, changes the dosage is not required.

Tablets should be taken, without chewing, with a little water, regardless of the meal.

Solution for infusion should be in/in slowly over 60 m. The product can be entered as in diluted, and undiluted. Solution Aveloksa^® compatible with the following solutions: Water for Injection, sodium chloride solution 0.9%, 1 m solution of sodium chloride, Dextrose 5%, Dextrose 10%, Dextrose 40%, solution of xylitol 20%, Ringer, solution Ringer-lactate, solution aminofuzina 10%, solution jonosterila. You should only use a transparent solution.

Avelox: side effects

Data about the side effects of the drug moxifloxacin 400 mg (the ingestion and step therapy) obtained from clinical studies and postmarketingovyh messages.

Determination of the frequency of adverse reactions: often (> 1%, < 10%), sometimes (> 0.1%, <1%), rarely (> 0.01%, <0.1%), rarely (< 0.01%).

Adverse events, classified as “often” observed less than 3% patients, In addition to nausea and diarrhea.

Cardio-vascular system: QT prolongation (often – in patients with concomitant gipokaliemiei, sometimes – in the remaining patients); sometimes – tachycardia and vasodilation (flushing); rarely – hypotension, arterial hypertension, swoon, jeludockove tahiaritmii; rarely – nonspecific arrhythmia (including jekstrasistoliju), polymorphic ventricular tachycardia (type of ventricular arrhythmia “pirouette”) or cardiac arrest in patients with predominantly predraspolagatmi to arrhythmias States, such as clinically significant bradycardia, acute myocardial ischaemia.

The respiratory system: sometimes – breathlessness, including astmaticescoe State.

From the digestive system: often – nausea, vomiting, stomach ache, diarrhea, transient increase transaminaz; sometimes – anorexia, constipation, dyspepsia, flatulence, gastroenteritis (Besides the erosive gastroenteritis), increase the level of amylase, bilirubin, abnormal liver function (including increasing the level of LDH), increased activity of GGT and ALP; rarely – dysphagia, stomatitis, psevdomembranoznыy colitis (in very rare cases associated with life-threatening complications), jaundice, hepatitis (mostly cholestatic); rarely – fulminant hepatitis, potentially resulting in zhizneugrozhajushhej of hepatic failure.

From the central and peripheral nervous system: often – dizziness, headache; sometimes – confusion, consciousness, disorientation, vertigo, drowsiness, tremor, paresthesia, dysesthesia, sleep disorders, anxiety, increased psychomotor activity, ažitaciâ; rarely – gipesteziya, abnormal dreams, incoordination (including violations of gait because of dizziness, in very rare cases, leading to injuries resulting from a fall, especially in elderly patients), convulsive fits with different clinical manifestations (incl. grand mal seizures), attention deficit disorder, speech disorder, amnesia, emotional lability, depression (in very rare cases it is possible to conduct with a tendency to samopovrezhdeniju), hallucinations; rarely – giperesteziya, depersonalization, psychotic reactions (potentially manifest in behavior with a tendency to samopovrezhdeniju).

From the senses: sometimes – disorders of taste, visual disturbances (blurring, reduced visual acuity, diplopia, especially in combination with dizziness and sputannostew consciousness); rarely – noise in ears, violation of smell, including anosmia; rarely – loss of taste sensitivity.

From the hematopoietic system: sometimes – anemia, leukopenia (including neutropenia), thrombocytopenia, thrombocytosis, the lengthening of the prothrombin time and INR reduction; rarely – change in the concentration of thromboplastin; rarely – increasing the concentration of prothrombin and decrease in INR, change in the concentration of prothrombin and INR.

On the part of the musculoskeletal system: sometimes artralgia, myalgia; rarely – Tendinitis, increased muscle tone and muscle cramps; rarely – tendon rupture, arthritis, gait due to damage to the musculoskeletal system.

On the part of the reproductive system: often – kandidoznaya superinfection, vaginitis.

From the urinary system: sometimes – degidratatsiya (caused by diarrhoea or decrease fluid intake); rarely – impairment of renal function, kidney failure as a result of dehydration, that can lead to kidney damage (particularly in elderly patients with the human kidney).

Dermatological reactions: rarely – Bullous skin reactions, eg, Stevens-Johnson Syndrome or toxic Epidermal Necrolysis (potentially dangerous for life).

Allergic reactions: sometimes – hives, itch, rash, eozinofilija; rarely – anaphylactic / anaphylactoid reaction, angioedema, including laryngeal edema (potentially life-threatening); rarely – anaphylactic shock (incl. life-threatening).

Metabolism: hyperlipidemia, giperglikemiâ, hyperuricemia.

From the body as a whole: sometimes – general malaise (including symptoms of ill health, nonspecific pain and sweating); rarely – swelling.

Avelox: Contraindications

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years;

-increased sensitivity to outbreaks and other components of the drug.

FROM caution apply for diseases of the CENTRAL NERVOUS SYSTEM (incl. for diseases, suspicious regarding the involvement of the CENTRAL NERVOUS SYSTEM), predisposing to the emergence of convulsions stroke and reduce the threshold sudorojna preparedness, When extending the QT interval, hypokalemia, ʙradikardii, acute myocardial ischemia, together with the admission of drugs, prolonging the QT interval, and antiaritmicakimi means IA and III classes, with severe liver failure.

Avelox: Pregnancy and lactation

Safety of Aveloksa^® during pregnancy has not been established, therefore its use is contraindicated.

A small amount of moxifloxacin is excreted in breast milk. Data on the use of moxifloxacin in women during lactation are not available. Therefore, the use of Aveloksa^® breastfeeding is also contraindicated.

IN experimental studies When examining the influence of moxifloxacin on reproductive function in rats, rabbits and monkeys proved, that moxifloxacin penetrates through the placental barrier. Research, conducted on rats (with the introduction of moxifloxacin inside and/) and monkeys (with the introduction of moxifloxacin inside), revealed no teratogenic action of moxifloxacin and its influence on fertility. When in/with the introduction of rabbits at a dose of moxifloxacin 20 mg/kg of skeletal malformations were observed. Revealed an increase in the number of miscarriages in monkeys and rabbits in the application of moxifloxacin in therapeutic dose. In rats decreased fetal weight, frequent miscarriages, a slight increase in the duration of pregnancy and increased spontaneous activity of the offspring of both sexes in the application of moxifloxacin, dose which 63 times recommended.

Avelox: Special instructions

It should be taken into account, that the appointment of Aveloksa^® increases the risk of convulsions stroke, so proceed with caution shall mean patients with diseases of the CENTRAL NERVOUS SYSTEM, causing convulsions or conducive to their development, or lowering the threshold sudorojna preparedness, as well as in case of such diseases and conditions.

We do not recommend the use of the drug in patients with severely impaired hepatic function (class C on the scale of Child-Pugh) due to the lack of sufficient clinical data.

We do not recommend the use of the drug in patients with complicated pelvic inflammatory diseases (eg, associated with tuboovarial'nymi or pelvic abscess).

When applying Aveloksa^® some patients may be observed elongation QT interval. Therefore, you should avoid the drug for patients with elongation QT interval, gipokaliemiei, as well as treatment with antiarrhythmic drugs class I A (quinidine, prokaynamyd) or class III (Amiodarone, sotalol), Since the experience of application of moxifloxacin in these patients is limited. Should be cautious appoint antibacterial drugs^® together with drugs, that lengthened QT interval (cisapride, Erythromycin, antipsychotics, tricyclic antidepressants), as well as patients with a predisposition to arrhythmias States, such as aetiology, acute myocardial ischaemia. Degree of elongation QT interval may increase with increasing concentrations of the drug, Therefore, you should not exceed the recommended dose. Elongation QT interval is associated with increased risk of ventricular arrhythmias, including the polymorphous ventricular tachycardia. In patients with pneumonia found no correlation between the concentration of moxifloxacin in blood plasma and elongation QT interval. None of the 9000 patients, treated with moxifloxacin, There was no associated with elongation QT cardiovascular complications and deaths. However, in patients with predraspolagatmi to arrhythmias States in the application of moxifloxacin may increase the risk of ventricular arrhythmias.

The therapy fluoroquinolones, incl. moxifloxacin, especially in the elderly and patients, receiving corticosteroids, the development of Tendonitis and tendon rupture. When you see the pain or signs of inflammation of the tendon to stop taking Aveloksa^® and decongest the affected limb.

The use of broad-spectrum antibacterial drugs carries a risk of psevdomembranoznogo colitis. This should be borne in mind when the treatment occurs Aveloksom^® severe diarrhea. In this case, the drug should be lifted immediately and appoint appropriate therapy.

There is a risk of hypersensitivity reactions and anaphylactic reactions when use of the drug. Very rare anaphylactic reaction can progress to anaphylactic shock. In such cases, the drug should cease immediately and that appropriate resuscitation (incl. anti-shock means).

In the application of quinolones marked photosensitivity reactions. However, preclinical, Clinical Research, as well as in the application Aveloksa^® in clinical practice, there has been no reactions fotosencibilization. Nonetheless, patients during the period of administration of the drug should avoid direct sunlight and UV radiation.

Patients of different ethnic groups do not require dose adjustment.

Use in Pediatrics

Effectiveness and safety of drug antibacterial drugs^® in children and adolescents is not installed.

Effects on ability to drive vehicles and management mechanisms

Despite, that moxifloxacin rarely causes adverse reactions on the part of the CENTRAL NERVOUS SYSTEM, asked about the possibility of driving or moving mechanisms individually after assessing the reaction of the patient receiving medication.

The results of experimental studies

The following pathological changes are manifestations of the toxic effects of moxifloxacin, like other fluoroquinolones: blood system (gipoplasia bone marrow in dogs and monkeys), CNS (convulsions in monkeys) and liver (increase in liver enzymes, single necrosis of hepatocytes in rats, dogs and monkeys). These violations occur, usually, After a long period of introduction of moxifloxacin in high doses.

Avelox: overdose

There has been no side effects when applying Aveloksa^® at a dose of 1200 mg once and software 600 mg over 10 days.

Treatment: in the case of an overdose, in accordance with the clinical situation simptomaticescuu therapy with ECG-monitoring. Application of activated carbon are expedient only if an overdose of moxifloxacin in pill form.

Avelox: drug interaction

No dose adjustment is required when Aveloksa^® with atenolol, ranitidine, kal'cijsoderzhashhimi additives, theophylline, oral contraceptives, glibenclamide, itraconazole, digoksinom, morphine, Probenecid (confirmed the absence of clinically meaningful interaction with moksifloksacinom).

Joint application of inside Aveloksa^® and antacids, minerals and vitamin-mineral complexes can disrupt the absorption of moxifloxacin due to formation of chelate complexes with cations polivalentnymi, contained in these preparations, and hence, reduce the concentration in the blood plasma of moxifloxacin. In this regard, antacid, antriretrovirusnye and other drugs, containing calcium, magnesium, aluminum, iron, sucralfate should take at least 4 hours before or after 2 hours after the intake of Aveloksa^®.

When combined with the application of Aveloksa^® Prothrombin time with warfarin and other blood coagulation parameters do not change.

Patients, receiving anticoagulants in combination with antibiotics, incl. with moksifloksacinom, There are instances of increase of Anticoagulant activity of anti-coagulants. Risk factors are the existence of infectious disease (and its accompanying inflammatory process), age and general condition of the patient. Despite, that interaction between warfarin and moksifloksacinom not detected, patients, receiving combined treatment with these drugs, It is necessary to conduct monitoring of MND and adjust dose of oral anti-coagulants.

Moxifloxacin and digoxin had little influence on the pharmacokinetic parameters of each other. When reappointing the moxifloxacin (C)_max digoxin increased approximately 30%. While the ratio of AUC and C_mix digoxin does not change.

Together with the use of activated charcoal and inside the dose of moxifloxacin 400 mg system bioavailability of drug reduces more, than 80% as a result of slowing its absorption. In the case of an overdose of application of activated carbon at an early stage prevents further increase suction system impact.

The absorption of moxifloxacin remains unchanged while eating (including dairy products). Moxifloxacin can be taken regardless of mealtimes.

Avelox: terms of dispensing from pharmacies

The drug is released under the prescription.

Avelox: terms and conditions of storage

List B. Tablets should be stored in a place inaccessible to children, dry place at temperatures no higher than 25 ° C. Shelf life – 5 years.

List B. Solution for infusion should be stored in a dry, the dark and out of reach of children at a temperature from 8° to 25° c; Do not freeze. Shelf life – 5 years.

After breeding compatible solvents solution Aveloksa^® It remains stable for 24 hours at room temperature. Because the solution cannot be to freeze or cool, It cannot be stored in the refrigerator. When cooling solution can precipitirovat', However, at room temperature, typically precipitate dissolves. The solution should be stored only in the original container.