Avelox (Moxifloxacin) 400mg 5 tablets

The composition and form of issue: 

Tablets, film-coated. 1 tablet contains:

moxifloxacin hydrochloride 436,8 mg

(corresponds to the base of moxifloxacin — 400 mg) 

excipients: lactose monohydrate — MCC 68 mg of 136 mg of croscarmellose sodium — 32 mg magnesium stearate 6 mg hypromellose iron oxide yellow macrogol 4000 titanium dioxide 

shell: hypromellose — 9-12 mg iron oxide red — 0,3–0,42 mg macrogol 4000 — 3-4,2 mg titanium dioxide — 2,7–3,78 mg 

in blistere 5 or 7 PCs per box 1 or 2 blister pack (5 pieces each) or 1 box (7 PCs.).

Solution for infusion. 250 ml contains:

moxifloxacin hydrochloride 436,8 mg

(corresponds to the base of moxifloxacin — 400 mg) 

auxiliary substances: sodium chloride 2 g hydrochloric acid 1N — 0,00–0,02 g sodium hydroxide solution 2N of 0.00–0.05 g water for injection 248,659–248,664 g 

in bottles of 250 ml cartons 1 a bottle.

Description pharmaceutical form:

Tablets: pink matte, oblong, convex, film-coated, napechatal in the form of the brand name “BAYER” on one side and “M400” on the other. Kind of on a break: homogeneous mass of white to light yellow with a greenish tint, surrounded by a film cover pink.

Infusion solution: clear solution, greenish-yellow color.

Feature:

Antimicrobial agent is a fluoroquinolone.

Pharmacokinetics:

Absorption and bioavailability. In oral administration is absorbed rapidly and almost completely. The absolute bioavailability of approximately 91%.

The pharmacokinetics of moxifloxacin when used in a dose of from 50 to 1200 mg once daily, and 600 mg/day for 10 days is linear. Steady state is achieved within 3 days.

After a single purpose 400 mg moxifloxacin C Max in the blood is achieved within 0.5–4 h and is 3.2 mg/L.

When taken with meals, a slight increase in time to reach Cmax (2 h) and a slight decrease in Cmax (approximately 16%), the duration of absorption is not changed. However, these data do not have clinical significance, and the drug can be applied regardless of the meal.

After a single infusion at a dose of 400 mg during 1 hour, the Cmax achieved at the end of the infusion and amounts to approximately 4,1 mg/l, which corresponds to its increase by approximately 26% compared to the value of this index when taking the drug inside. The exposition of the drug measured by AUC (area under the curve concentration-time) after the on/in the introduction, slightly greater than that in the employment drug inside. After repeated in/in infusion at a dose of 400 mg 1 h C Max ranges from 4.1 to 5.9 mg/L. The average stable concentration equal to 4.4 mg/l, achieved at the end of the infusion.

Distribution. Moxifloxacin is rapidly distributed in tissues and organs and is associated with the blood protein (mainly albumin) by about 45%. The volume of distribution is approximately 2 l/kg High concentrations of the drug than those in plasma, created in the lung tissue (alveolar macrophages) in the bronchial mucosa, the nasal sinuses, in the exudate of lesion of skin inflammation (for solution for infusion — the contents of bubbles in inflammatory lesions of the skin). In the interstitial fluid and in the saliva of the drug is determined in a free, not associated with the protein form, in concentrations higher than in plasma. In addition, high concentrations of the drug are determined in the abdominal organs and peritoneal fluids, and in tissues of the female genital organs.

Metabolism. After passing the 2nd phase of biotransformation moxifloxacin is excreted by the kidneys and gastrointestinal tract in an unmodified form and in the form of inactive glucuronides and sulfasalizine. Moxifloxacin no biotransformation by microsomal cytochrome P450.

Excretion. T1/2 of approximately 12 h Average total body clearance after oral or I/V administration at a dose of 400 mg is from 179 to 246 ml/min, About 19% of a single dose (400 mg) ingestion (22% in/in the introduction) is excreted unchanged by the kidneys, approximately 25% (26% — at/in the introduction) — gastrointestinal tract.

Pharmacokinetics in different patient groups

Age, gender and ethnicity. Not installed age, sex and ethnic clinically relevant differences in the pharmacokinetics of moxifloxacin.

Children. Pharmacokinetics of moxifloxacin in children have not been studied.

Renal failure. There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including patients with Cl creatinine <30 ml/min/1.73 m2) and those on continuous hemodialysis and prolonged outpatient peritoneal dialysis.

The liver dysfunction. Patients with insignificant and moderate liver dysfunction (stage A and b according to the classification of child-Pugh), the pharmacokinetics of moxifloxacin is not changed. For patients with severe liver dysfunction (child-Pugh stage C) data on the pharmacokinetics of moxifloxacin is not.

Description pharmacological action:

The preparationis bactericidal action due to inhibition of bacterial topoisomerase II and IV, which leads to disruption of DNA biosynthesis of microbial cells and, as a consequence, to the death of microbial cells. Minimum bactericidal concentration of the drug in General is comparable to its minimum inhibitory concentrations.

The mechanisms leading to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not violate the antibacterial activity of moxifloxacin. Cross-resistance between these groups of antibacterial drugs and moxifloxacin is not observed. So far there were no cases of plasmid stability. The overall frequency of development of resistance is very small (10-7-10 -10). Resistance to moxifloxacin develops slowly by multiple mutations. Repeated exposure of moxifloxacin on microorganisms at concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase MICK. There are cases of cross-resistance to chinolones. However, some resistant to other hinolonam gram-positive and anaerobic organisms are sensitive to moxifloxacin.

Moxifloxacin active in vitro against wide range of gram-negative and gram-positive organisms, anaerobes, acid-fast bacilli and atypical forms such as Mycoplasma, Chlamydia, Legionella. Moxifloxacin is effective against bacteria resistant to &beta – lactam and macrolide antibiotics.

Spectrum antibacterial activity of moxifloxacin includes the following microorganisms:

Gram-positive — Streptococcus pneumoniae (including strains resistant to penicillin and macrolides, and strains with multiple antibiotic resistance)* Streptococcus pyogenes (group a)*, Streptococcus milleri, Streptococcus mitis, Streptococcus agalactiae*, Streptococcus dysgalactiae, Streptococcus anginosus*, Streptococcus constellatus*, Staphylococcus aureus (including strains sensitive to methicillin)* Staphylococcus cohnii, Staphylococcus epidermidis (including strains sensitive to methicillin) Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae, Enterococcus faecalis (only the strains sensitive to vancomycin and gentamicin)*.

Gram-negative — Haemophilus influenzae (including strains producing and reproducirse &beta-lactamase)*, Haemophilus parainfluenzae*, Klebsiella pneumoniae*, Moraxella catarrhalis (including strains producing and reproducirse &beta-lactamase)* Escherichia coli* Enterobacter cloacae*, Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis* Proteus vulgaris Morganella morganii, Providencia rettgeri, Providencia stuartii, Gardnerella vaginalis.

Anaerobes — Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis*, Bacteroides ovatus, Bacteroides thetaiotaomicron*, Bacteroides uniformis, Fusobacterium spp., Peptostreptococcus spp.*, Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp., Propionibacterium spp., Clostridium perfringens*, Clostridium ramosum.

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

* — sensitivity to moxifloxacin is confirmed by clinical data.

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

Indications:

Treatment in adults with the following infections caused by sensitive microorganisms:

• acute sinusitis
• community-acquired pneumonia, including community acquired pneumonia caused by strains of microorganisms with multiple resistance to antibiotics*
• exacerbation of chronic bronchitis
• uncomplicated infections of skin and soft tissue
• complicated infections of skin and subcutaneous structures (including the infected diabetic foot)
• complicated intra-abdominal infections, including polymicrobial infections (including intra-abdominal abscesses)
• uncomplicated inflammatory disease of the pelvic organs (including salpingitis and endometritis).

* — Streptococcus pneumoniae with multiple resistance to antibiotics include strains resistant to penicillin, and strains resistant to two or more antibiotics of groups such as penicillins (with a minimum suppressive activity &ge2 mg/ml), cephalosporin II generation (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Contraindications:

• hypersensitivity to any component of the drug
• children up to age 18 years
• pregnancy
• breastfeeding.

WITH CAUTION

In the following diseases:

• diseases of the CNS (including disease, suspicious of the involvement of the CNS) that predispose to the occurrence of seizures and reduce the threshold for seizure activity
• prolonged QT interval
• hypokalemia
• bradycardia
• acute myocardial ischemia
• simultaneous reception with drugs, extension QT interval and antiarrhythmic means of IA and III classes
• severe liver failure.

Application of pregnancy and breast-feeding:

During pregnancy in humans safety not established.

A small amount of moxifloxacin is excreted in breast milk. Data on the use of moxifloxacin in women in lactation are not available. At the time of treatment should stop breastfeeding.

Bodies, subject to the maximum toxic effects of moxifloxacin, like other fluoroquinolones, are: hematopoietic system (bone marrow hypoplasia in dogs and monkeys), CNS (convulsions in monkeys) and the liver (increased liver enzymes, single cell necrosis in rats, dogs and monkeys). These changes occur usually after a long period of treatment with moxifloxacin in high doses.

In studying the effect of moxifloxacin on reproductive function in rats, rabbits and monkeys received information about the possibility of penetration of moxifloxacin through the placenta. Studies conducted on rats (when using moxifloxacin inside and in/in) and monkeys (when using moxifloxacin inside) did not reveal teratogenic effects of moxifloxacin and its effects on fertility. At/in the application of moxifloxacin in rabbits at a dose of 20 mg/kg was observed malformations of the skeleton. The identified increase in the number of abortions in monkeys and rabbits by administration of moxifloxacin at therapeutic dosage. In rats observed a decrease in fetus weight, increased abortions, a small increase of the duration of pregnancy and increase of spontaneous activity of the offspring of both sexes in the application of moxifloxacin, a dosage which is 63 times higher than the recommended.

Side effects:

Information about side effects of the drug moxifloxacin at a dose of 400 mg (the ingestion and step therapy) was obtained from clinical studies and post marketing messages. Listed below are adverse events, observed in the application Avelox, distributed by frequency of occurrence in accordance with the following gradation: often &ge1–<10% infrequently — &ge0,1–<1% rare — &ge0,01–<0,1% very rare <0,01%.

Adverse events categorized as “often” were observed less than 3% of patients, but nausea and diarrhea.

Cardiovascular system: prolongation of QT interval (often — in patients with concomitant hypokalemia, rarely, in other patients), rarely — tachycardia, palpitations, and vasodilatation (flushing to the face), rarely — hypotension, hypertension, ventricular tachyarrhythmia, syncope very rare — nonspecific arrhythmias (including extrasystole), polymorphic ventricular tachycardia (Torsade de Pointes) or heart failure, mainly in patients with predisposing to arrhythmia conditions such as clinically significant bradycardia, acute myocardial ischemia.

Respiratory system: infrequently — shortness of breath (including asthmatic condition).

The digestive system: often — nausea, vomiting, abdominal pain, diarrhea, transient increase of transaminases, rarely — anorexia, constipation, dyspepsia, flatulence, gastroenteritis (except for erosive gastroenteritis) increased amylase, bilirubin, liver function abnormalities (including increased LDH levels), increased level of GGT and alkaline phosphatase, rarely dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life threatening complications), jaundice, hepatitis (predominantly cholestatic) very rarely fulminant hepatitis potentially leading to liver failure ginepraia.

Nervous system: often — dizziness, headache, rarely — confusion, disorientation, vertigo, drowsiness, tremor, paresthesia/dysesthesia, sleep disturbances, rarely — hypoesthesia, abnormal dreams, impaired coordination (including gait disturbance due to dizziness, in very rare cases leading to injuries from falling, especially in elderly patients), seizures with different clinical manifestations ( including “grand mal” seizures), attention disorders, speech disorders, amnesia, very rarely — hypersensitivity.

Mental disorders: rare — anxiety, increased psychomotor activity, agitation, rarely — emotional lability depression (in very rare cases, may behavior with a tendency to harm), hallucinations, very rarely, depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to harm themselves).

The sensory organs: rare — disorders of taste, visual disturbances (blurring, decreased visual acuity, diplopia, especially when combined with dizziness and confusion), rarely — ringing in the ears, impaired sense of smell, including anosmia, very rarely — a loss of taste sensitivity.

Disorders blood and lymphatic system: rare — anemia, leukopenia (including neutropenia), thrombocytopenia, thrombocytosis, prolongation of PV and reduction of the INR, rarely — change in concentration of thromboplastin, very rarely — increased concentration of prothrombin and a decrease in INR, the change in the concentration of prothrombin and INR.

Musculoskeletal system: infrequently — artralgia, myalgia, rarely — tendinitis, increased muscle tone and seizures is very rare — tendon rupture, arthritis, disorder of gait due to damage to the musculoskeletal system.

Genitourinary system: often — candidal superinfection, vaginitis is infrequent — dehydration (caused by diarrhoea or reduced fluid intake), rarely — violation of the kidney, renal failure (due to dehydration, which can lead to kidney damage, especially in elderly patients with concomitant renal dysfunction).

Skin and subcutaneous tissue: very rare — bullous skin reactions (e.g. Stevens-Johnson syndrome or potentially life-threatening toxic epidermal necrolysis).

Allergic reactions: rare — urticaria, itching, rash, eosinophilia, rarely — anaphylactic/anaphylactoid reactions, angioneurotic edema (including potentially life-threatening laryngeal edema), very rare — anaphylactic shock (including life-threatening).

The body as a whole: rare — General malaise (including symptoms of illness, nonspecific pain and sweating), rarely — swelling.

Local reactions: (solution for infusion) is often nonspecific reaction at the site of infusion (swelling, pain, inflammation) rarely, phlebitis/thrombophlebitis.

Laboratory findings: hyperlipidemia, hyperglycemia, hyperuricemia.

The incidence of the following side effects when using sequential therapy with moxifloxacin (the on/in the introduction of the drug, followed by ingestion) above, than at reception of the drug inside: often — increasing the level of GGT rarely, ventricular tachyarrhythmia, hypotension, edema, pseudomembranous colitis (in rare cases associated with life threatening complications), seizures with various clinical manifestations (incl. “grand mal” seizures), hallucinations, hepatic failure and renal dysfunction as a result of dehydration, which can lead to kidney damage, especially in elderly patients with concomitant renal dysfunction.

Drug interactions:

No adjustment is required dosage in a joint application with atenolol, ranitidine, calcium supplements, theophylline, oral contraceptives, glibenclamide, Itraconazole, digoxin, morphine, probenecid (confirmed by the lack of clinically significant interactions with moxifloxacin).

Antacids, multivitamins, and minerals. The reception of moxifloxacin at the same time with antacids, multivitamins and minerals can lead to impaired absorption of moxifloxacin after oral administration, due to formation of chelate complexes with the multivalent cations contained in these preparations. As a result, the concentration of moxifloxacin in plasma may be significantly lower than desired. Therefore, anti-acid, anti-retroviral drugs (e.g. didanosine), sucralfate and other medications containing magnesium or aluminum and products containing iron or zinc, you should assign at least 4 hours before or 4 hours after ingestion of moxifloxacin.

Warfarin. With the combined use of warfarin PX and other parameters of blood coagulation are not changed.

Change the value of INR. In patients receiving anticoagulants in combination with synthetic antibacterial agents, including moxifloxacin, there are cases of increasing the anticoagulant activity of anticoagulant drugs. Risk factors are the presence of infectious disease (and accompanying inflammation), age and General condition of the patient. Despite the fact that the interaction between moxifloxacin and warfarin is not detected, in patients receiving concomitant treatment with these drugs need to monitor INR and adjust dose of oral anticoagulant drugs.

Digoxin. Moxifloxacin and digoxin do not have a significant effect on the pharmacokinetic parameters of each other. When appointing repeated doses of moxifloxacin maximum concentration of digoxin increased by approximately 30%, while the area under the curve “concentration-time” (AIS) and the minimum concentration of digoxin are not changed.

Activated carbon. While the use of activated carbon and moxifloxacin oral dose of 400 mg, the systemic bioavailability of the drug is reduced by more than 80% as a result of inhibition of its absorption.

At/in the introduction of moxifloxacin with simultaneous oral administration of activated charcoal systemic bioavailability of the drug slightly reduced (approximately 20%) due to adsorption of moxifloxacin in the lumen of the digestive tract in the process of enterohepatic recirculation.

Incompatibility. You cannot enter the recovery solution moxifloxacin simultaneously with other incompatible solutions, which include: sodium chloride solution 10 and 20% solution of sodium bicarbonate 4.2 and 8.4 percent.

Method of application and dose:

Inside, regardless of meals, without chewing, drinking plenty of water (as an infusion lasting at least 60 min).

Adults. The recommended dosage regimen of moxifloxacin 400 mg 1 time per day for any infections.

The duration of therapy

The duration of treatment is determined by the location and severity of infection and clinical effect.

In the initial stages of treatment can be applied Avelox solution for infusion and then to continue therapy if there is evidence the drug may be appointed into tablets.

Exacerbation of chronic bronchitis — 5 days.

Community-acquired pneumonia — the total duration of step therapy (in/in the introduction, and then the reception inside) 7-14 days (only by ingestion — 10 days).

Acute sinusitis — 7 days.

Uncomplicated infections of skin and soft tissue — 7 days.

Complicated infections of skin and subcutaneous structures — the total duration of sequential therapy with moxifloxacin (in/with the introduction of the drug, followed by ingestion) is 7-21 days.

Complicated intra-abdominal infections — the total duration of step therapy (in/in the introduction of the drug, followed by ingestion) is 5-14 days.

Uncomplicated inflammatory disease of the pelvic organs — 14 days.

According to clinical studies, the duration of treatment Avelox tablets and solution for infusion may reach 21 days.

Elderly patients: change of dosing regimen is not required.

Children: the efficacy and safety of moxifloxacin in children and adolescents is not established.

The impaired liver function: patients with minor liver dysfunction changes in dosing regimen is not required.

Renal insufficiency: in patients with impaired renal function (i.e. severe renal insufficiency with Cl creatinine &le30 ml/min/1.73 m2) and patients on continuous hemodialysis and prolonged outpatient peritoneal dialysis, changes in dosing regimen is not required.

Use in patients of different ethnic groups: change of dosing regimen is not required.

Instructions for use of the solution for infusion Avelox

The drug is injected in/in in the form of infusion, both in pure form and in conjunction with the following compatible solutions: water for injections, solutions of sodium chloride of 0.9%, or 1 mol/l solutions of dextrose 5, 10, or 40%, solution of xylitol 20%, ringer solution, ringer solution lactate solution Aminofusin 10%, the solution was Lanosterol.

A mixture solution of Avelox with the above infusion solutions remain stable for 24 hours at room temperature. Since the solution is not to freeze or cool, it cannot be stored in the refrigerator. After cooling the solution can precipitate, however, at room temperature, the precipitate normally dissolves. The solution should be stored in original container. Use only clear solution.

Overdose:

There were no side effects with the use of moxifloxacin in a dose of 1200 mg dose and 600 mg for more than 10 days. In case of overdose should be guided by clinical and symptomatic supportive therapy with ECG monitoring. The use of activated carbon for the treatment of overdose with intravenous administration of the drug is of very limited value.

Special instructions:

The use of drugs hinolonovogo series associated with a possible risk of development of a convulsive seizure. Moxifloxacin should be used with caution in patients with diseases of the Central nervous system and with the States, suspicious to the involvement of the CNS, predisposing to the occurrence of seizures or lowering the threshold of convulsive activity.

In the absence of sufficient clinical data, the use of moxifloxacin in patients with severe liver dysfunction (child-Pugh stage C) is not recommended.

When using moxifloxacin, like other drugs hinolonovogo series and macrolides, some patients may be a slight increase in the QT interval. In this regard, should be avoided moxifloxacin in patients with prolonged QT interval, hypokalemia, as well as those who receive antiarrhythmic medicines of class IA (quinidine, procainamide) or class III (amiodarone, sotalol) because the experience of using moxifloxacin for these patients is limited.

Moxifloxacin should be used with caution with drugs that prolong the QT interval (cisapride, erythromycin, antipsychotics, tricyclic antidepressants), because of possible additive effects, as well as in patients with predisposing to arrhythmia conditions such as bradycardia, acute myocardial ischemia.

The degree of QT prolongation may increase with increasing concentrations of the drug, so do not exceed the recommended dose and infusion rate (400 mg over 60 min). Prolonged QT interval is associated with increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. Patients with pneumonia were not found correlation between the concentration of moxifloxacin in plasma and prolongation of the QT interval.

None of the 9000 patients receiving moxifloxacin, there has been associated with prolonged QT interval cardiovascular complications and deaths. However, patients with predisposing to arrhythmia conditions for the use of moxifloxacin may increase the risk of developing ventricular arrhythmias.

During therapy with fluoroquinolones, including moxifloxacin, particularly in elderly patients and those who receive moxifloxacin along with corticosteroids, may develop tenosynovitis or rupture of the tendon. At the first sign of pain or inflammation at the site of injury admission drug should stop and unload the affected limb.

Application of antibacterial preparations of wide spectrum of action associated with risk of pseudomembranous colitis. This diagnosis should be borne in mind in patients whose treatment with moxifloxacin has been observed severe diarrhea. In this case, should be immediately assigned to the appropriate therapy.

In some cases after the first application of the drug may develop hypersensitivity and allergic reactions. You should immediately consult a doctor. Very rarely, anaphylactic reactions can progress to life-threatening anaphylactic shock, even after the first use of the drug. In these cases moxifloxacin should cancel and spend the necessary remedial measures (including shock).

When using quinolone observed reactions of photosensitivity. However, during the preclinical, clinical research and with the use of moxifloxacin in practice, there were no reactions of photosensitivity. However, patients receiving moxifloxacin should avoid direct sunlight and UV radiation.

Despite the fact that moxifloxacin rarely causes adverse reactions CNS, patients should know their reaction to the drug before driving/moving mechanisms.

Additionally, for infusion solution Avelox

In the appointment of moxifloxacin for infusion with other drugs, they must each be entered separately.

Patients follow a diet with reduced salt content (with congestive heart failure, renal failure, nephrotic syndrome) should take into account that the infusion solution contains sodium chloride.