2010/06/24

Avelox

Composition, structure and packing

Coated tablets pink color, matte, oblong, convex, with napechatkoy as a trademark "BAYER" on one side and "M400" - from the back, on the break - a homogeneous mass of white to light yellow to greenish color, surrounded by membrane shell pink.

1 tab. moxifloxacin hydrochloride 436.8 mg, which corresponds to the content of moxifloxacin 400 mg.

Excipient: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, gipromelloza, iron oxide red, 4000 macrogol, titanium dioxide. Solution for infusion transparent, greenish-yellow.

1 vial. moxifloxacin hydrochloride 436 mg, which corresponds to the content of moxifloxacin 400 mg.

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

Clinico-pharmacological group: antibacterial fluoroquinolone group.

Pharmacological action

Antibacterial fluoroquinolone group. Bactericidal action. The mechanism of action due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of DNA synthesis of microbial cells. In vitro drug is active against a broad spectrum of gram-negative and gram positive bacteria, mycoplasma, chlamydia, ureaplasma, Legionella, anaerobic pathogens. Effective against bacteria resistant to beta-lactam and macrolide antibiotics.

By Avelox susceptible Gram-positive aerobic bacteria: Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A), Streptococcus milled, Streptococcus mitis, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (including methicillin-sensitive strains), Staphylococcus cohnii, Staphylococcus epidermidis (including methicillin-sensitive strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae; Gram-negative aerobic bacteria: Haemophilus influenzae (including strains producing and β-lactamases neprodutsiruyuschie), Haemophilus parainfluenzae, Klebsiella pneumoniae , Moraxella catarrhalis (including producing strains and β-lactamases neprodutsiruyuschie), 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;

anaerobic bacteria: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp. (Including Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus), Prevotella spp., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum; and Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Coxiella burnettii.

Moxifloxacin less active against Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia.

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 antibacterial agents and moxifloxacin is not indicated. Overall incidence of very low resistance (10-7-10-10).

Resistance to moxifloxacin develops slowly by multiple mutation.

There are cases of cross-resistance to quinolones. Nevertheless, some resistant to other quinolones and gram-positive anaerobic organisms are susceptible to moxifloxacin.

Pharmacokinetics

Absorption

After oral moxifloxacin is absorbed rapidly and almost completely. After a single dose of moxifloxacin in a dose 400 mg Cmax in the blood achieved within 0.5-4 h and was 3.1 mg / l. When receiving moxifloxacin with food had been a slight increase in the time to reach C max (2 h) and a slight decrease in C max (about 16%), while 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 Avelox 400 mg for 1 h Cmax is achieved at the end of infusions and 4.1 mg / l, which corresponds to its increase by approximately 26% compared with the value of this index at intake. When multiple I / O infusions at a dose of 400 mg, duration 1 h Cmax varies from 4.1 mg / l to 5.9 mg / liter. Mean Css, equal to 4.4 mg / l, achieved at the end of infusion.

The absolute bioavailability of approximately 91%.

Distribution

Pharmacokinetics of moxifloxacin when receiving a dose of 50 to 1200 mg dose and 600 mg / day for 10 days is linear. The equilibrium state is achieved within 3 days. Moxifloxacin rapidly distributed in tissues and organs and is associated with blood proteins (mainly albumin) by about 45%. Vd is approximately 2 l / kg. High concentrations of the drug exceed those in plasma, created in lung tissue (including the alveolar macrophages) in the mucosa of the bronchi, sinuses, soft tissue, skin and subcutaneous structures, foci of inflammation. In the interstitial fluid and saliva drug is determined in a free, not protein-bound form, in concentrations higher than in plasma.

Metabolism

Biotransformiruetsya to inactive sulfosoedineny and glucuronide. Moxifloxacin not Biotransformation microsomal liver enzyme cytochrome P450.

Withdrawal

Excreted in the urine and the faeces as unchanged, and in the form of inactive metabolites. Approximately 19% of a single dose (400 mg) is excreted unchanged in the urine, about 25% - with the feces. T1 / 2 of approximately 12 h. The average total clearance after taking a dose of 400 mg range from 179 to 246 ml / min.

Pharmacokinetics in special clinical situations

There is no difference in pharmacokinetic parameters of moxifloxacin, depending on age, sex and race. Studies of the pharmacokinetics of moxifloxacin in children has not been conducted. There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including at QA <30 ml/min/1.73 m2) and of those who are on hemodialysis and continuous ambulatory peritoneal dialysis prolonged. In patients with mild and moderate hepatic impairment (class A or B on the scale of Child-Pugh) pharmacokinetics of moxifloxacin is not changed. In patients with severely impaired liver function (class C according to Child-Pugh scale) data on the pharmacokinetics of moxifloxacin not.

Statement

Infectious and inflammatory diseases in adults caused by microorganisms sensitive to the drug:
Acute sinusitis;
community-acquired pneumonia (including those caused by strains of microorganisms with multiple antibiotic resistance *);
exacerbation of chronic bronchitis;
uncomplicated infections of skin and soft tissues;
Complicated infections of skin and subcutaneous structures (including diabetic foot infection).

Streptococcus pneumoniae with multiple resistance to antibiotics include strains that are resistant to penicillin, and strains resistant to two or more antibiotics from groups such as the penicillins (with minimal inhibitory activity of ≥ 2 mg / ml), II generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim / sulfamethoxazole.

Dosage regimen

The drug is prescribed in and in / 400 mg 1 time / day. The duration of treatment when administered in / in the introduction determined by the severity of infection and clinical effect and it is: during exacerbation of chronic bronchitis - 5 days, with pneumonia the total duration of the step therapy - 7-14 days, first in /, then inside, or 10 days inward with acute sinusitis and uncomplicated skin infections and soft tissue - 7 days for complicated infections of the skin and subcutaneous tissue - the total length of the step therapy Avelox (w / introduction, followed by oral administration) is 7-21 days.

Duration of treatment Avelox in / up to 14 days, inside - 21 days.

Patients older patients with minor disorders of liver function (class A or B on the scale of Child-Pugh), patients with impaired renal function (including spacecraft at £ 30 ml/min/1.73 m2), as well as patients who are on continuous hemodialysis and long-term ambulatory peritoneal dialysis, changes in dosage regimen is not required.

Tablets should be taken, not liquid, squeezed a small amount of water, regardless of the meal. The solution for infusion should be administered in / in slowly for 60 minutes. The drug can be entered in the diluted and undiluted. Avelox solution compatible with the following solutions: water for injection, sodium chloride 0.9% solution of sodium chloride, 1M, dextrose 5% Dextrose 10% Dextrose 40%, 20% xylitol solution, Ringer's solution, Ringer-lactate solution aminofuzina 10% solution yonosterila. Use only clear solution.

Side effect
For the cardiovascular system: <3% - long QT patients with concomitant hypokalaemia; ≥ 0.1%, <1% - tachycardia, the lengthening of the interval QT, arrhythmia; ≥ 0.01%, <0.1% - ventricular tachyarrhythmia, hypotension, Arterial hypertension, a rush of blood to the face (due to vasodilation), <0.01% - polymorphic ventricular tachycardia (type "pirouette"), heart failure (predominantly in patients with predisposing to arrhythmia conditions such as clinically significant bradycardia, acute myocardial ischemia).
From the digestive system: ≥ 1% and <10% - nausea, diarrhea, <3% - abdominal pain, vomiting, symptoms of dyspepsia, transient increase in transaminase activity; ≥ 0.1%, <1% of - bloating, constipation, anorexia, gastroenteritis, increased activity of GGTP, amylase, bilirubin, transient abnormal liver function with increased LDH, transient increase in alkaline phosphatase; ≥ 0.01%, <0.1% - dysphagia, pseudomembranous colitis (in rare cases associated with life-threatening complications), jaundice, hepatitis ( predominantly cholestatic).
From the central nervous system and peripheral nervous system: <3% - dizziness, headache; ≥ 0.1%, <1% - disturbances of consciousness (confusion, disorientation), insomnia, dizziness, drowsiness, anxiety, tremor, paresthesia / dysesthesia, increased psychomotor activity; ≥ 0.01%, <0.1% - abnormal dreams, impaired coordination (including foot disorders as a result of dizziness and in rare cases leading to injuries from a fall, especially in older patients), seizures with different clinical manifestations (including am grand mal seizures), in violation of attention, speech disorders, amnesia, emotional lability, hallucinations, depression (in very rare cases, may conduct with a tendency to self-harm), hypoesthesia, <0.01% - hyperaesthesia, depersonalization, Psychotic Reactions (potentially manifest themselves in behavior with a tendency to self-harm). Adverse reactions associated with the chemotherapeutic effect of: <3% - moniliasis superinfection, including stomatitis, vaginitis.
On the part of hematopoiesis: ≥ 0.1%, <1% - anemia, leukopenia, thrombocytosis, thrombocytopenia, eosinophilia.
From the blood coagulation system: ≥ 0.01%, <0.1% - change in the content thromboplastin, increased prothrombin time / INR increased, <0.01% - increase in the level of prothrombin / decrease in MND.
On the part of the musculoskeletal system: ≥ 0.1%, <1% - arthralgia, myalgia; ≥ 0.01%, <0.1% - tendonitis, muscle cramps, <0.01% - tendon rupture, arthritis, gait disturbance due to side effects of the musculoskeletal system .
From the senses: ≥ 0.1%, <1% - disturbance of taste, blurred vision, reduced visual acuity, diplopia (particularly when associated with dizziness and confusion); ≥ 0.01%, <0.1% - tinnitus, a violation of smell, including anosmia.
On the part of the respiratory system: ≥ 0.1%, <1% - shortness of breath, asthmatic condition.
On the part of metabolism: ≥ 0.1%, <1% - hyperhidrosis, degitratatsiya (caused by diarrhea or decrease in fluid intake), hyperlipidemia; ≥ 0.01%, <0.1% - hyperglycemia, hyperuricemia.
From the urinary system: ≥ 0.01%, <0.1% - renal failure as a result of dehydration, which can lead to kidney damage, especially in elderly patients with concomitant impaired renal function. Allergic reactions: ≥ 0.1%, <1% - urticaria, pruritus, rash; ≥ 0.01%, <0.1% - anaphylactic reaction, anaphylactic shock (including life-threatening), angioedema (including swelling of face, throat, potentially life-threatening), <0.01% - Stevens-Johnson syndrome.

Other: ≥ 0.1%, <1% - asthenia, malaise; ≥ 0.01%, <0.1% - pelvic pain, swelling face, back pain, the pain in his legs.

Contraindications
Pregnancy
lactation (breastfeeding);
childhood and adolescence to 18 years;
hypersensitivity to moxifloxacin and other components of the drug.

Precautions to apply for central nervous system diseases (including the diseases suspected in the involvement of the CNS) that predisposes to the appearance of seizures and lowers the threshold of convulsive readiness, while lengthening the interval QT, hypokalemia, bradycardia, acute myocardial ischemia, while admission to the preparations, extending the interval QT, and antiarrhythmics IA and III classes, with severe hepatic insufficiency.

Pregnancy and lactation

Avelox and Safety in pregnancy has not been established, so 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 absent. Therefore the use of Avelox in the period of breastfeeding is also contraindicated.

In experimental studies, when studying the effect of moxifloxacin on the reproductive function in rats, rabbits and monkeys demonstrated that moxifloxacin penetrates the placental barrier. Research carried out on rats (in the introduction of moxifloxacin in and IV) and monkeys (with the introduction of moxifloxacin oral) have not revealed teratogenic action of moxifloxacin and its impact on fertility. When a / in the introduction of moxifloxacin in rabbits at a dose of 20 mg / kg were observed skeletal malformations. Revealed an increase in the number of miscarriages in monkeys and rabbits in the application of moxifloxacin in a therapeutic dose. In rats, decreased fetal weight, increased miscarriages, a slight increase in the duration of pregnancy and an increase in spontaneous activity of offspring of both sexes in the application of moxifloxacin, the dose is 63 times higher than recommended.

Application for violations of liver function

Patients with minor disturbances of liver function (class A or B on the scale of Child-Pugh) changes in dosage regimen is not required.

With caution used in severe hepatic failure.

Application for violations of renal function

Patients with impaired renal function (including at QA <30 ml/min/1.73 m2), as well as patients who are on hemodialysis and continuous ambulatory peritoneal dialysis, long-term, changes in dosage regimen is not required

Cautions

Please note that the appointment of Avelox increases the risk of seizures, so carefully prescribed the drug to patients with diseases of the CNS, accompanied by seizures or predisposing to their development or reduce the threshold of convulsive readiness, as well as suspected of such diseases and conditions.

In the absence of sufficient clinical data use of moxifloxacin in patients with severely impaired liver function (class C according to Child-Pugh scale) is not recommended. Treatment with fluoroquinolones, including moxifloxacin, especially in the elderly and patients receiving SCS, possibly the development of tendonitis and tendon rupture. If you have pain or signs of inflammation of the tendon, stop taking Avelox and unload the affected limb.

When using Avelox in some patients there may be lengthening the interval QT. In this regard, should avoid use of the drug to patients with prolonged interval QT, hypokalemia, and patients receiving antiarrhythmic drugs class IA (quinidine, procainamide) or class III (amiodarone, sotalol), since the experience of moxifloxacin in these patients only. Caution appoint Avelox, along with drugs that prolong the interval QT (tsizaprid, erythromycin, antipsychotic drugs, tricyclic antidepressants), as well as in patients with predisposing to arrhythmia conditions such as bradycardia, acute myocardial ischaemia. The degree of QT interval prolongation may increase with increasing concentration of the drug, so it should not exceed the recommended dose. Lengthening of QT interval associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. None of the 8000 patients treated with moxifloxacin, were noted associated with prolonged QT cardiovascular complications and fatalities. However, patients with predisposing to arrhythmias conditions applying moxifloxacin may increase the risk of ventricular arrhythmias. Antibiotics pose a risk of pseudomembranous colitis. This should be borne in mind in the event during the treatment Avelox severe diarrhea. In this case, the drug should be repealed and immediately assign the appropriate therapy.

There is a risk of hypersensitivity reactions and anaphylactic reactions in the primary use of the drug, such cases should immediately inform your doctor. Very rare anaphylactic reaction can progress to anaphylactic shock. In such cases, you should immediately cease injection of the preparation and conduct appropriate resuscitation (including anti-shock).

In the application of quinolones marked photosensitivity reactions. However, during the preclinical and clinical studies, as well as the application of Avelox in clinical practice was reported photosensitivity reactions. Nevertheless, patients in the period of drug administration should avoid direct sunlight and UV irradiation. Patients of different ethnic groups, dose adjustment is required.

Use in Pediatrics

Efficacy and safety of the drug Avelox in children and adolescents is not installed.

Effects on ability to drive vehicles and management mechanisms

In spite of the fact that moxifloxacin rarely causes side effects from the CNS, the possibility of driving or moving machinery solved individually after assessing patient response to receiving the drug.

Experimental Results

The following pathological changes are manifestations of the toxic effects of moxifloxacin, like other fluoroquinolones: a system of hematopoiesis (bone marrow hypoplasia in dogs and monkeys), CNS (convulsions in monkeys) and liver (increased liver enzymes, isolated necrosis of hepatocytes in rats, dogs and monkeys) . These violations occur, usually after a long period of administration of moxifloxacin in high doses.

Overdose

There have not been any side effects with a dose of Avelox to 1200 mg dose and 600 mg for more than 10 days. Treatment: In case of overdose, in accordance with the clinical situation spend symptomatically with EKG-monitored. Application of activated charcoal is advisable only when an overdose of moxifloxacin in tablet form.

Drug Interactions

Joint application inside Avelox and antacids, minerals and vitamin-mineral complexes can disrupt the absorption of moxifloxacin due to the formation of chelate complexes with polyvalent cations contained in these preparations, and consequently reduce the concentration of moxifloxacin in plasma. In this regard, Antacid, antriretrovirusnye and other products containing calcium, magnesium, aluminum, iron, should take at least 4 hours before or 2 hours after oral Avelox. Ranitidine, while applying slight changes absorption of moxifloxacin. When combined with the use of preparations containing calcium in high doses, clinically significant effect on the absorption of moxifloxacin were found except for a small reduction of the rate of absorption. When using Avelox with antiarrhythmic drugs class IA (quinidine, procainamide) or class III (amiodarone, sotalol), as well as drugs that prolong the interval QT (tsizaprid, erythromycin, antipsychotic drugs, tricyclic antidepressants) may be an additive effect on QT interval prolongation .

Moxifloxacin does not have any effect on the pharmacokinetics of theophylline (and vice versa), indicating that moxifloxacin does not interact with the CYP1A2 isoenzyme. With the combined use of Avelox with warfarin prothrombin time and other parameters of blood coagulation unaffected.

In patients treated with anticoagulants in combination with antibiotics, including with moxifloxacin, there are instances of increasing anticoagulant activity of anticoagulant drugs. Risk factors are the presence of an infectious disease (and the accompanying inflammatory process), age and general condition of the patient. Despite the fact that the interaction between moxifloxacin and warfarin is not detected, patients receiving combined treatment with these drugs, it is necessary to conduct monitoring of INR and adjust dose of oral anticoagulant drugs.

The interactions between moxifloxacin and oral contraceptives are not marked. There were no clinically significant interaction between glibenclamide and moxifloxacin. When combined therapy with moxifloxacin AUC itraconazole changed very slightly. In turn, itraconazole also no significant effect on the pharmacokinetic parameters of moxifloxacin.

Therefore, the joint application of these products change the dosage for them is not required. Moxifloxacin and digoxin did not significantly affect the pharmacokinetic parameters of each other. When parenteral administration of morphine and simultaneous oral Avelox reduce bioavailability of moxifloxacin is not indicated; C max of moxifloxacin significantly reduced (17%).

Pharmacokinetics of atenolol significantly change under the influence of Avelox. After receiving single dose AUC of atenolol increased by approximately 4%, while C max decreased by 10%. Probenecid does not affect the total clearance and renal clearance of moxifloxacin. With the combined use of moxifloxacin and probenecid dose correction is required. With the simultaneous use of activated charcoal and Avelox oral dose of 400 mg of systemic bioavailability is reduced by more than 80% as a result of slowing down its absorption. Pharmaceutical interaction of moxifloxacin infusion solution compatible with the following infusion solutions: sodium chloride 10% solution of sodium chloride 20% solution of sodium bicarbonate 4.2% solution of sodium bicarbonate 8.4%.

Terms and Conditions of storage

List B. The tablets should be stored out of reach of children, a dry place at temperatures not above 25 ° C.

Shelf life - 5 years. List B. The solution for infusion should be stored in dry, protected from light and away from children at a temperature of 8 ° to 25 ° C Do not freeze.

Shelf life - 5 years. After dilution with compatible solvents Avelox solution remains stable for 24 h at room temperature. Since the solution must not be frozen or cooled, it can not be stored in the refrigerator.

Upon cooling, the solution may Precipitatedisulphur, but at room temperature usually precipitate dissolves. The solution should be stored only in original container.