Heinemox tablets 400mg, No. 5

• Infectious and inflammatory diseases caused by sensitive microorganisms: acute sinusitis; exacerbation of chronic bronchitis; community-acquired pneumonia (including caused by strains of microorganisms with multiple antibiotic resistance);

• uncomplicated infections of the skin and soft tissues; complicated infections of the skin and subcutaneous structures (including an infected diabetic foot);

• complicated intra-abdominal infections, including polymicrobial infections, incl. intraperitoneal abscesses;

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

• It is necessary to take into account the current official guidelines on the rules for the use of antibacterial agents.

Inside or in / in a dose of 400 mg 1 time / day.

The duration of treatment for oral administration is determined by the severity of the infection and the clinical effect can be from 5 to 21 days.

Film-coated tablets of pinkish-red color, oval, biconvex, with a risk; at the break - a mass from white to light yellow with a greenish tint.

1 tab.

moxifloxacin hydrochloride 436.3 mg,

which corresponds to the content of moxifloxacin 400 mg

Excipients: corn starch - 52 mg, lactose monohydrate - 68 mg, sodium lauryl sulfate - 7.5 mg, purified talc - 15 mg, magnesium stearate - 6.5 mg, sodium carboxymethyl starch - 20 mg, silicon dioxide colloidal anhydrous - 3.5 mg, croscarmellose sodium - 6.5 mg, microcrystalline cellulose - 130.7 mg.

• A history of tendon pathology that developed as a result of treatment with quinolone antibiotics;

• in preclinical and clinical studies, after the introduction of moxifloxacin, a change in the electrophysiological parameters of the heart was observed, which was expressed in the prolongation of the QT interval.

• In this regard, the use of moxifloxacin is contraindicated in patients of the following categories: congenital or acquired documented prolongation of the QT interval, electrolyte disturbances, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; a history of rhythm disturbances accompanied by clinical symptoms; moxifloxacin should not be used with other drugs that prolong the QT interval;

• due to the limited amount of clinical data, the use of moxifloxacin is contraindicated in patients with impaired liver function (class C according to the Child-Pugh classification) and in patients with an increase in transaminases more than 5 times higher than ULN;

• pregnancy, breastfeeding;

• age under 18; hypersensitivity to moxifloxacin, other quinolones.

  Use with caution in diseases of the central nervous system (including diseases suspicious of involvement of the central nervous system), predisposing to the occurrence of seizures and lowering the threshold of convulsive readiness; in patients with a history of psychosis and / or psychiatric illness; in patients with potentially proarrhythmic conditions such as acute myocardial ischemia and cardiac arrest, especially in women and elderly patients; with myasthenia gravis; with cirrhosis of the liver; when taken simultaneously with drugs that reduce the content of potassium; in patients with a genetic predisposition or an actual deficiency of glucose-6-phosphate dehydrogenase.

pharmachologic effect

Antimicrobial agent from the group of fluoroquinolones, acts bactericidal. Shows activity against a wide range of gram-positive and gram-negative microorganisms, anaerobic, acid-fast and atypical bacteria: Mycoplasma spp., Chlamydia spp., Legionella spp. Effective against bacterial strains resistant to beta-lactams and macrolides. It is active against most strains of microorganisms: gram-positive - Staphylococcus aureus (including strains insensitive to methicillin), Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A); gram-negative - Haemophilus influenzae (including both ?-lactamase-producing and non-?-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including both producing,strains not producing ?-lactamase), Escherichia coli, Enterobacter cloacae; atypical - Chlamydia pneumoniae, Mycoplasma pneumoniae. According to in vitro studies, although the microorganisms listed below are sensitive to moxifloxacin, nevertheless, its safety and efficacy in the treatment of infections has not been established. Gram-positive microorganisms: Streptococcus milleri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus cohnii, Staphylococcus epidermidis (including strains susceptible to methicillin), Staphylococcus hemolyticus. Gram-negative microorganisms: Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius,Enterobacter sakazaki, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii. Anaerobic microorganisms: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaornicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp., Porphyromonas. ramosum. Atypical microorganisms: Legionella pneumophila, Caxiella burnettii. Blocks topoisomerases II and IV, enzymes that control the topological properties of DNA, and are involved in DNA replication, repair and transcription. The action of moxifloxacin depends on its concentration in blood and tissues.The minimum bactericidal concentrations are almost indistinguishable from the minimum inhibitory concentrations.

The mechanisms of development of resistance, inactivating penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines, do not affect the antibacterial activity of moxifloxacin. There is no cross-resistance between moxifloxacin and these drugs. No plasmid-mediated mechanism of resistance development was observed. The overall incidence of resistance is low. In vitro studies have shown that resistance to moxifloxacin develops slowly as a result of a series of successive mutations. With repeated exposure to microorganisms with subminimal inhibitory concentrations of moxifloxacin, the MIC values ??only slightly increase. Cross-resistance is observed between drugs from the fluoroquinolone group. However, some gram-positive and anaerobic microorganisms resistant to other fluoroquinolones,sensitive to moxifloxacin.

Pharmacokinetics

After oral administration, moxifloxacin is absorbed quickly and almost completely. The absolute bioavailability is about 91%. The pharmacokinetics of moxifloxacin when taken in a dose of 50 to 1200 mg once, as well as 600 mg / day for 10 days, is linear. After a single dose of moxifloxacin at a dose of 400 mg, Cmax in the blood is reached within 0.5-4 hours and is 3.1 mg / l.

After oral administration of moxifloxacin at a dose of 400 mg 1 time / day, Cssmax and Cssmin are 3.2 mg / l and 0.6 mg / l, respectively. After a single infusion of Avelox at a dose of 400 mg for 1 hour, Cmax is reached at the end of the infusion and is 4.1 mg / l, which corresponds to an increase of approximately 26% compared to the value of this indicator when taken orally. The exposure of the drug, determined by the AUC indicator, slightly exceeds that when the drug is taken orally.

With multiple intravenous infusions at a dose of 400 mg for 1 hour, Cssmax and Cssmin vary from 4.1 mg / L to 5.9 mg / L and from 0.43 mg / L to 0.84 mg / L, respectively. Average Css of 4.4 mg / L are reached at the end of the infusion. The equilibrium state is reached within 3 days. The binding to blood proteins (mainly albumin) is about 45%. Moxifloxacin is rapidly distributed in organs and tissues. Vd is approximately 2 l / kg. High concentrations of moxifloxacin, exceeding those in plasma, are created in lung tissue (including in epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoidal sinuses), in nasal polyps, foci of inflammation (in the contents of blisters with skin lesions ). In the interstitial fluid and in saliva, moxifloxacin is determined in a free form, not bound to proteins,in concentration higher than in plasma. In addition, high concentrations of moxifloxacin are found in the tissues of the abdominal organs, peritoneal fluid, and also in the tissues of the female genital organs. Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as through the intestine, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the cytochrome P450 microsomal system. 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 effect on the body in terms of safety and tolerability.high concentrations of moxifloxacin are determined in the tissues of the abdominal organs, peritoneal fluid, as well as in the tissues of the female genital organs. Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as through the intestine, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the cytochrome P450 microsomal system. 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 effect on the body in terms of safety and tolerability.high concentrations of moxifloxacin are determined in the tissues of the abdominal organs, peritoneal fluid, as well as in the tissues of the female genital organs. Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as through the intestine, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the cytochrome P450 microsomal system. 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 effect on the body in terms of safety and tolerability.Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as through the intestine, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the cytochrome P450 microsomal system. 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 effect on the body in terms of safety and tolerability.Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, as well as through the intestines, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the cytochrome P450 microsomal system. 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 effect on the body in terms of safety and tolerability.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 effect on the body in terms of safety and tolerability.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 effect on the body in terms of safety and tolerability.

1/2 is approximately 12 hours. The average total clearance after oral administration of the drug at a dose of 400 mg is 179-246 ml / min. Renal clearance is 24-53 ml / min. This indicates a partial tubular reabsorption of moxifloxacin. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% through the intestines.

Side effect

Infections: often fungal superinfections.

From the hematopoietic system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolongation of prothrombin time / increase in INR; rarely - a change in the concentration of thromboplastin; very rarely - an increase in the concentration of prothrombin / decrease in the INR.

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

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

Mental disorders: infrequently - anxiety, psychomotor hyperreactivity, agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm is possible, such as suicidal thoughts or suicidal attempts), hallucinations; very rarely - depersonalization, psychotic reactions (potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts).

From the side of the nervous system: often - dizziness, headache; infrequently - paresthesia, dysesthesia, disturbances in taste sensitivity (including in very rare cases ageusia), confusion, disorientation, sleep disturbances, tremor, vertigo, drowsiness; rarely - hypesthesia, impaired sense of smell (including anosmia), atypical dreams, impaired coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to injuries as a result of a fall, especially in elderly patients), seizures with various clinical manifestations (including h. 'grand mal' seizures), attention disorders, speech disorders, amnesia, peripheral neuropathy, polyneuropathy; very rarely - hyperesthesia.

From the side of the organ of vision: infrequently - visual impairment (especially with reactions from the central nervous system); very rarely - transient loss of vision (especially with reactions from the central nervous system).

From the side of the organ of hearing: rarely - tinnitus, hearing impairment, including deafness (usually reversible).

From the side of the cardiovascular system: often - prolongation of the QT interval in patients with concomitant hypokalemia; infrequently - lengthening of the QT interval, palpitations, tachycardia, vasodilation; rarely - increased blood pressure, decreased blood pressure, syncope, ventricular tachyarrhythmias; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (pirouette type), cardiac arrest (mainly in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

From the respiratory system: infrequently - shortness of breath, including an asthmatic condition.

From the digestive system: often - nausea, vomiting, abdominal pain, diarrhea; infrequently - decreased appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (except for 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 hepatic transaminases; infrequently - liver dysfunction (including an increase in LDH activity), an increase in the concentration of bilirubin, an increase in the activity of GGT and alkaline phosphatase; rarely - jaundice, hepatitis (mainly cholestatic); very rarely, fulminant hepatitis, potentially leading to life-threatening liver failure (including fatalities). On the part of the skin: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

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

From the urinary system: infrequently - dehydration (caused by diarrhea or decreased fluid intake); rarely - impaired renal function, renal failure as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal impairment).

From the side of the body as a whole: often - reactions at the injection / infusion site; infrequently - general malaise, nonspecific pain, sweating. The incidence of the following adverse reactions was higher in the group receiving stepwise therapy: often - increased GGT activity; infrequently - ventricular tachyarrhythmias, arterial hypotension, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including 'grand mal' seizures), hallucinations, impaired renal function, renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal impairment).

Application during pregnancy and lactation

The use of moxifloxacin during pregnancy and during breastfeeding is contraindicated.

Application for violations of liver function

Patients with impaired liver function do not need to change the dosage regimen. The drug should be used with caution in liver cirrhosis.

Application for impaired renal function

Patients with impaired renal function (including CC <30 ml / min / 1.73 m2), as well as patients on continuous hemodialysis and long-term outpatient peritoneal dialysis, do not need to change the dosage regimen.

Application in children

Contraindicated: children and adolescents under 18 years of age.

Use in elderly patients

Elderly patients do not need to change the dosage regimen. However, in order to avoid exacerbation of chronic diseases in this category of patients, moxifloxacin should be used with caution.

special instructions

In some cases, after the first moxifloxacin, hypersensitivity and allergic reactions may develop, and the doctor should be immediately informed about this. Very rarely, even after the first use, anaphylactic reactions can progress to life-threatening anaphylactic shock. In these cases, treatment with moxifloxacin should be discontinued and the necessary therapeutic measures (including anti-shock) should be started immediately. With caution in women and elderly patients. Because women have a longer QT interval compared to men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients are also more susceptible to drugs that affect the QT interval. The lengthening of the QT interval may increase with increasing concentration of moxifloxacin,therefore, the recommended dose should not be exceeded. Prolongation of the QT interval is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. The patient should be informed that in the event of symptoms of liver failure, symptoms of skin or mucous membrane lesions, symptoms of neuropathy (pain, burning, tingling, numbness or weakness), it is necessary to consult a doctor before continuing treatment with pmoxifloxacin. The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with the risk of developing pseudomembranous colitis. Drugs that inhibit intestinal motility are contraindicated in the development of severe diarrhea. Against the background of quinolone therapy, incl. moxifloxacin, tendonitis and tendon rupture are possible, especially in the elderly and patients,receiving GCS. Cases are described that occurred within a few months after the completion of treatment. At the first symptoms of pain or inflammation at the site of injury, the use of moxifloxacin should be discontinued and the affected limb should be relieved. During the treatment period, exposure to direct sunlight and UV radiation should be avoided. Moxifloxacin is not recommended for the treatment of methicillin-resistant strains of Staphylococcus aureus (MRSA). Suspected or confirmed MRSA infections should be treated with appropriate antibacterial drugs. The ability of moxifloxacin to inhibit the growth of mycobacteria may cause in vitro interaction of moxifloxacin with a test for Mycobacterium spp., Leading to false negative results in the analysis of patient samples.receiving moxifloxacin. Mental reactions may occur even after the first administration of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to suicidal thoughts and self-harming behaviors, including suicidal attempts. If such reactions develop in patients, moxifloxacin should be discontinued and the necessary measures taken. Caution should be exercised when using moxifloxacin in patients with a history of psychoses and / or psychiatric diseases. Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, monotherapy with moxifloxacin should not be used in the treatment of patients with pelvic inflammatory disease, unlesswhen the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If it is not possible to exclude the presence of fluoroquinolone-resistant N. gonorrhoeae, it is necessary to consider supplementing empiric therapy with moxifloxacin with an appropriate antibiotic that is active against N. gonorrhoeae (eg, cephalosporin). During therapy with moxifloxacin, dysglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When carrying out treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.Consideration should be given to supplementing empiric therapy with moxifloxacin with an appropriate antibiotic active against N. gonorrhoeae (eg, cephalosporin). During therapy with moxifloxacin, dysglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When carrying out treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.Consideration should be given to supplementing empiric therapy with moxifloxacin with an appropriate antibiotic active against N. gonorrhoeae (eg, cephalosporin). During therapy with moxifloxacin, dysglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When carrying out treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When carrying out treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When carrying out treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.

Influence on the ability to drive vehicles and mechanisms

Fluoroquinolones, including moxifloxacin, can interfere with the ability of patients to drive and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to the effect on the central nervous system and visual impairment.

Drug interactions

Consideration should be given to the possible additive effect of lengthening the QT interval of moxifloxacin and other drugs that affect the prolongation of the QT interval.

Due to the combined use of moxifloxacin and drugs that affect the prolongation of the QT interval, the risk of developing ventricular arrhythmias, including polymorphic ventricular tachycardia of the 'pirouette' type, increases.

The combined use of moxifloxacin with the following drugs that affect the prolongation of the QT interval is contraindicated: class IA antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide); antipsychotics (including phenothiazine, pimozide, sertindole, haloperidol, sultopride); tricyclic antidepressants; antimicrobial drugs (sparfloxacin, IV erythromycin, pentamidine, antimalarial drugs, especially halofantrine); antihistamines (terfenadine, astemizole, mizolastine); others (cisapride, vincamine IV, bepridil, diphemanil).

With the simultaneous ingestion of antacids, multivitamins and minerals, moxifloxacin absorption may be impaired 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 can be significantly lower than the therapeutic one. In this regard, antacids, antiretrovirals (for example, didanosine) and other drugs containing magnesium, aluminum, sucralfate, iron, zinc should be taken at least 4 hours before or 4 hours after oral administration of moxifloxacin.

In patients who received anticoagulants in combination with antibiotics, incl. with moxifloxacin, there have been cases of an increase in the anticoagulant activity of anticoagulant drugs. Risk factors are the presence of an infectious disease (and a concomitant inflammatory process), the age and general condition of the patient. Despite the fact that the interaction between moxifloxacin and warfarin is not detected, in patients receiving combined treatment with these drugs, it is necessary to monitor the INR and, if necessary, adjust the dose of indirect anticoagulants.

Moxifloxacin and digoxin do not significantly affect the pharmacokinetic parameters of each other.

With repeated administration of moxifloxacin, the Cmax of digoxin increased by approximately 30%. In this case, the value of AUC and Cmin of digoxin does not change.

With the simultaneous use of activated carbon and moxifloxacin orally at a dose of 400 mg, the systemic bioavailability of the drug decreases by more than 80% as a result of slowing down its absorption. In case of an overdose, the use of activated carbon at an early stage of absorption prevents a further increase in systemic exposure.