Moflaxia, 400 mg 5 pcs

Pharmacological action – antibacterial, broad-spectrum bactericidal.
Pharmacodynamics

The mechanism of action. Moxifloxacin is a broad-spectrum bactericidal antibacterial agent, 8-methoxyfluoroquinolone.

The bactericidal action of moxifloxacin is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of replication, repair and transcription of DNA biosynthesis of the microbial cell and, consequently, to death of microbial cells.

The minimum bactericidal concentrations of moxifloxacin are generally comparable to its MIC.

Mechanisms of resistance. Mechanisms leading to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not affect the antibacterial activity of moxifloxacin.

Cross-resistance between these groups of antibacterial drugs and moxifloxacin has not been observed. No cases of plasmid resistance have been observed so far either. The overall incidence of resistance is very low (10-7-10-10). Resistance to moxifloxacin develops slowly by multiple mutations. Repeated exposure of microorganisms to moxifloxacin in concentrations below the MIC is accompanied by only a slight increase in the MIC.

Cases of cross-resistance to quinolones have been reported. Nevertheless, some gram-positive and anaerobic microorganisms resistant to other quinolones retain sensitivity to moxifloxacin.

It has been established that the addition to the structure of the molecule of moxifloxacin of a methoxy group in the C8 position increases the activity of moxifloxacin and reduces the formation of resistant mutant strains of Gram-positive bacteria. The addition of the bicycloamino group at the C7 position prevents the development of active efflux, a mechanism of resistance to fluoroquinolones.

Moxifloxacin under in vitro conditions is active against a wide range of Gram-negative and Gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria such as Mycoplasma spp., Chlamydia spp., Legionella spp. and bacteria resistant to lactam and macrolide antibiotics.

The effect on human intestinal microflora. In two studies in volunteers, the following changes in intestinal microflora after oral administration of moxifloxacin were noted: a decrease in concentrations of Escherichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp., Klebsiella spp. as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within 2 weeks. Clostridium difficile toxin was not detected.

For certain strains, the spread of acquired resistance may vary by geographic region and over time. Therefore, it is desirable to have local information about resistance when testing strain sensitivity, especially when treating severe infections.

If inpatients have AUC/MIC90 values greater than 125 and Cmax in plasma/MIC90 is between 8 and 10, this suggests clinical improvement. In outpatients, the values of these surrogate parameters are usually lower: AUC/MIK90 >30-40.

Pharmacokinetics

Intake. When administered orally moxifloxacin is absorbed rapidly and almost completely. Absolute bioavailability is about 91%. Pharmacokinetics of moxifloxacin when administered in doses from 50 to 1200 mg single dose, as well as 600 mg / day for 10 days is linear. The equilibrium state is reached within 3 days.

After a single use of 400 mg of moxifloxacin Cmax in plasma is reached within 0.5-4 hours and is 3.1 mg/l. After oral administration of 400 mg of moxifloxacin once daily Css(max) and Css (min) are 3.2 and 0.6 mg/l, respectively.

When moxifloxacin is taken with food, a slight increase in Tmax (by 2 hours) and a slight decrease in Cmax (by about 16%) are observed, while the duration of absorption is not changed. However, these data have no clinical significance, and moxifloxacin can be used regardless of the time of food intake.

Distribution. Moxifloxacin is rapidly distributed in the tissues and organs and binds to plasma proteins (mainly to albumins) by approximately 45%. Vd is about 2 l/kg.

High concentrations of moxifloxacin that exceed those in the blood plasma are formed in the lung tissue (including epithelial fluid, alveolar macrophages), paranasal sinuses (maxillary and the labyrinth), nasal polyps, inflammation foci (in the contents of blisters when the skin is affected). In interstitial fluid and saliva moxifloxacin is determined in free form, not bound to proteins, at concentrations higher than in blood plasma. In addition, high concentrations of moxifloxacin are detected in the tissues of the abdominal cavity, peritoneal fluid and female reproductive organs.

Metabolism. Moxifloxacin undergoes biotranformation of the 2nd phase and is excreted by the kidneys and the intestine both as unchanged and as inactive sulfonic compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the microsomal cytochrome P450 system. Metabolites M1 and M2 are present in plasma concentrations lower than the parent compound. According to the results of preclinical studies it was proved that the mentioned metabolites have no negative effects on the body in terms of safety and tolerability.

Elimination. T1/2 of moxifloxacin is approximately 12 hours. Mean total clearance after administration at a dose of 400 mg is 179-246 ml/min.

Renal clearance is 24-53 ml/min. This indicates partial tubular reabsorption of moxifloxacin.

The mass balance of the parent compound and phase 2 metabolites is approximately 96-98%, indicating the absence of oxidative metabolism. About 22% of the single dose (400 mg) is excreted unchanged by the kidneys, about 26% – through the intestine.

Pharmacokinetics in different groups of patients

Age, sex and ethnicity. When studying pharmacokinetics of moxifloxacin in men and women a difference of 33% in terms of AUC and Cmax was found. Absorption of moxifloxacin did not depend on gender. Differences in AUC and Cmax were due to weight differences rather than gender and are not considered clinically significant.

There were no clinically significant differences in the pharmacokinetics of moxifloxacin among patients of different ethnic groups and different ages.

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

Kidney function impairment. No significant changes in pharmacokinetics of moxifloxacin were found in patients with impaired renal function (including patients with creatinine Cl< 30 ml/min/1.73 m2) and in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis.

Hepatic impairment. No significant differences in concentration of moxifloxacin were found in patients with impaired liver function (Child-Pugh grades A and B) compared to healthy volunteers and patients with normal liver function.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to moxifloxacin:

– acute sinusitis;

– exacerbation of chronic bronchitis;

– uncomplicated infections of skin and subcutaneous structures;

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

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

– complicated intra-abdominal infections, including polymicrobial infections, includingincluding intraperitoneal abscesses;

– uncomplicated pelvic inflammatory diseases (including salpingitis and endometritis).

*Streptococcus pneumoniae with multiple antibiotic resistance includes penicillin-resistant strains and strains resistant to two or more antibiotics from groups such as penicillins (at MIC ≥2 µg/mL), second generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole. Current official guidelines on the use of antibacterials must be taken into consideration.

Active ingredient

Composition

Core:

the active ingredient:

moxifloxacin hydrochloride 454.75 mg, equivalent to moxifloxacin 400.00 mg;

excipients: MCC – 186.05 mg; croscarmellose sodium – 32 mg; magnesium stearate – 6 mg

coating film: hypromellose – 12.6 mg; macrogol 4000 – 4.2 mg; titanium dioxide (E171) – 3.78 mg; iron oxide red dye (E172) – 0.42 mg.

How to take, the dosage

Overly, 1 tablet (400 mg) once daily for the infections listed above. The recommended dose should not be exceeded. The tablets should be swallowed whole, without chewing, with plenty of water, regardless of the time of meals.

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

– exacerbation of chronic bronchitis 5-10 days;

– acute sinusitis 7 days;

– uncomplicated infections of the skin and subcutaneous structures 7 days;

– community-acquired pneumonia total duration of step therapy (IUI followed by oral administration) is 7-14 days;

– complicated infections of the skin and subcutaneous structures – the total duration of step therapy with moxifloxacin (IV infusion followed by oral administration) is 7-21 days;

– Complicated intra-abdominal infections – total duration of step therapy (intravenous infusion followed by oral administration) is 5-14 days;

– uncomplicated inflammatory diseases of the pelvic organs – 14 days.

Do not exceed the recommended duration of treatment. According to clinical studies, the duration of treatment with the drug Moflaxia in tablets can be up to 21 days.

Patient special groups

The elderly. No change in dosing regimen is required in elderly patients.

Children Efficacy and safety of moxifloxacin use in children and adolescents has not been established.

Hepatic impairment. Patients with impaired liver function (classes A and B according to Child-Pugh classification) do not require change of dosage regimen (for use in patients with cirrhosis see “Cautionary Note”).

Renal dysfunction. In patients with impaired renal function (including patients with severe renal failure with creatinine Cl ≤30 ml/min/1.73 m2) as well as in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis a change of dosing regimen is not required.

Ethnicity. No change in dosing regimen is required in patients of different ethnic groups.

Interaction

In concomitant use with atenolol, ranitidine, calcium-containing supplements, theophylline, cyclosporine, oral contraceptives, glibenclamide, itraconazole, digoxine, morphine, probenecid (no clinically significant interaction with moxifloxacin has been confirmed) no dose adjustment is required.

Drugs prolonging the QT interval. Possible additive effect of QT interval prolongation of moxifloxacin and other drugs which affect the prolongation of the QT interval should be considered. Due to the simultaneous use of moxifloxacin and the medicines affecting the prolongation of the QT interval, the risk of ventricular arrhythmias, including polymorphic ventricular tachycardia, increases.

Continuous use of moxifloxacin with the following medicines which affect QT interval prolongation is contraindicated:

– antiarrhythmic medicines of class IA (incl.

– Class III antiarrhythmic drugs (including amiodarone, sotalol, dofetilide, ibutilide);

– neuroleptics (including phenothiazine, pimotazoleptics). phenothiazine, pimozide, sertindole, haloperidol, sultopride);

Tricyclic antidepressants;

Antimicrobials (sparfloxacin, erythromycin (IV), pentamidine, antimalarials, especially halofantrine);

– antihistamines (terfenadine, astemizole, misolastin);

– others (cisapride, vincamine (w/v), bepridil, difeminate).

Antacids, multivitamins and minerals. Taking moxifloxacin concomitantly with antacids, multivitamins and minerals can lead to impaired absorption of moxifloxacin due to the formation of chelate complexes with multivalent cations contained in these drugs. As a result, plasma concentration of moxifloxacin may be significantly lower than desired. In this regard, antacids, antiretroviral medicines (e.g. didanosine) and other drugs containing magnesium or aluminum, sucralfate and other medicines containing iron or zinc should be used at least 4 hours before or 4 hours after oral administration of moxifloxacin.

Warfarin. When concomitant use with warfarin, PV and other parameters of blood coagulation are not changed.

Change in INR value. In patients who received anticoagulants concomitantly with antibiotics, including moxifloxacin, there are cases of increase in anticoagulant activity of anticoagulants. Risk factors are the presence of infectious disease (and associated inflammatory process), age and general condition of the patient. Although no interaction between moxifloxacin and warfarin was found, in patients receiving these drugs simultaneously, it is necessary to monitor INR and adjust the dose of indirect anticoagulants, if necessary.

Digoxin. Moxifloxacin and digoxin have no significant effect on the pharmacokinetic parameters of each other. When using repeated doses of moxifloxacin, the Cmax of digoxin in plasma was increased by approximately 30%, while the AUC and Cmin of digoxin did not change.

Activated charcoal. When concomitant use of activated charcoal and moxifloxacin at a dose of 400 mg orally the systemic bioavailability of moxifloxacin decreases by more than 80% due to its reduced absorption. In case of overdose, the use of activated charcoal in the early stage of absorption prevents further increase in systemic exposure.

Special Instructions

When using the drug Moflaxia some patients may show prolongation of interval QT. The drug Moflaxia should be used with caution in women and elderly patients. Since women compared to men have a longer QT interval, they may be more sensitive to the drugs prolonging this interval. Older patients are also more susceptible to medications that affect the QT interval.

Long QT interval prolongation is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

The degree of QT interval prolongation may increase with increasing plasma concentration of moxifloxacin, so the recommended dose should not be exceeded. However, in patients with pneumonia the correlation between the concentration of moxifloxacin in plasma and prolongation of the QT interval was not observed. None of the 9000 patients who received moxifloxacin had cardiovascular complications and fatalities associated with prolongation of the QT interval. The risk of ventricular arrhythmias may increase in patients with predisposing to arrhythmias when using Mofloxacin.

In this regard, the drug Moflaxia is contraindicated in patients with alterations of electrophysiologic parameters of heart, manifested by prolongation of QT interval (congenital or acquired documented prolongation of QT interval); electrolyte disturbances, especially in unregulated hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; history of rhythm disturbances accompanied by clinical symptoms; in combination with other QT interval prolonging agents (see “Interaction “Interactions”).

The drug Moflaxia should be used with caution:

– in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest;

– in patients with cirrhosis (because the risk of QT interval prolongation cannot be excluded in this category of patients).

In case of fulminant hepatitis potentially leading to liver failure (including fatal cases) has been reported when taking moxifloxacin (see “Adverse effects”). The patient should be informed that if symptoms of liver failure occur, a physician should be consulted before continuing treatment with Moflaxia.

When taking moxifloxacin it was reported about the development of bullous skin lesions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see “Adverse effects”). The patient should be informed that in case of symptoms of skin lesions or mucous membranes it is necessary to consult a physician before continuing treatment with the drug Moflaxia.

The use of quinolone drugs involves a possible risk of seizures. The drug Moflaxia should be used with caution in patients with diseases of the CNS and with CNS disorders predisposing to the occurrence of seizures or reducing the threshold for seizure activity.

The use of broad-spectrum antibacterial agents, including Moflaxia, is associated with the risk of pseudomembranous colitis. This diagnosis should be kept in mind in patients who developed severe diarrhea during treatment with the drug Moflaxia. In this case, appropriate therapy should be prescribed immediately. Drugs which inhibit intestinal peristalsis are contraindicated in severe diarrhea.

The drug Moflaxia should be used with caution in patients with myasthenia gravis due to possible exacerbation of the disease.

With quinolones including moxifloxacin therapy, tendinitis and tendon rupture may develop, especially in elderly patients and patients receiving GCS. Cases have been described that occurred within a few months after completion of treatment. At the first symptoms (pain or inflammation at the site of injury) the drug Moflaxia should be discontinued and the affected limb should be unloaded.

Photosensitivity reactions have been reported with quinolones. However, in preclinical and clinical studies, as well as with the use of moxifloxacin in clinical practice photosensitivity reactions were not observed. Nevertheless, patients receiving the drug Moflaxia should avoid direct sunlight and UV exposure.

The use of Moflaxia in tablet form for oral administration is not recommended in patients with complicated pelvic inflammatory diseases (e.g., those associated with tubo-ovarian or pelvic abscesses).

The use of moxifloxacin for the treatment of infections caused by strains of Staphylococcus aureus that are resistant to methicillin is not recommended. In the case of suspected or confirmed infections caused by MRSA the appropriate antibacterial agents should be used for therapy (see “Pharmacodynamics”). The ability of moxifloxacin to inhibit the growth of mycobacteria may cause interaction under in vitro conditions of moxifloxacin with the test for Mycobacterium spp., which leads to false-negative results in the analysis of samples from patients who are treated with Moflaxia during this period.

In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients treated with Moflaxia should be warned to consult a physician immediately before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness, or weakness occur (see “Side effects”). Mental reactions may occur even after the first use of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts (see “Side effects”). If patients develop such reactions, Moflaxia should be discontinued and appropriate measures taken. Caution should be exercised when using the drug Moflaxia in patients with psychosis and mental illness in the anamnesis.

Because of the high prevalence and increasing incidence of infections caused by Neisseria gonorrhoeae resistant to fluoroquinolones, during the treatment of patients with pelvic inflammatory diseases should not be conducted monotherapy with moxifloxacin, except in cases when the presence of fluoroquinolone-resistant N. gonorrhoeae is excluded. If there is no way to exclude the presence of fluoroquinolone-resistant N. gonorrhoeae, it is necessary to consider supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. gonorrhoeae (e.g., cephalosporin).

Dysglycemia

As with other fluoroquinolones, during the use of the drug Moflaxia changes in blood glucose concentration were observed, including hypo-and hyperglycemia. During the therapy with moxifloxacin dysglycemia occurred mainly in elderly patients with diabetes receiving concomitant therapy with hypoglycemic drugs for oral administration (such as sulfonylureas) or insulin. Close monitoring of blood glucose concentrations is recommended during treatment in patients with diabetes mellitus (see “Side effects”).

Impact on the ability to perform potentially hazardous activities requiring particular attention and responsiveness (e.g., driving, operating moving machinery). Fluoroquinolones including moxifloxacin may impair the ability of patients to drive and engage in other potentially dangerous activities requiring particular attention and rapid psychomotor reactions due to the effect on the CNS and visual impairment.

Contraindications

– hypersensitivity to moxifloxacin, other quinolones or any other component of the drug;

– history of tendon pathology developed due to treatment with quinolone antibiotics;

– patients in the following categories: congenital or acquired documented QT interval prolongation, electrolyte abnormalities, especially uncorrected hypokalemia, clinically significant bradycardia, clinically significant chronic heart failure with reduced left ventricular ejection fraction, history of arrhythmias, accompanied by clinical symptomatology (in preclinical and clinical trials after moxifloxacin administration there were changes in electrophysiological parameters of heart, expressed in prolongation of QT interval);

– use with other drugs that prolong the QT interval;

– patients with impaired liver function (class C according to the Child-Pugh classification) and patients with increased transaminase activity more than 5 times the WHR (due to the limited clinical data);

– pregnancy;

– period of breastfeeding;

– age less than 18 years.

With caution: CNS diseases (including.

With caution: CNS diseases (including suspected CNS involvement) which predispose to seizures and decrease the seizure threshold, patients with psychosis and/or other mental illnesses in the history, patients with potentially proarrhythmic conditions (especially in women and elderly patients), such as acute myocardial ischemia and cardiac arrest, patients with cirrhosis of the liver; myasthenia gravis; concomitant administration with potassium-lowering drugs; patients with a genetic predisposition or actual presence of glucose-6-phosphate dehydrogenase deficiency.

Side effects

Infectious diseases: often – fungal superinfections.

Hematopoietic system: infrequent – anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, prolongation of prothrombin time/increase of INR; rarely – changes in thromboplastin concentration; very rare – increase of prothrombin concentration/reduction of INR.

The immune system: infrequent – allergic reactions, urticaria, pruritus, rash, eosinophilia, rare – anaphylactic/anaphylactoid reactions, angioedema, including laryngeal edema (potentially life-threatening), very rare – anaphylactic/anaphylactoid shock (including potentially life-threatening).

Metabolism: infrequent – hyperlipidemia; rare – hyperglycemia, hyperuricemia; very rare – hypoglycemia.

Psychiatric disorders: infrequent – anxiety, psychomotor hyperreactivity, agitation; rare – emotional lability, depression, hallucinations; very rare – depersonalization, psychotic reactions (potentially manifested in behavior with tendency to self-harm, such as suicidal thoughts or suicide attempts).

Nervous system disorders: Frequent – dizziness, headache; infrequent – paresthesias, dysesthesias, disorders of taste sensitivity (including in very rare cases aguesia), confusion, disorientation, sleep disorders, tremor, vertigo, somnolence; Rarely, hypoesthesia, olfactory disturbances (including anosmia), atypical dreams, coordination disorders (including gait disturbances due to vertigo or vertigo, very rarely leading to injuries from falling, especially in older patients), convulsions with various clinical manifestations (includingincluding “grand mal” seizures), attention disorders, speech disorders, amnesia, peripheral neuropathy, polyneuropathy; very rarely, hyperesthesia.

VIight: infrequent – visual disturbances (especially in CNS reactions); very rare – transient loss of vision (especially in CNS reactions).

Hearing organ: rare – tinnitus, hearing impairment, including deafness (usually reversible).

Cardiovascular system disorders: frequent – prolongation of the QT interval in patients with concomitant hypokalemia; infrequent – prolongation of the QT interval, palpitations, tachycardia, vasodilation; rare – increased BP, decreased BP, syncope, ventricular tachyarrhythmias; very rarely – nonspecific arrhythmias, polymorphic ventricular tachycardia (pirouette type), cardiac arrest (mainly in patients with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).

Respiratory system disorders: infrequent – dyspnea, asthmatic condition.

Digestive system disorders: frequent – nausea, vomiting, abdominal pain, diarrhea; infrequent – decreased appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (except erosive gastroenteritis), increased amylase activity; rare – dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).

Liver and biliary tract disorders: frequent – increased activity of liver transaminases; infrequent – liver dysfunction (including increased LDH activity), increased bilirubin concentration, increased GGT and alkaline phosphatase activity; rare – jaundice, hepatitis (mostly cholestatic); very rare – fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).

Skin and subcutaneous tissue disorders: very rare – bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).

Muscular system disorders: infrequent – arthralgia, myalgia; rare – tendinitis, increased muscle tone and cramps, muscle weakness; very rare – arthritis, tendon ruptures, gait disturbance due to musculoskeletal system damage, increased symptoms of myasthenia.

Urinary system disorders: infrequent – dehydration (caused by diarrhea or reduced fluid intake); rarely – renal impairment, renal failure due to dehydration, which can lead to renal damage, especially in elderly patients with pre-existing renal impairment.

Local reactions: often – reactions at the site of injection/infusion.

General reactions: infrequent – general malaise, nonspecific pain, sweating.

The incidence of the following adverse reactions was higher in the group receiving step therapy: frequently – increase in GGT activity; infrequently – ventricular tachyarrhythmias, arterial hypotension, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), convulsions with various clinical manifestations (including “grand mal” seizures).including “grand mal” seizures), hallucinations, renal dysfunction, and renal failure (as a result of dehydration, which may lead to renal damage, especially in elderly patients with pre-existing renal dysfunction).

Overdose

There are limited data on overdose of moxifloxacin. No adverse effects were observed when using moxifloxacin in dose up to 1200 mg once and 600 mg for 10 days or more.

Treatment: in case of overdose the clinical picture should be guided and symptomatic supportive therapy with ECG-monitoring should be conducted. The use of activated charcoal immediately after ingestion may help prevent excessive systemic exposure to moxifloxacin in case of overdose.

Pregnancy use

The safety of moxifloxacin use during pregnancy has not been established, so its use is contraindicated. Cases of reversible joint damage in children receiving some quinolones have been described, but no manifestation of this effect in the fetus has been reported (when used by the mother during pregnancy).

Reproductive toxicity has been identified in animal studies. The potential risk to humans is unknown.

Like other quinolones, moxifloxacin causes cartilage damage of large joints in premature animals.

In preclinical studies it was found that a small amount of moxifloxacin is excreted into breast milk. There are no data on its use in women during lactation. Therefore, the use of moxifloxacin during breastfeeding is contraindicated.

Similarities