Heinemox, 400 mg 5 pcs

Pharmacotherapeutic group: antimicrobial agent – fluoroquinolone.

ATX code: J01MA14

Pharmacological properties

Pharmacodynamics

Mechanism of action

Moxifloxacin is a broad-spectrum bactericidal antibacterial drug, 8-methoxifluoroquinolone. Bactericidal action of moxifloxacin is due to the inhibition of bacterial topoisomerases II and IV which leads to disruption of replication, repercussion and transcription of DNA biosynthesis of the microbial cell and, as a consequence, to death of microbial cells.

The minimal bactericidal concentrations of moxifloxacin are generally comparable to its minimal inhibitory concentrations.

Mechanisms of resistance

. The 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 agents 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 to 10^-10). Resistance to moxifloxacin develops slowly through multiple mutations. Repeated exposure of microorganisms to moxifloxacin in concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in the MIC. There are cases of cross-resistance to quinolones. 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 bacycloamino group at the C7 position prevents the development of active efflux, a mechanism of resistance to fluoroquinolones.

Moxifloxacin in vitro 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., as well as bacteria resistant to beta-lactam and macrolide antibiotics.

Effects on human gut microflora

The following changes in gut microflora after oral administration of moxifloxacin were noted in two studies conducted on volunteers.

There was a decrease in concentrations of Echerichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp, Klebsiella spp., as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. No Clostridium difficile toxin was detected.

Pharmacokinetics

absorption

After oral administration, moxifloxacin is absorbed rapidly and almost completely. Absolute bioavailability is about 91%.

The pharmacokinetics of moxifloxacin when administered in doses of 50 to 1200 mg once and 600 mg/day for 10 days is linear. The equilibrium state is reached within 3 days.

After a single administration of 400 mg of moxifloxacin C_max in the blood is reached within 0.5-4 hours and is 3.1 mg/L. After oral administration of 400 mg of moxifloxacin once daily, C_ss^max and C_ss^min are 3.2 mg/L and 0.6 mg/L, respectively.

When moxifloxacin is taken with food, there is a slight increase in time to reach C_max (by 2 h) and a slight decrease in C_max (by approximately 16%), with no change in absorption duration. However, these data are of no clinical significance and the drug may be used regardless of food intake.

Distribution

Moxifloxacin is rapidly distributed in tissues and organs and binds to blood proteins (mainly to albumin) by approximately 45%. The volume of distribution is approximately 2 L/kg.

High concentrations of moxifloxacin exceeding those in plasma are created in the lung tissue (including epithelial fluid, alveolar macrophages), sinuses (maxillary and ethmoid sinuses), nasal polyps, in the foci of inflammation (in the content of blisters in skin lesions). In interstitial fluid and saliva moxifloxacin is determined in free form, not bound to proteins, in concentrations higher than in blood plasma.

In addition, high concentrations of moxifloxacin are determined in the tissues of the abdominal cavity, peritoneal fluid and female reproductive organs.

Metabolism

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

Elimation

The half-life 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 the drug. The mass balance of the parent compound and phase 2 metabolites is approximately 96-98%, indicating no oxidative metabolism. About 22% of a 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 the differences in AUC and Cmax were found in 33%. 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 to be clinically significant. No clinically significant differences in pharmacokinetics of moxifloxacin were found in patients of different ethnic groups and different ages.

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

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

Liver function impairment. There were no significant differences in moxifloxacin concentrations in patients with impaired liver function (Child-Pugh class A, B, C) compared to healthy volunteers with normal liver function.

Indications

Infectious inflammatory diseases caused by microorganisms sensitive to moxifloxacin:

Active ingredient

Composition

Each film-coated tablet contains:

active ingredient: moxifloxacin hydrochloride 436.30 mg (corresponding to moxifloxacin – 400mg)

complementary substances: corn starch, 52 mg; sodium lauryl sulfate, 7.5 mg; purified talc, 15 mg; magnesium stearate, 6.5 mg; sodium carboxymethyl starch, 20 mg; colloidal anhydrous silicon dioxide, 3.5 mg; croscarmellose sodium, 6.5 mg; microcrystalline cellulose, 130.7 mg.

Shell: Opadry white (85G58977) Make-Colorcon (polyvinyl alcohol, titanium dioxide, talc, macrogol – 3000, lecithin (soy)) – 17.32 mg; iron oxide red – 0.68 mg.

How to take, the dosage

Ingestion. Swallow the tablet whole, without chewing, with plenty of water, regardless of meals (preferably after a meal). The recommended dosage should not be exceeded.

Infection

Dose every 24 hours (once daily)

.Strong>Treatment duration, days

Extra-hospital pneumonia

400 mg

7-14 (intravenous followed by oral administration)

In acute exacerbation of chronic bronchitis

400 mg

5-10

Acute bacterial sinusitis

400 mg

7

Uncomplicated skin and soft tissue infections

/p>

400 mg

7
Complicated infections of the skin and subcutaneous structures

400 mg

7-21 (intravenous followed by oral administration)

Complicated intra-abdominal infections

400 mg

5-14 (intravenous followed by oral administration)

Uncomplicated pelvic inflammatory disease

400 mg

14

The recommended duration of therapy should not be exceeded.
It is not required to change the dosage regimen:
– in elderly patients;
– in patients with impaired liver function (class A, B according to the Child-Pugh scale);
– in patients with impaired renal function (including In patients with impaired renal function (including with severe renal failure with creatinine clearance ≤ 30 ml/min/1.73 m2, as well as those undergoing continuous hemodialysis and prolonged ambulatory peritoneal dialysis);
– In patients from different ethnic groups;
– The effectiveness and safety of moxifloxacin in children and adolescents has not been established.

Interaction

There is no clinically significant interaction of moxifloxacin with atenololol, ranitidine, calcium supplements, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid. There is no need to correct the dosage regimen when co-administered with these drugs.

Antacids, minerals and multivitamins

. Simultaneous use of moxifloxacin and antacids, minerals and multivitamins can impair absorption of moxifloxacin due to the formation of chelate complexes with polyvalent cations contained in these drugs, and, consequently, reduce the concentration of moxifloxacin in plasma. In this regard, antacids, antiretroviral drugs (e.g. didanosine) and other drugs containing magnesium, aluminum, sucralfate, iron and zinc should be taken at least 4 hours before or 4 hours after oral administration of moxifloxacin.

Drugs that prolong the interval QT

. Because moxifloxacin affects QT interval prolongation, co-administration of moxifloxacin with the following drugs is contraindicated:

– antiarrhythmic IA (quinidine, hydroquinidine, disopyramide, etc.) and III (amiodarone, sotalol, dofetidil, ibutilide, etc.

– tricyclic antidepressants;

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

– antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine);

– antihistamines (astemizole, terfenadine, misolastin);

– others (cisapride, vincamine IV, bepridil, difeminil).

Warfarin

Protrombin time and other parameters of blood coagulation are not changed when co-administered with warfarin. However, in patients who received anticoagulants in combination with antibiotics, including moxifloxacin, there are cases of increase of anticoagulation activity of anticoagulants. Risk factors are the presence of infectious disease (and associated inflammatory process), age and general condition of the patient. Despite the fact that there is no interaction between moxifloxacin and warfarin, in patients receiving combined treatment with these drugs, it is necessary to monitor the INR value and, if necessary, adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin have no significant effect on the pharmacokinetic parameters of each other. Repeated doses of moxifloxacin increased maximum digoxin concentration by approximately 30%, while the area under the concentration-time curve (AUC) and minimum digoxin concentration did not change.

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

Glucocorticosteroids

The simultaneous use of moxifloxacin and glucocorticosteroids increases the risk of tendinitis and tendon rupture.

Special Instructions

In some cases, even after the first use of moxifloxacin hypersensitivity and allergic reactions may develop, which should immediately inform the doctor. Very rarely, even after the first use of moxifloxacin, anaphylactic reactions may progress to life-threatening anaphylactic shock. In these cases the treatment with moxifloxacin should be discontinued and the necessary therapeutic measures (including anti-shock) should be started immediately.

When using moxifloxacin some patients may show prolongation of the QT interval. Moxifloxacin should be used with caution in women and elderly patients. Since women have a longer QT interval compared with men, they may be more sensitive to the medicines prolonging the QT interval. Older patients are also more susceptible to QT interval medications.

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 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. When using moxifloxacin the risk of ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias.

In this regard moxifloxacin is contraindicated in: changes of electrophysiological parameters of the heart which manifests as prolongation of the QT interval: congenital or acquired documented prolongation of the QT interval, electrolyte disorders, especially uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; history of rhythm disorders with clinical symptoms; use with other drugs that prolong the QT interval (antiarrhythmic IA (quinidine, hydroquinidine, disopyramide, etc.) and III (amiodarone, sotalol, dofetidil, ibutilide, etc.) classes, tricyclic antidepressants, neuroleptics (phenothiazine, pimozide, sertindol, haloperidol, sultopride, etc.), antimicrobial drugs.), antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine), antihistamines (astemizole, terfenadine, misolastin) and others (cisapride, Vincamine IV, bepridil, difemanil).

Moxifloxacin should be used with caution: in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest; in patients with cirrhosis (since the risk of QT interval prolongation cannot be excluded in this category of patients).

When using moxifloxacin it was reported about the cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases) (see section “Adverse effects”). The patient should be informed that in case of symptoms of renal failure it is necessary to consult a physician before continuing treatment with moxifloxacin.

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

The use of quinolone drugs is associated with a possible risk of seizures. Moxifloxacin should be used with caution in patients with diseases of the CNS and with disorders of the CNS which predispose to seizures or reduce the threshold for seizure activity.

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

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

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

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

The use of moxifloxacin in tablet form for oral administration is not recommended in patients with complicated inflammatory disease of the pelvic organs (such as those associated with tubo-ovarian or pelvic abscesses)./p>

The use of moxifloxacin is not recommended for the treatment of infections caused by Staphylococcus aureus strains resistant to methicillin (MRSA). In cases of suspected or confirmed MRSA infections, treatment with appropriate antibacterial agents should be administered (see section on Pharmacodynamics).

The ability of moxifloxacin to inhibit the growth of mycobacteria may cause an interaction in vitro moxifloxacin with a test for Mycobacterium spp., leading to false-negative results when testing samples from patients treated with moxifloxacin during this period.

In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy leading to paresthesias, hypoesthesias, dysesthesias or weakness have been described. Patients who are treated with moxifloxacin should be warned about the need to immediately consult a physician before continuing treatment in case of symptoms of neuropathy, including pain, burning, tingling, numbness or weakness (see section “Side effects”).

Psychiatric reactions may occur even after the first prescription 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 section “Side effects”). In the case of development of any side effects on the central nervous system, including mental disorders it is necessary to immediately cancel moxifloxacin and initiate appropriate therapy. In such cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones if possible. Caution should be exercised when using moxifloxacin in patients with psychosis and/or psychiatric diseases in the history.

Because of the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, moxifloxacin monotherapy should not be used in the treatment of patients with pelvic inflammatory disease unless the presence of fluoroquinolone-resistant N. Gonorrhoeae excluded. Unless it is possible to rule out the presence of fluoroquinolone-resistant N. Gonorrhoeae, the issue of supplementing empirical therapy with moxifloxacin with an appropriate antibiotic that is active against N. Gonorrheae (e.g., cephalosporin).

Dysglycemia

As with other fluoroquinolones, during the use of moxifloxacin changes in blood glucose concentration were observed, including hypo-and hyperglycemia. During moxifloxacin therapy dysglycemia occurred more often in elderly patients and patients with diabetes receiving concomitant therapy with oral hypoglycemic drugs (e.g., sulfonylureas) or insulin. When using moxifloxacin in such patients the risk of hypoglycemia increases, up to hypoglycemic coma. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased heart rate, pale skin, sweating, trembling, weakness). If a patient develops hypoglycemia, it is necessary to immediately stop treatment with moxifloxacin and begin an appropriate therapy. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. During treatment with moxifloxacin in elderly patients, in patients with diabetes mellitus it is recommended to monitor closely the concentration of glucose in blood.

Influence on the ability to drive vehicles, mechanisms

Fluoroquinolones including moxifloxacin may impair the ability of patients to drive and engage in other potentially dangerous activities that require increased attention and rapid psychomotor reactions due to the impact on the CNS and visual impairment.

Synopsis

Contraindications

With caution

Side effects

Data on adverse reactions reported with moxifloxacin 400 mg (oral, step therapy [intravenous injection followed by oral administration] and intravenous only) were obtained from clinical trials and post-marketing reports (italicized).
Adverse reactions listed in the “frequently” group occurred with a frequency of less than 3%, except for nausea and diarrhea.
In each frequency group, adverse drug reactions are listed in descending order of significance. Frequency is defined as follows:
frequently (≥1/100 to < 1/10),
infrequently (≥1/1000 to < 1/100),
rarely (≥1/10000 to < 1/1000),
very rarely (< 1/10000),
frequency is unknown (it is not possible to determine the frequency of occurrence from the available data).

Infectious and parasitic diseases
Fungal superinfections

Hematopoietic system disorders
Anemia
Leukopenia Neutropenia Thrombocytopenia Thrombocythemia
Prothrombin time prolongation/International normalized ratio (INR) increase
br> Changes in thromboplastin concentration
Increased prothrombin concentration/ decreased INR

Immune system disorders

br> Allergic reactions
Itching
Rash
Urticaria
Eosinophilia
Anaphylactic/anaphylactoid reactions Angioedema, including laryngeal edema (potentially life-threatening)
Anaphylactic/anaphylactoid shock (including potentially life-threatening)/p>

Metabolism
Hyperlipidemia
Hyperglycemia
Hyperuricemia
Hypoglycemia

Psychiatric disorders
Anxiety Psychomotor hyper-activity/ agitation
Emotional lability
Depression (in very rare cases, self-harming behavior such as suicidal thoughts or suicide attempts are possible)br> Hallucinations
Depersonalization
Psychotic reactions (potentially manifesting in self-harming behaviors such as suicidal thoughts or suicide attempts)

Nervous system disorders
Headache
Dizziness

Skin and subcutaneous tissue
Bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening)

Musculoskeletal and connective tissue
Arthralgia
Myalgia
Tendinitis
Increased muscle tone and cramps
Muscle weakness
Tendon tears Arthritis
Gait disturbances due to musculoskeletal damage
Worsening symptoms of myasthenia gravis.

Renal and urinary tract disorders
Dehydration (caused by diarrhea or decreased fluid intake)

Renal impairment
Renal failure (due to dehydration, which may result in renal damage, especially in older patients with pre-existing renal impairment)/p>

General disorders and disorders at the injection site
Reactions at the injection/infusion site
General malaise
Nonspecific pain
Sweating Phlebitis/thrombophlebitis at the infusion site
Oedema

The incidence of the following adverse reactions was higher in the group that received step therapy:
Often: increased gamma-glutamyltransferase activity
Infrequent: Ventricular tachycardia, decreased blood pressure, edema, pseudo-membranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including “grand mal” seizures), hallucinations, renal dysfunction, renal failure (due to dehydration, which may lead to renal damage, especially in elderly patients with pre-existing renal impairment).

Overdose

There are limited data on overdose of moxifloxacin. No adverse effects were observed when using moxifloxacin in doses up to 1200 mg once and 600 mg for 10 days or more. In case of overdose the clinical picture should be guided and symptomatic supportive therapy with ECG monitoring should be carried out.

Pregnancy use

The safety of moxifloxacin use during pregnancy has not been established and 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 (when used by the mother during pregnancy) has been reported.

Reproductive toxicity has been shown 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 large 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