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 and inflammatory diseases caused by microorganisms sensitive to moxifloxacin:

uncomplicated infections of the skin and subcutaneous structures;
community-acquired pneumonia, including community-acquired pneumonia, the causative agents of which are strains of microorganisms with multiple resistance to antibacterial drugs*;
complicated infections of the skin and subcutaneous structures (including infected diabetic foot);
complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses;
uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).

For the treatment of the following infectious and inflammatory diseases, moxifloxacin can only be used as an alternative to other antimicrobial drugs:

acute sinusitis;
exacerbation of chronic bronchitis.

* Multidrug-resistant Streptococcus pneumoniae includes strains resistant to penicillin and strains resistant to two or more antibiotics from the following groups: penicillins (MIC ≥ 2 μg/ml), second-generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Current official guidelines on the use of antibacterial agents must be taken into account.

Pharmacological effect

Pharmacotherapeutic group: antimicrobial agent – ​​fluoroquinolone.

ATX code: J01MA14

Pharmacological properties

Pharmacodynamics

Mechanism of action

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

The minimum bactericidal concentrations of moxifloxacin are generally comparable to its minimum 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. There is no cross-resistance between these groups of antibacterial drugs and moxifloxacin. So far, no cases of plasmid resistance have been observed either. The overall incidence of resistance development is very low (10-7 – 10-10). Resistance to moxifloxacin develops slowly through multiple mutations. Repeated exposure of microorganisms to moxifloxacin at concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in MIC. Cases of cross-resistance to quinolones have been reported. However, some gram-positive and anaerobic microorganisms resistant to other quinolones remain sensitive to moxifloxacin.

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

Moxifloxacin is active in vitro 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.

Effect on human intestinal microflora

In two studies conducted on volunteers, the following changes in intestinal microflora were noted after oral administration of moxifloxacin.

There was a decrease in the 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

Suction

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

The pharmacokinetics of moxifloxacin when taken at a dose of 50 to 1200 mg once, as well as 600 mg/day for 10 days, is linear. The equilibrium state is achieved within 3 days.

After a single dose of 400 mg of moxifloxacin, Cmax in the blood is reached within 0.5-4 hours and is 3.1 mg/l. After oral administration of 400 mg of moxifloxacin 1 time per day, Cssmax and Cssmin are 3.2 mg/l and 0.6 mg/l, respectively.

When taking moxifloxacin with food, there is a slight increase in the time to reach Cmax (by 2 hours) and a slight decrease in Cmax (by approximately 16%), while the duration of absorption does not change. However, these data have no clinical significance, and the drug can be used regardless of food intake.

Distribution

Moxifloxacin is rapidly distributed in tissues and organs and binds to blood proteins (mainly 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 in epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoid sinuses), in nasal polyps, in foci of inflammation (in the contents of blisters with skin lesions). In interstitial fluid and saliva, moxifloxacin is determined in a free form, not bound to proteins, in a concentration higher than in blood plasma.

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

Metabolism

Moxifloxacin undergoes phase 2 biotransformation and is excreted from the body by the kidneys and also through the intestines, both unchanged and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin is not biotransformed by the microsomal cytochrome P450 system. Metabolites M1 and M2 are present in plasma in concentrations lower than the parent compound. Based on the results of preclinical studies, it was proven that these metabolites do not have a negative effect on the body in terms of safety and tolerability.

Removal

The half-life of moxifloxacin is approximately 12 hours. The average total clearance after administration of 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 parent compound and phase 2 metabolites is approximately 96-98%, indicating the absence of oxidative metabolism. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% through the intestines.

Pharmacokinetics in different patient groups

Age, gender and ethnicity. A study of the pharmacokinetics of moxifloxacin in men and women revealed differences of 33% in terms of AUC and Cmax. The absorption of moxifloxacin did not depend on gender. Differences in AUC and Cmax were due to differences in weight rather than gender and are not considered clinically significant. There were no clinically significant differences in the pharmacokinetics of moxifloxacin in patients of different ethnic groups and different ages.

Children. The pharmacokinetics of moxifloxacin in children has not been studied.

Kidney failure. There were no significant changes in the pharmacokinetics of moxifloxacin 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 dysfunction. There were no significant differences in moxifloxacin concentrations in patients with impaired liver function (Child-Pugh class A, B, C) compared with healthy volunteers with normal liver function.

Special instructions

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

When using moxifloxacin, some patients may experience prolongation of the QT interval. Moxifloxacin should be used with caution in women and elderly patients. Because women have a longer QT interval than 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.

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

The degree of QT prolongation may increase with increasing concentrations of moxifloxacin, so the recommended dose should not be exceeded. However, in patients with pneumonia, no correlation was observed between moxifloxacin plasma concentrations and QT interval prolongation. None of the 9,000 patients treated with moxifloxacin experienced cardiovascular complications or deaths associated with QT prolongation. When using moxifloxacin, the risk of developing ventricular arrhythmias may increase in patients with conditions predisposing to arrhythmias.

In this regard, moxifloxacin is contraindicated in case of: changes in electrophysiological parameters of the heart, expressed in prolongation of the QT interval: 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; 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, antipsychotics (phenothiazine, pimozide, sertindole, haloperidol, sultopride, etc.), antimicrobial drugs (sparfloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine), antihistamines (astemizole, terfenadine, mizolastine) 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 liver cirrhosis (since in this category of patients the risk of developing QT prolongation cannot be excluded).

Cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases), have been reported with the use of moxifloxacin (see section “Side effects”). The patient should be informed that if symptoms of renal failure occur, they should consult a physician before continuing treatment with moxifloxacin.

Cases of bullous skin lesions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported while taking moxifloxacin (see section “Side effects”). The patient should be informed that if symptoms of skin or mucous membrane lesions occur, they should consult a doctor before continuing to take moxifloxacin.

The use of quinolone drugs is associated with a possible risk of developing seizures. Moxifloxacin should be used with caution in patients with diseases of the central nervous system and with disorders of the central nervous system that predispose to seizures or lower the threshold for seizure activity.

The use of broad-spectrum antibacterial drugs, including moxifloxacin, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be considered in patients who develop severe diarrhea during treatment with moxifloxacin. In this case, appropriate therapy should be prescribed immediately. Drugs that inhibit intestinal motility 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.

During therapy with quinolones, including moxifloxacin, tendinitis and tendon rupture may develop in elderly patients receiving glucocorticosteroids. Cases have been described that occurred within several months after completion of treatment. At the first symptoms of pain or inflammation at the site of injury, you should stop taking the drug and unload the affected limb.

When using quinolones, photosensitivity reactions are observed. However, during preclinical and clinical studies, as well as the use of moxifloxacin in practice, no photosensitivity reactions were observed. However, patients receiving moxifloxacin should avoid exposure to direct sunlight and ultraviolet light.

The use of moxifloxacin in the form of oral tablets is not recommended in patients with complicated pelvic inflammatory diseases (for example, associated with tubo-ovarian or pelvic abscesses)

The use of moxifloxacin is not recommended to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In cases of suspected or confirmed infections caused by MRSA, treatment with appropriate antibacterial drugs should be prescribed (see section “Pharmacodynamics”).

The ability of moxifloxacin to inhibit the growth of mycobacteria may cause an in vitro interaction between moxifloxacin and the test for Mycobacterium spp., leading to false negative results when analyzing samples from patients who are being treated with moxifloxacin during this period.

In patients treated with quinolones, including moxifloxacin, cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia or weakness have been described. Patients being treated with moxifloxacin should be warned to seek immediate medical attention before continuing treatment if symptoms of neuropathy, including pain, burning, tingling, numbness or weakness, occur (see section “Side Effects”).

Psychiatric reactions can occur even after the first prescription of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a tendency to self-harm, including suicide attempts (see section “Side effects”). In case of development of any side effects from the central nervous system, including mental disorders, moxifloxacin should be immediately discontinued and appropriate therapy should be started. In such cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible. Caution should be exercised when using moxifloxacin in patients with a history of psychosis and/or psychiatric illness.

Due to the widespread and increasing incidence of infections caused by fluoroquinolone-resistant Neisseria gonorrhoeae, patients with pelvic inflammatory disease should not be treated with moxifloxacin monotherapy unless the presence of fluoroquinolone-resistant N. gonorrhoeae has been excluded. If the presence of fluoroquinolone-resistant N. Gonorrhoeae cannot be excluded, consideration should be given to supplementing empiric moxifloxacin therapy with an appropriate antibiotic that is active against N. Gonorrhoeae (eg, a cephalosporin).

Dysglycemia

As with other fluoroquinolones, changes in blood glucose concentrations, including hypo- and hyperglycemia, were observed with the use of moxifloxacin. During therapy with moxifloxacin, dysglycemia occurred more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin. When using moxifloxacin in such patients, the risk of developing hypoglycemia, including hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, ravenous appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, perspiration, trembling, weakness). If the patient develops hypoglycemia, treatment with moxifloxacin should be discontinued immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible. When treating moxifloxacin in elderly patients and patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended.

Impact on the ability to drive vehicles and machinery

Fluoroquinolones, including moxifloxacin, may impair the ability of patients to drive a car and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to their effects on the central nervous system and visual impairment.

Active ingredient

Moxifloxacin

Composition

Each film-coated tablet contains:

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

excipients: 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 silicon dioxide anhydrous – 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; red iron oxide – 0.68 mg.

Pregnancy

The safety of moxifloxacin during pregnancy has not been established and its use is contraindicated. Cases of reversible joint damage have been described in children receiving some quinolones, but this effect has not been reported in the fetus (when used by the mother during pregnancy).

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

Like other quinolones, moxifloxacin causes cartilage damage in large joints in premature animals. Preclinical studies have shown that large amounts of moxifloxacin are excreted into breast milk. There are no data on its use in women during lactation. Therefore, the use of moxifloxacin during breastfeeding is contraindicated.

Contraindications

hypersensitivity to moxifloxacin, other quinolones or other components of the drug;
children under 18 years of age;
allergic reactions to peanuts or soy;
tendon damage due to previous treatment with quinolones;
simultaneous use of drugs that prolong the QT interval (including antiarrhythmic drugs of class IA, III) – see section “Interaction with other drugs”;
the use of moxifloxacin leads to 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;
patients with impaired liver function (class C according to the Child-Pugh classification) and an increase in transaminase activity more than five times the upper limit of normal;
pregnancy and breastfeeding period.

With caution

for diseases of the central nervous system (including those suspected of involvement of the central nervous system), predisposing to the occurrence of seizures and reducing the threshold of seizure activity;
in patients with a history of psychosis and psychiatric diseases;
in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia, especially in women and elderly patients;
myasthenia gravis;
with cirrhosis of the liver;
when taken simultaneously with drugs that reduce potassium levels.

Side Effects

Adverse reactions reported with moxifloxacin 400 mg (oral, step-down [intravenous followed by oral], and intravenous alone) are derived from clinical studies and post-marketing reports (shown in italics).
Adverse reactions listed in the “common” group occurred with an incidence of less than 3%, with the exception of nausea and diarrhea.
In each frequency group, adverse drug reactions are listed in descending order of importance. The frequency is determined as follows:
often (from ≥1/100 to <1/10),
uncommon (≥1/1000 to <1/100),
rare (from ≥1/10000 to <1/1000),
very rare (< 1/10000),
frequency is unknown (it is not possible to determine the frequency of occurrence based on available data).

Infectious and parasitic diseases
Fungal superinfections

From the hematopoietic system
Anemia
Leukopenia Neutropenia Thrombocytopenia Thrombocythemia
Prolongation of prothrombin time/increase in international normalized ratio (INR)
Change in thromboplastin concentration
Increased prothrombin concentration/decrease INR

From the immune system
Allergic reactions
Itching
Rash
Urticaria
Eosinophilia
Anaphylactic/anaphylactoid reactions
Angioedema, including laryngeal edema (potentially life-threatening)
Anaphylactic/anaphylactoid shock (including potentially life-threatening)

Metabolism
Hyperlipidemia
Hyperglycemia
Hyperuricemia
Hypoglycemia

Mental disorders
Anxiety Psychomotor hyperactivity/agitation
Emotional lability
Depression (in very rare cases, self-harming behavior such as suicidal ideation or suicide attempts may occur)
Hallucinations
Depersonalization
Psychotic reactions (potentially manifested by self-harming behavior such as suicidal ideation or suicide attempts)

From the nervous system
Headache
Dizziness
Paresthesia/dysesthesia
Impaired taste sensitivity (including, in very rare cases, ageusia)
Confusion and disorientation
Sleep disorders
Tremor
Vertigo
Drowsiness
Hypoesthesia Smell disorders (including anosmia)
Atypical dreams Impaired coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to injury due to falls, especially in elderly patients) Seizures with various clinical manifestations (including “grand mal” seizures)
Attention disorders Speech disorders
Amnesia
Peripheral neuropathy and polyneuropathy
Hyperesthesia

From the side of the organ of vision
Visual impairment (especially with reactions from the central nervous system)
Transient loss of vision (especially against the background of reactions from the central nervous system)

Hearing and labyrinthine disorders
Tinnitus
Hearing impairment, including deafness (usually reversible)

From the cardiovascular system
Prolongation of the QT interval in patients with concomitant hypokalemia
Prolongation of the QT interval Palpitations Tachycardia
Vasodilation
Ventricular tachyarrhythmias
Fainting
Increased blood pressure
Reduced blood pressure
Nonspecific arrhythmias
Polymorphic ventricular tachycardia (torsades des pointes), cardiac arrest (mainly in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia)

From the respiratory system, chest organs and mediastinum
Dyspnea (including asthmatic conditions)

From the gastrointestinal tract
Nausea
Vomiting
Abdominal pain
Diarrhea
Decreased appetite and reduced food intake
Constipation
Dyspepsia
Flatulence
Gastroenteritis (except erosive gastroenteritis)
Increased amylase activity
Dysphagia
Stomatitis
Pseudomembranous colitis (in very rare cases associated with life-threatening complications)

From the liver and biliary tract
Increased activity of “liver” transaminases
Liver dysfunction (including increased lactate dehydrogenase levels)
Increased bilirubin concentration
Increased activity of gamma-glutamyltransferase
Increased alkaline phosphatase activity in the blood
Jaundice
Hepatitis (mainly cholestatic)
Fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases)

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

From the musculoskeletal and connective tissue side
Arthralgia
Myalgia
Tendinitis
Increased muscle tone and cramps
Muscle weakness
Tendon ruptures
Arthritis
Gait disturbances due to damage to the musculoskeletal system
Increased symptoms of myasthenia gravis.

From the kidneys and urinary tract
Dehydration (caused by diarrhea or decreased fluid intake)

Renal dysfunction
Renal failure (due to dehydration, which can lead to kidney damage, especially in older patients with pre-existing renal impairment)

General disorders and injection site disorders
Injection/infusion site reactions
General malaise
Nonspecific pain
Sweating
Phlebitis/thrombophlybitis at the infusion site
Edema

The incidence of the following adverse reactions was higher in the group receiving stepwise therapy:
Common: increased gamma-glutamyl transferase activity
Uncommon: ventricular tachycardia, decreased blood pressure, edema, pseudomembranous colitis (in very rare cases associated with life-threatening complications), convulsions with various clinical manifestations (including “grand mal” seizures), hallucinations, renal dysfunction, renal failure (due to dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal impairment).

Interaction

There is no clinically significant interaction of moxifloxacin with atenolol, ranitidine, calcium supplements, theophylline, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid. No dosage adjustment is required when used together with these drugs.

Antacids, minerals and multivitamins

The simultaneous use of moxifloxacin and antacid drugs, minerals and multivitamins may interfere with the 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 the blood plasma. In this regard, antacids, antiretroviral drugs (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.

Drugs that prolong the QT interval

Since moxifloxacin is known to prolong the QT interval, co-administration of moxifloxacin with the following drugs is contraindicated:

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

– tricyclic antidepressants;

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

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

– antihistamines (astemizole, terfenadine, mizolastine);

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

Warfarin

When used together with warfarin, prothrombin time and other blood coagulation parameters do not change. However, in patients receiving anticoagulants in combination with antibiotics, including moxifloxacin, there have been cases of increased anticoagulant activity of anticoagulants. Risk factors are the presence of an infectious disease (and concomitant inflammatory process), age and general condition of the patient. Despite the fact that no interaction has been identified between moxifloxacin and warfarin, in patients receiving concomitant 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 do not have a significant effect on each other’s pharmacokinetic parameters. With repeated doses of moxifloxacin, the maximum concentration of digoxin increased by approximately 30%, while the area under the concentration-time curve (AUC) and the minimum concentration of digoxin did not change.

Activated carbon

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

Glucocorticosteroids

With the simultaneous use of moxifloxacin and glucocorticosteroids, the risk of developing tendonitis and tendon rupture increases.

Overdose

There are limited data on overdose with moxifloxacin. No side effects were observed when using moxifloxacin at a dose of up to 1200 mg once and 600 mg for 10 days or more. In case of overdose, one should focus on the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

Storage conditions

Store at a temperature not exceeding 25°C.
Keep out of the reach of children.

Shelf life

5 years. Do not use after expiration date.

Manufacturer

Highglans Laboratories Pvt. Ltd, India