Moxifloxacin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOXIFLOXACIN

Composition:

Active substance: moxifloxacin;

1 tablet contains 436.8 mg of moxifloxacin hydrochloride, equivalent to 400 mg of moxifloxacin;

Excipients: microcrystalline cellulose, type 101; lactose monohydrate; sodium croscarmellose; magnesium stearate; coating mixture: hypromellose, titanium dioxide (E 171), polyethylene glycol (macrogol), iron oxide red (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, dull red in color, oval-shaped with a biconvex surface.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antibacterial agents of the quinolone group. ATC code J01M A14.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

In vitro, moxifloxacin is active against many Gram-positive and Gram-negative microorganisms. The bactericidal activity of moxifloxacin is due to inhibition of two types of topoisomerase II (DNA gyrase and topoisomerase IV), which are essential for bacterial DNA replication, transcription, and repair.

The C8-methoxy substituent is believed to enhance activity and reduce the selection of resistant mutants among Gram-positive bacteria compared to C8-H analogues. The presence of a bulky dicyclic amino group at position C-7 prevents active efflux mediated by the norA or pmrA genes found in some Gram-positive bacteria.

Pharmacodynamic studies indicate that moxifloxacin exhibits concentration-dependent bactericidal activity. Minimal bactericidal concentrations (MBC) are generally similar to minimal inhibitory concentrations (MIC).

Effect on human intestinal flora

In two studies involving healthy volunteers, the following changes in intestinal flora were observed after oral administration of moxifloxacin: reduced numbers of E. coli, Bacillus spp., Enterococcus, Klebsiella spp., and anaerobes including Bacteroides vulgatus, Bifidobacterium spp., Eubacterium, and Peptostreptococcus; an increase in Bacteroides fragilis was observed. The counts of the aforementioned microorganisms returned to normal within two weeks.

Mechanism of resistance

Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines do not affect the antibacterial efficacy of moxifloxacin. Other resistance mechanisms, such as permeability barriers (common in Pseudomonas aeruginosa) and efflux mechanisms, may influence susceptibility to moxifloxacin.

Development of resistance to moxifloxacin in vitro has been observed as a gradual process involving point mutations in both types of topoisomerase II: DNA gyrase and topoisomerase IV. Moxifloxacin is a weak substrate for active efflux mechanisms in Gram-positive microorganisms.

Cross-resistance with other fluoroquinolones occurs. However, because moxifloxacin inhibits both topoisomerases II and IV with similar potency in certain Gram-positive bacteria, these bacteria may be resistant to other quinolones but remain susceptible to moxifloxacin.

Clinical breakpoints

Table 1

Clinical MIC and disk diffusion breakpoints for moxifloxacin (01.01.2012) according to EUCAST (European Committee on Antimicrobial Susceptibility Testing)

*Species-unrelated breakpoints were established primarily based on pharmacokinetic/pharmacodynamic data and do not depend on the distribution of MICs for specific species. These data are used only for species for which species-specific breakpoints have not been established and are not used for species where interpretive criteria are subject to definition.

Microbiological susceptibility

The frequency of acquired resistance may vary depending on geographical region and over time, as defined for specific microorganisms. It is desirable to have access to local information on microbial resistance, especially when treating severe infections. When necessary, consultation with an expert in antibiotic resistance should be sought if local resistance prevalence is so high that the efficacy of a particular medicinal product against at least some infectious agents becomes questionable.

Susceptible species

Aerobic Gram-positive microorganisms: Gardnerella vaginalis, Staphylococcus aureus* (methicillin-susceptible), Streptococcus agalactiae (group B), Streptococcus milleri group* (S. anginosus, S. constellatus, and S. intermedius), *Streptoc游戏副本

*Intravenous administration of a single 400 mg dose.

110 hours after administration.

2Free concentration.

3From 3 to 36 hours after dose administration.

4At the end of infusion.

Metabolism

Moxifloxacin undergoes phase II biotransformation and is excreted via the kidneys as well as in feces/bile, both in unchanged form and as inactive sulfate conjugates (M1) and glucuronides (M2). M1 and M2 are the only metabolites relevant in humans; both are microbiologically inactive. During in vitro studies and phase I clinical trials, no metabolic pharmacokinetic interactions with other medicinal products involved in phase I biotransformation mediated by cytochrome P450 enzymes were observed. There is no evidence of oxidative metabolism.

Elimination

The elimination half-life of the drug is approximately 12 hours. The mean total clearance after administration of 400 mg ranges from 179 to 246 mL/min. Renal clearance is approximately 24–53 mL/min, indicating partial tubular reabsorption of the drug in the kidneys. After a 400 mg dose, cumulative excretion in urine (approximately 19% as unchanged drug, approximately 2.5% as M1, and approximately 14% as M2) and feces (approximately 25% as unchanged drug, approximately 36% as M1, and no excretion as M2) totaled approximately 96%. Concomitant administration of ranitidine and probenecid does not alter the renal clearance of the drug.

Elderly patients and patients with low body weight

Higher plasma concentrations of the drug were observed in healthy volunteers with low body weight (particularly in women) and in healthy elderly volunteers.

Renal impairment

No significant changes in moxifloxacin pharmacokinetics were observed in patients with impaired renal function (including patients with creatinine clearance > 20 mL/min/1.73 m²). As renal function declines, the concentration of metabolite M2 (glucuronide) increases up to 2.5-fold (in patients with creatinine clearance < 30 mL/min/1.73 m²).

Hepatic impairment

Based on pharmacokinetic data from studies involving patients with hepatic impairment (Child-Pugh classes A-C), it is not possible to determine whether there is a difference compared to healthy volunteers. Hepatic impairment was associated with higher plasma levels of metabolite M1, while exposure to the parent drug was comparable to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin to recommend its use in patients with hepatic impairment.

Clinical Characteristics

Indications

Treatment of the following bacterial infections caused by microorganisms sensitive to moxifloxacin (see sections "Pharmacological Properties", "Special Warnings and Precautions for Use", and "Adverse Reactions") in patients aged 18 years and older.

Moxifloxacin should be used for the following indications only when the use of other antibacterial agents typically recommended for treatment of such infections is considered inappropriate:

• Acute bacterial sinusitis.
• Acute exacerbation of chronic obstructive pulmonary disease, including bronchitis.

For the following indications, moxifloxacin should be used only when the use of other antibacterial agents typically recommended for initial treatment of the following infections is inappropriate, or when such treatment has been ineffective:

• Community-acquired pneumonia, excluding severe community-acquired pneumonia.
• Moderate to severe pelvic inflammatory disease (including infection of the upper genital tract in women, such as salpingitis and endometritis), not associated with tubo-ovarian abscess or pelvic abscesses. Moxifloxacin 400 mg film-coated tablets are not recommended for use as monotherapy in moderate to severe pelvic inflammatory disease, but may be used (except for moxifloxacin-resistant strains of Neisseria gonorrhoeae) in combination with other appropriate antibacterial agents (e.g., cephalosporins) due to increasing resistance of Neisseria gonorrhoeae to moxifloxacin (see sections "Pharmacological Properties" and "Special Warnings and Precautions for Use").

Moxifloxacin 400 mg film-coated tablets may be used to complete a treatment course initiated with intravenous moxifloxacin that has proven effective for the following indications:

• Community-acquired pneumonia;
• Complicated skin and soft tissue infections.

Moxifloxacin 400 mg film-coated tablets are not recommended for initial therapy of any skin and soft tissue infections or in cases of severe community-acquired pneumonia.

Consideration should be given to official guidelines on the appropriate use of antibacterial agents.

Contraindications

− Known hypersensitivity to moxifloxacin or to other quinolones, or to any of the excipients of the medicinal product.

− Age under 18 years.

− Pregnancy or breastfeeding (see section "Use in Pregnancy or Lactation").

− History of tendon disorders related to fluoroquinolone therapy.

During preclinical and clinical studies, moxifloxacin administration was associated with changes in cardiac electrophysiology, including QT interval prolongation. Therefore, for safety reasons, the drug is contraindicated in patients with:

− Congenital or diagnosed acquired QT prolongation;

− Electrolyte imbalances, particularly uncorrected hypokalemia;

− Clinically significant bradycardia;

− Clinically significant heart failure with reduced left ventricular ejection fraction;

− History of symptomatic arrhythmias.

Moxifloxacin should not be used concomitantly with other medicinal products that prolong the QT interval (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Due to limited clinical data, the drug is also contraindicated in patients with hepatic impairment (Child-Pugh class C) and in patients with elevated transaminase levels (more than 5 times the upper limit of normal).

Interaction with Other Medicinal Products and Other Forms of Interaction

An additive effect between moxifloxacin and other medicinal products that may prolong the QT interval cannot be excluded. This interaction may increase the risk of ventricular arrhythmias, including torsade de pointes. For this reason, concomitant use of moxifloxacin with any of the following medicinal products is contraindicated (see also section "Contraindications"):

• Class IA antiarrhythmics (e.g., quinidine, hydroquinidine, disopyramide);
• Class III antiarrhythmics (e.g., amiodarone, sotalol, dofetilide, ibutilide);
• Antipsychotics (e.g., phenothiazines, pimozide, sertindole, haloperidol, sulpiride);
• Tricyclic antidepressants;
• Certain antimicrobial agents (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials such as halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Others (cisapride, intravenous vinca alkaloids, bepridil, dofetilide).

Moxifloxacin should be administered with caution in patients taking medicinal products that may reduce potassium levels (e.g., loop and thiazide diuretics, enemas and laxatives (at high doses), corticosteroids, amphotericin B), or medicinal products whose effects are associated with clinically significant bradycardia.

An interval of approximately 6 hours should be maintained between the administration of products containing divalent or trivalent cations (such as antacids containing magnesium or aluminum, didanosine tablets, sucralfate, and medicinal products containing iron or zinc) and moxifloxacin.

Concomitant oral administration of activated charcoal and moxifloxacin 400 mg reduces systemic bioavailability of the drug by more than 80% due to inhibition of its absorption. Therefore, concomitant use of these two medicinal products is not recommended (except in cases of overdose; see also section "Overdose").

After repeated administration of moxifloxacin in healthy volunteers, an increase in digoxin Cmax of approximately 30% was observed, without affecting AUC or minimum concentration (Cmin). Therefore, no precautionary measures are required when digoxin is co-administered.

In studies involving volunteers and patients with diabetes mellitus, concomitant oral administration of moxifloxacin and glyburide resulted in a decrease in peak glyburide concentration of approximately 21%. The combination of glyburide with moxifloxacin may theoretically lead to mild, transient hyperglycemia. However, the observed pharmacokinetic changes did not result in changes in pharmacodynamic parameters (blood glucose levels, insulin levels). Thus, no clinically relevant interaction between moxifloxacin and glyburide has been identified.

Change in International Normalized Ratio (INR)

Numerous cases of increased anticoagulant activity have been reported in patients receiving oral anticoagulants in combination with antibacterial agents, including fluoroquinolones, macrolides, tetracyclines, co-trimoxazole, and certain cephalosporins. Risk factors include infectious diseases (and associated inflammatory processes), age, and the patient's overall condition. Due to these factors, it is difficult to determine whether infection or treatment causes INR deviations. As a precaution, more frequent monitoring of INR may be advisable. Dose adjustment of the oral anticoagulant should be performed as necessary.

Substances for which absence of clinically significant interaction with moxifloxacin has been demonstrated: ranitidine, calcium supplements, theophylline, oral contraceptives, cyclosporine, itraconazole, morphine administered parenterally, probenecid. In vitro studies of human cytochrome P450 enzymes confirmed the above. Based on these results, metabolic interaction via cytochrome P450 enzymes is unlikely.

Absorption of moxifloxacin is not affected by food intake (including dairy products).

Special precautions for use

Avoid using moxifloxacin in patients with a history of serious adverse reactions to drugs containing quinolones or fluoroquinolones (see section "Adverse reactions"). Treatment with moxifloxacin in such patients should only be initiated if no alternative therapy is available and after careful assessment of the benefit-risk ratio (see also section "Contraindications").

The benefits of moxifloxacin therapy, especially in mild infections, should be weighed against the information provided in this section.

QTc interval prolongation and clinical conditions associated with QTc prolongation

Moxifloxacin may cause QT interval prolongation on electrocardiogram (ECG) in some patients. Analysis of ECG data from clinical trials showed that QTc prolongation with moxifloxacin was 6 ms ± 26 ms (1.4%) compared to baseline. Since women generally have a longer QT interval than men, they may be more sensitive to drugs that prolong the QT interval. Elderly patients may also be more susceptible to drug-related effects on the QT interval.

Patients receiving moxifloxacin should use with caution drugs that may lead to hypokalemia (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions (particularly elderly patients and younger women), such as acute myocardial ischemia or QT interval prolongation, as this may increase the risk of ventricular arrhythmias, including torsade de pointes, and cardiac arrest (see section "Contraindications"). The degree of QT interval prolongation may increase with higher drug concentrations. Therefore, the recommended dose should not be exceeded.

If symptoms of arrhythmia occur during treatment, therapy should be discontinued and an ECG performed.

Hypersensitivity/allergic reactions

Cases of hypersensitivity and allergic reactions have been reported after the first dose of fluoroquinolones, including moxifloxacin. Anaphylactic reactions may manifest as life-threatening shock even after the first dose. In case of clinical manifestations of severe hypersensitivity reactions, moxifloxacin should be discontinued and appropriate therapy initiated (e.g., anti-shock treatment).

Severe hepatic impairment

Cases of fulminant hepatitis, which may lead to liver failure, including fatal outcomes, have been reported with moxifloxacin use (see section "Adverse reactions"). If symptoms of fulminant hepatitis occur, such as rapidly developing fatigue accompanied by jaundice, dark urine, bleeding tendency, or hepatic encephalopathy, patients should consult a physician before continuing treatment.

Liver function tests should be performed if signs of hepatic dysfunction appear.

Severe skin adverse reactions

Severe skin adverse reactions, including toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported during moxifloxacin use (see section "Adverse reactions"), some of which were life-threatening or fatal (see section "Adverse reactions"). Patients should be informed about signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms suggestive of such reactions occur, moxifloxacin should be immediately discontinued and alternative treatment considered. Moxifloxacin therapy should never be restarted in patients who have experienced severe skin reactions such as SJS, TEN, AGEP, or DRESS syndrome.

Patients predisposed to seizures

Quinolones are known to induce seizures. Therefore, they should be used with caution in patients with CNS disorders or other risk factors that may provoke seizures or lower the seizure threshold. If seizures occur, moxifloxacin should be discontinued and appropriate measures taken.

Prolonged, disabling, and potentially irreversible serious adverse reactions

Rare cases of prolonged (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various, sometimes multiple, organ systems (musculoskeletal, nervous, psychiatric, and sensory organs) have been reported in patients treated with quinolones and fluoroquinolones, regardless of patient age or existing risk factors. Moxifloxacin should be discontinued immediately upon the first symptoms of any serious adverse reaction, and patients should be advised to consult a physician.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients taking moxifloxacin should be advised to inform their physician if they develop symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness before continuing treatment to prevent potentially irreversible conditions (see section "Adverse reactions").

Psychiatric reactions

Psychiatric reactions may occur even after the first dose of fluoroquinolones, including moxifloxacin. In rare cases, depression or psychiatric reactions may progress to suicidal thoughts and self-harming behaviors such as suicide attempts (see section "Adverse reactions"). If such reactions occur, moxifloxacin should be discontinued and appropriate measures taken. Caution should be exercised when prescribing moxifloxacin to patients with psychiatric disorders, including those with a history of such conditions.

Diarrhea associated with antibiotic use, including colitis

Cases of antibiotic-associated diarrhea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been observed with broad-spectrum antibiotics, including moxifloxacin. The severity of these events may range from mild diarrhea to fatal colitis. Therefore, it is important to consider this diagnosis in patients who develop severe diarrhea during or after moxifloxacin therapy. If suspected or confirmed AAD or AAC, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. Additionally, infection control measures should be implemented to reduce transmission risk. Antiperistaltic agents are contraindicated in patients who develop severe diarrhea.

Patients with severe myasthenia gravis

Moxifloxacin should be used with caution in patients with severe myasthenia gravis, as symptoms may be exacerbated.

Tendon inflammation and tendon rupture

Tendon inflammation and ruptures (especially of the Achilles tendon), sometimes bilateral, may occur during therapy with quinolones and fluoroquinolones, developing within 48 hours of starting treatment and possibly occurring several months after discontinuation (see sections "Contraindications" and "Adverse reactions"). The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, solid organ transplant recipients, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of moxifloxacin with corticosteroids should be avoided.

If early symptoms of tendinitis (e.g., painful swelling, inflammation) occur, moxifloxacin should be discontinued and alternative therapy considered. Appropriate treatment (e.g., immobilization) should be initiated for the affected limb(s). Corticosteroids should not be used if symptoms of tendinopathy develop.

Aortic aneurysm and aortic dissection, valvular regurgitation/insufficiency

Epidemiological studies suggest an increased risk of aortic aneurysm and aortic dissection, particularly in elderly patients, and valvular regurgitation on the aortic and mitral valves following fluoroquinolone use. Rare cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal), and regurgitation/insufficiency of any cardiac valve have been reported in patients treated with fluoroquinolones (see section "Adverse reactions"). Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and consideration of alternative therapies in patients with a history of aortic aneurysm or congenital heart valve defect, diagnosed aortic aneurysm and/or aortic dissection, valvular heart disease, or other risk factors or conditions predisposing to aortic aneurysm and dissection or valvular regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis), or conditions such as vascular disorders (e.g., Takayasu arteritis or giant cell arteritis), known atherosclerosis, or Sjögren's syndrome, or valvular regurgitation/insufficiency (e.g., infective endocarditis).

The risk of aortic aneurysm, dissection, and rupture may be increased in patients receiving concomitant systemic corticosteroid therapy.

Patients should seek immediate medical attention if sudden abdominal, chest, or back pain occurs.

Patients should be advised to seek immediate medical help if acute shortness of breath, rapid heartbeat, or swelling of the abdomen or lower limbs develops.

Patients with renal impairment

Moxifloxacin should be used with caution in elderly patients with renal disorders who are unable to maintain adequate fluid volume, as dehydration increases the risk of renal impairment.

Visual disturbances

If visual deterioration or any effect on the eyes occurs, immediate consultation with an ophthalmologist is required (see sections "Ability to influence reaction rate when driving or operating machinery" and "Adverse reactions").

Dysglycemia

As with all fluoroquinolones, deviations in blood glucose levels, including both hypoglycemia and hyperglycemia, have been reported during moxifloxacin therapy (see section "Adverse reactions"). Dysglycemia occurred predominantly in elderly patients with diabetes mellitus receiving concomitant oral hypoglycemic agents (e.g., sulfonylureas) or insulin. Cases of hypoglycemic coma have been reported. Diabetic patients should closely monitor their blood glucose levels.

Prevention of photosensitization reactions

Quinolones have been shown to cause photosensitization reactions in patients. Although studies indicate a lower risk of photosensitization reactions with moxifloxacin, patients should avoid exposure to ultraviolet radiation and prolonged or intense sunlight during moxifloxacin therapy (see section "Adverse reactions").

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or a family history of this condition are prone to hemolytic reactions during quinolone therapy. Therefore, moxifloxacin should be used with caution in these patients.

Patients with pelvic inflammatory disease

Moxifloxacin 400 mg tablets are not recommended for patients with complicated pelvic inflammatory disease (e.g., associated with tubo-ovarian abscess or pelvic abscess) who require intravenous therapy.

Pelvic inflammatory disease may be caused by Neisseria gonorrhoeae resistant to fluoroquinolones. Therefore, empirical use of moxifloxacin in such cases should be combined with another appropriate antibiotic (e.g., a cephalosporin) if Neisseria gonorrhoeae resistant to moxifloxacin cannot be fully excluded. If there is no clinical improvement after 3 days of treatment, therapy should be reassessed.

Patients with specific complicated skin and soft tissue infections

The clinical efficacy of intravenous moxifloxacin in the treatment of severe infections associated with burns, fasciitis, and infected diabetic foot with osteomyelitis has not been established.

Effect on biological tests

Moxifloxacin therapy may interfere with microbiological testing for Mycobacterium spp. due to inhibition of mycobacterial growth, potentially leading to false-negative results in samples from patients currently taking moxifloxacin.

Patients with infections caused by methicillin-resistant Staphylococcus aureus (MRSA)

Moxifloxacin is not recommended for the treatment of infections caused by MRSA. In suspected or confirmed MRSA infection, appropriate antibacterial therapy should be initiated (see section "Pharmacological properties").

Children

Moxifloxacin causes cartilage damage in young animals (see section "Pharmacological properties"); therefore, its use in children (under 18 years of age) is contraindicated (see section "Contraindications").

Information on excipients

This medicinal product is contraindicated in patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

This medicinal product contains less than 1 mmol sodium (23 mg) per coated tablet, i.e., essentially "sodium-free."

Use during pregnancy or breastfeeding

Pregnancy

The safety of moxifloxacin use during pregnancy has not been established.

Animal studies indicate reproductive toxicity (see section "Pharmacological properties"). The potential risk to humans is unknown.

Due to the risk of fluoroquinolone-induced joint damage in young animals (based on experimental data) and reversible joint lesions described in children treated with certain fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section "Contraindications").

Breastfeeding

Moxifloxacin, like other quinolones, causes cartilage damage in young animals. Preclinical studies indicate that a small amount of moxifloxacin may pass into breast milk. There are no data on the use of this medicinal product in breastfeeding women. Therefore, moxifloxacin is contraindicated during breastfeeding (see section "Contraindications").

Fertility

Animal studies did not show any effect on fertility (see section "Pharmacological properties").

Ability to influence reaction rate when driving or operating machinery

No studies on the effect of moxifloxacin on the ability to drive or operate machinery have been conducted. However, fluoroquinolones, including moxifloxacin, may impair the ability to drive or operate machinery due to central nervous system effects (e.g., dizziness, acute transient visual disturbances, see section "Adverse reactions") or acute transient loss of consciousness (syncope, see section "Adverse reactions"). Patients should be advised to monitor their response to moxifloxacin before driving or operating machinery.

Method of Administration and Dosage

Dosage (adults)

It is recommended to take 1 tablet (400 mg) of moxifloxacin once daily.

Renal/Liver Function Impairment

Dose adjustment is not required in patients with moderate to severe renal impairment, as well as in patients undergoing continuous hemodialysis or long-term ambulatory peritoneal dialysis (see section "Pharmacological Properties").

There is no reliable information regarding patients with hepatic impairment (see section "Contraindications").

Elderly patients / patients with low body weight

Dose adjustment is not required in elderly patients or patients with low body weight.

Method of Administration

Tablets should be swallowed whole with sufficient amount of water. The drug may be taken regardless of food intake.

Duration of Therapy

The duration of treatment with moxifloxacin tablets depends on the type of infection and is as follows:

• Exacerbation of chronic obstructive pulmonary disease, including bronchitis –
  5–10 days;
• Community-acquired pneumonia – 10 days;
• Acute bacterial sinusitis – 7 days;
• Moderate to severe pelvic inflammatory disease – 14 days.

According to clinical studies, the duration of treatment with moxifloxacin tablets was up to 14 days.

Sequential (intravenous/oral) therapy

During clinical studies of sequential therapy, most patients switched from intravenous to oral administration of moxifloxacin within 4 days (community-acquired pneumonia) or 6 days (complicated skin and soft tissue infections). The recommended total duration of treatment with moxifloxacin tablets and infusion solution is 7–14 days for community-acquired pneumonia and 7–21 days for complicated skin and soft tissue infections.

The specified dose (400 mg once daily) and duration of treatment for each indication should not be exceeded.

Children

Moxifloxacin is contraindicated in children (under 18 years of age). The efficacy and safety of moxifloxacin in children have not been established (see also section "Contraindications").

Overdose

In case of accidental overdose, no specific measures are recommended. In the event of overdose, treatment should be based on clinical presentation and include symptomatic and supportive therapy, as well as ECG monitoring due to the potential for QT interval prolongation.

Concomitant administration of activated charcoal with a 400 mg oral dose of moxifloxacin results in more than 80% reduction in systemic bioavailability of the drug. In case of oral overdose, early administration of activated charcoal may be effective in preventing increased systemic exposure to moxifloxacin.

Side effects

The following adverse reactions were observed during clinical trials after administration of moxifloxacin at a dose of 400 mg once daily (intravenous therapy only, sequential [intravenous/oral], and oral) and in the post-marketing period. Adverse reactions are classified according to their frequency. All adverse reactions occurred with a frequency of less than 3%, except for nausea and diarrhea. Within each category, adverse reactions are listed in order of decreasing severity. Frequency is defined as follows: common (≥ 1/100, <1/10), uncommon (≥ 1/1,000, <1/100), rare (≥ 1/10,000, <1/1,000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

Infections and infestations: common – superinfection due to bacterial or fungal resistance, e.g. oral or vaginal candidiasis.

Blood and lymphatic system disorders: uncommon – anemia, leukopenia, neutropenia, thrombocytopenia, thrombocytosis, eosinophilia, prolonged prothrombin time/increased INR; rare – elevated prothrombin levels/decreased INR, agranulocytosis, pancytopenia.

Immune system disorders: uncommon – allergic reactions (see section "Special warnings and precautions for use"); rare – anaphylaxis, including rare cases of shock (life-threatening), angioedema, including laryngeal edema (potentially life-threatening) (see section "Special warnings and precautions for use").

Endocrine disorders: rare – syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolism and nutrition disorders: uncommon – hyperlipidemia; rare – hyperglycemia, hyperuricemia; very rare – hypoglycemia, hypoglycemic coma.

Psychiatric disorders*: uncommon – anxiety reactions, increased psychomotor activity/agitation; rare – mood lability, depression (in rare cases with possible self-harm, such as suicidal ideation/thoughts or suicide attempts (see section "Special warnings and precautions for use")), hallucinations, delirium; very rare – depersonalization, psychotic reactions (with possible self-harm, such as suicidal ideation/thoughts or suicide attempts (see section "Special warnings and precautions for use")).

Nervous system disorders*: common – headache, dizziness; uncommon – paresthesia/dysesthesia, taste disturbances (including ageusia in rare cases), confusion and disorientation, sleep disorders (mainly insomnia), tremor, vertigo, somnolence; rare – hypoesthesia, olfactory disturbances (including loss of smell), pathological dreams, coordination disorders (including gait disturbance due to dizziness or vertigo), seizures with various clinical manifestations (including grand mal seizures (see section "Special warnings and precautions for use")), attention disturbances, speech disorders, amnesia, peripheral neuropathy and polyneuropathy; very rare – hyperesthesia.

Eye disorders*: uncommon – visual disturbances, including diplopia and blurred vision (especially during CNS reactions (see section "Special warnings and precautions for use")); rare – photophobia; very rare – transient loss of vision (especially during CNS reactions (see sections "Special warnings and precautions for use" and "Effect on ability to drive and use machines")), uveitis, and bilateral acute iris transillumination (see section "Special warnings and precautions for use").

Ear and labyrinth disorders*: rare – tinnitus, hearing disturbances, including deafness (usually reversible).

Cardiac disorders** : common – QT interval prolongation in patients with hypokalemia (see sections "Special warnings and precautions for use" and "Contraindications"); uncommon – QT interval prolongation (see section "Special warnings and precautions for use"), palpitations, tachycardia, atrial fibrillation, angina pectoris; rare – ventricular tachyarrhythmias, syncope (i.e., acute and transient loss of consciousness); very rare – non-specific arrhythmias, torsade de pointes (see section "Special warnings and precautions for use"), cardiac arrest (see section "Special warnings and precautions for use").

Vascular disorders**: uncommon – vasodilation; rare – arterial hypertension, arterial hypotension; very rare – vasculitis.

Respiratory, thoracic and mediastinal disorders: uncommon – dyspnea, including asthmatic condition.

Gastrointestinal disorders: common – nausea, vomiting, abdominal pain, diarrhea; uncommon – decreased appetite and reduced food intake, constipation, dyspepsia, flatulence, gastritis, increased amylase levels; rare – dysphagia, stomatitis, antibiotic-associated colitis (including pseudomembranous colitis, in rare cases associated with life-threatening complications (see section "Special warnings and precautions for use")).

Hepatobiliary disorders: common – increased transaminase levels; uncommon – liver function abnormalities (including increased LDH [lactate dehydrogenase]), increased bilirubin levels, increased GGT (gamma-glutamyl transferase), increased alkaline phosphatase levels in blood; rare – jaundice, hepatitis (predominantly cholestatic); very rare – fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal outcomes (see section "Special warnings and precautions for use")).

Skin and subcutaneous tissue disorders: uncommon – pruritus, rash, urticaria, dry skin; very rare – bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, potentially life-threatening (see section "Special warnings and precautions for use"); frequency not known – acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (see section "Special warnings and precautions for use"), fixed drug eruption, photosensitivity reactions (see section "Special warnings and precautions for use").

Musculoskeletal and connective tissue disorders*: uncommon – arthralgia, myalgia; rare – tendinitis (see section "Special warnings and precautions for use"), muscle twitching, muscle cramps, muscle weakness; very rare – tendon rupture (see section "Special warnings and precautions for use"), arthritis, muscle rigidity, exacerbation of symptoms of myasthenia gravis (see section "Special warnings and precautions for use"); frequency not known – rhabdomyolysis.

Renal and urinary disorders: uncommon – dehydration; rare – renal function impairment (including increased blood urea nitrogen and plasma creatinine), renal failure (see section "Special warnings and precautions for use").

General disorders*: uncommon – general weakness (mainly asthenia or fatigue), pain (including back pain, chest pain, limb pain, pelvic pain), hyperhidrosis; rare – edema.

* Rare cases of prolonged (lasting months or years), disabling and potentially irreversible serious adverse reactions have been reported in patients treated with quinolones and fluoroquinolones, regardless of age or existing risk factors, affecting various organ systems and sensory organs, sometimes multiple (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy associated with paresthesia, depression, fatigue, memory impairment, sleep disorders, and disturbances of hearing, vision, taste, and smell, anxiety, suicidal thoughts, panic attacks, neuralgia, and concentration difficulties) (see section "Special warnings and precautions for use").

** Rare cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), and valvular regurgitation/insufficiency of any cardiac valve have been reported in patients treated with fluoroquinolones (see section "Special warnings and precautions for use").

Rare adverse reactions observed after treatment with other fluoroquinolones, which may possibly also occur with moxifloxacin, include: increased intracranial pressure (including idiopathic intracranial hypertension), hypernatremia, hypercalcemia, and hemolytic anemia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicine is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Packaging

5 tablets in a blister pack.

1 blister pack with the instruction for medical use in a cardboard box.

Prescription status

Prescription only.

Manufacturer

PJSC "Kyivmedpreparat"

Manufacturer's address and location of its business activities

139 Saksahanskoho Street, Kyiv, 01032, Ukraine.