Moxifloxacin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOXIFLOXACIN

Composition:

Active substance: moxifloxacin;

1 container (250 ml solution) contains moxifloxacin hydrochloride equivalent to 400 mg of moxifloxacin;

Excipients: sodium chloride, diluted hydrochloric acid, sodium hydroxide, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: clear yellow liquid.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Antibacterial agents of the quinolone group. ATC code J01MA14.

Pharmacological Properties

Pharmacodynamics

Mechanism of action

Moxifloxacin inhibits bacterial type II topoisomerases (DNA gyrase and topoisomerase IV), which are essential for replication, transcription, and repair of bacterial DNA.

Pharmacokinetics/pharmacodynamics

The ability of fluoroquinolones to kill bacteria is directly concentration-dependent. Pharmacodynamic studies of fluoroquinolones in animal models of infectious-inflammatory diseases and in humans indicate that the primary determinant of efficacy is the ratio between the area under the pharmacokinetic curve (AUC24) and the minimum inhibitory concentration (MIC).

Mechanism of resistance

Resistance to fluoroquinolones may arise due to mutations in DNA gyrase and topoisomerase IV. Other mechanisms include overexpression of efflux pumps, impermeability, and protein-mediated protection of DNA gyrase. Cross-resistance can be expected between moxifloxacin and other fluoroquinolones.

Resistance mechanisms characteristic of antibacterial agents belonging to other classes do not affect the antibacterial efficacy of moxifloxacin.

Breakpoints

Clinical MIC and disk diffusion breakpoints for moxifloxacin, as defined by EUCAST (European Committee on Antimicrobial Susceptibility Testing) (01.01.2012):

Microbiological susceptibility

The prevalence of acquired resistance in isolated species may vary depending on geographical location and time; therefore, local information on resistance is required, especially when treating severe infections. When necessary, consultation with specialists should be sought if the local prevalence of resistance has reached a level at which the benefit of using the agent is at least questionable for certain types of infections.

Pharmacokinetics

Absorption and Bioavailability

After a single 1-hour intravenous infusion of 400 mg moxifloxacin, maximum drug concentration is reached at the end of the infusion and is approximately 4.1 mg/l, which is about 26% higher than that observed after oral administration (3.1 mg/l). The AUC is approximately 39 mg·h/l following intravenous administration, slightly exceeding the value after oral administration (35 mg·h/l); absolute bioavailability is approximately 91%. With intravenous administration of moxifloxacin, dose adjustments according to patient age or gender are not required. Pharmacokinetics are linear within the range of 50–200 mg for single oral doses, up to 600 mg for single intravenous doses, and up to 600 mg for once-daily administration over 10 days.

Distribution

Moxifloxacin rapidly distributes into the extravascular space. The volume of distribution at steady state (Vss) is approximately 2 l/kg. In vitro and ex vivo studies indicate protein binding of approximately 40–42%, independent of drug concentration. Moxifloxacin binds primarily to serum albumin.

Maximum concentrations of 5.4 mg/kg and 20.7 mg/l (geometric mean values) were observed in bronchial mucosa and epithelial lining fluid, respectively, 2.2 hours after oral dosing. The corresponding maximum concentration in alveolar macrophages was 56.7 mg/kg. In skin blister fluid, a concentration of 1.75 mg/l was observed 10 hours after intravenous administration. The "free concentration–time" profile in interstitial fluid is similar to that in plasma, with a maximum free concentration of 1.0 mg/l (geometric mean) reached approximately 1.8 hours after intravenous administration.

Metabolism

Moxifloxacin undergoes phase II biotransformation and is eliminated via the kidneys (approximately 40%) and feces/bile (approximately 60%), both unchanged and as sulfate conjugate (M1) and glucuronide (M2). M1 and M2 are metabolites relevant only to humans; both are microbiologically inactive.

In vitro and Phase I clinical studies showed no metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation, including cytochrome P450 enzyme system. There is no evidence of oxidative metabolism.

Elimination

The elimination half-life of moxifloxacin in plasma is approximately 12 hours. Mean steady-state total clearance after 400 mg administration ranges from 179 to 246 ml/min. After intravenous administration of 400 mg, unchanged drug excreted in urine was approximately 22%, and in feces approximately 26%. Cumulative excretion (unchanged drug and metabolites) totaled approximately 98% after intravenous administration. Renal clearance is approximately 24–53 ml/min, indicating partial tubular reabsorption of the drug. Concomitant administration of ranitidine and probenecid does not alter the renal clearance of the drug.

Renal Impairment

No significant changes in moxifloxacin pharmacokinetics were observed in patients with renal dysfunction (including those with creatinine clearance >20 ml/min/1.73 m²). With decreasing renal function, the concentration of metabolite M2 (glucuronide) increases by almost 2.5-fold (in patients with creatinine clearance <30 ml/min/1.73 m²).

Hepatic Impairment

Pharmacokinetic data from studies in patients with hepatic impairment (Child–Pugh classes A and B) do not conclusively determine whether there are differences between patients with hepatic dysfunction and healthy volunteers. Hepatic impairment was associated with increased plasma exposure to metabolite M1, while exposure to the parent drug was similar to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin to recommend its use in patients with hepatic impairment.

Preclinical Safety Data

In traditional repeated-dose toxicity studies in animals, moxifloxacin showed hematological toxicity and hepatotoxicity. Toxic effects on the central nervous system (CNS) were also observed. These effects occurred after administration of high doses of moxifloxacin or prolonged treatment.

High oral doses in animals (≥60 mg/kg), resulting in plasma concentrations ≥20 mg/l, caused changes in electroretinogram parameters and, in some cases, retinal atrophy.

Systemic toxicity after intravenous administration was most pronounced when moxifloxacin was administered as bolus injections (45 mg/kg), and was not observed when 40 mg/kg was administered by slow infusion over 50 minutes.

After intraarterial administration, inflammatory changes extending into perivascular soft tissues were observed, indicating that intraarterial administration of moxifloxacin must be avoided.

Moxifloxacin was genotoxic in in vitro tests using bacteria or mammalian cells. However, no genotoxicity was observed in in vivo studies, even with very high doses of moxifloxacin. Moxifloxacin showed no carcinogenic potential in animal carcinogenicity studies.

In vitro, moxifloxacin at high concentrations affected cardiac electrophysiological parameters, potentially leading to QT interval prolongation.

After intravenous administration of moxifloxacin to animals at 30 mg/kg by 15-, 30-, or 60-minute infusions, the degree of QT interval prolongation was infusion-rate-dependent: shorter infusion times resulted in greater QT prolongation. No QT prolongation was observed when the 30 mg/kg dose was administered by 60-minute infusion.

In studies of moxifloxacin's effects on animal reproductive function, it was demonstrated that moxifloxacin crosses the placenta. Animal studies did not reveal teratogenic effects or impaired fertility after moxifloxacin administration. Slight increases in the incidence of spinal and rib developmental abnormalities were observed in animals, but only after administration of a dose (20 mg/kg intravenously) associated with marked maternal systemic toxicity. Increased rates of pregnancy loss were observed in animals at plasma concentrations corresponding to the therapeutic range expected in humans.

It is known that quinolones, including moxifloxacin, cause damage to cartilage of large diarthrodial joints in immature animals.

Clinical Characteristics

Indications

Community-acquired pneumonia.

Complicated skin and soft tissue infections.

Moxifloxacin should only be used when other antibacterial agents typically recommended for initial treatment of these infections are inappropriate.

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

Contraindications

• Hypersensitivity to moxifloxacin, other quinolone antibiotics, or any of the excipients of the medicinal product;
• Pregnancy or breastfeeding (see section "Use in pregnancy or breastfeeding");
• Pediatric age (under 18 years);
• History of tendon disorders related to quinolone use.

During preclinical and clinical studies, administration of moxifloxacin was associated with changes in cardiac electrophysiological parameters, manifested as QT interval prolongation. For this reason, moxifloxacin is contraindicated in patients with:

• Congenital or acquired QT prolongation;
• Electrolyte imbalance, particularly uncorrected hypokalemia;
• Clinically significant bradycardia;
• Clinically significant heart failure with reduced left ventricular ejection fraction;
• History of symptomatic arrhythmias.

Moxifloxacin must not be co-administered with medicinal products that prolong the QT interval (see also section "Interaction with other medicinal products and other forms of interaction").

Due to insufficient clinical experience, moxifloxacin is contraindicated in patients with hepatic impairment (Child-Pugh class C) and in those with transaminase levels elevated five times or more above the upper limit of normal.

Special precautions

The medicinal product container is intended for single use only. Any unused solution must be discarded.

The following solutions have been shown to be compatible with the 400 mg moxifloxacin infusion solution: water for injections; 0.9% sodium chloride solution; 1-molar sodium chloride solution; 5%, 10%, 40% glucose solutions; 20% xylitol solution; Ringer's solution; compound sodium lactate solutions (Hartmann's solution, lactated Ringer's solution).

Moxifloxacin infusion solution must not be administered simultaneously with other medicinal products. The product must not be used if visible particulate matter or cloudiness is present.

Do not use if the container seal is broken or if the container contents are not clear.

Precipitation may occur during storage in a cool place, but dissolves at room temperature. Therefore, storage of the infusion solution below 15°C is not recommended.

Interaction with other medicinal products and other forms of interaction

Interaction with medicinal products

An additive effect between moxifloxacin and other medicinal products capable of causing QTc interval prolongation cannot be excluded. This effect may lead to the development of ventricular arrhythmias, including polymorphic ventricular tachycardia of the torsades de pointes type. Therefore, the use of moxifloxacin in combination 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);
• Other medicinal products: cisapride, intravenous vinca alkaloids, bepridil, difemanyl.

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

In healthy volunteers receiving multiple doses of moxifloxacin, an increase in the maximum concentration (Cmax) of digoxin by approximately 30% was observed, without affecting AUC or the concentration-time curve.

In studies involving diabetic volunteers, concomitant oral administration of moxifloxacin and glyburide resulted in a decrease in plasma glyburide Cmax by approximately 21%. The combination of glyburide with moxifloxacin may theoretically provoke mild, short-term hyperglycemia. However, the observed changes in glyburide pharmacokinetics did not result in changes in pharmacodynamic parameters (blood glucose, insulin levels). Therefore, there is no clinically significant interaction between moxifloxacin and glyburide.

Change in International Normalized Ratio (INR). Numerous cases of increased activity of oral anticoagulants have been reported in patients receiving antimicrobial agents, particularly fluoroquinolones, macrolides, tetracyclines, cotrimoxazole, and certain cephalosporins. Risk factors include infection and inflammatory processes, advanced age, and poor general condition. Thus, it is difficult to determine whether changes in INR are due to the infection itself or to treatment. As a precautionary measure, INR may be monitored more frequently. Dose adjustment of the oral anticoagulant should be performed as needed.

In clinical studies, the absence of clinically significant interaction with moxifloxacin has been demonstrated for the following substances: ranitidine, probenecid, oral contraceptives, calcium supplements, intravenous morphine, theophylline, cyclosporine, or itraconazole.

In vitro studies using human cytochrome P450 enzymes have confirmed these results. Therefore, metabolic interaction via cytochrome P450 enzymes is unlikely.

Interaction with food

Moxifloxacin does not exhibit clinically significant interaction with food, including dairy products.

Special precautions for use

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

The benefits of moxifloxacin treatment, especially in mild infections, should be evaluated considering the information provided in this section.

Prolongation of the QTc interval and clinical conditions in which QTc prolongation may occur

Moxifloxacin therapy should be discontinued at the first sign of symptoms that may be associated with cardiac arrhythmia, regardless of whether this is confirmed by ECG findings.

Moxifloxacin should be used with caution in patients with conditions predisposing to arrhythmia (e.g., acute myocardial ischemia), as such patients have an increased risk of developing ventricular arrhythmias (including polymorphic ventricular tachycardia such as torsade de pointes) and cardiac arrest (see also sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction"). Moxifloxacin should be used with caution in patients receiving medicinal products that may reduce potassium levels (see also sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

Moxifloxacin should be prescribed with caution to patients receiving medicinal products associated with clinically significant bradycardia (see also section "Contraindications").

Women and elderly patients may exhibit increased sensitivity to the effects of drugs that prolong the QTc interval, such as moxifloxacin; therefore, these patients require special attention.

Hypersensitivity / Allergic reactions

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

Severe hepatic impairment

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

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

Severe skin 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 with moxifloxacin use, which may be life-threatening or result in death (see section "Adverse reactions"). Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored during treatment. If signs or symptoms suggestive of these reactions occur, moxifloxacin should be discontinued immediately and alternative therapy considered. If a patient develops a serious reaction such as TEN, SJS, AGEP, or DRESS syndrome during moxifloxacin therapy, re-administration of moxifloxacin to this patient is absolutely contraindicated.

Patients predisposed to seizures

Quinolones are known to induce seizures. They should be used with caution in patients with central nervous system 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 several months or years), disabling, and potentially irreversible serious adverse reactions affecting one or more organ systems (musculoskeletal, nervous system, psychiatric, sensory organs) have been reported in patients treated with quinolones and fluoroquinolones, regardless of patient age or presence of risk factors. Moxifloxacin should be discontinued immediately upon the first symptoms of any serious adverse reaction; patients should be advised to consult a physician.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hyposthesia, dysesthesia, or weakness have been reported in patients receiving quinolones, including moxifloxacin. Patients receiving moxifloxacin should be advised to inform their physician about the development of neuropathic symptoms 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 have progressed to suicidal ideation and self-harming behaviors such as suicide attempts (see section "Adverse reactions"). If such reactions occur, moxifloxacin therapy should be discontinued and appropriate measures taken. Caution should be exercised when prescribing moxifloxacin to patients with a history of psychiatric disorders or current psychiatric 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-induced diarrhea, have been observed with the use of 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 AAD or AAC is suspected or confirmed, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. Additionally, infection control measures should be implemented to reduce the risk of transmission. 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 rupture (particularly of the Achilles tendon), sometimes bilateral, may occur during therapy with quinolones and fluoroquinolones, developing as early as 48 hours after initiation of treatment and persisting for 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, patients with solid organ transplants, and patients receiving concomitant corticosteroid therapy. Therefore, concomitant use of moxifloxacin with corticosteroids should be avoided.

Moxifloxacin should be discontinued at the first sign of tendinitis (e.g., painful swelling or inflammation) 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 indicate an increased risk of aortic aneurysm and dissection, particularly in elderly patients, as well as aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and cases of regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Adverse reactions"). Therefore, fluoroquinolones should be used only after careful benefit-risk assessment and consideration of alternative therapeutic options in patients with a family history of aneurysm or congenital heart valve defect, patients with existing diagnosis of aortic aneurysm and/or dissection, patients with heart valve disease, or patients with other risk factors, including:

• Risk factors for both aortic aneurysm/dissection and valvular regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, arterial hypertension, rheumatoid arthritis;
• Risk factors for aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;
• Risk factors for valvular regurgitation/insufficiency: infective endocarditis.

The risk of aortic aneurysm, dissection, and rupture is increased if patients are concurrently receiving systemic corticosteroids.

Patients should seek immediate medical attention in case of sudden abdominal, chest, or back pain.

Patients should be advised to seek immediate medical help if acute dyspnea, new onset palpitations, or development of abdominal or lower limb edema occurs.

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 failure.

Visual disturbances

In case of visual impairment or any effect on the eyes, immediate consultation with an ophthalmologist is required (see also sections "Ability to influence reaction speed when driving or operating machinery" and "Adverse reactions").

Dysglycemia

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

Prevention of photosensitization reactions

Photosensitization reactions have been reported in patients receiving quinolones. However, study data indicate that the risk of photosensitization reactions with moxifloxacin is low. Patients should avoid prolonged and/or intense exposure to sunlight or ultraviolet radiation during moxifloxacin therapy (see section "Adverse reactions").

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with glucose-6-phosphate dehydrogenase deficiency, as well as those with a family history of this condition, are prone to hemolytic reactions during quinolone therapy. Therefore, moxifloxacin should be used with caution in this patient group.

Periarterial tissue inflammation

Moxifloxacin infusion solution is intended for intravenous use only. Intraarterial administration should be avoided, as periarterial tissue inflammation has been observed in preclinical studies with this route of administration.

Patients with specific complicated skin and soft tissue infections

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

Sodium content

The medicinal product contains 787 mg (approximately 34 µmol) of sodium per dose. Patients on a sodium-restricted diet should take this into account.

Effect on biological tests

Moxifloxacin may affect test results for Mycobacterium spp. by inhibiting mycobacterial growth, which may lead to false-negative results in patients receiving moxifloxacin.

Infections caused by methicillin-resistant Staphylococcus aureus

Moxifloxacin is not recommended for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). If MRSA infection is suspected or confirmed, appropriate antibacterial therapy should be initiated (see section "Pharmacodynamics").

Use during pregnancy or breastfeeding

Pregnancy

The safety of moxifloxacin use during pregnancy in humans has not been established. Animal studies indicate reproductive toxicity (see section "Pharmacological properties"). The potential risk to humans has not been established. Given the experimentally demonstrated harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals and cases of reversible joint disorders in children treated with certain fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section "Contraindications").

Breastfeeding period

There are no data on the use of moxifloxacin during breastfeeding in women. Preclinical studies indicate that a small amount of moxifloxacin passes into breast milk. Due to the lack of data on effects in breastfed infants and considering the experimentally demonstrated risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals, breastfeeding is contraindicated during moxifloxacin therapy (see section "Contraindications").

Fertility

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

Ability to influence reaction speed when driving or operating machinery

Studies on the effect of moxifloxacin on the ability to drive or operate machinery have not been conducted. However, fluoroquinolones, including moxifloxacin, may affect reaction speed during driving or operating machinery by causing central nervous system reactions (e.g., dizziness, acute transient loss of vision) or acute and short-term loss of consciousness (syncope) (see section "Adverse reactions"). Patients are advised to assess their individual response to moxifloxacin before driving or operating machinery.

Method of Administration and Dosage

Dosage

The recommended dosage regimen is 400 mg of moxifloxacin administered as an infusion once daily.

Initial intravenous therapy may be continued with oral administration of 400 mg moxifloxacin tablets, provided there are clinical indications.

In clinical trials, most patients switched to oral moxifloxacin within 4 days (community-acquired pneumonia) or 6 days (complicated skin and soft tissue infections). The recommended total duration of intravenous and oral treatment is 7–14 days for community-acquired pneumonia and 7–21 days for complicated skin and soft tissue infections.

Method of Administration

The medicinal product should be administered intravenously as a continuous infusion lasting at least 60 minutes (see also section "Special Warnings and Precautions for Use").

If indicated, the infusion solution may be administered through a Y-type catheter together with compatible infusion solutions (see section "Special Precautions for Safety").

Renal/Hepatic Impairment

Patients with mild to severe renal impairment, as well as patients undergoing chronic dialysis, such as those receiving hemodialysis or long-term ambulatory peritoneal dialysis, do not require dose adjustment (see section "Pharmacological Properties" for further details).

There is insufficient information regarding patients with hepatic impairment (see section "Contraindications").

Other Special Patient Groups

Elderly patients and patients with low body weight do not require dose adjustment.

Children

The efficacy and safety of moxifloxacin in children and adolescents have not been established.

Due to the negative effects of moxifloxacin on cartilage in young animals (see section "Pharmacological Properties"), the use of this medicinal product is contraindicated in children (under 18 years of age) (see section "Contraindications").

Overdose

No specific measures are recommended following accidental overdose. In case of overdose, symptomatic treatment should be administered. Since QT interval prolongation may occur, ECG monitoring is required. Concomitant administration of activated charcoal with a 400 mg dose of moxifloxacin, given either orally or intravenously, reduces the systemic bioavailability of the drug by over 80% or 20%, respectively. Administration of activated charcoal in the early phase of absorption may effectively prevent excessive systemic exposure to moxifloxacin in cases of oral overdose.

Adverse Reactions

Listed below are adverse reactions observed during clinical trials and in the post-marketing period with the use of moxifloxacin at a dose of 400 mg once daily (intravenous therapy only, sequential [intravenous/oral], and oral) and their frequencies.

All adverse reactions, except nausea and diarrhea, were observed at a frequency of less than 3%. Within each category, adverse events are listed in order of decreasing severity. Frequency is defined as follows: common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), infrequent (≥ 1/10,000, < 1/1000), rare (< 1/10,000), frequency not known (cannot be estimated from available data).

* In patients who have received quinolones and fluoroquinolones, regardless of age and presence of risk factors, rare cases of prolonged (lasting several months or years), disabling and potentially irreversible serious adverse reactions have been observed, affecting sometimes multiple organ systems, including sensory organs. Such reactions include tendinitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathy associated with paresthesia and neuralgia, fatigue, psychiatric symptoms (including sleep disturbances, anxiety, panic attacks, depression, and suicidal thoughts), memory and concentration impairment, hearing, vision, taste, and smell disturbances (see section "Special precautions").

** In patients who have received fluoroquinolones, cases of aneurysm and aortic dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any heart valve have been observed (see section "Special precautions").

The incidence of the following effects is higher with intravenous administration of the drug, with or without subsequent oral therapy.

Common: increased gamma-glutamyl transferase levels.

Uncommon: ventricular tachyarrhythmia, arterial hypotension, edema, antibiotic-associated colitis (including pseudomembranous colitis, rarely with life-threatening complications, see section "Special precautions"), seizures (including grand mal seizures) (see section "Special precautions"), hallucinations, renal function impairment (including increased blood urea nitrogen and creatinine levels), renal failure (see section "Special precautions").

Rarely, following treatment with other fluoroquinolones, adverse effects have been reported that are likely to potentially occur also during moxifloxacin treatment: increased intracranial pressure (including idiopathic intracranial hypertension), hypernatremia, hypercalcemia, hemolytic anemia.

Reporting of suspected adverse reactions

Reporting of adverse reactions after marketing authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions

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

Keep out of reach and sight of children.

Incompatibilities

Moxifloxacin infusion solution must not be administered simultaneously with other incompatible solutions, including 10% sodium chloride solution, 20% sodium chloride solution, 4.2% sodium bicarbonate solution, and 8.4% sodium bicarbonate solution.

This medicinal product should not be mixed with other medicinal products except those specified in the section "Special precautions".

Packaging. 250 ml in a polypropylene container, 1 container in a cardboard package.

Prescription status. Prescription only.

Manufacturer. Subsidiary enterprise "Farmatreyd".

Manufacturer's location and address of place of business

85 Sambirska Street, Drohobych, Lviv Oblast, Ukraine