Avetsin-n

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AVECIN-N (AVECIN-N)

Composition:

Active substance: moxifloxacin;

1 vial (250 ml) contains moxifloxacin 400 mg, equivalent to 436 mg of moxifloxacin hydrochloride;

Excipients: sodium sulfate anhydrous, sodium acetate trihydrate, glacial acetic acid (for pH adjustment), water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear yellow solution, free from visible particles.

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 as a result of 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 values and disk diffusion test 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 the geographical area and time; therefore, local information on resistance patterns is necessary, especially when treating severe infections. When the local prevalence of resistance has reached a level at which the benefit of using the medicinal product is questionable, at least for certain types of infections, consultation with specialists should be sought.

Pharmacokinetics.

Absorption and bioavailability

After a single 1-hour intravenous infusion of 400 mg moxifloxacin, maximum concentration (Cmax) 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 of moxifloxacin (3.1 mg/l). The AUC is approximately 39 mg×h/l after intravenous administration, which slightly exceeds 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 administered once daily for 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 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. A concentration of 1.75 mg/l was observed in blister fluid 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 of moxifloxacin.

Metabolism

Moxifloxacin undergoes phase II biotransformation and is eliminated via the kidneys (approximately 40 %) and feces/bile (approximately 60 %), both unchanged and as sulfated (M1) and glucuronide (M2) metabolites. M1 and M2 are metabolites relevant only in humans, and both are microbiologically inactive. No metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation, including cytochrome P450 enzymes, were observed during in vitro and phase I clinical studies. 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 administration of 400 mg ranges from 179 to 246 ml/min. After intravenous administration of 400 mg, approximately 22 % of moxifloxacin is excreted unchanged in urine and 26 % in feces. Cumulative excretion (unchanged moxifloxacin and metabolites) totals approximately 98 % after intravenous administration. Renal clearance is approximately 24–53 ml/min, indicating partial tubular reabsorption of the drug from the kidneys. Concomitant administration of ranitidine and probenecid does not alter the renal clearance of moxifloxacin.

Renal impairment

No significant changes in moxifloxacin pharmacokinetics have been observed in patients with renal dysfunction (including patients with creatinine clearance > 20 ml/min/1.73 m²). With decreasing renal function, plasma concentration of the M2 metabolite (glucuronide) increases by almost 2.5-fold (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 allow definitive conclusions regarding 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 repeat-dose toxicity studies in animals, hematological toxicity and hepatotoxicity were observed with moxifloxacin. Toxic effects on the central nervous system (CNS) were also noted. 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.

After intravenous administration, systemic toxicity was most pronounced when moxifloxacin was given as bolus injections (45 mg/kg) and was not observed when 40 mg/kg was administered via slow infusions over 50 minutes. After intra-arterial administration, inflammatory changes extending into perivascular soft tissues were observed, indicating that intra-arterial administration of moxifloxacin should be avoided.

Moxifloxacin was genotoxic in in vitro tests using bacteria or mammalian cells. However, no genotoxicity was observed in vivo, 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 via 15-, 30-, or 60-minute infusions, the degree of QT prolongation was dependent on infusion rate: shorter infusion times resulted in more pronounced QT prolongation. No QT prolongation was observed when the 30 mg/kg dose was administered over 60 minutes.

In studies of moxifloxacin's effects on animal reproductive function, it was demonstrated that moxifloxacin crosses the placenta. Animal studies revealed no teratogenic effects or impairment of fertility after moxifloxacin administration. Slight increases in the incidence of spinal and rib malformations were observed in animals, but only after intravenous administration of 20 mg/kg, a dose associated with severe maternal toxicity. Increased rates of pregnancy loss were observed in animals at therapeutic plasma concentrations predicted for human use.

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

Clinical characteristics.

Indications.

Community-acquired pneumonia.

Complicated skin and soft tissue infections.

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

Official recommendations on appropriate use of antibacterial agents should be taken into account.

Contraindications.

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

During preclinical and clinical studies, administration of moxifloxacin was associated with changes in cardiac electrophysiological parameters, manifested by 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 used concomitantly 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 elevations five times or more above the upper limit of normal.

Special precautions.

Each vial is intended for single use only. Any unused solution must be discarded.

The following diluents 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%, and 40% glucose solutions; 20% xylitol solution; Ringer's solution; compound sodium lactate solutions (Hartmann's solution, lactated Ringer's solution). The moxifloxacin infusion solution must not be administered simultaneously with other medicinal products.

Do not use the medicinal product if visible particulate matter or cloudiness is present.

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

Interaction with other medicinal products and other forms of interaction.

Interaction with medicinal products

An additive effect of 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);
• Antipsychotic agents (e.g., phenothiazines, pimozide, sertindole, haloperidol, sulpiride);
• Tricyclic antidepressants;
• Certain antimicrobial agents (sacquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarials such as halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Other medicinal products (cisapride, intravenous vinca alkaloids, bepridil, difemanil).

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

Repeated administration of moxifloxacin in healthy volunteers resulted in an approximately 30% increase in digoxin Cmax without affecting AUC or trough levels.

In studies involving volunteers with diabetes, concomitant oral administration of moxifloxacin and glyburide resulted in a decrease of approximately 21% in glyburide plasma Cmax. 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, co-trimoxazole, and certain cephalosporins. Risk factors include infection and inflammatory processes, age, and general patient condition. Therefore, it is difficult to determine whether changes in INR are due to the infection or the treatment. As a precaution, INR should be monitored more frequently. Dose adjustment of the oral anticoagulant should be performed as necessary.

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

In vitro studies using human cytochrome P450 enzymes confirmed these results. Thus, 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.

The use of moxifloxacin should be avoided 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 be initiated only when 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 evaluated considering the information provided in this section.

QTc interval prolongation and clinical conditions associated with QTc interval prolongation
Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram (ECG) in some patients. The degree of QT prolongation may increase with higher plasma concentrations of the drug during rapid intravenous infusion. Therefore, the recommended duration of infusion should be at least 60 minutes, and the intravenous dose should not exceed 400 mg once daily. For further details, see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction".

Moxifloxacin therapy should be discontinued if symptoms suggestive of cardiac arrhythmia occur, regardless of whether they are confirmed by ECG. Moxifloxacin should be used with caution in patients with conditions predisposing to arrhythmias (e.g., acute myocardial ischemia), as such patients are at increased risk of ventricular arrhythmias (including polymorphic ventricular tachycardia such as torsades de pointes) and cardiac arrest (see also sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction"). Caution is also advised when administering moxifloxacin to patients taking 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 be more sensitive to the effects of drugs that prolong the QTc interval, such as moxifloxacin, and therefore require special attention.

Hypersensitivity/allergic reactions

Cases of hypersensitivity and allergic reactions have been reported following the first dose of fluoroquinolones, including moxifloxacin. Anaphylactic reactions may be life-threatening and may occur even after the first administration of the drug. In the event of clinically significant 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 treatment (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 appear.

Severe skin adverse reactions

Severe skin adverse reactions (SSARs), 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), which may be life-threatening or fatal, have been reported with moxifloxacin (see section "Adverse reactions"). Patients should be informed about the signs and symptoms of severe skin reactions and monitored closely 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 SJS, TEN, AGEP, or DRESS during moxifloxacin treatment, re-administration of moxifloxacin is contraindicated in that patient.

Patients predisposed to seizures

Quinolones are known to induce seizures. They should be used with caution in patients with central nervous system (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 several months or years), disabling, and potentially irreversible serious adverse reactions affecting multiple organ systems (musculoskeletal, nervous system, psychiatric, and sensory organs) have been reported in patients receiving quinolones and fluoroquinolones, regardless of patient age or presence of risk factors. Patients should be advised to discontinue moxifloxacin immediately and consult a physician if they experience early symptoms of any serious adverse reaction.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones, including moxifloxacin. Patients should be advised to inform their physician immediately if they experience symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness before continuing treatment, to prevent irreversible damage (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.

Antibiotic-associated diarrhea, including colitis

Cases of antibiotic-associated diarrhea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhea, have been reported with broad-spectrum antibiotics, including moxifloxacin. The severity of these events may range from mild diarrhea to fatal colitis. It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after moxifloxacin treatment. If AAD or AAC is suspected or confirmed, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. In addition, 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 ruptures (especially of the Achilles tendon), sometimes bilateral, may occur during treatment with quinolones and fluoroquinolones, developing within 48 hours of starting therapy and potentially 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, solid organ transplant recipients, and those receiving concomitant corticosteroid therapy. Therefore, concomitant use of moxifloxacin with corticosteroids should be avoided.

If early symptoms of tendinitis (e.g., painful swelling or inflammation) occur, moxifloxacin should be discontinued and alternative therapy considered. Appropriate treatment of the affected limb (e.g., immobilization) should be initiated. Corticosteroids should not be used in cases of tendonopathy.

Patients with renal impairment

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

Visual disturbances

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

Dysglycemia

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

Prevention of photosensitization reactions

Quinolones have been shown to cause photosensitization reactions in patients. However, studies indicate that moxifloxacin has a lower risk of inducing such reactions. Nevertheless, patients should avoid exposure to ultraviolet radiation or prolonged and/or intense sunlight during moxifloxacin treatment (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 at risk of developing hemolytic reactions during treatment with quinolones. Therefore, moxifloxacin should be used with caution in these patients.

Periarterial tissue inflammation

Moxifloxacin infusion solution is intended for intravenous use only. Intra-arterial 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 treating severe infections associated with burns, fasciitis, and infected diabetic foot with osteomyelitis has not been established.

Aortic aneurysm and dissection and cardiac valve regurgitation/insufficiency

Epidemiological studies have reported an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation following fluoroquinolone use, especially in older individuals. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones.

Therefore, fluoroquinolones should be used only after careful benefit-risk assessment and consideration of alternative treatment options in patients with a personal or family history of aneurysm or congenital heart valve defects, diagnosed aortic aneurysm or dissection, existing heart valve disease, or other risk factors such as:

• risk factors for both aortic aneurysm/dissection and cardiac valve regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet’s disease, 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 cardiac valve regurgitation/insufficiency: infective endocarditis.

The risk of aortic aneurysm, dissection, and rupture is increased in patients receiving systemic corticosteroids concomitantly.

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

Patients should be advised to seek immediate medical help if they develop acute shortness of breath, new-onset palpitations, or swelling of the abdomen or lower limbs.

Impact on biological tests

Moxifloxacin may affect the results of Mycobacterium spp. testing by suppressing mycobacterial growth, potentially leading to false-negative results in patients taking moxifloxacin.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA)

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

Important information about excipients

The medicinal product contains 678.6 mg (approximately 29.52 mmol) of sodium per dose. Patients on a sodium-controlled diet should take this into account.

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 in humans is unknown. Given the experimentally demonstrated risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals, and considering the occurrence of reversible joint damage in children treated with certain fluoroquinolones, moxifloxacin should not be administered to pregnant women (see section "Contraindications").

Breastfeeding

There are no data on the use of moxifloxacin during breastfeeding. 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 experimental risk of harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals, breastfeeding is contraindicated during moxifloxacin treatment (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 affect reaction speed when driving or operating machinery by causing central nervous system reactions (e.g., dizziness, acute transient loss of vision) or acute 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.

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 to do so. In clinical trials, most patients switched to oral moxifloxacin within 4 days (for community-acquired pneumonia) or 6 days (for complicated skin and skin structure 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 skin structure infections.

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 clinically indicated, the infusion solution may be administered via a Y-site 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 (e.g., hemodialysis or long-term ambulatory peritoneal dialysis), do not require dose adjustment (for further details, see section "Pharmacological Properties").

There is insufficient data regarding the use of moxifloxacin in 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

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

The efficacy and safety of moxifloxacin in children and adolescents have not been established (see section "Contraindications").

Overdose

No specific interventions 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 orally or intravenously reduces systemic bioavailability by more than 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 the adverse reactions observed during clinical trials and the post-marketing period with moxifloxacin at a dose of 400 mg once daily (intravenous therapy, sequential [intravenous/oral] therapy, and oral therapy), along with their frequency. All adverse reactions, except nausea and diarrhea, occurred at a frequency of less than 3%. Within each category, adverse reactions are listed in descending order of severity. Frequency is defined as follows: common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

* Very rare cases of prolonged (several months or years), disabling and potentially irreversible serious reactions involving multiple organ systems and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and disturbances of hearing, vision, taste, and smell) have been reported in association with the use of quinolones and fluoroquinolones, regardless of the presence of risk factors (see section "Special Warnings and Precautions for Use").

** Cases of aneurysms and dissections of the aorta, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been observed in patients receiving fluoroquinolones (see section "Special Warnings and Precautions for Use").

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

Frequent: Increased levels of gamma-glutamyltransferase.

Uncommon: Ventricular tachyarrhythmia, arterial hypotension, oedema, antibiotic-associated colitis (including pseudomembranous colitis, rarely with life-threatening complications; see section "Special Warnings and Precautions for Use"), seizures (including grand mal seizures; see section "Special Warnings and Precautions for Use"), hallucinations, renal dysfunction (including increased blood urea nitrogen and creatinine levels), renal failure (see section "Special Warnings and Precautions for Use").

Very rare cases of the following adverse reactions have been reported after treatment with other fluoroquinolones and may also possibly occur during treatment with moxifloxacin: increased intracranial pressure (including idiopathic intracranial hypertension), hypernatraemia, hypercalcaemia, haemolytic anaemia.

Anxiety, suicidal thoughts, panic attacks, neuralgia, and disturbances in attention concentration have also been reported as potential aspects of prolonged and disabling adverse reactions caused by fluoroquinolones.

Reporting of suspected adverse reactions

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

Shelf life. 3 years.

Storage conditions. To protect from light, keep the vial in the outer packaging.

Do not cool. Do not freeze. Keep out of the reach of children.

Incompatibilities. Moxifloxacin infusion solution must not be administered simultaneously with other solutions incompatible with it, including: 10% sodium chloride solution; 20% sodium chloride solution; 4.2% sodium bicarbonate solution; 8.4% sodium bicarbonate solution. This medicinal product should not be mixed with other medicinal products except those specified in section "Special Precautions for Use".

Packaging. 250 mL in a vial. 1 vial in a carton or 10 vials in a box.

Prescription status. Prescription only.

Manufacturer.

VIOSEAR S.A. PARENTERAL SOLUTIONS INDUSTRY (unpacked product, primary packaging, secondary packaging, control).

PHARMASELL LLC (batch release).

Manufacturer's address and site of operations.

9th km National Road Trikala-Larissa, Taxiarchis Trikala, 42100, Greece.

Ukraine, 07408, Kyiv Oblast, Brovary District, village Kvitneve, Prorizna Street, 3.