Moximac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MOXIMAK

Composition:

Active substance: moxifloxacin;

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

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

Pharmaceutical form. Infusion solution.

Main physicochemical properties: yellow transparent liquid.

Pharmacotherapeutic group.
Antibiotics 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 according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) (01.01.2012):

Table

Microbiological susceptibility

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

Pharmacokinetics.

Absorption and bioavailability

After a single 1-hour infusion of 400 mg moxifloxacin, maximum concentration is reached at the end of the infusion and is approximately 4.1 mg/l, which is about 26 % higher than this parameter after oral administration of moxifloxacin (3.1 mg/l). The AUC value is about 39 mg*h/l after intravenous administration, slightly exceeding this parameter after oral administration of moxifloxacin (35 mg*h/l); absolute bioavailability is approximately 91 %. With intravenous administration of moxifloxacin, there is no need for dose adjustment according to patient age or gender. Pharmacokinetics are linear within the range of 50–200 mg for a single oral dose, up to 600 mg for a single intravenous dose, 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 about 2 l/kg. In vitro and ex vivo studies show that plasma protein binding is approximately 40–42 %, independent of drug concentration. Moxifloxacin binds mainly 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 administration. The corresponding maximum concentration in alveolar macrophages was 56.7 mg/kg. A concentration of 1.75 mg/l was observed in skin blister fluid 10 hours after intravenous administration. The "free concentration-time" profile for interstitial fluid is similar to that of plasma, reaching a maximum free concentration of 1.0 mg/l (geometric mean) approximately 1.8 hours after intravenous administration of moxifloxacin.

Metabolism

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

During in vitro studies and Phase I clinical trials, no metabolic pharmacokinetic interactions were observed with other medicinal products involved in phase I biotransformation, including cytochrome P450 enzymes. There is no evidence of oxidative metabolism.

Elimination

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

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, the concentration of metabolite M2 (glucuronide) increases by almost 2.5 times (with creatinine clearance < 30 ml/min/1.73 m²).

Hepatic impairment

Pharmacokinetic studies conducted in patients with hepatic insufficiency (Child-Pugh classes A and B) do not allow definitive conclusions regarding differences in parameters between patients with impaired liver function and healthy volunteers. Hepatic dysfunction was associated with higher plasma exposure to M1, whereas exposure to the parent drug was similar to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin use for treatment of patients with hepatic impairment.

Preclinical safety data

In traditional repeated-dose toxicity studies in animals, hematological toxicity and hepatotoxicity were observed with moxifloxacin. Toxic effects on the central nervous system (CNS) were 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 administered as bolus injections (45 mg/kg) and was not observed when moxifloxacin (40 mg/kg) was administered via slow infusions over 50 minutes. After intra-arterial administration, inflammatory changes extending to periarterial 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. In in vivo studies, genotoxicity was not observed, despite administration of very high doses of moxifloxacin. Moxifloxacin did not show carcinogenic effects in animal carcinogenicity studies.

In vitro, moxifloxacin at high concentrations affected electrophysiological parameters of cardiac activity, potentially causing QT interval prolongation. After intravenous administration of moxifloxacin to animals at a dose of 30 mg/kg via infusions lasting 15, 30, or 60 minutes, the degree of QT interval prolongation was dependent on infusion rate: the shorter the infusion time, the more pronounced the QT interval prolongation. QT interval prolongation was not observed when the 30 mg/kg dose was administered via a 60-minute infusion.

Studies on the effect of moxifloxacin on animal reproductive function have demonstrated that moxifloxacin crosses the placenta. Animal studies did not reveal teratogenic effects of moxifloxacin or impaired fertility after its administration. In animals, a slight increase in the frequency of spinal and rib developmental abnormalities was observed, but only when the dose (20 mg/kg intravenously) was associated with severe maternal toxicity. An increased number of pregnancy interruptions were observed in animals at therapeutic plasma concentrations predicted for human use.

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 be used only when the use of other antibacterial agents typically recommended for initial treatment of these infections is inappropriate. Official guidelines on the proper use of antibacterial agents should be taken into account.

Contraindications.

• Hypersensitivity to moxifloxacin, other quinolone antibiotics, or to any of the excipients;
• Pregnancy or breastfeeding (see section "Use in 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 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 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 levels elevated five times or more above the upper limit of normal.

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 torsade 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 including halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Other medicinal products (cisapride, intravenous vincamine, 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 (at high doses), corticosteroids, amphotericin B), or medicinal products associated with clinically significant bradycardia.

After repeated administration of moxifloxacin in healthy volunteers, an increase in digoxin Cmax by approximately 30% was observed, without affecting AUC or trough levels. In studies involving diabetic volunteers, concomitant oral administration of moxifloxacin and glyburide resulted in a decrease of approximately 21% in the maximum plasma concentration of glyburide. The combination of glyburide with moxifloxacin may theoretically provoke mild, short-term hyperglycemia. However, the observed pharmacokinetic changes of glyburide did not result in changes in pharmacodynamic parameters (blood glucose levels, insulin levels). Therefore, there is no clinically significant interaction between moxifloxacin and glyburide.

Changes 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 infectious diseases and inflammatory processes, age, and general patient condition. Therefore, 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 necessary.

In clinical studies, the absence of clinically significant interaction with moxifloxacin has been demonstrated for the following substances: ranitidine, probenecid, oral contraceptives, calcium supplements, morphine administered parenterally, 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

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 should be initiated in such patients only when 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 contained in this section.

QTc interval prolongation and clinical conditions associated with potential QTc interval prolongation

Moxifloxacin therapy should be discontinued if symptoms that may be associated with cardiac arrhythmia occur, 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 torsades 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 QTc-prolonging agents such as moxifloxacin; therefore, these patients require special attention.

Increased sensitivity / allergic reactions

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

Severe liver function disorders

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

Liver function tests should be performed if signs of impaired liver function appear.

Severe skin adverse reactions

Severe skin adverse reactions (SSARs) associated with moxifloxacin use have been reported, 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 result in death (see "Adverse reactions"). Patients receiving moxifloxacin should be informed about signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms indicative of these reactions occur, moxifloxacin should be discontinued immediately and alternative treatment considered. If a patient develops a serious adverse reaction such as SJS, TEN, AGEP, or DRESS during moxifloxacin treatment, re-administration of moxifloxacin to this patient is absolutely contraindicated.

Patients predisposed to seizures

Quinolones are known to induce seizures. They should be prescribed with caution to 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 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 receiving quinolones and fluoroquinolones, regardless of patient age or existing risk factors. Moxifloxacin should be discontinued immediately upon the onset of 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, 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 the development of 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 in a patient, 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-associated diarrhea, have been observed in association 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 the possibility of this diagnosis in patients who develop severe diarrhea during or after moxifloxacin treatment. If suspected or confirmed AAD or AAC occurs, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. Additionally, appropriate infection control measures should be implemented to reduce the risk of transmission. Medicinal products that inhibit peristalsis are contraindicated in patients who develop severe diarrhea.

Patients with severe myasthenia

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

Tendon inflammation, tendon rupture

Tendon inflammation and ruptures (particularly of the Achilles tendon), sometimes bilateral, may occur during therapy with quinolones, including moxifloxacin, even within 48 hours of starting treatment and may persist for several months after discontinuation of therapy. The risk of tendinitis and tendon rupture is increased in elderly patients and in patients receiving concomitant corticosteroid therapy. If pain or inflammation occurs, moxifloxacin should be discontinued, the affected limb(s) should be rested, and the patient should seek immediate medical attention for appropriate management (e.g., immobilization) of the affected tendon (see sections "Contraindications" and "Adverse reactions").

Aortic aneurysm and aortic dissection, and valvular regurgitation/insufficiency

Epidemiological studies suggest an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and regurgitation of aortic and mitral valves following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and valvular 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 positive family history of aneurysm or congenital heart valve defects, or in patients with existing diagnoses of aneurysm and/or aortic dissection, or heart valve disease, or in the presence of other risk factors or predisposing conditions:

• for both aortic aneurysm and dissection, and valvular regurgitation/insufficiency (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis), or additionally
• for aortic aneurysm and dissection (e.g., vascular disorders such as Takayasu arteritis or giant cell arteritis, known atherosclerosis, or Sjögren's syndrome), or additionally
• for valvular regurgitation/insufficiency (e.g., infective endocarditis). The risk of aortic aneurysm and dissection and their rupture may be increased in patients receiving systemic corticosteroids concomitantly.

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

Patients should be advised to seek immediate medical help if they develop acute dyspnea, new-onset palpitations, or develop abdominal or lower limb edema.

Patients with renal function impairment.

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

Disorders of visual organs.

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

Dysglycemia.

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

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. Nevertheless, 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 (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 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.

Patients on salt-controlled diets.

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

Effect on biological tests.

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

Patients with 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").

Special safety precautions.

One vial of the medicinal product is intended for single use only. Unused solution should be discarded.

The following diluents have been shown to be compatible with moxifloxacin 400 mg 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 should not be administered concomitantly with other medicinal products. The medicinal product should not be used if visible particulate matter or cloudiness is present in the solution.

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

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 considering the development of reversible joint lesions 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 therapy (see section "Contraindications").

Fertility.

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

Ability to affect reaction rate 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 rate when driving or operating machinery by causing central nervous system reactions (e.g., dizziness, acute transient visual loss) 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.

Dosage and Administration

Dosage

The recommended dosage 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 when clinically indicated. In clinical studies, most patients switched to oral moxifloxacin within 4 days (for community-acquired pneumonia) or 6 days (for 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.

Administration method

The medicinal product should be administered intravenously as a continuous infusion over not less than 60 minutes (see also section "Special precautions for administration").

If indicated, the infusion solution may be administered via a Y-site catheter together with compatible infusion solutions (see section "Special precautions for administration").

Renal/hepatic impairment

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

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

Due to the negative effects observed 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

Specific interventions are not 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 over 80% or 20%, respectively. Administration of activated charcoal at the early stage of absorption may effectively prevent excessive systemic exposure to moxifloxacin in case of oral overdose.

Adverse reactions.

The adverse reactions listed below were 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 group, 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 (≥ 1/10000, < 1/1000), rare (< 1/10000), frequency not known (cannot be estimated based on available data).

* Rare cases of prolonged (lasting for months or years), disabling and potentially irreversible serious adverse reactions affecting various, sometimes multiple, organ systems and sensory organs (including such reactions as tendonitis, 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) have been reported in patients treated with quinolones and fluoroquinolones, regardless of age and existing risk factors (see section "Special precautions for use").

** Cases of aneurysms and aortic dissections, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Special precautions for use").

The incidence of the following effects is higher with intravenous administration of moxifloxacin followed by oral therapy or without such transition.

Common: increased gamma-glutamyl transferase levels.

Uncommon: ventricular tachyarrhythmia, arterial hypotension, edema, antibiotic-associated colitis (including pseudomembranous colitis, which in rare cases may be associated with life-threatening complications; see section "Special precautions for use"), seizures (including grand mal seizures) (see section "Special precautions for use"), hallucinations, renal dysfunction (including increased blood urea nitrogen and creatinine levels), renal failure (see section "Special precautions for use").

Rarely, following treatment with other fluoroquinolones, adverse effects have been reported that may also potentially occur during moxifloxacin treatment: hypernatremia, hypercalcemia, hemolytic anemia, rhabdomyolysis.

Description of selected adverse reactions

Anxiety, suicidal thoughts, panic attacks, neuralgia, and disturbances in attention concentration are potential components of prolonged and disabling fluoroquinolone-induced adverse reactions, which may lead to loss of work capacity.

Reporting suspected adverse reactions

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

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging. Do not freeze.

Keep out of reach and sight of children.

Incompatibilities.

The moxifloxacin infusion solution must not be co-administered with other incompatible solutions, including: 10% sodium chloride solution; 20% sodium chloride solution; 4.2% sodium bicarbonate solution; 8.4% sodium bicarbonate solution. The medicinal product should not be mixed with other medicinal products except those specified in the section "Special precautions for safety."

Packaging.

250 ml in a polypropylene container; 1 container in a cardboard box.

250 ml in a polyvinyl chloride container; 1 container in a polymer film within a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Subsidiary enterprise "Farmatreyd".

Manufacturer's address and location of business activity.

85 Sambirska Street, Drohobych, Lviv Oblast, Ukraine.