Famox

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FAMOX (FAMOX)

Composition:

Active substance: moxifloxacin;

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

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

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear liquid ranging from yellow to yellow-green in color.

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 dependent on their concentration. 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 values and disk diffusion test breakpoints for moxifloxacin, as defined by EUCAST (European Committee on Antimicrobial Susceptibility Testing) (01.01.2012):

Table 1

*Non-species-related breakpoints were primarily established based on the relationship between pharmacokinetic and pharmacodynamic data and are independent of the MIC values for individual species. These breakpoints apply to species without individually defined breakpoints and are not applicable to species for which interpretive criteria need to be determined.

Microbiological susceptibility

The prevalence of acquired resistance in isolated species may vary geographically and over time; therefore, local information on resistance patterns is necessary, especially when treating severe infections. If needed, expert consultation should be sought when local resistance prevalence has reached a level at which the benefit of using the agent is questionable, at least for certain types of infections.

Pharmacokinetics.

Absorption and bioavailability

After a single 1-hour infusion of 400 mg, the maximum concentration of the drug is reached at the end of the infusion and is approximately 4.1 mg/l, which is about 26 % higher than with oral administration (3.1 mg/l). The AUC value is about 39 mg*h/l after intravenous administration, which slightly exceeds this parameter after oral administration (35 mg*h/l); absolute bioavailability is approximately 91 %. With intravenous administration of moxifloxacin, no dose adjustment is required according to patient age or gender. Pharmacokinetics is 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 approximately 2 l/kg. In vitro and ex vivo studies indicate protein binding of approximately 40–42 %, independent of drug concentration. Moxifloxacin is mainly bound 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 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.

Metabolism

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

During in vitro studies and phase I clinical trials, no metabolic pharmacokinetic interactions with other drugs involved in phase I biotransformation, including cytochrome P450 enzymes, were observed. 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 400 mg, unchanged drug excretion 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 with moxifloxacin does not alter the renal clearance of the parent drug.

Renal impairment

No significant changes in moxifloxacin pharmacokinetics were observed in patients with impaired renal function (including patients with creatinine clearance > 20 ml/min/1.73 m²). 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 data from studies involving patients with hepatic impairment (Child-Pugh classes A and B) do not allow definitive conclusions regarding differences between patients with hepatic impairment and healthy volunteers. Hepatic impairment was associated with higher plasma exposure to M1, while exposure to the parent drug was similar to that in healthy volunteers. There is insufficient clinical experience with moxifloxacin use for treating patients with hepatic impairment.

Preclinical safety data

In traditional repeated-dose toxicity studies, moxifloxacin showed hematological toxicity and hepatotoxicity in animals. Toxic effects on the central nervous system (CNS) were 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 given as bolus injections (45 mg/kg) and was not observed when moxifloxacin (40 mg/kg) was administered via slow infusions over 50 minutes.

After intraarterial administration, inflammatory changes extending to periarterial soft tissues were observed, indicating that intraarterial administration of moxifloxacin should be avoided.

Moxifloxacin was genotoxic in in vitro tests using bacteria or mammalian cells. However, no genotoxicity was observed in in vivo studies, despite the use of very high doses of moxifloxacin. Moxifloxacin did not show carcinogenic effects in animal carcinogenicity studies.

In vitro, moxifloxacin at high concentrations affected cardiac electrophysiological parameters, 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, a relationship between the degree of QT interval prolongation and infusion rate was observed: the shorter the infusion time, the more pronounced the QT interval prolongation. No QT interval prolongation was observed when the 30 mg/kg dose was administered via a 60-minute infusion.

In studies of the effects of moxifloxacin on animal reproductive function, it has been demonstrated that moxifloxacin crosses the placenta. Animal studies did not reveal teratogenic effects or impaired fertility after moxifloxacin administration. Slight increases in the frequency of spinal and rib malformations were observed in animals, but only after administration of a dose (20 mg/kg intravenously) 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 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 other antibacterial agents, usually recommended for initial treatment of these infections, are inappropriate.

Official guidelines on the proper use of antibacterial agents should be taken into account.

Contraindications.

• Hypersensitivity to moxifloxacin, other quinolone antibiotics, or any of the excipients;
• Pregnancy or breastfeeding (see section "Use during 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 drugs 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 drug vial is intended for single use only. Any unused solution must be discarded.

Solutions compatible with the 400 mg moxifloxacin infusion solution are: 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 concomitantly with other drugs.

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

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.

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 antiarrhythmic agents (e.g.: quinidine, hydroquinidine, disopyramide);
• Class III antiarrhythmic agents (e.g.: amiodarone, sotalol, dofetilide, ibutilide);
• Antipsychotic agents (e.g.: phenothiazines, pimozide, sertindole, haloperidol, sulpiride);
• Tricyclic antidepressants;
• Certain antimicrobial agents (saquinavir, sparfloxacin, intravenous erythromycin, pentamidine, antimalarial agents, particularly halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Other medicinal products (cisapride, intravenous vinca alkaloids, bepridil, difemanyl).

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

After multiple dosing of moxifloxacin in healthy volunteers, an increase in digoxin Cmax by approximately 30% was observed, without affecting AUC or the shape of the concentration-time curve.

In studies involving volunteers and diabetic patients, 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 could 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 infectious diseases and inflammatory processes, advanced age, and the patient's general condition. Therefore, it is difficult to determine whether changes in INR are caused by the infection or by the treatment. As a precautionary measure, INR can be monitored more frequently. Dose adjustment of the oral anticoagulant should be performed as needed.

Clinical studies have demonstrated the absence of clinically significant interaction between moxifloxacin and 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 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 treatment with moxifloxacin, especially in mild infections, should be evaluated considering the information contained in this section.

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

Therapy with moxifloxacin 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 used cautiously in 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.

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 the drug. In case of clinical manifestations of severe hypersensitivity reactions, moxifloxacin should be discontinued and appropriate treatment initiated (e.g., shock therapy).

Severe liver dysfunction

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 liver dysfunction occur.

Severe skin reactions

Cases of severe skin 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), have been reported during moxifloxacin therapy, which may be life-threatening or fatal (see section "Adverse reactions"). Patients should be warned about signs and symptoms of severe skin reactions and closely monitored during treatment. Moxifloxacin should be immediately discontinued and alternative therapy considered if symptoms suggestive of such reactions occur. Moxifloxacin therapy should never be resumed in patients who have developed severe skin reactions such as SJS, TEN, AGEP, or DRESS during treatment with moxifloxacin.

Patients predisposed to seizures

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

Prolonged, disabling, and potentially irreversible serious adverse reactions

Rare cases of prolonged (lasting several months or years), disabling, and potentially irreversible serious adverse reactions affecting various body systems (musculoskeletal, nervous system, psychiatric, and sensory organs) have been reported in patients treated with quinolones and fluoroquinolones, regardless of patient age or presence of risk factors. Moxifloxacin should be immediately discontinued at the first signs 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, hypoesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. 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 progressed to suicidal thoughts 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 diarrhea associated with Clostridium difficile, have been observed with the use of broad-spectrum antibiotics, including moxifloxacin. The severity of these conditions may range from mild diarrhea to fatal colitis. Therefore, it is important to consider the possibility of such a diagnosis in patients who develop severe diarrhea during or after moxifloxacin therapy. If suspected or confirmed AAD or AAC occurs, antimicrobial therapy, including moxifloxacin, should be discontinued immediately and appropriate therapeutic measures initiated. Additionally, appropriate measures to control infection and reduce transmission risk should be implemented. Antimotility agents are contraindicated in patients who develop severe diarrhea.

Patients with severe myasthenia

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

Tendon inflammation and tendon rupture

Tendon inflammation and ruptures (particularly of the Achilles tendon), sometimes bilateral, may occur during therapy with quinolones and fluoroquinolones, developing even within 48 hours of starting treatment and may persist for several months after discontinuation of therapy (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 those receiving concomitant corticosteroid therapy. Therefore, concomitant use with corticosteroids should be avoided.

If symptoms of tendinitis (e.g., painful swelling or inflammation) occur, moxifloxacin should be discontinued and alternative therapy considered. Appropriate treatment (e.g., immobilization) is required 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 aortic dissection, particularly in elderly patients, and development of regurgitation on aortic and mitral valves following fluoroquinolone use. Rare cases of aortic aneurysm and aortic dissection, sometimes complicated by rupture (including fatal), as well as regurgitation/insufficiency of any cardiac valve have been reported in patients treated with fluoroquinolones (see section "Adverse reactions"). Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and consideration of alternative therapies in patients with a history of aneurysm or congenital heart valve defect, in patients with diagnosed aortic aneurysm and/or aortic dissection, in patients with heart valve disease, and in the presence of other risk factors such as:

• Risk factors for both aortic aneurysm/dissection and valvular 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 valvular regurgitation/insufficiency: infective endocarditis.

The risk of developing aortic aneurysm and dissection, as well as rupture, is increased in patients receiving concomitant systemic corticosteroid therapy.

In case of sudden abdominal pain, chest pain, or back pain, patients should seek immediate medical help.

Patients should be advised to seek immediate medical attention if acute shortness of breath, rapid heartbeat, or development of abdominal or lower limb swelling 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 disorders

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

Prevention of photosensitization reactions

Photosensitization reactions have been reported in patients receiving quinolones. However, study data indicate that the risk of inducing 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 reduced glucose-6-phosphate dehydrogenase activity, 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. 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 the treatment of severe infections related to burns, fasciitis, and infected diabetic foot associated with osteomyelitis has not been established.

Effect on biological tests

Moxifloxacin may affect the results of tests 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

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").

Information about excipients

This medicinal product contains 787 mg (approximately 34 µmol) of sodium in 1 vial (250 ml infusion solution), equivalent to 39.35% of the maximum daily sodium intake for an adult (2 g) according to WHO recommendations.

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 for humans has not been established. Due to the experimentally demonstrated risk of 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 this medicinal product in women during breastfeeding. Preclinical studies indicate that a small amount of moxifloxacin passes into breast milk. Due to the lack of data on the effects on infants who are breastfed 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 influence 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 speed when 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.

Dosage and Administration

Dosage

The recommended dosage regimen is 400 mg of moxifloxacin administered as an intravenous 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.

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 via a Y-site catheter together with compatible infusion solutions (see section "Special Precautions for Use").

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 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 negative effects 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

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 administered orally or intravenously reduces systemic bioavailability by more than 80% or 20%, respectively. Administration of activated charcoal at the initial stage of absorption may effectively prevent excessive systemic exposure to moxifloxacin in cases of overdose following oral intake of the drug.

Adverse Reactions

The adverse reactions listed below were observed during clinical trials and the post-marketing period of moxifloxacin use at a dose of 400 mg once daily (intravenous therapy only, sequential [intravenous/oral], and oral). Adverse reactions are classified according to their frequency.

All adverse reactions, except nausea and diarrhea, occurred with 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), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from available data).

Infections and infestations

Common: superinfections associated with resistant bacteria or fungi, e.g., oral and vaginal candidiasis.

Blood and lymphatic system disorders

Uncommon: anemia, leukopenia, neutropenia, thrombocytopenia, thrombocytosis, eosinophilia, prolonged prothrombin time / increased INR.

Rare: elevated prothrombin levels / decreased INR, agranulocytosis, pancytopenia.

Immune system disorders

Uncommon: allergic reactions (see section "Special precautions for use").

Rare: anaphylaxis, including life-threatening shock in rare cases (see section "Special precautions for use"), angioedema / allergic edema, including potentially life-threatening laryngeal edema (see section "Special precautions for use").

Endocrine disorders

Rare: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolism and nutrition disorders

Uncommon: hyperlipidemia.

Rare: hyperglycemia, hyperuricemia.

Very rare: hypoglycemia, hypoglycemic coma.

Psychiatric disorders*

Uncommon: anxiety reactions, increased psychomotor activity/agitation.

Rare: mood lability, depression (in rare cases with self-aggression manifested as suicidal ideation/thoughts or suicide attempts) (see section "Special precautions for use"), hallucinations, delirium.

Very rare: depersonalization, psychotic reactions (sometimes with self-aggression manifested as suicidal ideation/thoughts or suicide attempts) (see section "Special precautions for use").

Nervous system disorders*

Common: headache, dizziness.

Uncommon: paresthesia/dysesthesia, taste disturbances (including ageusia in rare cases), confusion and disorientation, sleep disorders (mainly insomnia), tremor, vertigo, somnolence.

Rare: hypoesthesia, smell disturbances (including loss of smell), pathological dreams, coordination disorders (including gait disturbances due to dizziness or vertigo), seizures (including grand mal seizures) (see section "Special precautions for use"), attention disturbances, speech disorders, amnesia, peripheral neuropathy and polyneuropathy.

Very rare: hyperesthesia.

Eye disorders*

Uncommon: visual disturbances, including diplopia and blurred vision (especially during CNS reactions) (see section "Special precautions for use").

Rare: photophobia.

Very rare: transient visual loss (especially during CNS reactions) (see sections "Special precautions for use", "Ability to influence reaction rate when driving vehicles or operating machinery"), uveitis and bilateral acute iris transillumination (see section "Special precautions for use").

Ear and labyrinth disorders*

Rare: tinnitus, hearing disturbances including deafness (usually reversible).

Cardiac disorders**

Common: QT interval prolongation in patients with hypokalemia (see sections "Contraindications", "Special precautions for use").

Uncommon: QT interval prolongation (see section "Special precautions for use"), palpitations, tachycardia, atrial fibrillation, angina pectoris.

Rare: ventricular tachyarrhythmias, syncope (e.g., acute and brief loss of consciousness).

Very rare: non-specific arrhythmias, torsade de pointes (see section "Special precautions for use"), cardiac arrest (see section "Special precautions for use").

Vascular disorders**

Uncommon: vasodilation.

Rare: arterial hypertension, hypotension.

Very rare: vasculitis.

Respiratory, thoracic and mediastinal disorders

Uncommon: dyspnea (including asthmatic condition).

Gastrointestinal disorders

Common: nausea, vomiting, abdominal pain and discomfort, diarrhea.

Uncommon: decreased appetite and reduced food intake, constipation, dyspepsia, flatulence, gastritis, elevated amylase levels.

Rare: dysphagia, stomatitis, antibiotic-associated colitis (including pseudomembranous colitis, which in rare cases may lead to life-threatening complications) (see section "Special precautions for use").

Hepatobiliary disorders

Common: elevated transaminase levels.

Uncommon: liver function disorders (including elevated LDH [lactate dehydrogenase], elevated bilirubin, GGT [gamma-glutamyl transferase], alkaline phosphatase).

Rare: jaundice, hepatitis (mainly cholestatic).

Very rare: fulminant hepatitis, which may lead to life-threatening liver failure (see section "Special precautions for use").

Skin and subcutaneous tissue disorders

Uncommon: pruritus, rash, urticaria, dry skin.

Very rare: bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, which may be life-threatening (see section "Special precautions for use").

Frequency not known: acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) (see section "Special precautions for use"), fixed drug eruption, photosensitivity reactions (see section "Special precautions for use").

Musculoskeletal and connective tissue disorders*

Uncommon: arthralgia, myalgia.

Rare: tendinitis (see section "Special precautions for use"), increased muscle tone, muscle cramps, muscle weakness.

Very rare: tendon rupture (see section "Special precautions for use"), arthritis, increased muscle rigidity as a symptom of myasthenia gravis (see section "Special precautions for use").

Frequency not known: rhabdomyolysis.

Renal and urinary disorders

Uncommon: dehydration.

Rare: renal function disorders (including increased blood urea nitrogen and creatinine levels), renal failure (see section "Special precautions for use").

General disorders and administration site conditions*

Common: injection and infusion site reactions.

Uncommon: malaise (mainly asthenia or fatigue), pain (including back, chest, pelvic and limb pain), increased sweating, (thrombo-)phlebitis at infusion site.

Rare: edema.

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

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

The following effects occur more frequently with intravenous administration of the drug, with or without subsequent oral therapy:

Common: elevated gamma-glutamyl transferase levels.

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

Rare adverse effects reported after treatment with other fluoroquinolones, which are likely to occur also during moxifloxacin therapy, include: increased intracranial pressure (including idiopathic intracranial hypertension), hypernatremia, hypercalcemia, hemolytic anemia.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk profile of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Incompatibilities

The 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; 8.4% sodium bicarbonate solution.

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

Storage conditions.

No special storage conditions are required for this medicinal product. Do not refrigerate or freeze during storage. Keep out of reach of children.

Packaging.

250 ml in a vial. 1 vial in a carton.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's address and location of its business activity.

74 Kyrylivska Street, Kyiv, 04080, Ukraine.