Moflaxa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Moflaxa® (Moflaxa®)

Composition:

Active substance: moxifloxacin;

1 ml of infusion solution contains 1.6 mg of moxifloxacin as moxifloxacin hydrochloride;

1 vial (250 ml solution) contains 400 mg of moxifloxacin as moxifloxacin hydrochloride;

Excipients: sodium chloride, sodium lactate solution, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical properties: light yellowish-green clear solution, practically free from mechanical 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 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 breakpoints and disk diffusion breakpoints for moxifloxacin according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) (01.01.2015):

Microbiological susceptibility

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

Pharmacokinetics.

Absorption and Bioavailability

After a single 1-hour intravenous infusion of 400 mg, the maximum drug concentration 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 is about 39 mg*h/L after intravenous administration and only slightly exceeds that observed after oral administration (35 mg*h/L); the absolute bioavailability is approximately 91%.

There is no need to adjust the dose of moxifloxacin according to patient age or gender when administered intravenously.

Pharmacokinetics are linear following single oral doses in the range of 50–1200 mg, single intravenous doses up to 600 mg, and repeated daily doses of up to 600 mg 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 that plasma protein binding is about 40–42%, independent of drug concentration.

Moxifloxacin binds primarily to serum albumin.

Maximum concentrations of 5.4 mg/kg and 20.7 mg/L (geometric mean values) were observed in bronchial mucosa and epithelial lining fluid, respectively, at 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.

Metabolism

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

In vitro studies and Phase I clinical trials have shown no metabolic pharmacokinetic interactions with other drugs metabolized by phase I pathways, including cytochrome P450 enzymes. There is no evidence of oxidative metabolism.

Elimination

The elimination half-life of moxifloxacin in 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 drug excreted in urine is about 22% and in feces about 26%. Cumulative excretion (unchanged drug and metabolites) totals approximately 98% after intravenous administration. Renal clearance is approximately 24–53 mL/min, indicating partial tubular reabsorption of the drug. Concomitant administration of moxifloxacin with ranitidine or probenecid does not alter the renal clearance of the parent drug.

Renal Impairment

No significant changes in moxifloxacin pharmacokinetics have been observed in patients with renal impairment (including those with creatinine clearance > 20 mL/min/1.73 m²). However, as renal function declines, the concentration of metabolite M2 (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 insufficiency (Child–Pugh classes A and B) are insufficient to definitively determine whether differences exist between patients with impaired liver function and healthy volunteers. Hepatic impairment was associated with higher plasma concentrations of metabolite M1, while concentrations of the parent drug were similar to those 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, moxifloxacin caused hematological and hepatotoxic effects. Toxic effects on the central nervous system (CNS) were also observed. These effects occurred after administration of high doses 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 administered as slow infusions (40 mg/kg 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 vitro in bacterial and mammalian cell assays. However, no genotoxicity was observed in vivo, even with very high doses of moxifloxacin. Moxifloxacin did not show 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 infusion-rate-dependent: the shorter the infusion duration, the greater the QT prolongation. No QT prolongation was observed when the 30 mg/kg dose was administered over 60 minutes.

Studies on the effects of moxifloxacin on animal reproductive function have demonstrated that moxifloxacin crosses the placenta. Animal studies did not reveal teratogenic effects or impaired fertility after moxifloxacin administration. Slight increases in the incidence of spinal and rib malformations were observed in animals, but only at doses associated with marked maternal toxicity (20 mg/kg intravenously). Increased rates of pregnancy loss were observed in animals at plasma concentrations comparable to therapeutic levels expected in humans.

It is known that quinolones, including moxifloxacin, cause damage to cartilage in 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 typically recommended for initial treatment of these infections are inappropriate.

Official guidelines on the appropriate use of antibacterial agents should be followed.

Contraindications.

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

During preclinical and clinical studies, changes in electro-physiological parameters of cardiac activity, manifested as QT interval prolongation, were observed after moxifloxacin administration. 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 administered concomitantly with drugs that prolong the QT interval (see 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.

Moflaxa® infusion solution should be used immediately after first opening. The medicinal product is intended for single use only in its original form. Any unused solution must be disposed of according to local regulations.

Moflaxa®, 400 mg/250 ml infusion solution, is compatible with the following infusion solutions:

• Water for injections;
• 0.9% Sodium chloride solution (9 mg/ml);
• 1 Molar Sodium chloride solution (1 mol/l);
• 5% Glucose solution (50 mg/ml);
• 10% Glucose solution (100 mg/ml);
• 40% Glucose solution (400 mg/ml);
• 20% Xylitol solution (200 mg/ml);
• Ringer's solution;
• Mixture of sodium lactate solution (Hartmann's solution, Lactated Ringer's solution).

Moxifloxacin infusion solution must not be administered simultaneously with other medicinal products.

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

Issues related to incompatibility are discussed in the section "Incompatibility".

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 QT 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 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, antimalarials including halofantrine);
• Certain antihistamines (terfenadine, astemizole, mizolastine);
• Other medicinal products (cisapride, intravenous vinpocetine, bepridil, difeminal).

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

After multiple doses of moxifloxacin in healthy volunteers, an increase in digoxin Cmax of approximately 30% was observed, without affecting AUC or trough levels.

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

Change in International Normalized Ratio (INR)

Numerous cases of increased activity of oral anticoagulants have been reported in patients receiving antimicrobial agents, particularly fluoroquinolones, macrolides, tetracyclines, cotrimoxazole, and certain cephalosporins. Risk factors include infectious diseases and inflammatory processes, 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. More frequent monitoring of INR is recommended. If necessary, appropriate dose adjustment of the oral anticoagulant should be performed.

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

In vitro studies using human cytochrome P450 enzymes have 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.

Moxifloxacin should be avoided in patients who have previously experienced serious adverse reactions to drugs containing quinolone or fluoroquinolone (see section "Adverse reactions"). Treatment with moxifloxacin in these patients should only be initiated if no alternative therapy is available and after careful assessment of the benefit-risk ratio (see also section "Contraindications").

The benefits of moxifloxacin therapy, especially in the case of mild infections, must be evaluated considering the information contained in this section.

QT interval prolongation and clinical conditions in which QT interval prolongation may occur

Therapy with moxifloxacin should be discontinued if symptoms that may be related to cardiac arrhythmia occur during treatment, regardless of whether these are 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 arrhythmia (including polymorphic ventricular tachycardia such as torsades de pointes) and cardiac arrest (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction"). Moxifloxacin should be used cautiously in patients receiving medicinal products that may reduce potassium levels (see 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 section "Contraindications").

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

Aortic aneurysm and dissection, valvular regurgitation/incompetence

Epidemiological studies have reported an increased risk of aortic aneurysm and dissection, particularly in elderly patients, as well as aortic and mitral valve regurgitation following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal outcomes), and regurgitation/incompetence 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 positive family history of aneurysm or congenital valvular disease, or in patients diagnosed with existing aortic aneurysm and/or dissection or valvular disease, or in the presence of other risk factors, or in predisposing conditions:

• for both aortic aneurysm and dissection, and valvular regurgitation/incompetence (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/incompetence (e.g., infective endocarditis).

The risk of aortic aneurysm, dissection, and rupture may also be increased in patients concurrently receiving systemic corticosteroids.

Patients should be advised to seek immediate medical attention at an emergency department 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 palpitations, or the development of abdominal or lower limb edema.

Hypersensitivity/allergic reactions

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

Severe hepatic impairment

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

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

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) 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 fatal (see section "Adverse reactions"). Patients receiving moxifloxacin should be informed about the signs and symptoms of severe skin reactions and closely monitored. If signs or symptoms suggestive of these reactions occur, moxifloxacin should be immediately discontinued and alternative therapy considered. If a serious adverse reaction such as SJS, TEN, AGEP, or DRESS develops 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 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

Very rare cases of prolonged (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric, and sensory systems) have been reported in patients receiving quinolones and fluoroquinolones, regardless of age or pre-existing risk factors. Moxifloxacin should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and patients should contact the prescribing physician.

Peripheral neuropathy

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

Psychiatric reactions

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

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 observed 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 suspected or confirmed AAD or AAC occurs, antimicrobial therapy, including moxifloxacin, should be discontinued and appropriate therapeutic measures initiated immediately. Additionally, appropriate infection control measures should be implemented to reduce transmission risk. Antiperistaltic agents 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 rupture (particularly, but not limited to, Achilles tendon), sometimes bilateral, may occur during therapy with quinolones or fluoroquinolones, including moxifloxacin. These may develop within 48 hours of starting treatment and may persist for several months after discontinuation. 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 early signs of tendinitis (e.g., painful swelling, inflammation) occur, moxifloxacin treatment should be discontinued and alternative therapy considered. The affected limb(s) should be appropriately managed (e.g., immobilization). Corticosteroids should not be used if signs of tendinopathy are present (see sections "Contraindications" and "Adverse reactions").

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

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

Dysglycemia

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

Prevention of photosensitivity reactions

Photosensitivity reactions have been observed in patients receiving quinolones. However, clinical studies indicate that the risk of photosensitivity reactions with moxifloxacin is low. Nevertheless, patients should avoid prolonged and/or intense exposure to sunlight or ultraviolet radiation during moxifloxacin treatment (see section "Adverse reactions").

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as well as those with a family history of this condition, are prone to hemolytic reactions during quinolone therapy. Therefore, moxifloxacin should be used cautiously 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.

Effect on biological tests

Moxifloxacin may affect the results of tests for Mycobacterium spp. by suppressing mycobacterial growth, potentially leading 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 (MRSA). If MRSA infection is suspected or confirmed, appropriate antibacterial therapy should be initiated (see section "Pharmacodynamics").

Patients on a salt-restricted diet

The medicinal product contains 811.9 mg (approximately 35.3 µmol) of sodium in 250 mL of solution. Patients on a salt-restricted 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 to humans is unknown. Due to experimentally demonstrated harmful effects of fluoroquinolones on weight-bearing cartilage in immature animals, and considering the development of reversible joint damage in children treated with certain fluoroquinolones, moxifloxacin is contraindicated in pregnant women (see section "Contraindications").

Breastfeeding

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

Fertility

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

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

Dosage

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

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

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

Method of Administration

The drug should be administered intravenously as a continuous infusion over not less than 60 minutes (see section "Special Instructions").

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

Renal 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 (see section "Pharmacological Properties" for more details).

Hepatic Impairment

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 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 is possible, ECG monitoring is required. Concomitant administration of activated charcoal with a 400 mg dose of moxifloxacin, whether given orally or intravenously, may reduce systemic bioavailability by more than 80% or 20%, respectively. Administration of activated charcoal during the early stages of absorption may effectively prevent excessive systemic exposure to moxifloxacin in cases of oral overdose.

Adverse Reactions

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

All adverse reactions, except nausea and diarrhea, occurred at a frequency of less than 3%.

Within each group, adverse events are listed in decreasing order of frequency. Frequency categories are defined as follows: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), infrequent (≥1/10000, <1/1000), rare (<1/10000), and frequency not known (cannot be estimated based on available data).

1See section "Special precautions".

2Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious adverse reactions associated with the use of quinolones and fluoroquinolones affecting multiple, sometimes numerous, organ system classes and sensory organs (including such reactions as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbance, neuropathy (associated with paresthesia and neuralgia), fatigue, psychiatric symptoms (including sleep disorders, anxiety, panic attacks, depression and suicidal thoughts), memory and concentration impairment, and hearing, vision, taste and smell disturbances), regardless of existing risk factors (see section "Special precautions").

3See sections "Special precautions", "Effect on ability to drive and use machines".

4In patients receiving fluoroquinolones, cases of aneurysms and aortic dissection, sometimes complicated by rupture (including fatal outcomes), and regurgitation/insufficiency of any cardiac valve have been reported (see section "Special precautions").

5See sections "Contraindications", "Special precautions".

The frequency of occurrence of the following effects is higher when the intravenous route of administration is used, with or without subsequent oral therapy.

Common: increased gamma-glutamyl transferase levels.

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

Rarely, after treatment with other fluoroquinolones, adverse effects have been reported which may also occur during treatment with moxifloxacin: increased intracranial pressure (including pseudotumor cerebri), hypernatraemia, hypercalcaemia, haemolytic anaemia, rhabdomyolysis.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, 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. 5 years.

Immediate use after first opening.

Storage conditions.

This medicinal product does not require special temperature storage conditions. Keep out of the reach and sight of children.

Incompatibilities.

The medicinal product is incompatible with the following solutions:

• sodium chloride solutions 10% (100 mg/ml) and 20% (200 mg/ml);
• sodium bicarbonate solutions 4.2% (42 mg/ml) and 8.4% (84 mg/ml).

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

Packaging.

250 ml infusion solution in a vial; 1, 5 or 10 vials in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto/KRKA, d.d., Novo mesto.

Address of the manufacturer and location of its business operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia/Smarjeska cesta 6, 8501 Novo mesto, Slovenia.